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163 Cards in this Set
- Front
- Back
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What are the ways a HCP can order medication/drugs?
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Prescriptions can be given by written orders, telephone orders (TO or PO), and verbal orders (VO) by a licensed health care provider.
TO must be received and documented by an RN, and then cosigned by the provider who gave them within 24 hours. (Week 1) |
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Who can write a prescription?
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Physicians - MD, DO
Advanced Practice Nurses - APRN Physician Assistants - PA Dentists - DDS, DMD Podiatrists - DPM (Week 1) |
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Who fills prescriptions and administers medication?
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A licensed pharmacist fulls prescriptions. Medications are administered by a licensed nurse, RN or LPN.
(Week 1) |
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What information is required on a medication order?
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Date and time of order
Drug name (generic preferred) Drug dosage Route of administration Frequency and duration (e.g. BID x7 days) Any special instructions (e.g. AC) HCP signature or name if TO or VO RN signature taking the order (Week 1) |
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What are the types of drug orders?
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Standing orders
One-time (single) orders PRN orders STAT orders *Narcotic orders are not automatically refilled. If extended, a new prescription is needed. (Week 1) |
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What are the principles of drug administration?
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Traditional 5 Rights:
right client right drug right dose right time right route (Week 1) |
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What are the additional principles of drug administration?
(These are particularly important to the nurse.) |
Additional 5 Rights:
right assessment right documentation client's right to education right evaluation client's right to refuse (Week 1) |
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Guidelines for Medication Preparation
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Preparation
1. Wash hands before preparing medications. 2. Check for drug allergies; check the assessment history and Kardex. 3. Check medication order with health care provider's orders, Kardex, medicine sheet, and medicine card. 4. Check label on drug container three times. 5. Check expiration date on drug label, card, and Kardex; use only if date is current. 6. Recheck drug calculation of drug dose with another nurse as needed or by policy. 7. Verify doses of drugs that are potentially toxic with another nurse or pharmacist. 8. Pour tablet or capsule into the cap of the drug container. With unit dose, open packet at bedside after verifying client identification. 9. Pour liquid at eye level. The meniscus (the lower curve of the liquid) should be at the line of desired dose (see Figure 4-2). 10. Dilute drugs that irritate the gastric mucosa (e.g., potassium, aspirin), or give with meals. (p. 33) |
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Guidelines for Medication Administration
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Administration
11. Administer only drugs that you have prepared. Do not prepare medications to be administered by another person. 12. Identify the client by ID band or ID photo. 13. Offer ice chips to numb the client's taste buds when giving bad-tasting drugs. 14. When possible, give bad-tasting medications first, followed by pleasant-tasting liquids. 15. Assist the client to an appropriate position, depending on the route of administration. 16. Provide only liquids allowed on the diet. 17. Stay with the client until the medications are taken. 18. Administer no more than 2.5 to 3 mL of solution intramuscularly at one site. Infants receive no more than 1 mL of solution intramuscularly at one site and no more than 1 mL subcutaneously. Never recap needles (Universal Precautions). 19. When administering drugs to a group of clients, give drugs last to clients who need extra assistance. 20. Discard needles and syringes in appropriate containers. 21. Drug disposal is dependent on agency policy and state law. For example, discard drugs in the sink or toilet, not in the trash can. Controlled substances must be returned to the pharmacy. Some disposals need signatures of witnesses. 22. Discard unused solutions from ampules. 23. Appropriately store (some require refrigeration) unused stable solutions from open vials. 24. Write date and time opened and your initials on the label. 25. Keep narcotics in a double-locked drawer or closet. Medication carts must be locked at all times when a nurse is not in attendance. 26. Keys to the opioids drawer must be kept by the nurse and not stored in a drawer or closet. 27. Keep opioids in a safe place, out of reach of children and others in the home. 28. Avoid contamination of one's own skin or inhalation to minimize chances of allergy or sensitivity development. (p. 33) |
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Guideline for Recording Medication Administration
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Recording
29. Report drug error immediately to the client's health care provider and to the nurse manager. 30. Complete an incident report. 31. Charting: record drug given, dose, time, route, and your initials. 32. Record drugs promptly after given, especially STAT doses. 33. Record effectiveness and results of medication administered, especially PRN medications. 34. Report to the client's health care provider and record drugs that were refused with the reason for refusal. 35. Record amount of fluid taken with medications on input and output chart. ID, Identification; PRN, as needed; STAT, immediately. (p. 33) |
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Do not use these abbreviations:
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U or IU – write: units or international units
QD –write: every day or daily QOD – write: every other day MSO4 & MS – write: morphine sulfate MgSO4 – write: magnesium sulfate Trailing zero after whole #(2.0mg) - Write: “2 mg” Lack of leading zero (.2mg) - Write: “0.2 mg” c.c. – use: ml or millimeter g – use: mcg or microgram > - write: greater than < - write: less than Drug names – write: full name Apothecary units – use: metric units @ - write: “at” |
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What are the three phases a drug taken by mouth goes through?
(The 3 Phases of Drug Action) |
drug taken by mouth goes through three phases—pharmaceutic (dissolution), pharmacokinetic, and pharmacodynamic—as drug actions occur. In the pharmaceutic phase, the drug becomes a solution so that it can cross the biologic membrane. When the drug is administered parenterally by subcutaneous (subQ), intramuscular (IM), or intravenous (IV) routes, there is no pharmaceutic phase. The second phase, the pharmacokinetic phase, is composed of four processes: absorption, distribution, metabolism (or biotransformation), and excretion (or elimination). In the pharmacodynamic phase, a biologic or physiologic response results. (p. 3)
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pharmacokinetics
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Pharmacokinetics is the process of drug movement to achieve drug action. The four processes are absorption, distribution, metabolism (or biotransformation), and excretion (or elimination). The nurse applies knowledge of pharmacokinetics when assessing the client for possible adverse drug effects. The nurse communicates assessment findings to members of the health care team in a timely manner to promote safe and effective drug therapy for the client. (p. 4)
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absorption
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Absorption is the movement of drug particles from the GI tract to body fluids by passive absorption, active absorption, or pinocytosis. Most oral drugs are absorbed into the surface area of the small intestine through the action of the extensive mucosal villi. Absorption is reduced if the villi are decreased in number because of disease, drug effect, or the removal of small intestine. Protein-based drugs such as insulin and growth hormones are destroyed in the small intestine by digestive enzymes.
The GI membrane is composed mostly of lipid (fat) and protein, so drugs that are lipid soluble pass rapidly through the GI membrane. Water-soluble drugs need a carrier, either enzyme or protein, to pass through the membrane. Large particles pass through the cell membrane if they are nonionized (have no positive or negative charge). Weak acid drugs such as aspirin are less ionized in the stomach, and they pass through the stomach lining easily and rapidly. REMEMBER: Drugs that are lipid soluble and nonionized are absorbed faster than water-soluble and ionized drugs. Blood flow, pain, stress, hunger, fasting, food, and pH affect drug absorption. Poor circulation as a result of shock, vasoconstrictor drugs, or disease hampers absorption. Pain, stress, and foods that are solid, hot, and fatty can slow gastric emptying time, so the drug remains in the stomach longer. Exercise can decrease blood flow by causing more blood to flow to the peripheral muscle, thereby decreasing blood circulation to the GI tract. Drugs given IM are absorbed faster in muscles that have more blood vessels (e.g., the deltoids) than in those that have fewer blood vessels (e.g., the gluteals). Subcutaneous tissue has fewer blood vessels, so absorption is slower in such tissue. (p. 4) |
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first-pass effect
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First Pass Effect – Drug passes through liver before entering systemic circulation; Chemical and biological barriers in GI environ (Week 1)
Some drugs do not go directly into the systemic circulation following oral absorption but pass from the intestinal lumen to the liver via the portal vein. In the liver, some drugs may be metabolized to an inactive form that may then be excreted, thus reducing the amount of active drug. Some drugs do not undergo metabolism at all in the liver, and others may be metabolized to drug metabolite, which may be equally or more active than the original drug. The process in which the drug passes to the liver first is called the first-pass effect, or hepatic first pass. Examples of drugs with first-pass metabolism are warfarin (Coumadin) and morphine. Lidocaine and some nitroglycerins are not given orally because they have extensive first-pass metabolism and therefore most of the dose would be destroyed. (p. 4) |
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How and where are drugs metabolized?
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Drugs can be metabolized in both the GI tract and liver; however, the liver is the primary site of metabolism. Most drugs are inactivated by liver enzymes and are then converted or transformed by hepatic enzymes to inactive metabolites or water-soluble substances for excretion. A large percentage of drugs are lipid soluble; thus the liver metabolizes the lipid-soluble drug substance to a water-soluble substance for renal excretion. However, some drugs are transformed into active metabolites, causing an increased pharmacologic response. Liver diseases such as cirrhosis and hepatitis alter drug metabolism by inhibiting the drug-metabolizing enzymes in the liver. When the drug metabolism rate is decreased, excess drug accumulation can occur and lead to toxicity. ( p. 6)
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distribution & protein-binding effect
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Process by which drug becomes available to body fluids & tissues. (Week 1)
Distribution is the process by which the drug becomes available to body fluids and body tissues. Drug distribution is influenced by blood flow, the drug's affinity to the tissue, and the protein-binding effect (Figure 1-3). In addition, volume of drug distribution (Vd) is dependent on drug dose and its concentration in the body. Drugs with a larger volume of drug distribution have a longer half-life and stay in the body longer. As drugs are distributed in the plasma, many are bound to varying degrees (percentages) with protein (primarily albumin). Drugs that are greater than 89% bound to protein are known as highly protein-bound drugs; drugs that are 61% to 89% bound to protein are moderately highly protein-bound; drugs that are 30% to 60% bound to protein are moderately protein-bound; and drugs that are less than 30% bound to protein are low protein-bound drugs. The portion of the drug that is bound is inactive because it is not available to receptors, and the portion that remains unbound is free, active drug. Only free drugs (drugs not bound to protein) are active and can cause a pharmacologic response. As the free drug in the circulation decreases, more bound drug is released from the protein to maintain the balance of free drug. When two highly protein-bound drugs are given concurrently, they compete for protein-binding sites, thus causing more free drug to be released into the circulation. In this situation, drug accumulation and possible drug toxicity can result. Also, a low protein level decreases the number of protein-binding sites and can cause an increase in the amount of free drug in the plasma. Drug overdose may then result. Drug dose is prescribed according to the percentage in which the drug binds to protein. Some drugs bind with a specific protein component such as albumin or globulin. Most anticonvulsants bind primarily to albumin. Some basic drugs such as antidysrhythmics (e.g., lidocaine, quinidine) bind mostly to globulins. Clients with liver or kidney disease or those who are malnourished may have an abnormally low serum albumin level. This results in fewer protein-binding sites, which in turn leads to excess free drug and eventually to drug toxicity. Older adults are more likely to have hypoalbuminemia. To avoid possible drug toxicity, checking the protein-binding percentage of all drugs administered to a client is important. The nurse should also check the client's plasma protein and albumin levels, because a decrease in plasma protein (albumin) decreases protein-binding sites, permitting more free drug in the circulation. Depending on the drug, the result could be life-threatening. (pp. 5-6) |
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What does it mean to be highly protein bound?
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Drugs that are greater than 89% bound to protein are known as highly protein-bound drugs; drugs that are 61% to 89% bound to protein are moderately highly protein-bound; drugs that are 30% to 60% bound to protein are moderately protein-bound; and drugs that are less than 30% bound to protein are low protein-bound drugs. (p. 5)
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How are drugs usually excreted?
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The main route of drug elimination is through the kidneys (urine). Other routes include bile, feces, lungs, saliva, sweat, and breast milk. The kidneys filter free unbound drugs, water-soluble drugs, and drugs that are unchanged. Protein-bound drugs cannot be filtered through the kidneys. Once the drug is released from the protein, it is a free drug and is eventually excreted in the urine. The lungs eliminate volatile drug substances and products metabolized to carbon dioxide (CO2) and water (H2O).
The urine pH influences drug excretion. Urine pH varies from 4.5 to 8. Acidic urine promotes elimination of weak base drugs, and alkaline urine promotes elimination of weak acid drugs. Aspirin, a weak acid, is excreted rapidly in alkaline urine. If a person takes an overdose of aspirin, sodium bicarbonate may be given to change the urine pH to alkaline to help potentiate excretion of the drug. Large quantities of cranberry juice can decrease urine pH, causing acidic urine and thus inhibiting the elimination of aspirin. With a kidney disease that results in decreased glomerular filtration rate (GFR) or decreased renal tubular secretion, drug excretion is slowed or impaired. Drug accumulation with possible severe adverse drug reactions can result. A decrease in blood flow to the kidneys can also alter drug excretion. The most accurate test to determine renal function is creatinine clearance (CLcr). Creatinine is a metabolic by-product of muscle that is excreted by the kidneys. The creatine clearance test compares the level of creatine in the urine with the level of creatine in the blood. Creatinine clearance varies with age and gender. Lower values are expected in older adult and female clients because of their decreased muscle mass. A decrease in renal GFR results in an increase in serum creatinine level and a decrease in urine creatinine clearance. With renal dysfunction either in older adults or as a result of kidney disorders, drug dosage usually needs to be decreased. In these cases, the creatinine clearance needs to be determined to establish appropriate drug dosage. When the creatinine clearance is decreased, drug dosage likewise may need to be decreased. Continuous drug dosing according to a prescribed dosing regimen without evaluating creatinine clearance could result in drug toxicity. The creatinine clearance test consists of a 12- or 24-hour urine collection and a blood sample. Normal creatinine clearance is 85 to 135 mL/min. This rate decreases with age because aging decreases muscle mass and results in a decrease in functioning nephrons. Older adult clients may have a creatinine clearance of 60 mL/min. For this reason, the drug dosage in older adults may need to be decreased. (pp. 6-7) |
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pharmacodynamics
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Pharmacodynamics is the study of drug concentration and its effects on the body. Drug response can cause a primary or secondary physiologic effect or both. The primary effect is desirable, and the secondary effect may be desirable or undesirable. An example of a drug with a primary and secondary effect is diphenhydramine (Benadryl), an antihistamine. The primary effect of diphenhydramine is to treat the symptoms of allergy, and the secondary effect is a central nervous system depression that causes drowsiness. The secondary effect is undesirable when the client drives an automobile, but at bedtime it could be desirable because it causes mild sedation.
ll drugs have a maximum drug effect (maximal efficacy). For example, morphine and propoxyphene hydrochloride (Darvon) are prescribed to relieve pain. The maximum efficacy of morphine is greater than propoxyphene hydrochloride, regardless of how much propoxyphene hydrochloride is given. The pain relief with the use of propoxyphene hydrochloride is not as great as it is with morphine. (p. 7) |
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bioavailability
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Bioavailability - % drug that reaches systemic circulation
PO drugs always < 100% IV drugs usually 100% (no first pass effect) (Week 1) Bioavailability is a subcategory of absorption. It is the percentage of the administered drug dose that reaches the systemic circulation. For the oral route of drug administration, bioavailability occurs after absorption and hepatic drug metabolism. The percentage of bioavailability for the oral route is always less than 100%, but for the intravenous route it is usually 100%. Oral drugs that have a high first-pass hepatic metabolism may have a bioavailability of only 20% to 40% on entering systemic circulation. To obtain the desired drug effect, the oral dose could be three to five times larger than the drug dose for IV use. Factors that alter bioavailability include (1) the drug form (e.g., tablet, capsule, sustained-release, liquid, transdermal patch, rectal suppository, inhalation), (2) route of administration (e.g., oral, rectal, topical, parenteral), (3) GI mucosa and motility, (4) food and other drugs, and (5) changes in liver metabolism caused by liver dysfunction or inadequate hepatic blood flow. A decrease in liver function or a decrease in hepatic blood flow can increase the bioavailability of a drug, but only if the drug is metabolized by the liver. Less drug is destroyed by hepatic metabolism in the presence of liver disorder. (pp. 4-5) |
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half-life
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The half-life (t½) of a drug is the time it takes for one half of the drug concentration to be eliminated. Metabolism and elimination affect the half-life of a drug. For example, with liver or kidney dysfunction, the half-life of the drug is prolonged and less drug is metabolized and eliminated. When a drug is taken continually, drug accumulation may occur.
A drug goes through several half-lives before more than 90% of the drug is eliminated. If the client takes 650 mg of aspirin and the half-life is 3 hours, it takes 3 hours for the first half-life to eliminate 325 mg, 6 hours for the second half-life to eliminate an additional 162 mg, and so on until the sixth half-life (or 18 hours), when 10 mg of aspirin is left in the body (Table 1-2). A short half-life is considered to be 4 to 8 hours, and a long one is 24 hours or longer. If the drug has a long half-life (such as digoxin at 36 hours), it takes several days for the body to completely eliminate the drug. By knowing the half-life, the time it takes for a drug to reach a steady state of serum concentration can be computed. Administration of the drug for three to five half-lives saturates the biologic system to the extent that the intake of drug equals the amount metabolized and excreted. An example is digoxin, which has a half-life of 36 hours with normal renal function. It would take approximately 5 days to 1 week (three to five half-lives) to reach a steady-state for digoxin concentration. Steady-state serum concentration is predictive of therapeutic drug effect. (p. 6) |
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onset, peak, & duration of action
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One important aspect of pharmacodynamics is knowing the drug's onset, peak, and duration of action. Onset of action is the time it takes to reach the minimum effective concentration (MEC) after a drug is administered. Peak action occurs when the drug reaches its highest blood or plasma concentration. Duration of action is the length of time the drug has a pharmacologic effect.
It is necessary to understand the time response in relationship to drug administration. If the drug plasma or serum level decreases below threshold or MEC, adequate drug dosing is not achieved; too high a drug level above the minimum toxic concentration (MTC) can result in toxicity. (p. 7) |
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agonists vs antagonists
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Drugs that produce a response are called agonists, and drugs that block a response are called antagonists. Isoproterenol (Isuprel) stimulates beta1 and beta2 receptors, so it is an agonist. Cimetidine (Tagamet), an antagonist, blocks the histamine (H2) receptor, thus preventing excessive gastric acid secretion. The effects of an antagonist can be determined by the inhibitory (I) action of the drug concentration on the receptor site. IC50 is the antagonist drug concentration required to inhibit 50% of the maximum biological response.
Many agonists and antagonists, lack specific and selective effects. A receptor produces a variety of physiologic responses, depending on where in the body that receptor is located. (p. 8) |
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naloxone
(Narcan) |
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4 categories of drug action
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The four categories of drug action include (1) stimulation or depression, (2) replacement, (3) inhibition or killing of organisms, and (4) irritation. In drug action that stimulates, the rate of cell activity or the secretion from a gland increases. In drug action that depresses, cell activity and function of a specific organ are reduced. Replacement drugs such as insulin replace essential body compounds. Drugs that inhibit or kill organisms interfere with bacterial cell growth (e.g., penicillin exerts its bactericidal effects by blocking the synthesis of the bacterial cell wall). Drugs also can act by the mechanism of irritation (e.g., laxatives irritate the inner wall of the colon, thus increasing peristalsis and defecation).
Drug action might last hours, days, weeks, or months. The length of action depends on the half-life of the drug; therefore the half-life is a reasonable guide for the determination of drug dosage intervals. Drugs with a short half-life such as penicillin G (2 hours) are given several times a day. Drugs with a long half-life such as digoxin (36 hours) are given once a day. If a drug with a long half-life is given two or more times a day, drug accumulation in the body and drug toxicity are likely to result. If there is liver or renal impairment, the half-life of the drug increases. In these cases, high doses of the drug or too-frequent dosing can result in drug toxicity. (pp. 8-9) |
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therapeutic index
therapeutic range therapeutic window |
Therapeutic index
Low: Narrow margin of safety High: Wide margin of safety (Week 1) The safety of drugs is a major concern. The therapeutic index (TI) estimates the margin of safety of a drug through the use of a ratio that measures the effective (therapeutic or concentration) dose (ED) in 50% of persons or animals (ED50) and the lethal dose (LD) in 50% of animals (LD50) (Figure 1-8). The closer the ratio is to 1, the greater the danger of toxicity. TI = LD50/ED50 In some cases, the ED may be 25% (ED25) or 75% (ED75). Drugs with a low therapeutic index have a narrow margin of safety (Figure 1-9, A). Drug dosage might need adjustment, and plasma (serum) drug levels need to be monitored because of the small safety range between ED and LD. Drugs with a high therapeutic index have a wide margin of safety and less danger of producing toxic effects (Figure 1-9, B). Plasma (serum) drug levels do not need to be monitored routinely for drugs with a high TI. The therapeutic range (therapeutic window) of a drug concentration in plasma should be between the minimum effective concentration in the plasma for obtaining desired drug action and the minimum toxic concentration (the toxic effect). When the therapeutic range is given, it includes both protein-bound and unbound portions of the drug. Drug reference books give many plasma (serum) therapeutic ranges of drugs. If the therapeutic range is narrow, such as for digoxin (0.5 to 1 ng/mL), the plasma drug level should be monitored periodically to avoid drug toxicity. Monitoring the therapeutic range is not necessary if the drug is not considered highly toxic. (p. 9) |
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peak drug level
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Peak drug level is the highest plasma concentration of drug at a specific time. Peak drug levels indicate the rate of absorption. If the drug is given orally, the peak time might be 1 to 3 hours after drug administration. If the drug is given IV, the peak time might occur in 10 minutes. A blood sample should be drawn at the proposed peak time, according to the route of administration. (p. 9)
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trough drug level
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The trough drug level is the lowest plasma concentration of a drug, and it measures the rate at which the drug is eliminated. Trough levels are drawn immediately before the next dose of drug is given, regardless of route of administration. Peak levels indicate the rate of absorption of the drug, and trough levels indicate the rate of elimination of the drug. Peak and trough levels are requested for drugs that have a narrow therapeutic index and are considered toxic, such as the aminoglycoside antibiotics (Table 1-4). If either the peak or trough level is too high, toxicity can occur. If the peak is too low, no therapeutic effect is achieved. (p. 9)
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loading dose
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When immediate drug response is desired, a large initial dose, known as the loading dose, of drug is given to achieve a rapid minimum effective concentration in the plasma. After a large initial dose, a prescribed dosage per day is ordered. Digoxin, a digitalis preparation, requires a loading dose when first prescribed. Digitalization is the process by which the minimum effective concentration level for digoxin is achieved in the plasma within a short time. (p.10)
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types of drug interactions
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Additive effects: Sum of the effects
Synergism or potentiation: clinical effect is greater than simply the combined effect of the two Drug Interference: one creates a difference in the other Displacement: one takes the place of another Antagonism: one cancels the effect of the other (that’s why we give Narcan in an overdose situation) |
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side effects
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Side effects are physiologic effects not related to desired drug effects. All drugs have side effects, desirable or undesirable. Even with a correct drug dosage, side effects occur and are predicted. Side effects result mostly from drugs that lack specificity, such as bethanechol (Urecholine). In some health problems, side effects may be desirable (e.g., the use of diphenhydramine HCl [Benadryl] at bedtime when its side effect of drowsiness is beneficial). At times, however, side effects are called adverse reactions. The terms side effects and adverse reactions are sometimes used interchangeably in the literature and in speaking but they are different. Some side effects are expected as part of drug therapy. The occurrence of these expected but undesirable side effects is not a reason to discontinue therapy. The nurse's role includes teaching clients to report any side effects. Many can be managed with dosage adjustments, changing to a different drug in the same class of drugs, or implementing other interventions. It is important to know that the occurrence of side effects is one of the primary reasons clients stop taking the prescribed medication. (p. 10)
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adverse reactions
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Adverse reactions are more severe than side effects. They are a range of untoward effects (unintended and occurring at normal doses) of drugs that cause mild to severe side effects, including anaphylaxis (cardiovascular collapse). Adverse reactions are always undesirable. Adverse effects must always be reported and documented because they represent variances from planned therapy. (p. 10)
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toxicity
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Toxic effects, or toxicity, of a drug can be identified by monitoring the plasma (serum) therapeutic range of the drug. However, for drugs that have a wide therapeutic index, the therapeutic ranges are seldom given. For drugs with a narrow TI, such as aminoglycoside antibiotics and anticonvulsants, the therapeutic ranges are closely monitored. When the drug level exceeds the therapeutic range, toxic effects are likely to occur from overdosing or drug accumulation. (pp. 10-11)
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pharmacogenetics
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Pharmacogenetics is the scientific discipline studying how the effect of a drug action varies from a predicted drug response because of genetic factors or hereditary influence. Because people have different genetic makeup, they do not always respond identically to a drug dosage or planned drug therapy. Genetic factors can alter the metabolism of the drug in converting its chemical form to an inert metabolite; thus the drug action can be enhanced or diminished. Some persons are less or more sensitive to drugs and their drug actions because of genetic factors. For example, African Americans do not respond as well as Caucasians to some classes of antihypertensive medications such as ACE inhibitors. (p. 11)
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tolerance
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Tolerance refers to a decreased responsiveness over the course of therapy. In contrast, Tachyphylaxis refers to a rapid decrease in response to the drug. In essence, tachyphylaxis is an “acute tolerance.” Drug categories that can cause tachyphylaxis include narcotics, barbiturates, laxatives, and psychotropic agents. For example, drug tolerance to narcotics can result in decreased pain relief for the client. If the nurse does not recognize the development of drug tolerance, the client's request for more pain medication might be interpreted as drug-seeking behavior associated with addiction. Prevention of tachyphylaxis should always be part of the therapeutic regimen. (p. 11)
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placebo
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A placebo effect is a psychological benefit from a compound that may not have the chemical structure of a drug effect. The placebo is effective in approximately one third of persons who take a placebo compound. Many clinical drug studies involve a group of subjects who receive a placebo. The nurse can increase the therapeutic effect of the drug (e.g., narcotics for pain management) but violate the truth-telling ethical principle if a nontherapeutic drug is presented as a therapeutic agent. Hence it is required that participants in drug trials be told from the start that they might receive a placebo (p. 11)
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What are some common herbal supplements patients take and why?
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Chamomile – GI complaints
Echinacea – immune system enhancer Garlic – lower cholesterol & triglycerides, < BP, < blood clotting Ginger – boost immune system Gingko – improve memory Ginseng - < stress, boost energy, digestion St. John’s wart - antidepressant Concerns: Lack of standards Largely unregulated by FDA Possible interactions with drugs Should not be used: If pregnant or nursing By infants or small children With chemotherapy In large quantities (Week 1) |
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FDA Pregnancy Categories
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The FDA has developed a classification system related to the effects of drugs on the fetus. Table 3-3 lists the FDA's pregnancy categories and describes each category's effect on the fetus. NOTE: Prescription drug labeling revisions for health care providers are expected from the FDA. The purpose of the changes is to optimize informed decision making for pregnant women and for women of childbearing age who may wish to become pregnant. The proposed changes include a summary, with data, of risks to the fetus or breastfeeding infant in the pregnancy and lactation subsections of the labeling. The current pregnancy categories are expected to be eliminated when the revisions have been completed. (p. 31)
Classifies drug risks to fetus Categories A, B, C, D, X Categories A & B considered safe during pregnancy, esp. 1st trimester (Week 1) |
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pregnancy category A
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No risk to fetus. Studies have not shown evidence of fetal harm. (p. 31)
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pregnancy category B
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No risk in animal studies, and well-controlled studies in pregnant women are not available. It is assumed there is little to no risk in pregnant women. (p. 31)
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pregnancy category C
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Animal studies indicate a risk to the fetus. Controlled studies on pregnant women are not available. Risk versus benefit of the drug must be determined. (p. 31)
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pregnancy category D
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A risk to the human fetus has been proved. Risk versus benefit of the drug must be determined. It could be used in life-threatening conditions. (p. 31)
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pregnancy category X
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A risk to the human fetus has been proved. Risk outweighs the benefit, and drug should be avoided during pregnancy. (p. 31)
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The Controlled Substances Act, 1970
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In 1970 the Controlled Substances Act (CSA) of the Comprehensive Drug Abuse Prevention and Control Act, Title II, was passed by Congress. This act, designed to remedy the escalating problem of drug abuse, included several provisions: (1) the promotion of drug education and research into the prevention and treatment of drug dependence; (2) the strengthening of enforcement authority; (3) the establishment of treatment and rehabilitation facilities; and (4) the designation of schedules, or categories, for controlled substances according to abuse liability.
Controlled substances are described in five schedules, or categories, and are listed in Table 6-1. Schedule I drugs are not approved for medical use; schedule II through V drugs have accepted medical use. In addition, the abuse potential and extent of physical and psychological dependence are greatest with schedule I drugs. This dependency decreases as one moves through the schedule, with schedule V drugs having only limited abuse potential. Some drugs might be listed in more than one schedule category. Codeine is a schedule II drug, but when it is added to acetaminophen, it becomes a schedule III drug, and when it is used in combination as a cough preparation, it becomes a schedule V drug. (p. 110) |
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morphine
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Health Insurance Portability and Accountability Act (HIPAA), 2003
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The Health Insurance Portability and Accountability Act (HIPAA) sets the standards for the privacy of individually identifiable health information as of 2003. This rule gives clients more control over their health information, including boundaries on the use and release of health records. (p. 111)
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neurotransmitters & their function
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From moods and emotions flow the various thoughts, feelings, and actions of individuals, which are communicated throughout the central nervous system (CNS) by chemical neurotransmitters. An impulse is communicated by traveling through the presynaptic neuron across the synaptic cleft and binding to a receptor on the postsynaptic neuron, as illustrated in the figure.
Neurotransmitters (chemicals in the body) are synthesized in the cytoplasm in the presynaptic neuron and stored in vesicles. The vesicle safeguards neurotransmitters from being destroyed by enzymes. When an impulse arrives by way of an action potential at a presynaptic neuron, vesicles are triggered to move to the cell membrane wall and release the transmitter into the synaptic cleft. Neurotransmitters function with the help of receptors, which are embedded in the membrane of the postsynaptic neuron. Receptors are configured in size and shape to interlock with specific transmitters. Immediately upon connection of neurotransmitters to receptors, an action is exerted and the transmitter is removed. Once released, transmitters can be broken down into inactive substances by enzymes, diffused away from the synapse into intracellular fluid, or returned to the presynaptic neuron in a process called reuptake. (p 380) |
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inactivation of neurotransmitters
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After the transmitter (e.g., norepinephrine) has performed its function, the action must be stopped to prevent prolonging the effect. Transmitters are inactivated by (1) reuptake of the transmitter back into the neuron (nerve cell terminal), (2) enzymatic transformation or degradation, and (3) diffusion away from the receptor. The mechanism of norepinephrine reuptake plays a more important role in inactivation than the enzymatic action. Following the reuptake of the transmitter in the neuron, the transmitter may be degraded or reused. The two enzymes that inactivate the metabolism of norepinephrine are (1) monoamine oxidase (MAO), which is inside the neuron; and (2) catechol-O-methyltransferase (COMT), which is outside the neuron.
Drugs can stop the termination of the neurotransmitter (e.g., norepinephrine) by either (1) inhibiting the norepinephrine reuptake, which prolongs the action of the transmitter or (2) inhibiting the degradation of norepinephrine by enzyme action. (p. 260) FIGURE A, Direct-acting sympathomimetics; B, indirect-acting sympathomimetics; C, mixed-acting sympathomimetics. |
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peripheral nervous system
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The peripheral nervous system (PNS), located outside of the brain and spinal cord, is made up of two divisions: the autonomic and the somatic. After interpretation by the CNS, the PNS receives stimuli and initiates responses to those stimuli.
The autonomic nervous system (ANS), also called the visceral system, innervates (acts on) smooth muscles and glands. Its functions include control and regulation of the heart, respiratory system, gastrointestinal (GI) tract, bladder, eyes, and glands. The ANS is an involuntary nervous system over which a person has little or no control. We breathe, our hearts beat, and peristalsis continues without our realizing it. However, unlike the ANS, the somatic nervous system is a voluntary system that innervates skeletal muscles over which there is control. The two sets of neurons in the autonomic component of the PNS are the (1) afferent (sensory) neurons and the (2) efferent (motor) neurons. The afferent neurons send impulses to the CNS, where they are interpreted. The efferent neurons receive the impulses (information) from the brain and transmit those impulses through the spinal cord to the effector organ cells. The efferent pathways in the ANS are divided into two branches: the sympathetic and the parasympathetic nerves. Collectively, these two branches are called the sympathetic nervous system and the parasympathetic nervous system (p. 255) |
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sympathetic nervous system
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The sympathetic nervous system is also called the adrenergic system because at one time it was believed that adrenaline was the neurotransmitter that innervated smooth muscle. The neurotransmitter, however, is norepinephrine.
The adrenergic receptor organ cells are of four types: alpha1, alpha2, beta1, and beta2. Norepinephrine is released from the terminal nerve ending and stimulates the cell receptors to produce a response. (p. 255) Drugs that stimulate the SNS are called: Adrenergics Adrenergic Agonists Sympathomimetics or Adrenomimetics (Week 1) |
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parasympathetic nervous system
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The parasympathetic nervous system is called the cholinergic system because the neurotransmitter at the end of the neuron that innervates the muscle is acetylcholine. (p. 255)
Drugs that stimulate this system: Cholinergics Cholinergic Agonist Parasympathomimetic (Week 1) |
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sympathetic and parasympathetic responses to drugs
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Drugs that mimic the neurotransmitters norepinephrine and acetylcholine produce responses opposite to each other in the same organ. For example, an adrenergic drug (sympathomimetic) increases the heart rate, whereas a cholinergic drug (parasympathomimetic) decreases the heart rate (see Figure V-2). However, a drug that mimics the sympathetic nervous system and a drug that blocks the parasympathetic nervous system can cause similar responses in the organ. For instance, the sympathomimetic and the parasympatholytic (block impulses from PNS) drugs both increase the heart rate; the adrenergic blocker and the cholinergic drug both decrease heart rate. (p. 255)
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adrenergic agonists
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Drugs that stimulate the sympathetic nervous system are called adrenergics, adrenergic agonists, sympathomimetics, or adrenomimetics because they mimic the sympathetic neurotransmitters (i.e., norepinephrine, epinephrine). They act on one or more adrenergic receptor sites located in the cells of muscles, such as the heart, bronchiole walls, gastrointestinal (GI) tract, urinary bladder, and ciliary muscle of the eye. There are many adrenergic receptors. The four main receptors are alpha1, alpha2, beta1, and beta2, which mediate the major responses.
The alpha-adrenergic receptors are located in the vascular tissues (vessels) of muscles. When the alpha1 receptor is stimulated, the arterioles and venules constrict, increasing peripheral resistance and blood return to the heart. Circulation is improved and blood pressure is increased. When there is too much stimulation, blood flow is decreased to the vital organs. The alpha2 receptor is located in the postganglionic sympathetic nerve endings. When stimulated it inhibits the release of norepinephrine, leading to a decrease in vasoconstriction. This results in vasodilation and a decrease in blood pressure. The beta1 receptors are located primarily in the heart. Stimulation of the beta1 receptor increases myocardial contractility and heart rate. The beta2 receptors are found mostly in the smooth muscles of the lung, the arterioles of skeletal muscles, and the uterine muscle. Stimulation of the beta2 receptor causes (1) relaxation of the smooth muscles of the lungs, resulting in bronchodilation; (2) an increase in blood flow to the skeletal muscles; and (3) relaxation of the uterine muscle, resulting in a decrease in uterine contraction (Figure 18-2; see Table 18-1). Another adrenergic receptor is dopaminergic and is located in the renal, mesenteric, coronary, and cerebral arteries. When this receptor is stimulated, the vessels dilate and blood flow increases. Only dopamine can activate this receptor. (pp. 258-259) |
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cholinergic drug
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Cholinergic receptors are located in the bladder, heart, blood vessels, lungs, and eyes. A drug that stimulates or blocks the cholinergic receptors affects all anatomic sites of location. Drugs that affect various sites are nonspecific drugs and have properties of nonspecificity. Bethanechol (Urecholine) may be prescribed for postoperative urinary retention to increase bladder contraction. This drug stimulates the cholinergic receptor located in the bladder, and urination occurs by strengthening bladder contraction. Because bethanechol affects the cholinergic receptor, other cholinergic sites are also affected. The heart rate decreases, blood pressure decreases, gastric acid secretion increases, the bronchioles constrict, and the pupils of the eye constrict (Figure 1-6). These other effects may be either desirable or harmful. Drugs that evoke a variety of responses throughout the body have a nonspecific response. (p. 8)
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anticholinergic
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Drugs that inhibit the actions of acetylcholine by occupying the acetylcholine receptors are called anticholinergics or parasympatholytics. Other names for anticholinergics are cholinergic blocking agents, cholinergic or muscarinic antagonists, antiparasympathetic agents, antimuscarinic agents, and antispasmodics. The major body tissues and organs affected by the anticholinergic group of drugs are the heart, respiratory tract, GI tract, urinary bladder, eyes, and exocrine glands. By blocking the parasympathetic nerves, the sympathetic (adrenergic) nervous system dominates. Anticholinergic and adrenergic agonists produce many of the same responses.
Anticholinergic and cholinergic agonists have opposite effects. The major responses to anticholinergics are a decrease in GI motility, a decrease in salivation, dilation of pupils (mydriasis), and an increase in pulse rate. Other effects of anticholinergics include decreased bladder contraction, which can result in urinary retention, and decreased rigidity and tremors related to neuromuscular excitement. An anticholinergic can act as an antidote to the toxicity caused by cholinesterase inhibitors and organophosphate ingestion. The various effects of anticholinergics are described in Table 19-3. Muscarinic receptors, also called cholinergic receptors, are involved in tissue and organ responses to anticholinergics, because anticholinergics inhibit the actions of acetylcholine by occupying these receptor sites. Figure 19-3 illustrates this action of anticholinergic drugs. Anticholinergic drugs may block the effect of direct-acting parasympathomimetics such as bethanechol and pilocarpine and of indirect-acting parasympathomimetics such as physostigmine and neostigmine. (p. 276) |
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What are symptoms of psychiatric disorders?
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Usually > 1 symptom:
Difficulty in processing information Difficulty coming to a conclusion Delusions Hallucinations Incoherence Catatonia Aggressive/violent behavior (Week 2) |
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delusion
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A false belief in which one’s own thoughts, feelings, or fears cannot be distinguished from reality (delusions of persecution, grandeur, of control)
(Week 1) |
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hallucination
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A false perception having no relation to reality…may be visual, auditory, tactile, gustatory, or olfactory
(Week 1) |
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types of psychiatric agents
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Antipsychotics (psychotic disorders particularly schizophrenia)
Anxiolytics (anxiety disorders, insomnia, nausea and vomiting in cancer therapy) Antidepressants (depression-reactive, major and bipolar disorders) Mood stabilizers (antidepressant---bipolar disorders) (Week 1) |
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What are important neurotransmitters for psychiatric medications?
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The major neurotransmitters affecting psychopathology include gamma-aminobutyric acid (GABA), serotonin, dopamine, norepinephrine, and acetylcholine.
Faulty release, reuptake, or elimination of neurotransmitters may lead to an imbalance of neurotransmission and pathology. Mental disorders can then develop and affect an individual's thoughts, feelings, and behaviors. (p. 380) Dopamine: Movement, attention, learning, reward and reinforcement of addictive drugs Serotonin: Role in mood, sleep rhythms and arousal Epinephrine and Norepinephrine: Vigilance, fight-or flight response Acetylcholine: Muscular movement GABA: Regulation of anxiety (Week 1) |
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GABA
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The GABA neurotransmitter is associated with the regulation of anxiety. When the level of GABA neurotransmitters is reduced, anxiety disorders may result. Benzodiazepines (antianxiety drugs) act by binding to a GABA receptor site, making the postsynaptic receptor more sensitive to GABA and its neurotransmission. This connection decreases signs and symptoms of anxiety. (p. 380)
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serotonin
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erotonin neurotransmission is associated with arousal and general activity levels of the CNS. Serotonin functions to regulate sleep, wakefulness, and mood, as well as the delusions, hallucinations, and withdrawal of schizophrenia. Antidepressants block the reuptake of serotonin into the presynaptic neuron. A structurally specific drug is more likely to affect only the specific receptors for which it is intended and not the receptors specific for other neurochemicals, which would produce unintended effects or side effects. Selective serotonin reuptake inhibitor (SSRI) drugs are specific and generally produce fewer side effects in the treatment of depression than older antidepressants such as monoamine oxidase inhibitors (MAOIs). (p. 380)
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dopamine
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Dopamine-containing neurons are thought to be involved in regulation of cognition, emotional responses, and motivation, and dopamine neurotransmitters are associated with schizophrenia and other psychoses. Antipsychotic drugs block dopamine receptors in the postsynaptic neuron. (p. 380)
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norepinephrine
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Norepinephrine is associated with control of arousal, attention, vigilance, mood, affect, and anxiety. This transmitter is involved with thinking, planning, and interpreting. Tricyclic antidepressants block the reuptake of norepinephrine into the presynaptic neuron and effectively treat depressive disorders. MAOIs inactivate norepinephrine, dopamine, and serotonin by inhibiting the monoamine oxidase enzyme to relieve signs and symptoms of depression. (p. 380)
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acetylcholine
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Acetylcholine plays a role in sleep and wakefulness. Alzheimer's disease is associated with a reduction of acetylcholine. (p. 380)
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antipsychotics
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Antipsychotics are also known as neuroleptics or psychotropics, but the preferred name for this group is either antipsychotics or neuroleptics. Neuroleptic refers to any drug that modifies psychotic behavior and exerts an antipsychotic effect. Anxiolytics are also called antianxiety drugs or sedative-hypnotics. Certain anxiolytics are used to treat sleep disorders, seizures, and withdrawal symptoms from alcohol intoxication. Some of these drugs are also used for conscious sedation and anesthesia supplementation. (p. 382)
The theory is that psychotic symptoms result from an imbalance in the neurotransmitter dopamine in the brain. Sometimes these antipsychotics are called dopamine antagonists. Antipsychotics block D2 dopamine receptors in the brain, reducing psychotic symptoms. Many antipsychotics block the chemoreceptor trigger zone and vomiting (emetic) center in the brain, producing an antiemetic (an agent that prevents or relieves nausea and vomiting) effect. When dopamine is blocked, however, extrapyramidal symptoms (EPS)/extrapyramidal reactions of parkinsonism (Parkinson's disease, a chronic neurologic disorder that affects the extrapyramidal motor tract) such as tremors, masklike facies, rigidity, and shuffling gait may develop. Many clients who take high-potency antipsychotic drugs may require long-term medication for parkinsonian symptoms. (p. 382) AKA: Neuroleptics - “taking hold of the brain” Psychotropics-“acting upon the mind” Antipsychotics (Week 1) |
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How do antipsychotics work?
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Antipsychotics block the actions of dopamine and thus may be classified as dopaminergic antagonists. There are five subtypes of dopamine receptors: D1 through D5. All antipsychotics block the D2 (dopaminergic) receptor, which in turn promotes the presence of EPS, resulting in pseudoparkinsonism. Atypical antipsychotics have a weak affinity to D2 receptors, a stronger affinity to D4 receptors, and they block the serotonin receptor. These agents cause fewer EPS than the typical (phenothiazines) antipsychotic agents, which have a strong affinity to D2 receptors (p. 382)
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categories of antipsychotics
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Antipsychotics are divided into two major categories: typical (or traditional) and atypical. (p. 382)
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typical antipsychotics
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The typical antipsychotics, introduced in 1952, are subdivided into phenothiazines and nonphenothiazines. Nonphenothiazines include butyrophenones, dibenzoxazepines, dihydroindolones, and thioxanthenes. The phenothiazines and thioxanthenes block norepinephrine, causing sedative and hypotensive effects early in treatment. The butyrophenones block only the neurotransmitter dopamine. (p. 382)
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types of typical antipsychotics
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The typical antipsychotics, introduced in 1952, are subdivided into phenothiazines and nonphenothiazines. (p. 382)
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phenothiazines
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In 1952 chlorpromazine hydrochloride (Thorazine) was the first phenothiazine introduced for treating psychotic behavior in clients in psychiatric hospitals. (p. 383)
Three groups differ mostly by side effects: 1) aliphatic, 2) piperazine, 3)piperidine: 1. Chlorpromazine (Thorazine) Strong sedative effect! ↓ BP Moderate EPS 2. Fluphenazine (Prolixin) Low sedative effect Strong antiemetic effect Little effect on BP > EPS than other phenothiazines 3. Thioridazine (Mellaril) Few EPS Can cause life threatening dysrhythmias |
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nonphenothiazines
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Many groups
Haloperidol (Haldol) Frequently prescribed Similar to phenothiazines Potent antipsychotic Smaller dosages used Prolonged QTc |
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atypical antipsychotics
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Atypical antipsychotics make up the second category of antipsychotics. Clozapine, discovered in the 1960s and made available in Europe in 1971, was the first atypical antipsychotic agent. It was not marketed in the United States until 1990 because of adverse hematologic reactions. Atypical antipsychotics are effective for treating schizophrenia and other psychotic disorders in clients who do not respond to or are intolerant of typical antipsychotics. Because of their decreased side effects, atypical antipsychotics may be used instead of traditional typical antipsychotics as first-line therapy. (p. 382)
A new category of antipsychotics was marketed in the United States in the early 1990s. This group, atypical antipsychotics, differs from the typical/traditional antipsychotics, because the atypical agents are effective in treating both positive and negative symptoms of schizophrenia. The typical antipsychotics have not been effective in the treatment of negative symptoms. Two advantages of the atypical agents are that (1) they are effective in treating negative symptoms, and (2) they are not likely to cause EPS or tardive dyskinesia. The atypical drugs available include clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), and paliperidone (Invega). These agents have a greater affinity for blocking serotonin and dopaminergic D4 receptors than primarily blocking the dopaminergic D2 receptor responsible for mild and severe EPS. Weight gain is a common side effect of atypical antipsychotics. (pp. 387-388) |
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antipsychotic drug administration
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Drugs that modify psychotic behavior:
Must be taken consistently Must be given the appropriate amount of time to attain a FULL therapeutic response Given PO, IM, or IV Liquid form preferred Peak serum levels in 2-3 hrs Highly protein bound Drug excretion slow May cause harmless pinkish to red-brown urine Full therapeutic effects may take 3-6 weeks Therapeutic response 7-10 days Noncompliance is common In older adults, start low |
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antipsychotic administration in older adults
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Older adults usually require smaller doses of antipsychotics—from 25% to 50% less than young and middle-aged adults. Regular to high doses of antipsychotics increase the risk of severe side effects. Dosage amounts need to be individualized according to the client's age and physical status. In addition, dosage changes may be necessary during antipsychotic therapy. (p. 387)
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What herbal supplement must you be concerned about for antipsychotics?
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Kava kava may increase the risk and severity of dystonic reactions when taken with phenothiazines.
Kava kava may increase the risk and severity of dystonia when taken concurrently with fluphenazine. (p. 383) |
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most common antipsychotic side effects
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Most common is drowsiness
Many have some anticholinergic effects (Dry mouth,↑HR, urinary retention, constipation) (Week 1) |
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adverse reactions antipsychotics
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EPS
Sudden Death (Both typical and atypical) Case reports of QTc (time between heart contractions) prolongation with both IV and oral Haloperidol More predominant with atypicals Diabetes and other metabolic reactions Hyperglycemia Dyslipidemia Hypertension (Week 1) There are several common side effects associated with antipsychotics. The most common side effect for all antipsychotics is drowsiness. Many of the antipsychotics have some anticholinergic effects: dry mouth, increased heart rate, urinary retention, and constipation. Blood pressure decreases with the use of antipsychotics; aliphatics and piperidines cause a greater decrease in blood pressure than the others. Extrapyramidal symptoms can begin 5 to 30 days after initiation of antipsychotic therapy and are most prevalent with the phenothiazines, butyrophenones, and thioxanthenes. These symptoms include pseudoparkinsonism, akathisia, dystonia (prolonged muscle contractions with twisting, repetitive movements), and tardive dyskinesia. Tardive dyskinesia may develop in 20% of clients taking antipsychotics for long-term therapy. Antiparkinsonian anticholinergic drugs may be given to control EPS, but they are not always effective in treating tardive dyskinesia. High dosing or long-term use of some antipsychotics can cause blood dyscrasias (blood cell disorders) such as agranulocytosis. White blood cell (WBC) count should be closely monitored and reported to the health care provider if there is an extreme decrease in leukocytes. Dermatologic side effects seen early in drug therapy are pruritus and marked photosensitivity. Clients are urged to use sunscreen, hats, and protective clothing and to stay out of the sun. (p. 386) |
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extra pyramidal syndrome
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Side effect of antipsychotics.
Caused by blocking dopamine receptors. Consists of pseudoparkinsonism, acute dystonia, akathasia, and tardive dyskinesia. Occurs with 5-30 days. |
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pseudoparkinsonism
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Pseudoparkinsonism, which resembles symptoms of Parkinson's disease, is a major side effect of typical antipsychotic drugs. Symptoms of pseudoparkinsonism, or EPS, include stooped posture, masklike facies, rigidity, tremors at rest, shuffling gait, pill-rolling motion of the hand, and bradykinesia. When clients take high-potency typical antipsychotic drugs, these symptoms are more pronounced. Clients who take low-strength antipsychotics such as chlorpromazine (Thorazine) are not as likely to have symptoms of pseudoparkinsonism as those who take fluphenazine (Prolixin). (p. 382)
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acute dsytonia
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The symptoms of acute dystonia usually occur in 5% of clients within days of taking typical antipsychotics. Characteristics of the reaction include muscle spasms of face, tongue, neck, and back; facial grimacing; abnormal or involuntary upward eye movement; and laryngeal spasms that can impair respiration. This condition is treated with anticholinergic/antiparkinsonism drugs such as benztropine (Cogentin). The benzodiazepine lorazepam (Ativan) may also be prescribed. (p. 383)
Acute dystonia (occurs within days of taking drug) Treat with anticholinergic or antiparkinsonism drugs, e.g., Benztropine (Cogentin) Or benzodiazepines, e.g.,Lorazepam (Ativan) (Week 1) |
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akathisia
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ncidence of akathisia occurs in approximately 20% of clients who take a typical antipsychotic drug. With this reaction, the client has trouble standing still, is restless, paces the floor, and is in constant motion (e.g., rocks back and forth). Akathisia is best treated with a benzodiazepine (e.g., lorazepam) or a beta blocker (e.g., propranolol). (p. 383)
Akathisia (can also occur early in treatment) Treat with benzodiazepines, e.g.,Lorazepam (Ativan) Or a beta blocker, e.g., Propanolol (Inderal) (Week 1) |
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tardive dyskinesia
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Tardive dyskinesia is a serious adverse reaction occurring in clients who have taken a typical antipsychotic drug for more than a year. The likelihood of developing tardive dyskinesia depends on the dose and duration of the antipsychotic factor. Characteristics of tardive dyskinesia include protrusion and rolling of the tongue, sucking and smacking movements of the lips, chewing motion, and involuntary movement of the body and extremities. In older adults, these reactions are more frequent and severe. The antipsychotic drug should be stopped in all who experience tardive dyskinesia. Other benzodiazepines, calcium channel blockers, or beta-blockers are helpful in some cases in decreasing tardive dyskinesia. No one agent is effective for all clients. High doses of vitamin E may be helpful, and its use to treat tardive dyskinesia is currently under investigation. Clozapine has also been effective for treating tardive dyskinesia. Figure 27-1 shows the characteristics of pseudoparkinsonism, acute dystonia, akathisia, and tardive dyskinesia. (p. 383)
Tardive dyskinesia (typically > 1 year) Serious adverse reaction Drug should be stopped!! In older adults, rx > frequent & severe Depends on dose & duration Treatment may include: Other benzodiazepines, e.g., Ca++ channel blockers or β blockers High doses Vitamin E may be helpful (Week 1) |
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neuroleptic malignant syndrome
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Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal condition associated with antipsychotic drugs. NMS symptoms involve muscle rigidity, sudden high fever, altered mental status, blood pressure fluctuations, tachycardia, dysrhythmias, seizures, rhabdomyolysis, acute renal failure, respiratory failure, and coma. Treatment of NMS involves immediate withdrawal of antipsychotics, adequate hydration, hypothermic blankets, and administration of antipyretics, benzodiazepines, and muscle relaxants such as dantrolene (Dantrium). (p. 383)
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types of anxiety
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There are two types of anxiety—primary and secondary. Primary anxiety is not caused by a medical condition or by drug use; secondary anxiety is related to selected drug use or medical or psychiatric disorders. Anxiolytics are not usually given for secondary anxiety unless the medical problem is untreatable, severe, and causes disability. In this case, an anxiolytic could be given for a short period to alleviate any acute anxiety attacks. These agents treat the symptoms but do not cure them. Long-term use of anxiolytics is discouraged, because tolerance develops within weeks or months, depending on the agent. Drug tolerance can occur in less than 2 to 3 months in clients who take meprobamate or phenobarbital. (p. 391)
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anxiolytics
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Anxiolytics, or antianxiety drugs, are primarily used to treat anxiety and insomnia. The major anxiolytic group is benzodiazepines (a minor tranquilizer group). Long before benzodiazepines were prescribed for anxiety and insomnia, barbiturates were used. Benzodiazepines are considered more effective than barbiturates, because they enhance the action of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter within the CNS. Benzodiazepines have fewer side effects and may be less dangerous in overdosing. Long-term use of barbiturates causes drug tolerance and dependence and may cause respiratory distress. Currently barbiturates are not drugs of choice for treating anxiety.
A certain amount of anxiety may make one more alert and energetic, but when anxiety is excessive, it can be disabling, and anxiolytics may be prescribed. The action of anxiolytics resembles that of the sedative-hypnotics but not that of the antipsychotics. (p. 391) Long term use discouraged Tolerance in weeks or months Nonpharmacologic measures should be used 1st! (Week 1) |
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benzodiazepines
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Benzodiazepines have multiple uses as anticonvulsants, sedative-hypnotics, preoperative drugs, and anxiolytics. Most of the benzodiazepines are used mainly for severe or prolonged anxiety. Examples include chlordiazepoxide (Librium), diazepam (Valium), clorazepate dipotassium (Tranxene), lorazepam (Ativan), and alprazolam (Xanax). The most frequently prescribed benzodiazepine is lorazepam (Ativan). Many of the benzodiazepines are used for more than one purpose.
Benzodiazepines are lipid-soluble and are absorbed readily from the GI tract. They are highly protein-bound (80% to 98%). Benzodiazepines are primarily metabolized by the liver and excreted in urine, so the drug dosage for clients with liver or renal disease should be lowered accordingly to avoid possible cumulative effects. Traces of benzodiazepine metabolites could be present in the urine for weeks or months after the person has stopped taking the drug. These are controlled substance schedule IV (CSS IV) drugs. In 1962 the first benzodiazepine, chlordiazepoxide (Librium), became widely used for its sedative effect. Diazepam (Valium) was the most frequently prescribed drug in the early 1970s and was called a miracle drug by many. (p. 392) *Kava kava should not be combined with benzodiazepines, because it increases the sedative effect. (p. 392) |
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side effects & adverse reactions of benzos
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The side effects associated with benzodiazepines are sedation, dizziness, headaches, dry mouth, blurred vision, rare urinary incontinence, and constipation. Adverse reactions include leukopenia (decreased WBC count) with symptoms of fever, malaise, and sore throat; tolerance to the drug dosage with continuous use; and physical dependency.
Benzodiazepines should not be abruptly discontinued, because withdrawal symptoms are likely to occur. Withdrawal symptoms caused by short-term benzodiazepine use are similar to those from the sedative-hypnotics (agitation, nervousness, insomnia, tremor, anorexia, muscular cramps, sweating). However, they are slow to develop, taking 2 to 10 days, and can last several weeks, depending on the benzodiazepine's half-life. When discontinuing a benzodiazepine, the drug dosage should be gradually decreased over a period of days, depending on dose or length of time on the drug. Withdrawal symptoms from long-term, high-dose benzodiazepine therapy include paranoia, delirium, panic, hypertension, and status epilepticus. Convulsions during withdrawal may be prevented with simultaneous substitution of an anticonvulsant. Alcohol and other CNS depressants should not be taken with benzodiazepines, because respiratory depression could result. Tobacco, caffeine, and sympathomimetics decrease the effectiveness of benzodiazepines. Benzodiazepines are contraindicated during pregnancy because of possible teratogenic effects on the fetus. (p. 394) |
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treatment for benzo overdose
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Suggested Treatment for Overdose of Benzodiazepines
1. Administer an emetic, and follow with activated charcoal if the client is conscious; use gastric lavage if the client is unconscious. 2. Administer the benzodiazepine antagonist flumazenil (Romazicon) IV if required. 3. Maintain an airway, give oxygen as needed for decreased respirations, and monitor vital signs. 4. Give IV vasopressors for severe hypotension. 5. Request a mental health consultation for the client. Note: Dialysis has little value in removing benzodiazepine from the bloodstream. (pp. 394-395) |
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lorazepam
(Ativan) |
Lorazepam is highly lipid-soluble, and the drug is rapidly absorbed from the GI tract. The drug is highly protein-bound, and the half-life is 10 to 20 hours. Lorazepam is excreted primarily in the urine.
Lorazepam acts on the limbic, thalamic, and hypothalamic levels of the CNS. The onset of action is 15 to 30 minutes by mouth and 1 to 5 minutes by IV. The serum levels of most oral doses of benzodiazepines peak in 2 hours. Oxazepam levels peak in 3 hours. Duration of action varies. The average is 2 to 3 hours when given orally; when given IV, the longest duration of action is 1 hour. It is recommended that benzodiazepines be prescribed for no longer than 3 to 4 months. Beyond 4 months, the effectiveness of the drug lessens. (p. 393) |
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depression
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There are many theories about the cause of major depression. A common one suggests an insufficient amount of brain monoamine neurotransmitters (norepinephrine, serotonin, perhaps dopamine). It is thought that decreased levels of serotonin permit depression to occur, and decreased levels of norepinephrine cause depression. However, there can be other physiologic causes of depression as well as social and environmental factors. (p. 397)
Depression is the most common psychiatric problem, affecting approximately 10% to 20% of the population. Only 33% of depressed persons receive medical or psychiatric help. Women between the ages of 25 and 45 years are two to three times more likely to experience major depression than men. Depression is characterized primarily by mood changes and loss of interest in normal activities. It is second only to hypertension as the most common chronic clinical condition. Contributing causes of depression include genetic predisposition, social and environmental factors, and biologic conditions. Some signs of major depression include loss of interest in most activities, depressed mood, weight loss or gain, insomnia or hypersomnia, loss of energy, fatigue, feelings of despair, decreased ability to think or concentrate, and suicidal thoughts. Approximately 66% of all suicides are related to depression. Depressed men, especially older white men, are more likely to commit suicide than depressed women. Antidepressants can mask suicidal tendencies. (p. 397) |
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types of depression
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The three types of depression are (1) reactive, (2) major, and (3) bipolar affective disorder (previously referred to as manic depression). (p. 397)
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reactive depression
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Reactive depression usually has a sudden onset after a precipitating event (e.g., depression resulting from a loss, such as death of a loved one). The client knows why he or she is depressed and may call this the “blues.” Usually this type of depression lasts for months. A benzodiazepine agent may be prescribed. (p. 397)
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major depression
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Major depression is characterized by loss of interest in work and home, inability to complete tasks, and deep depression (dysphoria). Major depression can be either primary (i.e., not related to other health problems) or secondary to a health problem (e.g., physical or psychiatric disorder or drug use). Antidepressants have been effective in treating major depression. (p. 397)
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bipolar affective disorder
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ipolar affective disorder (manic-depressive illness) involves swings between two moods, the manic (euphoric) and the depressive (dysphoria). Lithium was originally the drug of choice for treating this type of disorder. However, divalproex sodium (Depakote) is currently the drug of choice for bipolar disorder. (p. 397)
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antidepressants
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Antidepressants are divided into four groups: (1) tricyclic antidepressants (TCAs), or tricyclics; (2) selective serotonin reuptake inhibitors (SSRIs); (3) atypical antidepressants that affect various neurotransmitters; and (4) monoamine oxidase inhibitors (MAOIs). The tricyclics and MAOIs were marketed in the late 1950s, and many of the SSRIs and atypical antidepressants were available in the 1980s. The SSRIs are popular antidepressants because they do not cause sedation, hypotension, anticholinergic effects, or cardiotoxicity as do many of the TCAs. Users of SSRIs can experience sexual dysfunction, which can be managed. (p. 397)
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tricyclic antidepressants (TCAs)
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The tricyclic antidepressants (TCAs) are used to treat major depression, because they are effective and less expensive than SSRIs and other drugs. Imipramine was the first TCA marketed in the 1950s.
The action of TCAs is to block the uptake of the neurotransmitters norepinephrine and serotonin in the brain. The clinical response of TCAs occurs after 2 to 4 weeks of drug therapy. If there is no improvement after 2 to 4 weeks, the antidepressant is slowly withdrawn and another antidepressant is prescribed. Polydrug therapy, the practice of giving several antidepressants or antipsychotics together, should be avoided because of possible serious side effects. The effectiveness of TCAs in treating major depression is well documented. This group of drugs elevates mood, increases interest in daily living and activity, and decreases insomnia. For agitated depressed persons, amitriptyline (Elavil), doxepin (Sinequan), or trimipramine (Surmontil) may be prescribed, because of their highly sedative effect. Frequently TCAs are given at night to minimize problems caused by their sedative action. When discontinuing TCAs, the drugs should be gradually decreased to avoid withdrawal symptoms such as nausea, vomiting, anxiety, and akathisia. Imipramine hydrochloride (Tofranil) is used for the treatment of enuresis (involuntary discharge of urine during sleep in children). (pp. 397-398) The TCAs have many side effects: orthostatic hypotension, sedation, anticholinergic effects, cardiac toxicity, and seizures. Rising from a sitting position too rapidly can cause dizziness and lightheadedness, so the client should be instructed to rise slowly to an upright position to avoid orthostatic hypotension. This group of antidepressants blocks the histamine receptors; thus sedation is likely to occur initially but decreases with continuous use of the drug. Because TCAs block the cholinergic receptors, they can cause anticholinergic effects such as tachycardia, urinary retention, constipation, dry mouth, and blurred vision. Other side effects of TCAs include allergic reactions (skin rash, pruritus, and petechiae) and sexual dysfunction (impotence and amenorrhea). Most TCAs can cause blood dyscrasias (leukopenia, thrombocytopenia, and agranulocytosis) requiring close monitoring of blood cell counts. Amitriptyline may lead to extrapyramidal symptoms (EPS). Clomipramine may cause neuroleptic malignant syndrome (NMS). Seizure threshold is decreased by TCAs; therefore clients with seizure disorders may need to have the TCA dose adjusted. The most serious adverse reaction to TCAs is cardiac toxicity, such as dysrhythmias that may result from high doses of the drug. The therapeutic serum range is 100 to 200 ng/mL. Alcohol, hypnotics, sedatives, and barbiturates potentiate central nervous system (CNS) depression when taken with TCAs. Concurrent use of MAOIs with amitriptyline may lead to cardiovascular instability and toxic psychosis. Antithyroid medications taken with amitriptyline may increase the risk of dysrhythmias. (p. 399) |
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selective serotonin reuptake inhibitors (SSRIs)
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In the late 1980s, a group of antidepressants that did not have TCA chemical structure were identified. This group was first classified as second-generation antidepressants. They have since been reclassified as selective serotonin reuptake inhibitors (SSRIs). The SSRIs block the reuptake of serotonin into the nerve terminal of the CNS, thereby enhancing its transmission at the serotonergic synapse. These drugs do not block the uptake of dopamine or norepinephrine, nor do they block cholinergic and alpha1-adrenergic receptors. Selective serotonin reuptake inhibitors are more commonly used to treat depression than are the TCAs. They are more costly but have fewer side effects than TCAs.
The primary use of SSRIs is for major depressive disorders. They are also effective for treating anxiety disorders such as obsessive-compulsive disorder, panic, phobias, posttraumatic stress disorder, and other forms of anxiety. Fluvoxamine (Luvox) is useful for treating obsessive-compulsive disorder in children and adults. SSRIs have also been used to treat eating disorders and selected drug abuses. Miscellaneous uses for SSRIs include decreasing premenstrual tension syndrome, preventing migraine headaches, and preventing or minimizing aggressive behavior in clients with borderline personality disorder. The SSRIs include fluoxetine (Prozac), fluvoxamine (Luvox), sertraline (Zoloft), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro). Fluoxetine (Prozac) has been effective in 50% to 60% of clients who fail to respond to TCA therapy (TCA-refractory depression). Of all the SSRIs, sertraline (Zoloft) is the most commonly prescribed antidepressant. The U.S. Food and Drug Administration (FDA) approved a weekly fluoxetine dose of 90 mg. However, before taking the weekly dose, the client should respond to a daily maintenance dose of 20 mg/day without serious effects. It has been reported that there are some side effects to the weekly 90 mg fluoxetine dose. Note: Many SSRIs have an interaction with grapefruit juice that can lead to possible toxicity. It is recommended that daily intake be limited to 8 ounces of grapefruit juice or one half of a grapefruit. Do not confuse Celexa with Celebrex (antiinflammatory), because the names look similar. Some clients may experience sexual dysfunction when taking SSRIs. Men have discontinued taking fluoxetine (Prozac) after experiencing a decrease in sexual arousal. Some women have become anorgasmic when taking paroxetine HCl (Paxil). The side effects often decrease or cease over the 2- to 4-week period of waiting for the therapeutic effect to emerge. (p. 399) |
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fluoxetine
(Prozac) |
SSRI
Fluoxetine is strongly protein-bound. The half-life is 2 to 3 days; therefore a cumulative drug effect may result from long-term use. Fluoxetine is metabolized and excreted by the kidneys. Fluoxetine is well absorbed; however, its antidepressant effect develops slowly over several weeks. The onset of fluoxetine's antidepressant effect is between 1 and 4 weeks, and peak concentration is at 4 to 8 hours after ingestion. The drug dose for older adults should be decreased to reduce side effects. Fluoxetine produces common side effects such as dry mouth, blurred vision, insomnia, headache, nervousness, anorexia, nausea, diarrhea, and suicidal ideation. Fluoxetine has fewer side effects than amitriptyline (see Table 28-1). Some clients may experience sexual dysfunction when taking SSRIs. Men have discontinued taking fluoxetine (Prozac) after experiencing a decrease in sexual arousal. Some women have become anorgasmic when taking paroxetine HCl (Paxil). The side effects often decrease or cease over the 2- to 4-week period of waiting for the therapeutic effect to emerge. (p. 399) |
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atypical antidepressants
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Atypical (heterocyclic) antidepressants, or second-generation antidepressants, became available in the 1980s and have been used for major depression, reactive depression, and anxiety. They affect one or two of the three neurotransmitters: serotonin, norepinephrine, and dopamine. One of the first atypical antidepressants marketed was amoxapine (Asendin), and others include bupropion (Wellbutrin), maprotiline (Ludiomil), nefazodone (Serzone), trazodone (Desyrel), mirtazapine (Remeron), and venlafaxine (Effexor). Amoxapine and maprotiline are sometimes considered to be TCAs because of their pharmacologic similarities. Atypical antidepressants should not be taken with MAOIs and should not be used within 14 days after discontinuing MAOIs. Trazodone may have a potential drug interaction with ketoconazole, ritonavir, and indinavir that may lead to increased trazodone levels and adverse effects. (pp. 399-400)
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monoamine oxidase inhibitors (MAOIs)
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The fourth group of antidepressants is the monoamine oxidase inhibitors (MAOIs). The enzyme monoamine oxidase inactivates norepinephrine, dopamine, epinephrine, and serotonin. By inhibiting monoamine oxidase, the levels of these neurotransmitters rise. In the body there are two forms of monoamine oxidase (MAO) enzyme: MAO-A and MAO-B. These enzymes are found primarily in the liver and brain. MAO-A inactivates dopamine in the brain, whereas MAO-B inactivates norepinephrine and serotonin. The MAOIs are nonselective, inhibiting both MAO-A and MAO-B. Inhibition of MAO by MAOIs is thought to relieve the symptoms of depression. Three MAOIs are currently prescribed: tranylcypromine sulfate (Parnate), isocarboxazid (Marplan), and phenelzine sulfate (Nardil). These MAOIs are detailed in Table 28-2.
For the treatment of depression, MAOIs are as effective as TCAs, but because of adverse reactions such as the risk of hypertensive crisis resulting from food and drug interactions, only 1% of clients taking antidepressants take an MAOI. Currently MAOIs are not the antidepressants of choice and are usually prescribed when the client does not respond to TCAs or second-generation antidepressants. However, MAOIs are still used for mild, reactive, and atypical depression (chronic anxiety, hypersomnia, fear). MAOIs and TCAs should not be taken together when treating depression. Side effects of MAOIs include CNS stimulation (agitation, restlessness, insomnia), orthostatic hypotension, and anticholinergic effects. (p. 403) |
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drug and food alerts for MAOIs
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Certain drug and food interactions with MAOIs can be fatal. Any drugs that are CNS stimulants or sympathomimetics (e.g., vasoconstrictors and cold medications containing phenylephrine and pseudoephedrine) can cause a hypertensive crisis when taken with an MAOI. In addition, foods that contain tyramine (cheese [cheddar, Swiss, bleu], cream, yogurt, coffee, chocolate, bananas, raisins, Italian green beans, liver, pickled herring, sausage, soy sauce, yeast, beer, and red wines) have sympathomimetic-like effects and can cause a hypertensive crisis (Table 28-3). These types of food and drugs must be avoided by MAOI users. Frequent blood pressure monitoring is essential, and client teaching regarding foods and over-the-counter (OTC) drugs to avoid is an important nursing responsibility. Because of the danger associated with a hypertensive crisis, many psychiatrists will not prescribe MAOIs for depression unless they sense the client's ability to comply with the drug and food regimen. However, if properly taken this group of drugs is effective for treating depression. (p. 403)
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herbal supplements for depression
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St. John's wort and gingko biloba have been suggested for the management of mild depression. St. John's wort can decrease reuptake of the neurotransmitters serotonin, norepinephrine, and dopamine. The use of these and many herbal products should be discontinued 1 to 2 weeks before surgery. The client should check with the health care provider regarding herbal treatments.
Feverfew may interfere with SSRI antidepressants such as fluoxetine (Prozac). St. John's wort interacts with SSRIs, which may cause serotonin syndrome (dizziness, headache, sweating, and agitation). (p. 397) |
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mood stabilizers
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Mood stabilizers are used to treat bipolar affective disorder. Lithium was the first drug used to manage this disorder. Lithium was first used as a salt substitute in the 1940s, but because of lithium poisoning, it was banned from the market.
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lithium
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Some refer to lithium as an antimania drug that is effective in controlling manic behavior that arises from underlying bipolar disorder. Lithium has a calming effect without impairing intellectual activity. It controls any evidence of flight of ideas and hyperactivity. If the person stops taking lithium, manic behavior may return. (pp. 403-404)
Lithium is an inexpensive drug that must be closely monitored. Lithium has a narrow therapeutic serum range: 0.5 to 1.5 mEq/L. Serum lithium levels greater than 1.5 to 2 mEq/L are toxic. The serum lithium level should be monitored biweekly until the therapeutic level has been obtained and then monitored monthly on the maintenance dose. Serum sodium levels also need to be monitored because lithium tends to deplete sodium. Lithium must be used with caution, if at all, by clients taking diuretics. (p. 404) More than 95% of lithium is absorbed through the gastrointestinal (GI) tract. The average half-life of lithium is 24 hours; however, in older adults the half-life can be up to 36 hours. Because of its long half-life, cumulative drug action may result. Lithium is metabolized by the liver, and most of the drug is excreted unchanged in the urine. Lithium is prescribed mostly for the stabilization of bipolar affective disorder. The onset of action is fast, but the client may not achieve the desired effect for 5 to 6 days. Increased sodium intake increases renal excretion, so the sodium intake needs to be closely monitored. Increased urine output can result in body fluid loss and dehydration. Adequate fluid intake of 1 to 2 L should be maintained daily. The many side effects of lithium—dry mouth, thirst, increased urination (loss of water and sodium), weight gain, bloated feeling, metallic taste, and edema of the hands and ankles—can be annoying to the client. If taken during pregnancy, lithium may have teratogenic effects on the fetus. Lithium and nonsteroidal antiinflammatory drugs (NSAIDs) should not be given together on a continuous basis and should not be prescribed for clients who have a cardiac “sick sinus syndrome.” If the client has taken lithium for a long period, laboratory tests to determine thyroid function should be closely monitored. (p. 405) |
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basic structures of respiratory tract
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The respiratory tract is divided into two major parts: (1) the upper respiratory tract, which consists of the nares, nasal cavity, pharynx, and larynx, and (2) the lower respiratory tract, which consists of the trachea, bronchi, bronchioles, alveoli, and alveolar-capillary membrane. Air enters through the upper respiratory tract and travels to the lower respiratory tract, where gas exchanges occur.
The chest cavity is a closed compartment bounded by 12 ribs, the diaphragm, thoracic vertebrae, sternum, neck muscles, and intercostal muscles between the ribs. The pleura are membranes that encase the lungs. The lungs are divided into lobes; the right lung has three lobes, and the left lung has two lobes. The heart, which is not attached to the lungs, lies on the mid-left side in the chest cavity. (p. 587) |
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phases of respiration
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Ventilation and respiration are distinct terms and should not be used interchangeably. Ventilation is the movement of air from the atmosphere through the upper and lower airways to the alveoli. Respiration is the process whereby gas exchange occurs at the alveolar-capillary membrane. Respiration has three phases: ventilation, perfusion, and diffusion.
1. Ventilation is the phase in which oxygen passes through the airways. With every inspiration, air is moved into the lungs, and with every expiration, air is transported out of the lungs. 2. Perfusion involves blood flow at the alveolar-capillary bed. Perfusion is influenced by alveolar pressure. For gas exchange to occur, the perfusion of each alveolus must be matched by adequate ventilation. Factors such as mucosal edema, secretions, and bronchospasm increase resistance to air flow and decrease ventilation and diffusion of gases. 3. Diffusion (molecules move from higher to lower concentration) of gases takes place when oxygen passes into the capillary bed to be circulated, and carbon dioxide leaves the capillary bed and diffuses into the alveoli for ventilatory excretion. (p. 587) |
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drugs for upper respiratory disorders
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antihistamine, decongestant, antitussive, and expectorant drug groups
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antihistamines
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Antihistamines, H1 blockers or H1 antagonists, compete with histamine for receptor sites, preventing a histamine response. The two types of histamine receptors, H1 and H2, cause different responses. When the H1 receptor is stimulated, the extravascular smooth muscles, including those lining the nasal cavity, are constricted. With stimulation of the H2 receptor, an increase in gastric secretions occurs, which is a cause of peptic ulcer (see Chapter 48). These two types of histamine receptors should not be confused. Antihistamines decrease nasopharyngeal secretions by blocking the H1 receptor.
Although antihistamines are commonly used as cold remedies, these agents can also treat allergic rhinitis. However, the antihistamines are not useful in an emergency situation such as anaphylaxis. Most antihistamines are rapidly absorbed in 15 minutes, but they are not potent enough to combat anaphylaxis. (p. 589) |
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first-generation antihistamines
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The antihistamine group can be divided into first and second generations. Most first-generation antihistamines cause drowsiness, dry mouth, and other anticholinergic symptoms, whereas second-generation antihistamines have fewer anticholinergic effects and a lower incidence of drowsiness. Many OTC cold remedies contain a first-generation antihistamine, which can cause drowsiness; therefore clients should be alerted not to drive or operate dangerous machinery when taking such medications. The anticholinergic properties of most antihistamines cause dryness of the mouth and decreased secretions, making them useful in treating rhinitis caused by the common cold. Antihistamines also decrease the nasal itching and tickling that cause sneezing.
The first-generation antihistamine diphenhydramine (Benadryl) has been available for years and is frequently combined with other ingredients in cold remedy preparations. Its primary use is to treat rhinitis. (p. 589) The most common side effects of first-generation antihistamines are drowsiness, dizziness, fatigue, and disturbed coordination. Skin rashes and anticholinergic symptoms (e.g., dry mouth, urine retention, blurred vision, wheezing) may also occur. (p. 591) |
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diphenhydramine
(Benadryl) |
Diphenhydramine can be administered orally, intramuscularly (IM), or intravenously (IV). It is well absorbed from the gastrointestinal (GI) tract, but systemic absorption from topical use is minimal. It is highly protein-bound (98%) and has an average half-life of 2 to 7 hours. Diphenhydramine is metabolized by the liver and excreted as metabolites in the urine.
Pharmacodynamics Diphenhydramine blocks the effects of histamine by competing for and occupying H1 receptor sites. It has anticholinergic effects and should not be used by clients with narrow-angle glaucoma. Drowsiness is a major side effect of the drug; in fact, it is sometimes used in sleep-aid products. Diphenhydramine is also used as an antitussive (i.e., it alleviates cough). Its onset of action can occur in as few as 15 minutes when taken orally and IM. IV administration results in an immediate onset of action. The duration of action is 4 to 8 hours. Diphenhydramine can cause CNS depression if taken with alcohol, narcotics, hypnotics, or barbiturates. (pp. 589-590) |
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second-generation antihistamines
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The second-generation antihistamines are frequently called nonsedating antihistamines because they have little to no effect on sedation. In addition, these antihistamines cause fewer anticholinergic symptoms. Although a moderate amount of alcohol and other central nervous system (CNS) depressants may be taken with second-generation antihistamines, many clinicians advise against such use.
The second-generation antihistamines cetirizine (Zyrtec), fexofenadine (Allegra), and loratadine (Claritin) have half-lives between 7 and 15 hours. Azelastine (Astelin,) is a second-generation antihistamine that has a half-life of 22 hours and is administered by nasal spray. (p. 589) |
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lortadine
(Claritin) |
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nasal decongestants
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Nasal congestion results from dilation of nasal blood vessels caused by infection, inflammation, or allergy. With this dilation, there is a transudation of fluid into the tissue spaces, resulting in swelling of the nasal cavity. Nasal decongestants (sympathomimetic amines) stimulate the alpha-adrenergic receptors, producing vascular constriction (vasoconstriction) of the capillaries within the nasal mucosa. The result is shrinking of the nasal mucous membranes and a reduction in fluid secretion (runny nose).
Nasal decongestants are administered by nasal spray or drops or in tablet, capsule, or liquid form. Frequent use of decongestants, especially nasal spray or drops, can result in tolerance and rebound nasal congestion (rebound vasodilation instead of vasoconstriction). Rebound nasal congestion is caused by irritation of the nasal mucosa. (pp. 591-592) |
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systemic decongestants
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Systemic decongestants (alpha-adrenergic agonists) are available in tablet, capsule, and liquid form and are used primarily for allergic rhinitis, including hay fever and acute coryza (profuse nasal discharge). Examples of systemic decongestants are ephedrine (Ephedrine), phenylephrine (Neo-Synephrine), and pseudoephedrine (Sudafed). In the past, phenylpropanolamine was used in many cold remedies; however, the U.S. Food and Drug Administration (FDA) ordered its removal from OTC cold remedies and weight-loss aids because of reports that suggested the drug might cause stroke, hypertension, renal failure, and cardiac dysrhythmias. Ephedrine, phenylephrine, and pseudoephedrine are frequently combined with an antihistamine, analgesic, or antitussive in oral cold remedies. The advantage of systemic decongestants is that they relieve nasal congestion for a longer period than nasal decongestants; however, currently there are long-acting nasal decongestants. Nasal decongestants usually act promptly and cause fewer side effects than systemic decongestants. (p. 592)
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expectorants
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Expectorants loosen bronchial secretions so they can be eliminated by coughing. They can be used with or without other pharmacologic agents. Expectorants are found in many OTC cold remedies along with analgesics, antihistamines, decongestants, and antitussives. The most common expectorant in such preparations is guaifenesin. Hydration is the best natural expectorant. (p. 595)
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antitussives
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Antitussives act on the cough-control center in the medulla to suppress the cough reflex. The cough is a naturally protective way to clear the airway of secretions or any collected material. A sore throat may cause coughing that increases throat irritation. If the cough is nonproductive and irritating, an antitussive may be taken. Hard candy may decrease the constant, irritating cough. Dextromethorphan, a nonnarcotic antitussive, is widely used in OTC cold remedies. (p. 593)
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chronic obstructive pulmonary disease (COPD)
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Chronic obstructive pulmonary disease (COPD) and restrictive pulmonary disease are the two major categories of lower respiratory tract disorders. COPD is caused by airway obstruction with increased airway resistance of airflow to lung tissues. Four major pulmonary disorders cause COPD: chronic bronchitis, bronchiectasis, emphysema, and asthma. Chronic bronchitis, bronchiectasis, and emphysema frequently result in irreversible lung tissue damage. The lung tissue changes resulting from an acute asthmatic attack are normally reversible; however, if the asthma attacks are frequent and asthma becomes chronic, irreversible changes in the lung tissue may result. Clients with COPD usually have a decrease in forced expiratory volume in 1 second (FEV1) as measured by pulmonary function tests.
Cigarette smoking is the most common risk factor for COPD, especially with chronic bronchitis and emphysema. There is no cure for COPD at this time; however, it remains preventable in most cases. Because cigarette smoking is the most directly related cause, not smoking significantly prevents COPD from developing. Quitting smoking will slow the disease process. Medications frequently prescribed for COPD include the following: Bronchodilators such as sympathomimetics (adrenergics), parasympatholytics (anticholinergic drug, Atrovent), and methylxanthines (caffeine, theophylline) are used to assist in opening narrowed airways. Glucocorticoids (steroids) are used to decrease inflammation. Leukotriene modifiers reduce inflammation in the lung tissue, and cromolyn and nedocromil act as antiinflammatory agents by suppressing the release of histamine and other mediators from the mast cells. Expectorants are used to assist in loosening mucus from the airways. Antibiotics may be prescribed to prevent serious complications from bacterial infections. (pp. 600-601) |
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asthma
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Asthma is an inflammatory disorder of the airway walls associated with a varying amount of airway obstruction. This disorder is triggered by stimuli such as stress, allergens, and pollutants. When activated by stimuli, the bronchial airways become inflamed and edematous, leading to constriction of air passages. Inflammation aggravates airway hyperresponsiveness to stimuli, causing bronchial cells to produce more mucous, which obstructs air passages. This obstruction contributes to wheezing, coughing, dyspnea (breathlessness), and tightness in the chest, particularly at night or early morning.
Bronchial asthma, one of the COPD lung diseases, is characterized by bronchospasm (constricted bronchioles), wheezing, mucus secretions, and dyspnea. There is resistance to airflow caused by obstruction of the airway. In acute and chronic asthma, minimal to no changes are seen in the structure and function of lung tissues when the disease process is in remission. In chronic bronchitis, emphysema, and bronchiectasis, there is permanent, irreversible damage to the physical structure of lung tissue. Symptoms are similar to those of asthma in these three pulmonary disorders, except wheezing does not occur. Frequently there is a steady deterioration over a period of years. (p. 600) |
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chronic bronchitis
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Chronic bronchitis is a progressive lung disease caused by smoking or chronic lung infections. Bronchial inflammation and excessive mucous secretion result in airway obstruction.
Productive coughing is a response to excess mucus production and chronic bronchial irritation. Inspiratory and expiratory rhonchi may be heard on auscultation. Hypercapnia (increased carbon dioxide retention) and hypoxemia (decreased blood oxygen) lead to respiratory acidosis. (p. 600) |
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emphysema
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Emphysema is a progressive lung disease caused by cigarette smoking, atmospheric contaminants, or lack of the alpha1-antitrypsin protein that inhibits proteolytic enzymes that destroy alveoli (air sacs). Proteolytic enzymes are released in the lung by bacteria or phagocytic cells. The terminal bronchioles become plugged with mucus, causing a loss in the fiber and elastin network in the alveoli. Alveoli enlarge as many of the alveolar walls are destroyed. Air becomes trapped in the overexpanded alveoli, leading to inadequate gas (oxygen and carbon dioxide) exchange. (p. 600)
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bronchiectasis
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In bronchiectasis there is abnormal dilation of the bronchi and bronchioles secondary to frequent infection and inflammation. The bronchioles become obstructed by the breakdown of the epithelium of the bronchial mucosa. Tissue fibrosis may result. (p. 600)
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glucocorticoids
(steroids) |
Glucocorticoids, members of the corticosteroid family, are used to treat respiratory disorders, particularly asthma. These drugs have an antiinflammatory action and are indicated if asthma is unresponsive to bronchodilator therapy or if the client has an asthma attack while on maximum doses of theophylline or an adrenergic drug. It is thought that glucocorticoids have a synergistic effect when given with a beta2 agonist.
Glucocorticoids can be given using the following methods: • MDI inhaler: beclomethasone (Vanceril, Beclovent) • Tablet: triamcinolone (Aristocort), dexamethasone (Decadron), prednisone, prednisolone, and methylprednisolone • Intravenous: dexamethasone (Decadron), hydrocortisone Inhaled glucocorticoids are not helpful in treating a severe asthma attack, because it may take 1 to 4 weeks for an inhaled steroid to reach its full effect. When maintained on inhaled glucocorticoids, asthmatic clients demonstrate an improvement in symptoms and a decrease in asthma attacks. Inhaled glucocorticoids are more effective for controlling symptoms of asthma than beta2 agonists, particularly in the reduction of bronchial hyperresponsiveness. The use of an oral inhaler minimizes the risk of adrenal suppression associated with oral systemic glucocorticoid therapy. Inhaled glucocorticoids are preferred over oral preparations unless they fail to control the asthma. Clients with acute asthma exacerbations are usually given systemic glucocorticoids (i.e., IV) for rapid effectiveness in large doses (20 to 40 mg prednisone for 5 days; 1 to 2 mg/kg/day for children for 3 to 5 days). An additional week with a reduced dose may be needed. With a single dose or short-term use, glucocorticoids may be discontinued abruptly after symptoms are controlled. Suppression of adrenal function does not usually occur within 1 to 2 weeks. When severe asthma requires prolonged glucocorticoid therapy, weaning or tapering of the dose may be necessary to prevent an exacerbation of asthma symptoms and suppression of adrenal function. Previously, alternate-day therapy (ADT) with oral prednisone was used in some asthmatic clients. Currently, inhaled glucocorticoids are thought to be preferable in the treatment of most clients with asthma. Glucocorticoids can irritate the gastric mucosa and should be taken with food to avoid ulceration. A combination drug containing the glucocorticoid fluticasone propionate 100 mcg and salmeterol 50 mcg (Advair Diskus 100/50) is effective in controlling asthma symptoms. Advair is used every day, but requires only one inhalation in the morning and one at night. This drug does not replace fast-acting inhalers for sudden symptoms. The purpose of Advair is to alleviate airway constriction and inflammation. Side Effects and Adverse Reactions Side effects associated with orally inhaled glucocorticoids are generally local (e.g., throat irritation, hoarseness, dry mouth, coughing) rather than systemic. Oral, laryngeal, and pharyngeal fungal infections have occurred but can be reversed with discontinuation and antifungal treatment. Candida albicans oropharyngeal infections may be prevented by using a spacer with the inhaler to reduce drug deposits in the oral cavity, rinsing the mouth and throat with water after each dose, and washing the apparatus (cap and plastic nose or mouthpiece) daily with warm water. Oral and injectable glucocorticoids have many side effects when used long-term, but short-term use usually causes no significant side effects. Most adverse reactions are seen within 2 weeks of glucocorticoid therapy and are usually reversible. Side effects that may occur include headache, euphoria, confusion, sweating, insomnia, nausea, vomiting, weakness, and menstrual irregularities. Adverse effects may include depression, peptic ulcer, loss of bone density and development of osteoporosis, and psychosis. When oral and IV steroids are used for prolonged periods, electrolyte imbalance, fluid retention (puffy eyelids, edema in the lower extremities, moon face, weight gain), hypertension, thinning of the skin, purpura, abnormal subcutaneous (fat) distribution, hyperglycemia, and impaired immune response are likely to occur. (pp. 611-612) |
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intranasal glucocorticoids
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Intranasal glucocorticoids or steroids are effective for treating allergic rhinitis. Because these agents are steroids, they have an antiinflammatory action, thus decreasing the allergic rhinitis symptoms of rhinorrhea, sneezing, and congestion. The following are six examples of intranasal steroids:
• Beclomethasone (Beconase, Vancenase, Vanceril) • Budesonide (Rhinocort) • Dexamethasone (Decadron) • Flunisolide (Nasalide) • Fluticasone (Flonase) • Triamcinolone (Nasacort) These drugs may be used alone or in combination with an H1 antihistamine. With continuous use, dryness of the nasal mucosa may occur. It is rare for systemic effects of steroids to occur, but they are more likely to result with the use of intranasal dexamethasone, which should not be used for longer than 30 days. The other intranasal glucocorticoids undergo rapid deactivation after absorption. Most allergic rhinitis is seasonal; therefore the drugs are for short-term use unless otherwise indicated by the health care provider. Table 40-3 lists the intranasal glucocorticoids and their dosages, uses, and considerations. (p. 593) |
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albuterol
(Proventil, Ventolin) |
The newer beta-adrenergic drugs for asthma are more selective for beta2 receptors. High doses or overuse of the beta2-adrenergic agents for asthma may cause some degree of beta1 response such as nervousness, tremor, and increased pulse rate. The ideal beta2 agonist is one that has a rapid onset of action, longer duration of action, and few side effects. Albuterol (Proventil, Ventolin) is a selective beta2 drug that is effective for treatment and control of asthma by causing bronchodilation with long duration of action. (p. 602)
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mucolytics
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Mucolytics act like detergents to liquefy and loosen thick mucous secretions so they can be expectorated. Acetylcysteine (Mucomyst) is administered by nebulization. The drug should not be mixed with other drugs. When clients with asthma or hyperactive airway disease produce increased secretions that obstruct bronchial airways, acetylcysteine may be administered as an adjunct to a bronchodilator (not mixed together). The bronchodilator should be given 5 minutes before the mucolytic. Side effects include nausea and vomiting, stomatitis (oral ulcers), and “runny nose.” (p. 612)
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drugs categories for heart disorders
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cardiac glycosides, antianginals, and antidysrhythmics
*regulate heart contraction, heart rate and rhythm, and blood flow to the myocardium (p.619) diuretics *decrease hypertension (lower blood pressure) and to decrease edema (peripheral and pulmonary) in heart failure (HF) and renal or liver disorder (p. 639) antihypertensives *sympatholytics (beta blockers, centrally acting and peripherally acting alpha blockers, alpha and beta blockers), direct-acting vasodilators, and angiotensin antagonists (p. 652) anticoagulants, antiplatelets, and thrombolytics *The anticoagulants prevent the formation of clots that inhibit circulation. The antiplatelets prevent platelet aggregation (clumping together of platelets to form a clot). The thrombolytics, popularly called clot busters, attack and dissolve blood clots that have already formed. (p. 670-671) antihyperlipidemics and peripheral vasodilators *Drugs that lower blood lipids are called antihyperlipidemics, antilipidemics, antilipemics, and hypolipidemics. Drugs used to lower lipoproteins are called antihyperlipidemics. Peripheral vasodilators are drugs that dilate vessels that have been narrowed by vasospasm. (p. 684) |
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cardiac glycosides
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Digitalis began being used as early as 1200 AD, making it one of the oldest drugs. It is still used in a purified form. Digitalis is obtained from the purple and white foxglove plant, and it can be poisonous. In 1785, William Withering of England used digitalis to alleviate “dropsy,” edema of the extremities caused by kidney and cardiac insufficiency. Withering and his medical colleagues did not realize that dropsy was the result of heart failure, however. Digitalis preparations have come to be known for their effectiveness in treating heart failure (HF), also known as cardiac failure (CF), and previously referred to as congestive heart failure (CHF). When the heart muscle (myocardium) weakens and enlarges, it loses its ability to pump blood through the heart and into the systemic circulation. This is called heart failure, or pump failure.
Naturally occurring cardiac glycosides are found in a number of plants, including Digitalis. Also called digitalis glycosides, they are a group of drugs that inhibit the sodium-potassium pump, resulting in an increase in intracellular sodium. This increase leads to an influx of calcium, causing the cardiac muscle fibers to contract more efficiently. Digitalis preparations have three effects on heart muscle: (1) a positive inotropic action (increases myocardial contraction stroke volume), (2) a negative chronotropic action (decreases heart rate), and (3) a negative dromotropic action (decreases conduction of the heart cells). The increase in myocardial contractility strengthens cardiac, peripheral, and kidney function by enhancing cardiac output, decreasing preload, improving blood flow to the periphery and kidneys, decreasing edema, and promoting fluid excretion. As a result, fluid retention in the lung and extremities is decreased. Digoxin does not prolong life. It acts by increasing the force and velocity of myocardial systolic contraction. Today the cardiac glycoside digoxin is a secondary drug for HF. First-line drugs used to treat acute HF include inotropic agents (dopamine and dobutamine) and phosphodiesterase inhibitors (inamrinone [Inocor], formerly known as amrinone, and milrinone [Primacor]). Other drugs prescribed for HF include diuretics, beta blockers, ACE inhibitors, angiotensin-receptor blockers (ARBs), calcium channel blockers, and vasodilators. Cardiac glycosides are also used to correct atrial fibrillation (cardiac dysrhythmia with rapid uncoordinated contractions of atrial myocardium) and atrial flutter (cardiac dysrhythmia with rapid contractions of 200 to 300 beats/min). This is accomplished by the negative chronotropic effects (decreases heart rate) and negative dromotropic effects (decreases conduction through the atrioventricular [AV] node). Digoxin does not convert atrial fibrillation to normal heart rhythm. For management of atrial fibrillation, a calcium channel blocker, such as verapamil (Calan) may be prescribed. To prevent thromboemboli resulting from atrial fibrillation, warfarin (Coumadin) is prescribed concurrently with other drug therapy. (pp. 619-620) |
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antianginals
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Antianginal drugs are used to treat angina pectoris. This is a condition of acute cardiac pain caused by inadequate blood flow to the myocardium due to either plaque occlusions within or spasms of the coronary arteries. With decreased blood flow, there is a decrease in O2 to the myocardium, which results in pain. Anginal pain is frequently described by the client as tightness, pressure in the center of the chest, and pain radiating down the left arm. Referred pain felt in the neck and left arm commonly occurs with severe angina pectoris. Anginal attacks may lead to MI, or heart attack. Anginal pain usually lasts for only a few minutes. Stress tests, echocardiogram, cardiac profile laboratory tests, and cardiac catheterization may be needed to determine the degree of blockage in the coronary arteries. (p. 624)
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types of angina pectoris
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The frequency of anginal pain depends on many factors, including the type of angina. There are three types of angina:
• Classic (stable): Occurs with stress or exertion • Unstable (preinfarction): Occurs frequently with progressive severity unrelated to activity • Variant (Prinzmetal, vasospastic): Occurs during rest The first two types are caused by a narrowing or partial occlusion of the coronary arteries; variant angina is caused by vessel spasm (vasospasm). It is common for a client to have both classic and variant angina. Unstable angina often indicates an impending MI. This is an emergency that needs immediate medical intervention. (p. 624) |
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nonpharmacologic treatment of angina
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Proper nutrition
Moderate exercise (with HCP approval) Adequate rest & sleep Relaxation techniques Avoid: Heavy meals Smoking Extremes in weather changes Strenuous exercise Emotional upset (Week 3) |
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treatment for angina
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types of antianginal drugs
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Antianginal drugs increase blood flow either by increasing oxygen supply or by decreasing oxygen demand by the myocardium. Three types of antianginals are nitrates, beta blockers, and calcium channel blockers. The major systemic effect of nitrates is a reduction of venous tone, which decreases the workload of the heart and promotes vasodilation. Beta blockers and calcium channel blockers decrease the workload of the heart and decrease oxygen demands.
Nitrates and calcium channel blockers are effective in treating variant (vasospastic) angina pectoris. Beta blockers are not effective for this type of angina. With stable angina, beta blockers can effectively be used to prevent angina attacks. Table 42-3 lists the effects of antianginal drug groups on angina. With unstable angina, immediate medical care is necessary. Nitrates are usually given subcutaneously and intravenously as needed. If the cardiac pain continues, a beta blocker is given intravenously, and if the client is unable to tolerate beta blockers, a calcium channel blocker may be substituted. (pp. 624-625) |
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nitrates
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Nitrates, developed in the 1840s, were the first agents used to relieve angina. They affect coronary arteries and blood vessels in the venous circulation. Nitrates cause generalized vascular and coronary vasodilation, which increases blood flow through the coronary arteries to the myocardial cells. This group of drugs reduces myocardial ischemia but can cause hypotension.
The sublingual (SL) nitroglycerin tablet, absorbed under the tongue, comes in various dosages, but the average dose prescribed is 0.4 mg or gr 1/150 following cardiac pain. If pain has not subsided or worsened, then 911 should be called. The effects of SL nitroglycerin last for 10 minutes. The SL tablets decompose when exposed to heat and light, so they should be kept in their original airtight glass containers. The tablets themselves are normally dispensed in these original glass containers, which have screw-cap tops that are not childproof. This facilitates emergency use by older adults who may have reduced manual dexterity and are experiencing an anginal attack. After a dose of nitroglycerin, the client may experience dizziness, faintness, or headache as a result of the peripheral vasodilation. If pain persists, the client should immediately call for medical assistance. Sublingual (SL) nitroglycerin is the most commonly used nitrate. It is not swallowed, because it undergoes first-pass metabolism by the liver, which decreases its effectiveness. Instead, it is readily absorbed into the circulation through the SL vessels. Nitroglycerin is also available in other forms: topical (ointment, transdermal patch), buccal extended-release tablet, oral extended-release capsule and tablet, aerosol spray (inhalation), and IV. Prototype Drug Chart 42-2 summarizes the action of nitroglycerin (nitrates). There are various types of organic nitrates. Isosorbide dinitrate (Isordil, Sorbitrate) can be administered in SL tablet form and is also available as chewable tablets, immediate-release tablets, and sustained-release tablets and capsules. Isosorbide mononitrate (Imdur) can be given orally in immediate-release and sustained-release tablets. Nitroglycerin, taken SL, is absorbed rapidly and directly into the internal jugular vein and the right atrium. Approximately 40% to 50% of nitrates absorbed through the gastrointestinal (GI) tract are inactivated by liver metabolism (first-pass metabolism in the liver). The nitroglycerin in Nitro-Bid ointment and in the Transderm-Nitro patch is absorbed slowly through the skin. It is excreted primarily in the urine. Pharmacodynamics Nitroglycerin acts directly on the smooth muscle of blood vessels, causing relaxation and dilation. It decreases cardiac preload (the amount of blood in the ventricle at the end of diastole) and afterload (peripheral vascular resistance) and reduces myocardial O2 demand. With dilation of the veins, there is less blood return to the heart, and with dilation of the arteries, there is less vasoconstriction and resistance. The onset of action of nitroglycerin depends on the method of administration. With SL and IV use, the onset of action is rapid (1 to 3 minutes); it is slower with the transdermal method (30 to 60 minutes). The duration of action of the transdermal nitroglycerin patch is approximately 24 hours. Because Nitro-Bid ointment is effective for only 6 to 8 hours, it must be reapplied three to four times a day. The use of Nitro-Bid ointment has declined since the advent of the transdermal nitroglycerin patch, which is applied only once a day. It is important to note that the patch should be removed nightly to allow for an 8- to 12-hour nitrate-free interval. This is also true for most other forms of nitroglycerin. This is necessary to avoid tolerance associated with uninterrupted use or continued dosage increases of nitrate preparations. Side Effects and Adverse Reactions Headaches are one of the most common side effects of nitroglycerin, but they may become less frequent with continued use. Otherwise acetaminophen may provide some relief. Other side effects include hypotension, dizziness, weakness, and faintness. When nitroglycerin ointment or transdermal patches are discontinued, the dose should be tapered over several weeks to prevent the rebound effect of severe pain caused by myocardial ischemia (lack of blood supply to the heart muscle). In addition, reflex tachycardia may occur if the nitrate is given too rapidly. The heart rate increases greatly because of overcompensation of the cardiovascular system. Drug Interactions Beta blockers, calcium channel blockers, vasodilators, and alcohol can enhance the hypotensive effect of nitrates. IV nitroglycerin may antagonize the effects of heparin. (pp. 625-626) |
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beta blockers
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Beta-adrenergic blockers block the beta1- and beta2-receptor sites. Beta blockers decrease the effects of the sympathetic nervous system by blocking the action of the catecholamines (epinephrine and norepinephrine), thereby decreasing the heart rate and blood pressure. They are used as antianginal, antidysrhythmic, and antihypertensive drugs. Beta blockers are effective as antianginals because by decreasing the heart rate and myocardial contractility, they reduce the need for oxygen consumption and consequently reduce anginal pain. These drugs are most useful for classic (stable) angina.
Beta blockers should not be abruptly discontinued. The dose should be tapered over a specified number of days to avoid reflex tachycardia and recurrence of anginal pain. Clients who have decreased heart rate and blood pressure usually cannot take beta blockers. Clients who have second- or third-degree AV block should not take beta blockers. Beta blockers, discussed in detail in Chapter 18, are subdivided into nonselective beta blockers (blocking beta1 and beta2) and selective (cardiac) beta blockers (blocking beta1). Examples of nonselective beta blockers are propranolol (Inderal), nadolol (Corgard), and pindolol (Visken). These drugs decrease the heart rate and can cause bronchoconstriction. The cardioselective beta blockers act more strongly on the beta1 receptor, which decreases the heart rate but avoids bronchoconstriction because of their lack of activity at the beta2 receptor. Examples of selective beta blockers are atenolol (Tenormin) and metoprolol (Lopressor, Toprol-XL). Selective beta blockers are the group of choice for controlling angina pectoris. (p. 626) Pharmacokinetics Beta blockers are well absorbed orally. Absorption of sustained-release capsules is slow. The half-life of propranolol (Inderal) is 3 to 6 hours. Of the selective beta blockers, atenolol (Tenormin) has a half-life of 6 to 7 hours, and metoprolol (Lopressor) has a half-life of 3 to 7 hours. Propranolol and metoprolol are metabolized and excreted by the liver. Half an oral dose of atenolol is absorbed from the GI tract, the remainder excreted unchanged in feces. When given IV, 85% of a dose is excreted in urine within 24 hours. Pharmacodynamics Because beta blockers decrease the force of myocardial contraction, oxygen demand by the myocardium is reduced. Therefore, the client can tolerate increased exercise with less oxygen requirement. Beta blockers tend to be more effective for classic (stable) angina than for variant (vasospastic) angina. The onset of action of the nonselective beta blocker propranolol is 30 minutes, its peak action is reached in 1 to 1.5 hours, and its duration is 4 to 12 hours. For the cardioselective beta blockers, the onset of action of atenolol is 60 minutes, its peak action occurs in 2 to 4 hours, and its duration of action is 24 hours. The onset of action of selective metoprolol is reached in 15 minutes, and the duration of action is 6 to 12 hours. Side Effects and Adverse Reactions Both nonselective and selective beta blockers cause a decrease in heart rate and blood pressure. For the nonselective beta blockers, bronchospasm, behavioral or psychotic response, and impotence (with use of Inderal) are potential adverse reactions. Vital signs need to be closely monitored in the early stages of beta blocker therapy. When discontinuing use, the dosage should be tapered for 1 or 2 weeks to prevent a rebound effect such as reflex tachycardia or life-threatening cardiac dysrhythmias. (p. 628) |
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metoprolol
(Lopressor) |
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calcium channel blockers
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Calcium channel blockers (CCBs), or calcium blockers, were introduced in 1982 for the treatment of stable and variant angina pectoris, certain dysrhythmias, and hypertension. Calcium activates myocardial contraction, increasing the workload of the heart and the need for more oxygen. CCBs relax coronary artery spasm (variant angina) and relax peripheral arterioles (stable angina), decreasing cardiac oxygen demand. They also decrease cardiac contractility (negative inotropic effect that relaxes smooth muscle), decrease afterload, decrease peripheral resistance, and reduce the workload of the heart, which decreases the need for oxygen. CCBs achieve their effect in controlling variant (vasospastic) angina by relaxing coronary arteries and in controlling classic (stable) angina by decreasing oxygen demand.
Pharmacokinetics Three calcium channel blockers—verapamil (Calan), nifedipine (Procardia), and diltiazem (Cardizem)—have been effectively used for the long-term treatment of angina. Eighty to ninety percent of CCBs are absorbed through the GI mucosa. However, first-pass metabolism by the liver decreases the availability of free circulating drug, and only 20% of verapamil, 45% to 65% of diltiazem, and 35% to 40% of nifedipine are bioavailable. All three drugs are highly protein-bound (80% to 90%), and their half-lives are 2 to 9 hours. Several other CCBs are available, such as nicardipine HCl (Cardene), amlodipine (Norvasc), bepridil HCl (Vascor), felodipine (Plendil), and nisoldipine (Sular). All are highly protein-bound (greater than 95%). Nicardipine has the shortest half-life at 5 hours. Bepridil is used for angina pectoris. Pharmacodynamics Bradycardia is a common problem with the use of verapamil, the first calcium blocker. Nifedipine, the most potent of the calcium blockers, promotes vasodilation of the coronary and peripheral vessels, and hypotension can result. The onset of action is 10 minutes for verapamil and 30 minutes for nifedipine and diltiazem. Verapamil's duration of action is 3 to 7 hours when given orally and 2 hours when given IV. The duration of action for nifedipine and diltiazem is 6 to 8 hours. Side Effects and Adverse Reactions The side effects of calcium blockers include headache, hypotension (more common with nifedipine and less common with diltiazem), dizziness, and flushing of the skin. Reflex tachycardia can occur as a result of hypotension. Peripheral edema may occur with several CCBs including nicardipine, nifedipine, and verapamil. CCBs can cause changes in liver and kidney function. Serum liver enzymes should be checked periodically. CCBs are frequently given with other antianginal drugs such as nitrates to prevent angina. Nifedipine, in its immediate-release form (10- and 20-mg capsules), has been associated with an increased incidence of sudden cardiac death, especially when prescribed in high doses for outpatients. This is not true of the sustained-release preparations (Procardia XL, Adalat CC). For this reason, immediate-release nifedipine is usually prescribed only as needed in the hospital setting for acute rises in blood pressure. (pp. 628-629) |
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amlodipine
(Norvasc) |
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nifedipine
(Procardia) |
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antidysrhthmic drugs
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A cardiac dysrhythmia (arrhythmia) is defined as any deviation from the normal rate or pattern of the heartbeat. This includes heart rates that are too slow (bradycardia), too fast (tachycardia), or irregular. The terms dysrhythmia (disturbed heart rhythm) and arrhythmia (absence of heart rhythm) are used interchangeably, despite the slight difference in meaning. (p. 630)
The desired action of antidysrhythmic (antiarrhythmic) drugs is to restore the cardiac rhythm to normal. The antidysrhythmics are grouped into four classes: (1) fast (sodium) channel blockers IA, IB, and IC; (2) beta blockers; (3) drugs that prolong repolarization; and (4) slow (calcium) channel blockers. (p. 631) Mechanisms of Action: Block adrenergic stimulation of the heart Depress myocardial excitability and contractility Decrease conduction velocity in cardiac tissue Increase recovery time (repolarization) of the myocardium Suppress automaticity (spontaneous depolarization to initiate beats) (p. 631) It should be noted that all antidysrhythmic drugs are potentially prodysrhythmic. This is because of both the pharmacologic activity of the drug on the heart and the inherently unpredictable activity of a diseased heart, with or without the use of drugs. In some cases, life-threatening ventricular dysrhythmias can result from appropriate and skillful attempts at drug therapy to treat clients with heart disease. For these reasons, antidysrhythmic drug therapy is often initiated during continuous cardiac monitoring of the client's heart rhythm in a hospital setting (p. 635) |
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hypertension
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Hypertension is an increase in blood pressure such that the systolic pressure is greater than 140 mmHg and the diastolic pressure is greater than 90 mmHg. Essential hypertension is the most common type, affecting 90% of persons with high blood pressure. The exact origin of essential hypertension is unknown; however, contributing factors may include (1) a family history of hypertension, (2) hyperlipidemia, (3) African-American background, (4) diabetes, (5) obesity, (6) aging, (7) stress, and (8) excessive smoking and alcohol ingestion. Ten percent of hypertension cases are related to renal and endocrine disorders and are classified as secondary hypertension. (p. 653)
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stages of hypertension
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Blood pressure guidelines for determining hypertension have been revised and are contained in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, or JNC 7. The purpose of these guidelines is to decrease the risk of cardiovascular disease (CVD) in the American population. The guideline for normal blood pressure is less than 120/80 mm Hg. Prehypertension is the second category, defined as a systolic blood pressure (SBP) 120 to 139 and a diastolic blood pressure (DBP) 80 to 89. Stage 1 hypertension falls between 140/90 and 159/99, and stage 2 hypertension is 160/100 or greater. Table 44-1 lists the JNC 7 guidelines for hypertension.
Two out of three clients with hypertension have uncontrolled blood pressure or are not optimally treated. The SBP is more important than the DBP as a CVD risk for clients age 50 years or older. According to the JNC 7, if the blood pressure is greater than 20/10 mm Hg above goal, a drug regimen should be started. CVD risk doubles with each increase of 20/10 mm Hg, starting at 115/75 mm Hg. (p. 654) |
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physiological risk factors for HTN
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Certain physiologic risk factors contribute to hypertension. A diet with excess fat and carbohydrates can increase blood pressure. Carbohydrate intake can affect sympathetic nervous activity. Alcohol increases renin secretions, causing the production of angiotensin II. Obesity affects the sympathetic and cardiovascular systems by increasing cardiac output, stroke volume, and left-ventricular filling. Two thirds of hypertensive persons are obese. Normally weight loss can decrease hypertension, as can mild to moderate sodium restriction. (p. 653)
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older adults with HTN
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By age 65 years, 26% of men and 30% of women are hypertensive. Between ages 65 and 75 years, 30% of men and 45% of women are hypertensive. Both systolic and diastolic hypertension are associated with increased cardiovascular morbidity and mortality. With antihypertensive therapy, the greatest decrease in cardiovascular disorders is 34% for stroke and 19% for coronary heart disease.
One of the troublesome side effects of the use of antihypertensive agents in older adults, especially frail or institutionalized persons, is orthostatic hypotension. If orthostatic hypotension occurs, the antihypertensive drug dose may need to be decreased or another antihypertensive drug used. Older adults with hypertension should be instructed to modify their lifestyle activities. This includes restricting dietary sodium to 2.4 g (2,400 mg) daily, avoiding tobacco, modifying diet, and exercising. (p. 654) |
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nonpharmacologic control of HTN
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A sufficient decrease in blood pressure can be accomplished by nonpharmacologic methods. There are many nonpharmacologic ways to decrease blood pressure, but if the systolic pressure is greater than 140 mm Hg, antihypertensive drugs are generally ordered. Nondrug methods to decrease blood pressure include: (1) stress-reduction techniques, (2) exercise (increases high-density lipoproteins [HDL]), (3) salt restriction, (4) decreased alcohol ingestion, and (5) weight reduction.
When hypertension cannot be controlled by nonpharmacologic means, antihypertensive drugs are prescribed. However, nonpharmacologic methods should be combined with antihypertensive drugs to control hypertension. (p. 654) |
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cultural response to antihypertensives
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African Americans are more likely to develop hypertension at an earlier age than white Americans. They also have a higher mortality rate from hypertension than the white population. The use of beta-adrenergic blockers (beta blockers) and angiotensin-converting enzyme (ACE) inhibitors is less effective for the control of hypertension in African Americans unless the drug is combined or given with a diuretic. This group is susceptible to low-renin hypertension, therefore they do not respond well to beta blockers and ACE inhibitors. The antihypertensive drugs that are effective for African Americans are the alpha1 blockers and calcium channel blockers (calcium blockers). African-American clients do respond to diuretics as the initial monotherapy for controlling hypertension. White clients usually have high-renin hypertension and respond well to all antihypertensive agents.
Asian Americans are twice as sensitive as whites to beta blockers and other antihypertensives. A reduction in antihypertensive dosing is frequently needed. American Indians have a reduced or lower response to beta blockers compared with whites. Monitoring blood pressure and drug dosing should be an ongoing assessment for these cultural groups. (pp. 653-654) |
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antihypertensive drugs
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An individualized approach to the treatment of hypertension is used by many health care providers. All drugs are considered initial agents when first prescribed for hypertension. Reduction of other cardiovascular risk factors and the use of fewer drugs (i.e., substituting instead of adding drugs) at the lowest effective doses are emphasized. It has been suggested that after a client has taken an antihypertensive drug for a year, the drug dose and its effect on blood pressure should be evaluated.
Antihypertensive drugs, used either singly or in combination with other drugs, are classified into six categories: (1) diuretics, (2) sympatholytics (sympathetic depressants), (3) direct-acting arteriolar vasodilators, (4) ACE inhibitors, (5) angiotensin II receptor blockers (ARBs), and (6) calcium channel blockers. (p. 654) |
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diuretics
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Diuretics are used for two main purposes: to decrease hypertension (lower blood pressure) and to decrease edema (peripheral and pulmonary) in heart failure (HF) and renal or liver disorders. Hypertension is an elevated blood pressure. Diuretics discussed in this chapter are used either alone or in combination to decrease blood pressure and edema.
Diuretics produce increased urine flow (diuresis) by inhibiting sodium and water reabsorption from the kidney tubules. Most sodium and water reabsorption occurs throughout the renal tubular segments (proximal, loop of Henle [descending loop and ascending loop], and collecting tubule). Diuretics can affect one or more segments of the renal tubules. Figure 43-1 illustrates the renal tubule along with the normal process of water and electrolyte reabsorption and diuretic effects on the tubules. Every 1.5 hours, the total volume of the body's extracellular fluid (ECF) goes through the kidneys (glomeruli) for cleansing; this is the first process for urine formation. Small particles such as electrolytes, drugs, glucose, and waste products from protein metabolism are filtered in the glomeruli. Larger products such as protein and blood cells are not filtered with normal renal function, and they remain in the circulation. Sodium and water are the largest filtrate substances. Normally 99% of the filtered sodium that passes through the glomeruli is reabsorbed. From 50% to 55% of sodium reabsorption occurs in the proximal tubules, 35% to 40% in the loop of Henle, 5% to 10% in the distal tubules, and less than 3% in the collecting tubules. Diuretics that act on the tubules closest to the glomeruli have the greatest effect in causing natriuresis (sodium loss in the urine). A classic example is the osmotic diuretic mannitol. The diuretic effect depends on the drug reaching the kidneys and its concentration in the renal tubules. Diuretics have an antihypertensive effect because they promote sodium and water loss by blocking sodium and chloride reabsorption. This causes a decrease in fluid volume, lowering blood pressure. With fluid loss, edema (fluid retention in body tissues) should decrease, but if sodium is retained, water is also retained, and blood pressure increases. Many diuretics cause the loss of other electrolytes, including potassium, magnesium, chloride, and bicarbonate. The diuretics that promote potassium excretion are classified as potassium-wasting diuretics, and those that promote potassium retention are called potassium-sparing diuretics. The following five categories of diuretics are effective in removing water and sodium: • Thiazide and thiazide-like • Loop or high-ceiling • Osmotic • Carbonic anhydrase inhibitor • Potassium-sparing The thiazide, loop or high-ceiling, and potassium-sparing diuretics are most frequently prescribed for hypertension and for edema associated with HF. Except for those in the potassium-sparing group, all diuretics are potassium-wasting. Combination diuretics that contain both potassium-wasting and potassium-sparing drugs have been marketed primarily for the treatment of hypertension. Combinations have an additive effect in reducing blood pressure and are discussed in more detail in the section on potassium-sparing diuretics. (p p. 639-640) |
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furosemide
(Lasix) |
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sympatholytics
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Sympatholytics (Sympathetic Depressants)
The sympatholytics comprise five groups of drugs: (1) beta-adrenergic blockers, (2) centrally acting alpha2 agonists, (3) alpha-adrenergic blockers, (4) adrenergic neuron blockers (peripherally acting sympatholytics), and (5) alpha1- and beta1-adrenergic blockers. Beta-adrenergic blockers block the beta receptors, and alpha-adrenergic blockers block the alpha receptors. (p. 655) |
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beta-adrenergic blockers
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Beta-adrenergic blockers, frequently called beta blockers, are used as antihypertensive drugs or in combination with a diuretic. Beta blockers are also used as antianginals and antidysrhythmics and are discussed in that context in Chapter 42.
Beta (β+ and β–)-adrenergic blockers reduce cardiac output by diminishing the sympathetic nervous system response to decrease basal sympathetic tone. With continued use of beta blockers, vascular resistance is diminished, and blood pressure is lowered. Beta blockers reduce heart rate, contractility, and renin release. There is a greater hypotensive response in clients with higher renin levels. African-American hypertensive clients do not respond well to beta blockers for the control of hypertension. Instead, hypertension can be controlled by combining beta blockers with diuretics. There are numerous types of beta blockers. Nonselective beta blockers such as propranolol (Inderal) inhibit beta1 (heart) and beta2 (bronchial) receptors. Heart rate slows (blood pressure decreases secondary to the decrease in heart rate), and bronchoconstriction occurs because of unopposed parasympathetic tone. Cardioselective beta blockers are preferred, because they act mainly on the beta1 rather than the beta2 receptors and bronchoconstriction is less likely to occur. Acebutolol (Sectral), atenolol (Tenormin), betaxolol (Kerlone), bisoprolol (Zebeta), and metoprolol (Lopressor) are cardioselective beta blockers that block beta1 receptors. (pp. 655-656) |
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propanolol (Inderal)
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metoprolol
(Lopressor) |
Pharmacokinetics
Metoprolol is well absorbed from the gastrointestinal (GI) tract. Its half-life is short and its protein-binding power is low. Pharmacodynamics Cardioselective beta-adrenergic blockers block beta1 receptors, thereby decreasing heart rate and blood pressure. The nonselective beta blockers block beta1 and beta2 receptors, which can result in bronchial constriction. Beta blockers cross the placental barrier and are excreted in breast milk. The onset of action of oral beta blockers is usually 30 minutes or less, and the duration of action is 6 to 12 hours. When beta blockers are administered intravenously (IV), the onset of action is immediate, peak time is 20 minutes (compared with 1.5 hours orally), and duration of action is 4 to 10 hours. Side Effects and Adverse Reactions Side effects and adverse reactions include decreased pulse rate, markedly decreased blood pressure, and (with noncardioselective beta1 and beta2 blockers) bronchospasm. Beta blockers should not be abruptly discontinued, because rebound hypertension, angina, dysrhythmias, and myocardial infarction can result. Beta blockers can cause insomnia, depression, nightmares, and sexual dysfunction (p. 656) Noncardioselective beta blockers inhibit the liver's ability to convert glycogen to glucose in response to hypoglycemia. Because of this side effect, beta blockers should be used with caution in clients with diabetes mellitus. In addition, the depression of heart rate masks the symptom (tachycardia) of hypotension. (p. 656) |
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angiotensin-converting enzyme (ACE) inhibitors
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Drugs in this group inhibit ACE, which in turn inhibits the formation of angiotensin II (vasoconstrictor) and blocks the release of aldosterone. Aldosterone promotes sodium retention and potassium excretion. When aldosterone is blocked, sodium is excreted along with water, and potassium is retained. ACE inhibitors cause little change in cardiac output or heart rate, and they lower peripheral resistance. Figure 44-1 illustrates the renin-angiotensin- aldosterone system (RAAS). These drugs can be used in clients who have elevated serum renin levels.
The ACE inhibitors are used primarily to treat hypertension; some of these agents are also effective in treating heart failure. The first ACE inhibitor, captopril (Capoten), became available in the early 1970s. By the mid-1990s there were five ACE inhibitors, and in the late 1990s there were 10. These 10 ACE inhibitors include benazepril (Lotensin), captopril (Capoten), enalapril maleate (Vasotec), fosinopril (Monopril), lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril (Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril (Mavik). These drugs can be used for first-line antihypertensive therapy, but thiazide diuretics are recommended by the JNC 7. African Americans and older adults do not respond to ACE inhibitors with the desired reduction in blood pressure, but when taken with a diuretic, blood pressure usually will be lowered. ACE inhibitors should not be given during pregnancy, because they reduce placental blood flow. For clients with renal insufficiency, reduction of the drug dose (except for fosinopril [Monopril]), is necessary. With the exception of moexipril (Univasc), which should be taken on an empty stomach for maximum effectiveness, ACE inhibitors can be administered with food. Side Effects and Adverse Reactions The primary side effect of ACE inhibitors is a constant, irritated cough. Other side effects include nausea, vomiting, diarrhea, headache, dizziness, fatigue, insomnia, serum potassium excess (hyperkalemia), and tachycardia. The major adverse effects are first-dose hypotension and hyperkalemia. Hypotension results because of the vasodilating effect. First-dose hypotension is more common in clients also taking diuretics. Contraindications ACE inhibitors should not be given during pregnancy; harm to the fetus due to reduction in placental blood flow could occur. This group of drugs should not be taken with potassium-sparing diuretics such as spironolactone (Aldactone) or salt substitutes that contain potassium, because of the risk of hyperkalemia (serum potassium excess). (pp. 663-664) |
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angiotensin II receptor blockers (ARBs)
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Angiotensin II receptor blockers or ARBs are another group of antihypertensive drugs. These agents are similar to ACE inhibitors in that they prevent the release of aldosterone (sodium-retaining hormone). They act on the renin-angiotensin-aldosterone system (RAAS). The difference between ARBs and ACE inhibitors is that ARBs block angiotensin II from the AT1 receptors found in many tissues, whereas ACE inhibitors inhibit the angiotensin-converting enzyme in the formation of angiotensin II. The ARBs cause vasodilation and decrease peripheral resistance. They do not cause the constant, irritated cough ACE inhibitors can. Like ACE inhibitors, ARBs should not be taken during pregnancy.
Losartan (Cozaar), valsartan (Diovan), irbesartan (Avapro), candesartan cilexetil (Atacand), eprosartan (Teveten), olmesartan medoxomil (Benicar), and telmisartan (Micardis) are examples of ARBs. These agents block the vasoconstrictor effects of angiotensin II at the receptor site. The Food and Drug Administration (FDA) approves them for the treatment of hypertension. The combination of losartan potassium and hydrochlorothiazide tablets and valsartan and hydrochlorothiazide tablets and others should not cause serum potassium excess or loss. ARBs may be used as a first-line treatment for hypertension. (p. 664) |
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anticoagulatants
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Anticoagulants are used to inhibit clot formation. Unlike thrombolytics, they do not dissolve clots that have already formed, but rather act prophylactically to prevent new clots from forming. Anticoagulants are used in clients with venous and arterial disorders that put them at high risk for clot formation. Venous problems include deep vein thrombosis (DVT) and pulmonary embolism, and arterial problems include coronary thrombosis (myocardial infarction), presence of artificial heart valves, and cerebrovascular accidents (CVAs, or stroke). (p. 671)
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antiplatelets
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Antiplatelets are used to prevent thrombosis in the arteries by suppressing platelet aggregation. Heparin and warfarin prevent thrombosis in the veins.
Antiplatelet drug therapy is mainly for prophylactic use in (1) prevention of myocardial infarction or stroke for clients with familial history, (2) prevention of a repeat myocardial infarction or stroke, and (3) prevention of a stroke for clients having transient ischemic attacks (TIAs). Long-term, low-dose aspirin therapy has been found to be both an effective and inexpensive treatment for suppressing platelet aggregation. Aspirin inhibits cyclooxygenase, an enzyme needed by platelets to synthesize thromboxane A2 (TxA2). For clients with familial history of stroke or myocardial infarction, the recommended aspirin dose is 81, 162, or 325 mg/day. Because aspirin has prolonged antiplatelet activity, it should be discontinued at least 7 days before surgery. (pp. 675-676) ther antiplatelet drugs include dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix), anagrelide HCl (Agrylin), abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat). Clopidogrel, dipyridamole, and ticlopidine have similar effects as aspirin, but they are known as adenosine diphosphate (ADP) antagonists affecting platelet aggregation. Cilostazol (Pletal) inhibits platelet aggregation and is a vasodilator that may be used for intermittent claudication. Clopidogrel (Plavix) is an antiplatelet drug frequently used after myocardial infarction or stroke to prevent a second event. It may be prescribed singly or with aspirin. It has been stated that Plavix and aspirin are more effective in inhibiting platelet aggregation if used together than if used as separate antiplatelet therapies. (p. 677) |
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thrombolytics
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Thromboembolism (occlusion of an artery or vein caused by a thrombus or embolus) results in ischemia (deficient blood flow) that causes necrosis (death) of the tissue distal to the obstructed area. It takes approximately 1 to 2 weeks for the blood clot to disintegrate by natural fibrinolytic mechanisms. If a new thrombus or embolus can be dissolved more quickly, tissue necrosis is minimized, and blood flow to the area is reestablished faster. This is the basis for thrombolytic therapy.
Thrombolytics have been used since the early 1980s to promote the fibrinolytic mechanism (converting plasminogen to plasmin, which destroys the fibrin in the blood clot). The thrombus, or blood clot, disintegrates when a thrombolytic drug is administered within 4 hours after an acute myocardial infarction (AMI) (an acute heart attack). Necrosis resulting from the blocked artery is prevented or minimized, and hospitalization time may be decreased. The need for cardiac bypass or coronary angioplasty can be evaluated soon after thrombolytic treatment. A thrombolytic drug should be administered within 3 hours of a thrombolic stroke. These drugs are also used for pulmonary embolism, DVT, noncoronary arterial occlusion from an acute thromboembolism, and thrombolic stroke. Five commonly used thrombolytics are streptokinase, urokinase, alteplase, reteplase (Retavase), and tenecteplase (TNKase). Streptokinase and urokinase are enzymes that act systemically to promote the conversion of plasminogen to plasmin. Alteplase, also known as tissue plasminogen activator (tPA), is clot-specific and binds to the fibrin surface of a clot, promoting the conversion of plasminogen to plasmin. Plasmin, an enzyme, digests the fibrin in the clot. Plasmin also degrades fibrinogen, prothrombin, and other clotting factors. These five drugs all induce fibrinolysis (fibrin breakdown). Streptokinase may cause hypotension when first administered. Drug dosage may need to be adjusted. Reteplase (Retavase), a derivative of tPA, is a fairly recent thrombolytic drug. Anticoagulants and antiplatelet drugs increase the risk of hemorrhage; therefore they should be avoided until the thrombolytic effect has passed. The health care provider needs to determine whether or not the client has taken any of these drugs before seeking treatment. (p. 680) |
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antihyperlipidemics
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Drugs that lower lipid levels include bile-acid sequestrants, fibrates (fibric acid), nicotinic acid, cholesterol absorption inhibitor, and hepatic 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins). The statins have fewer adverse effects and are well tolerated.
One of the first antihyperlipidemics was cholestyramine (Questran), introduced in 1959. It is a bile-acid sequestrant that reduces LDL cholesterol (LDL-C) levels by binding with bile acids in the intestine. It is effective against hyperlipidemia type II. This group may be used as an adjunct to the statins. The drug comes in a gritty powder, which is mixed thoroughly in water or juice. Colestipol (Colestid) is another resin antihyperlipidemic similar to cholestyramine. Both are effective in lowering cholesterol. Colesevelam HCl, another bile acid sequestrant similar to cholestyramine and colestipol, is an agent that has fewer side effects (less constipation, flatulence, and cramping). Colesevelam also has less effect on the absorption of fat-soluble vitamins than the older agents and is usually the first-choice bile-acid sequestrant drug. Gemfibrozil (Lopid) is a fibric acid derivative that is more effective at reducing triglyceride and VLDL levels than reducing LDL. It is used primarily to reduce hyperlipidemia type IV, but can also be used for type II hyperlipidemia. This drug is highly protein-bound and should not be taken with anticoagulants, because they compete for protein sites. Anticoagulant dose should be reduced during antihyperlipidemic therapy, and the international normalized ratio (INR) should be closely monitored. Fenofibrate, approved in 1998, has similar actions and some of the same side effects as gemfibrozil. If taken with warfarin, bleeding might occur. It is highly protein-bound. Nicotinic acid, or niacin (vitamin B2), reduces VLDL and LDL. Nicotinic acid is actually very effective at lowering cholesterol levels, and its effect on the lipid profile is highly desirable. Because it has numerous side effects and large doses are required, as few as 20% of clients can initially tolerate niacin. However, with proper counseling, careful drug titration, and concomitant use of aspirin, this number can be increased to as high as 60% to 70%. Ezetimibe (Zetia) is a cholesterol absorption inhibitor that acts on the cells in the small intestine to inhibit cholesterol absorption. It decreases cholesterol from dietary absorption, reducing serum cholesterol, LDL, triglycerides, and apoB levels. Ezetimibe causes only a small increase in HDL. It must be combined with a statin for optimum effect (ezetimibe and simvastatin [Zocor], marketed as Vytorin). (p. 686) |
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statins
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The statin drugs, first introduced in 1987, inhibit the enzyme HMG CoA reductase in cholesterol biosynthesis; thus the statins are called HMG CoA reductase inhibitors. By inhibiting cholesterol synthesis in the liver, this group of antihyperlipidemics decreases the concentration of cholesterol, decreases LDL, and slightly increases HDL cholesterol. Reduction of LDL cholesterol may be seen as early as 2 weeks after initiating therapy. The statin group has been useful in decreasing CAD and reducing mortality rates.
Numerous statins have been approved since they were first introduced. The present group of statins includes atorvastatin calcium (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin sodium (Pravachol), simvastatin (Zocor), and rosuvastatin calcium (Crestor). Lovastatin was the first statin used to decrease cholesterol. It is effective in lowering LDL (hyperlipidemia type II) within several weeks. Gastrointestinal (GI) disturbances, headaches, muscle cramps, and tiredness are early complaints. With all statins, serum liver enzymes should be monitored, and an annual eye examination is needed, because cataract formation may result. The client should report immediately any muscle aches or weakness, which can lead to rhabdomyolysis, a muscle disintegration that can become fatal. The statins have actions in decreasing serum cholesterol, LDL, VLDL, and triglycerides, and they slightly elevate HDL. Atorvastatin (Lipitor), lovastatin (Mevacor), and simvastatin (Zocor) are more effective at lowering LDL than the other statins. Atorvastatin (Lipitor) and simvastatin (Zocor) are at the top of the list of most prescribed drugs in the United States. The statin drugs can be combined with other drugs to decrease blood pressure and blood clotting and to enhance the antihyperlipidemic effect. Examples are Advicor (lovastatin and niacin), Caduet (atorvastatin and amlodipine), and Vytorin (simvastatin and ezetimibe). These combination drugs, their doses, uses, and effects can be found in Table 46-4. If antihyperlipidemic therapy is withdrawn, cholesterol and LDL levels return to pretreatment levels. The client taking an antihyperlipidemic should understand that antihyperlipidemic drug therapy is a lifetime commitment for maintaining a decrease in serum lipid levels. Abruptly stopping the statin drug could cause the client to have a threefold rebound effect that may cause death from an AMI. (pp. 686-687) |
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atorvastatin (Lipitor)
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Atorvastatin (Lipitor) decreases LDL by 25% with lower doses and by 55% with higher doses. It increases HDL, but not to the levels of some of the other statins (pravastatin and simvastatin). It decreases the triglyceride levels by 20% with lower doses and by 50% with higher doses, a greater reduction than with other statins. Atorvastatin is highly protein-bound, so it is usually prescribed as a once-daily dose. It has a half-life of 14 hours, which is moderately long; the half-life for its metabolites is 20 to 30 hours.
Pharmacodynamics The positive effect of lowering the lipids with atorvastatin is seen in about 2 weeks. The peak time after a dose of atorvastatin is 1 to 2 hours; however, it takes 2 to 4 weeks for therapeutic effect of the drug to be achieved. When the client is taking high doses of atorvastatin or any statins, myopathy and rhabdomyolysis (disintegration of striated muscle fibers) may occur. If the client complains of muscle pain or tenderness, it should be reported immediately. Side Effects and Adverse Reactions Side effects and adverse reactions of cholestyramine include constipation and peptic ulcer. Constipation can be decreased or alleviated by increasing intake of fluids and foods high in fiber. Early signs of peptic ulcer are nausea and abdominal discomfort, followed later by abdominal pain and distention. To avoid GI discomfort, the drug must be taken with and followed by sufficient fluids. The many side effects of nicotinic acid (e.g., GI disturbances, flushing of the skin, abnormal liver function [elevated serum liver enzymes], hyperglycemia, hyperuricemia) decrease its usefulness. However, as mentioned, aspirin and careful drug titration can reduce side effects to a manageable level in most clients. The statin drugs can cause a dose-related increase in liver enzyme levels. Serum liver enzyme levels (alkaline phosphatase, alanine aminotransferase, gamma-glutamyl transferase) should be monitored. Baseline liver enzyme studies should be obtained before initiating statin drug therapy. A slight transient increase in serum liver enzyme level may be within normal value for the client, but it should be rechecked in a week or so. Clients with acute hepatic disorder should not take a statin drug. The serious skeletal muscle adverse effect known as rhabdomyolysis has been reported with the use of the statin drug class. Clients should be advised to promptly report to the health care provider any unexplained muscle tenderness or weakness, especially if accompanied by fever or malaise. (pp. 688-689) |
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peripheral vasodilators
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A common problem in older adults is peripheral arterial (vascular) disease (PAD, PVD). It is characterized by numbness and coolness of the extremities, intermittent claudication (pain and weakness of limb when walking but no symptoms at rest), and possible leg ulcers. The primary cause is arteriosclerosis and hyperlipidemia, resulting in atherosclerosis. The arteries become occluded.
Peripheral vasodilators increase blood flow to the extremities. They are used in peripheral vascular disorders of venous and arterial vessels. They are more effective for disorders resulting from vasospasm (Raynaud's disease) than from vessel occlusion or arteriosclerosis (arteriosclerosis obliterans, thromboangiitis obliterans [Buerger's disease]). In Raynaud's disease, cold exposure or emotional upset can trigger vasospasm of the toes and fingers; these clients have benefited from vasodilators. Clients with diabetes mellitus are more likely to have PAD by two to four times the usual rate and are at risk of claudication. Although the following drugs have different actions, they all promote vasodilation: isoxsuprine (Vasodilan) and papaverine (Para-Time). Papaverine is a direct-acting peripheral vasodilator. The alpha-blocker prazosin (Minipress) and the calcium channel blocker nifedipine (Procardia) have also been used as peripheral vasodilators. Individuals with PAD who are treated with HMG-CoA reductase inhibitors (statins) for dyslipidemia may get improvement for claudication symptoms as well as a decrease in serum lipids. Also, clients with PAD who are hypertensive receive improvement for both conditions when taking the antihypertensive drug ramipril (Altace), an ACE inhibitor. The antiplatelet drugs clopidogrel (Plavix) and aspirin have been used to decrease PAD symptoms. Another antiplatelet drug, cilostazol (Pletal), has been approved by the U.S. Food and Drug Administration (FDA) for treating intermittent claudication. It decreases arterial thrombi. The herb ginkgo biloba, taken with an antiplatelet drug, has been used to treat intermittent claudication, because of its vasodilating and antioxidant effects, although this herb has not been approved by the FDA. Most of the group of drugs used for treating PAD do not cure the health problem, but can aid in relieving PAD symptoms. Isoxsuprine hydrochloride, a beta-adrenergic antagonist with slight alpha-adrenergic antagonist effects, is effective for relaxing the arterial walls within skeletal muscles. (p. 689) |
