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360 Cards in this Set
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28-yr-old chemist presents w/ MPTP exposure, what neurotransmitter is depleted?
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Dopamine (MPTP causes parkinsonism)
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What clinical manifestations would be seen in a women taking tetracycline who exhibits photosensitivity
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Rash on sun-exposed areas of the body
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African American man exhibits hemolytic anemia after taking mlarial prophylaxis, What enzyme is deficient
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Glucose-6-phosphate dehydrogenase
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Farmer presents w/ dyspnea, salivation, miosis, diarrhea, cramping and blurry vision. What casued this and what is the MOA?
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Insectiside poisoning
Ingibits acetylcholinestarse |
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27-yr-old female w/ a hisotry of psychiatric illness now how urinary retention due to a neuorleptic, what do you treat it with?
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Bethanechol
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Patient w/ recent kidney transplant is on cyclosporine for immunosuprresion. Requires antifungal agent for candiadiasis, what antifungal drug would result in cyclosporine toxicity?
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Ketoconazole
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What routine workup should be done on a patient who is taking carbamazepine?
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LFTs
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23-yr-0ld female who is on rifampin for TB prphylaxis and on birht control (estrogen) gets pregnant , why?
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Rifampin augments estrgen metabolism in the liver, rendering it less effective
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Define:
Volume of distribution (Vd) Clearnce (CL) Half life (t1/2) |
Vd - amount of drug in the body/plasma concentration
CL - Rate of elimination of the drug/Plasma drug concentration T1/2 - .7*Vd/CL |
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Vd of plamsa protien bound drugs can be altered by?
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liver and kidney disease
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A drug infused at a constant rate reaches about 94% of steady state after?
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4T1/2
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What would the concentration of a drug be after 1, 2 3 and 3.3 half lives? (percentage of amount of drug left)
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1 - 50%
2 - 75% 3- 87.5% 3.3 - 90% |
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Loading dose
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Cp(target plasma concentration)*Vd/F(bioavailabiltiy)
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Maintance dose
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Cp*CL/F
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How is the loading dose and the maintance dose affected in patients w/ impaired hepatic or renal function
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Loading dose stays the same but the loading dose changes
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Describe Zero oder elimination, what are some examples of drugs?
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Rate of elimination is constant regardless of plasma concentration. (constant AMOUNT is eliminanted) Cp decreases linearly w/ time
Ethanol, phenytoid and aspirin (at high or toxic concentrations) |
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Describe first order eliminaion
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Rate of elimination is proportional to the drug concentration (constant FRACTION is eliminated per unit time). Cp decreases exponentially w/ time
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MAOI
**drugs: Moa: Use: |
Phenelzine and tranlcypromine, selegeline, tranylcypromine
inhibit MOAa and MOAb (increases NE, 5-HT...) atypical depression |
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**What do you worry about w/ MAOI?
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Hypertensive crisis (inc. BP, arrhythmias, excitation, hyperthermia...) from increase of NE
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Which drug inhibits the metabolism of tyramine, what can this cause?
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MAOI - ihnibits GI MOA-A so tyramine can't be metabolized; tyramine can induce catacholamine release and lead to hypertensive crisis (tyramine is found in red wine and cheeses have tyramine.)
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Tryciclic antidepressants (TCAs)
Drugs: MOA: Uses: |
amitriptyline, imipramine, clomipramine
non-specific block of NE and 5HT re-uptake Major depression Neuropathic pain (diabetics or protherpetic neuralgia (painful condition caused by varciella zoster virus in a dermotomal distribution)) Enuresis - antimuscarinic properties |
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**ADR of TCA's
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Cardiovascular (orthostatic hypotension, dysrhythmias)
Anticholinergic (dry mouth, constipation, blurred vision, urinary retention) CNS (Seizures, sedation...) |
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**Coma, convusions and cardiotoxicity is the common toxicity for what drug?
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TCA's
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SSRI (selective seretonin uptake inhibitors)
Drugs: MOA: Uses: |
fluoxetine, paroxetine, sertraline, citalopram, escitalopram
selectivley blocks the uptake of seretonin Major depression, OCD, anxiety disorders, PMS |
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**ADR and toxicity of SSRI's
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Serotonin syndrome
Sexual dysfunction (libido) Weight loss |
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What is thought to be the cause of depression?
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decrease in NE and 5-HT, medications are aimed at increasing these levels
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What drugs are typically used to treat depression?
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SSRI and non-cyclic SNRI
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What is the mainstay of tx for bipolar disordre
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lithium
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What antidepressant is associated w/ cardiac arrhythmias and priapism (48hr erection that needs surgery)
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Trazadone
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This antidepressant is a dopamine re-uptake inhibitor and is used in smoking cessation and depression?
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Bupropion
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Lithium
uses: MOA: |
Bipolar disorder
prevents recycling of inositol (dec. PIP2)...disrupts G2 pathways: Ach, NE, 5HT |
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Lithium ADR
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Narrow therapeutic index
Nephrogenic diabetes insipidus(dec ADH); manage w/ amiloride |
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Lithium and pregnancy
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Teratogenic...CV malformations- use clonazepam or gabapentin if think they are pregnant
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What two drugs are used to tx ADHD?
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methylphenidate, and Atomoxetine (selective NE reuptake inhibitor)
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What is the most rapid route of absorption?
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Inhalation
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What is the only form of a drug that can cross the biomembranes and contribute to its concentration gradient?
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Free and unionized form (lipid drugs are most soluble and cross the membrane the best)
Note: ionized form is better renally excreted |
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What pH is best for the abosoprtion Vs excretion of drugs that are Weak acids and weak bases?
What are some examples of drugs that are weak acids and weak bases? |
Weak acids (Aspirin) - better absorbed in acid media (stomach), better excreted in basic media
Weak bases (amphetamines and PCP) are better excreted in acidic media and better absorbed in basic media (small intestine) NOTE: THIS FOLLOWS THE PRINCIPLE OF IONIZATION |
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what is the solubility of a drug that is ionized vs non-ionized
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ionized - water soluble
nonionized - lipid soluble |
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what are some examples of things that you can give to Acidify and Alkalinize the urine?
How does ionization help w/ excretion of a drug? |
Acidify - NH4CL, vit C
Alkalinize - NaHCO3 As long a drug is free (not bound to protein) it can be filtered, ionized forms of drug are not reabsorbed increasing there excretion |
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How does a pH>pka affect drugs that are weak acids or bases?
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Weak base will be in unionized form
Weak acid will be ionized form increasing excretion Note: the reverse is true for pH<pka |
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What is bioavailability (f)?
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The fraction of the drug that reaches the systemic circulation
IV dose has 100% bioavailability the number used is 1 for this |
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How does adding a sulfonamide drug effect the distribution (from systemic circulation to target organ)of warfarin?
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Increases the distribution of warfarin and its toxicity (bleeding)...they both compete for binding sites to plasma proteins. Increases the free warfarin fraction
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What is the affect of sulfonamides in a neonate on its bilirubin level?
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increases bilirubin can result in kernicterus and encephalopathy
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What is the apparent volume of distribution (Vd) equation?
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Vd=Dose/Czero (initial plasma level)
used to calculate the loading dose |
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How does the duration of action of a CNS drug different from your typical drugs?
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CNS drugs - duration of action may depend more on redistribution (lipophilic drugs can deposit in fat and when blood levels drop the stored drug is released) rate than on half life
In addition to crossing the BBB, lipid soluble drugs redistribute to fat prior to elimination. CNS drugs second dose may be more effctive that first due to lower Blood/fat ratio |
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What does the liver typically due to a drug?
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metabolic conversion so that it is more water-soluble and more readily excreted or in some cases activated
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What is a good example of a drug that has an active metabolite after biotransformation (metabolic conversion) in the liver?
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Benzodiazepines diazepam...formation of nordiazepam, a metabolite w/ sedative hypnotic activity
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What are the types of biotransformation?
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Phase I and II
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VHY
What is the phase I reaction of biotransformation? |
Modification of a drug via oxidation, reduction or hydrolysis
VHY: cytocrome P450 does this |
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VHY
What are the Cytochrome P450 isozymes |
major enzyme system involved in phase I rxns...localized in the SER of cells (ESPECIALLY THE LIVER, but includes GI, Lungs and kidney)
NEED Oxygen molecules and NADPH to function |
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VHY
What induces (causes the liver to make more) the CYP450 isozyme 1A2? |
Aromatic hydorcarbons (SMOKE)
NOTE: 1A2 substrate is theophyline and acetaminophen |
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VHY
What induces the CYP450 isozymes 2C9 and 3A4? |
anticonvulsants (barbiturates, phenytoin, carbamezepine)
Antibiotics (Rifampin) Chronic Alcohol |
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VHY
60% of drugs in the PDR are metabolized in the phase I rxn of _________CYP450 isozyme? |
3A4
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VHY
What drugs inhibit (inhibit metabolism) the CYP450 isozyme 3A4? |
anti-ulcer - CIMETIDINE
antibiotic - macrolides (azithromycin, clarithromycin, erythromycin grape fruit juice acute alcohol |
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VHY
Theophylline given w/ _______drug will increases its levels making it toxic? |
Erythromycin (macrolide)
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VHY
What food can increase the plasma level of statins (e.g.atarvostatin)? |
Grapefruit juice (active component;furanocoumarins) by inhibiting cyp450 3A4
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VHY
This enzyme is part of the phase I rxn but is not one of the typical CYP450 isoenzymes it metabolizes tyramine? What foods is tyramine found in? |
Monoamine oxidases
found in Beef, RED WINE, cheese, and FISH NOTE: MAOI can cause Increase in tyramine resulting in HTN crisis |
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VHY
What are the phase II rxns of biotransformation (metabolic conversion of drugs) |
conjugation w/ endogenous compounds via transferases
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What are the two diseases that have a Deficiency of the transferases, enzymes involved in the conjugation of drugs during phase II reactions of biotransformation?
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Gilbert
Crigler-Najjar syndromes |
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VHY
What is the most common type of conjugation that occurs during the phase II rxn of biotransformation? What age group has reduced activity of this type of conjugation and what can it result in? |
VHY:Glucuronidation
VHY:Neonates - choramphenicol not conjugated and accumalates leading to Grey baby syndrome (vomitting, grey color, hypotension) |
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VHY
What drugs are involved in Drug-induced lupus (fever, arthralgia, inc. BP? Why do these patients develop drug induced lupus? |
Hydralazine(vasodilator;SM relaxant)>procainamide(cardiac arrhythmias)>isoniazid (TB)
SLOW ACETYLATORS note:Stop-drug and lupus goes away you will see ANTI-HISTONE antibodies |
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VHY
What are the drugs w/ zero order elimination rate, what does this mean? |
Ethanol
salicylates (toxic doses) Phenytoin (at high therapeutic doses) constant amount is eliminated per unit time (linear graph) NOTE: rate is constant but t1/2 is variable |
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How is elimination of a drug affected by plasma concentration or amount in the body?
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Independent
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What is first oder-elimination of a drug?
The rate of eliminantion is directly porpotional to? |
constant fraction of a drug is eliminanted per unit time (exponetial graphically)
amount eliminated is variable but t1/2 is constant DIRECTLY PORORTIONAL TO plasma level |
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What molecule is used to estimate GFR?
What is a normal GFR? |
Inulin (neither secreted or absorbed
120ml/min |
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The time to reach steady state (Rate in = Rate out) depends only on?
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1/2 life
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VHY
Clinical steady state is considered to be reached after how many half lives? |
4-5 = 95% (actually)
7 half lives is mathmatical steady state = 100% |
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How does dose/rate of infusion affect the time to reach steady state?
What does dose determine then? |
the time to reach steady state (Css) is the same but the plasma level at steady state will be will be different
Determines your initial concentration |
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WHat is the purpose of a loading dose (giving a higher dose)?
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to more rapidly achieve an EFFECTIVE blood level. Remember the time to steady state wont change but where the blood level starts can be influenced by dose.
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VHY
what is the equation for volume of distribution? |
Vd = D(dose)/C zero (initial concentration)
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VHY
what is the equation for half life? |
t1/2 = .7 x vd/cl(clearnce)
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VHY
What is the loading dose equation? |
LD = Vd x Css (steady stae conc.)
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VHY
What is the equation for maintance dose? |
MD = CL x Css x t (how often given)
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Patient has fever and chills, labs show hematocrit of 23% and urine tests are positive for blood...paitent is taking one durg for his "irregular heart beat" what drug is most likley w/ these signs and symptoms?
How does it cause these sympotoms |
Quinidine - antiarrythmic drug
causes hemolytic anemia by forming immune complexes w/ RBC...RBC is recognized as foreign and is destroyed...quinidine then forms another immune complex... |
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41 yr old diabetic women presents w/ GI distress and heart burn particularly after meals, what would you prescribe to relieve her symptoms?
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anti-emetic like Prochlorperazine for the nausea (D2 receptor antogonist at the Chemoreceptor trigger zone in the medulla)...but the underlying problem is gastric motility due to nerve damage from her diabetes causing GI problems (best to tx underlying motility problem)
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If diabetic patient has GERD secondary to her diabetes what is a good drug to use to help w/ lower esophageal tone?
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metoclopromide - increases lower esophageal tone helping prevent GERD (and barrets)
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35 yr old women arrives at her physicians officice complaining of anxiety. What drug would help relieve her anxiety w/ minimum unwanted side-effects, it is a nonbenzodiazepine?
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Buspirone - nonbenzodiazepine anxiolytic this has no sedative, anticovulsant or muscle relaxant properties...it is a partial agonist at 5-HT1a receptors
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VHY
Women being treated for non-hodgkins lymphoma, develops blood in her urine. What antineoplastic drug is most likley responsible? |
Cyclophosphamide
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VHY
What is the notable ADR for the antineoplastic drug Bleomycin? |
polmonary toxicity
typically an adjucnt drug |
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VHY
What is the notable ADR for the antineoplastic drug cisplatin? What is it usually used for? |
nephrotoxicity
ototoxicity Testicular and lung cancer |
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VHY
What is the notable ADR for the antineoplastic drug doxorubicin? |
Cardiotoxicity
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VHY
What is the notable ADR for the antineoplastic drug Plicamycin? When is it used? |
hemorrhagic diathasis - can see blood in the urine
Not used to treat lymphomas but testicular cancer and hypercalcemia |
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VHY
What is the notable ADR for the antineoplastic drug Vincristine? When is it used? |
Dose limiting neurotoxicity
As part of the MOPP regimen for Hodgkin disease and other cancers or diseases |
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IF you know the clearnce 4L/hr and vd of 80L of a drug how do you determine its half life?
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CL = k x Vd
t1/2 = .7/k answer is 14 |
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How can a partial agonsit act as an antagnoist?
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When given w/ a full agonsit it can displasce the full agonist and the response is reduced
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What affect w/ Pindolol have on a patient if they are already taking epinephrine?
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They both act at the same receptor and pindolol will displace epinephrine lowering its efficacy and cause a slowing of the heart rate because it acts as an antoagonist
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What is the most commonly used drug for treatment of breast cancer that is a selective receptor estrogen modulator and a partial agonist
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Tamoxifen
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VHY
What are some good examples of non-competitive inhibitors? |
PHenoxybenzamine (only alpha blocker that is non-competitive)
DIgoxin Allopurinol Proton pump inhibitors Aspirin |
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In a graded dose response curve (pg 23 Kaplan pharm book) how will a competitive antagonist and a drug that causes potentiation (in response to drug) look compared to the control?
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Antagonist - parallel shigt to the right or away from the y-axis
Potention - shift to the left |
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How do competitve and non-competitve inhibitors affect Km and Vmax?
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CI - increase Km (decrease substrates "ability" or affinity to bind) but the Vmax stays the same (the maximal response is the same)
NCI - km dosent change but Vmax goes down (the rate at which it can preform has gone down) |
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Protamine binding to heparin to reduce its action is an example of?
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Chemical antagonism: formation of a complex between effector drug and another compound
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What phase of metablism is lost in Geriatric patients first?
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Phase I (cytocrome P-450)
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On a agonist dose response curve (pg 196 in the Step 1 book) what do the curves look like when a competitive agonist Vs a irreversible antagonist/non-competitive antagonist are added?
Agonist dose is the X-axis and percent of maximum effect is the y-axis. |
Competitve agonist - curve shifts away from the y-axis because the affinity of the agonist goes down as it has to compete w/ the antagonist and. Also becuase it requires a higher dose to overcome the antagonist
Non-competitve/irreversible antagonist the height of the curve is markedly lower and no amount of increase in dose can overcome the problem |
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What is potentiation
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adding a drug that increases the effectivness of another drug
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In a system w/ spare receptors the EC50(median effective concentration; the concentration at which you get half of the drug effectivness) is lower than the Kd (concentration of the drug required to bind 50% of receptor sites) indicating what?
PG 196 Step 1 book for visual image |
TO achieve 50% of maximum effect less than 50% of the receptors need to be activated
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How does a partial agonist compare to a full agonist (that acts on the same recepotr) in a comparison dose response curve?
pg 197 step 1 book Can the partial agonist be more potent (effect based on dose) that the full agonist? |
Partial agonist has less maximal efficacy (lower height on the curve, can't produce equivalent response) than the full agonist.
It can be more potent than the full agonist (achieves its full capcity at lower doses compared to full agonist)This is seen on the curve as being closer to the Y-axis |
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What happens when a partial agonist is given w/ a full agonist?
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It begins to displace the full agonist (acts as a competive inhibitor so to speak) and if the dose continues to increase it acts as an antagonist and the effectivess of the full agonist decreases (seen as a lower height on the curve)
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What is the therapeutic index (TI)?
What does TD50 and ED50 stand for? Is a higher or lower TI better? |
TD50/ED50
TD50 - dose at which get toxicity in half of the population ED50 - Dose at which get effectivness in 50% of the population. The higher the better (takes a higher dose to get into toxic range) |
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4 drugs that have very high TI?
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1. Warfarin
2. Digoxin 3. Theophylline 4. Lithium |
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What happens before a drug be investigated on humans?
How many years does it take? |
In vitro studies followed by animal studies
about 4 years |
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Initiation of human studies requires an investigational new drug (IND) exemption. What are the 4 phases of clinical testing?
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Phase 1 - (Is it safe, pharmakodynamics; done on volunteers who do not have the disease)
Phase 2 (Does it work in pateints, 1st efficacy test, used on patients w/ the disease) Phase 3 (How well does it work, further efficacy and side affects) 1-3 phases take 8-9 years Phase 4 (Posmarketing surveillance, look for rare side effects)Its on the market |
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What are the different classification of drugs and Pregnancy?
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A - very safe
B - Safe C - maybe safe D - Benefits out weigh risks X - Risks out weigh benefits |
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What are some examples of drugs that pregancy category D and X
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D-ACEI, ARBS, anticonvulsants
X-Statins, OCP, misoprostol(induces abortion), High dose Vitamin A (derivatives for acne) |
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VHY
What are the neurotransmitters released and the receptors of the parasympathetic autonomic nervous system (PANS)? |
Ach onto nicotonic receptors at the first ganglia and then Releases Ach onto a muscarinic recpetor at the target organ
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VHY
What are the target organs for the parasympathetic system? |
cardiac and smooth muslce, glands and nerve terminals
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VHY
What are the nuerotransmitters released and the receptors of the sympathetic autonomic nerveous system (SANS) |
At the chain ganglia which is just by the vertebral column, Ach is released onto a nictonic receptor then at the next synapse NE is released onto an adrenergic receptor (alpha or beta)
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VHY
What are some of the ways that the SANS differs from the general rule in the type of neurotransmitter it releases and the receptor it binds to? |
Ach released onto the chain ganglia but then Dopamine is released onto onto a D1 receptor at the Renal vascular smooth muscle or mesentary vascular beds
The other exception is Ach instead of being released onto the chain ganglia is released onto the adrenal medulla which then releases NE and Epinephrine into the blood THE SANS alos releases Ach onto a muscarinc receptor if it is a sweat gland |
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What tissues are under the control of the SANS
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Sweat glands (Ach, M)
cardiac and smooth muscle, glands, and nerve terminals (NE, alpha and beta) Renal vascular smooth muslce and mesentary vascualr bed (Dopamine, D1) |
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How is skeletal or voluntary muscle innervated?
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the nerve goes directly to the muscle w/o an intermediate gangia like the ANS
Ach is released onto a nicotinic receptor |
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How is the SANS differ from the PANS in terms of length of pre and postganglionic nerve fibers?
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SANS - short long
PANS - long short |
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What neurotransmitter is released onto denervated tissue (exam trick)
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Epinephrine because it is carried in the blood
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What branch of the ANS controls thermoregulatory sweat glands?
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SANS- but it releases Ach
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Describe the second messenger pathway for the Gq protein class?
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1.phospholipase C stimulated
2.Converts lipids to PIP2 - 3. PIP2 is converted into IP3 and DAG 4. IP3 releases intracellular Ca which helps DAG stimulate protein kinase C 5. it phosphorylates proteins and causes gene expression |
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Describe the second messenger pathway for the Gs protein class
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1. Adenylcyclase stimulated
2. converts ATP to cAMP 3. Protien A is stimulated 4. tissue transciption factors are activated and protiens are phosphorylated |
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Describe the second messenger pathway for the Gi protein class
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1. Adenyl cyclase (I think it is inhibited or causes the reverse action)
2. dec. cAMP 3. dec. protein kinase A |
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What receptors are linked to the Gq, Gs and and Gi second messenger system.
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Gq (HAVE 1 M&M) - H1, alpha1,V1, M1, and M3
Gi (MAD 2s) - M2, alpha 2, D2 Gs - B1, D1, B2, H2, V2 |
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What recepotor and G protein must be activated for the following response to occur:
Increase in vascular smooth muscle contraction (arterioles and veins), mydriasis, constrict prostrate SM (BPH) |
alpha 1, Gq
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What recepotor and G protein must be activated for the following response to occur:
decrease sympathetic outflow (NE synthesis and release) and insulin release |
alpha 2, Gi
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What recepotor and G protein must be activated for the following response to occur:
increase heart rate, contractility, inc. RENIN release, lipolysis, aquous humor formation? |
Beta 1, Gs
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What recepotor and G protein must be activated for the following response to occur:
vasodilation, bronchodilation, glucagon release increased? |
Beta 2, Gs
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What recepotor and G protein must be activated for the following response to occur:
CNS affects |
M (ach), Gq
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What recepotor and G protein must be activated for the following response to occur:
Decrease in heart rate (e.g reflex bradychardia) |
M2, Gi
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What recepotor and G protein must be activated for the following response to occur:
Has to do w/ things located in the periphery, Exocrine glands, eye muslces (miosis), Lungs (broncioles and glands), stomach and intestine (not the glands in GI tract), Bladder, sphincters and BLOOD VESSELS? |
M3, Gq
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What recepotor and G protein must be activated for the following response to occur:
Relaxed renal vascular smooth mulsce |
D1, Gs
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What recepotor and G protein must be activated for the following response to occur:
MOdulates transmitter release, especially in the brain? |
D2, Gi
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What recepotor and G protein must be activated for the following response to occur:
Increase nasal and bronchial mucous production, contraction or bronchioles, pruritis and pain (e.g allergic reaction) |
H1, Gq
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What recepotor and G protein must be activated for the following response to occur:
Increase in gastric acid secrtion? |
H2, Gs
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What recepotor and G protein must be activated for the following response to occur:
Increase vascular smooth muscle contraction (not alpha 1) |
V1, Gq
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What recepotor and G protein must be activated for the following response to occur:
Increase H2O permaeability and reabsorption in the collecting tubules of the kidney? |
V2, Gs
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Where is NO synthesized and what is its signaling mechanism?
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Made by endothelial cells
Causes increas in cGMP, causing deposphorylation of myosin light chain and thus causing smooth muscle to relax and vasodilation to occur |
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What are the NO activators?
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histamine, bradykinin and Ach
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What is the general mechanism by which insulin, PDGF and EGF act by to induce there effect on a cell?
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VIA a transmembrane enzyme (receptor on outside and enzyme activity on the inside) usually a tyrosine kinase
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What are the receptors for cytokines like?
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Transmembrane enzymes called JAKS and activate a transcription molecule that affects gene transcription (its like a steriod and insulin receptor combined)
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What does muscarinc (cholinergic) stimulation of the eye result in?
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Miosis (sphincter muscle) and Accomadation (ciliary muscle)
note: Cycloplegia is paralysis of accomadation which would be caused by anticholinergic drugs |
|
|
VHY
What does alpha 1 stimulation of the eye result in? |
Mydriasis only (radial muscle), it has no effect on ACCOMADATION
|
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How does tropicamide and phenylephrine differ on there effects on the eye?
|
Muscarinic Ach antagonist (mydriasis and cycloplegia)
Phenylephrine (alpha-adrenergic agonist) causing mydriasis but no affect on accomadation |
|
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VHY
Describe the cycle of Ach at the cholinergic neuroeffector junction (i.e. nicotinic or muscarinic receptor and axon) REFER TO IMAGE PG 200 STEP of 1 |
1. Choline is recycled back into the axon
2. Choline acetyl transferase combines choline and acetyl CoA 3. They are stored in vesicles 4. When nerve is deoploarized voltage gated calcium channels are opend and CA2+ enters and trigers release of Ach containg vesicles 5. Ach is released and binds to a receptor 6. Achesterase breaks down Ach to choline and acetate 7. Choline is recycled |
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VHY
What drug blocks the recycling or reputake of Ach by the neruon? |
Hemicholinium
|
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VHY
What drug blocks the storage of Ach in storage vesicles in nerve terminals? |
Vesamicol
|
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VHY***
What drug blocks the fusion and relase of Ach storge vesicles into synaptic cleft of cholinergic neurons? What is one of the primary protiens it interacts w/? |
Botulism
Synaptobrevin |
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|
ALL muscarinic drugs that are either activors or blockers have this type of specificity?
|
THEY ARE ALL NONSPECIFIC
|
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|
VHY concept
Where is the location of the M3, M2 and M1 receptors in a nut shell |
M3 - think peripheral
M2 - Heart M1 - CNS M receptors function on CV function is to decrease it |
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VHY**
WHat is unique about the M3 recepotor found on blood vessels (endothelium) |
1.It can only be activated pharmacologically, it causes dilatation...the body causes dilatation of Blood vessels by NO
2. There is no innervation so indirect agonist don't work here because no ACHesterase |
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|
What happens if a cholinergic agonist (e.g. Bethanechol) drug is given and then atropine after that?
|
atropine can block agonist affect by acting at M3 blood vessel receptor
|
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What is the difference between direct and indirect cholinergic agonist (e.g Bethanechol Vs physostigmine)
|
Bethanocol can act at the blood vessel receptor M3 and physostigmine cannont
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|
Blood vessels are solely innervated by?
WHat hapens when autonomic ganglia are stimulated? |
Sympathetic ANS
Vasconstriction results |
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The GI tract is dominated by The parasympathetic nervous system. What happens whent the autonomic ganglia are stimualted?
|
Inc. GI motility and secretions
|
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|
Is there a second messenger associated w/ nicotinic receptors?
|
NOPE, just activation of Na/K channels
|
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VHY
What are the effects of Nicotine? |
Most of its affects are PANS except blood vessels (get vasoconstriction)
|
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|
VHY
What are the Muscarinic agonist? (stimulate M1-3) |
1.Bethanechol
2.Methacholine 3.pilocarpine 4.carbachol 5.Ach - obviously but no clinical use NOTE: remember they are non-selective for the type of muscarinic receptor (M1-3) and they are not broken down by Achesterase inhibitor |
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VHY
Which Muscarinic direct agonist (ACh mimetric) would you use to treat postoperative or neurogenic ileus and/or ***URINARY incontinence? What is its action? |
Bethanecol
activates BOWEL and BLADDER smooth muscle but resistant to AChE |
|
|
VHY
What Direct muscarinic agonists can be used to treat gluacoma? What is the mechanism |
Pilocarpine and Carbechol
Activates the ciliary muscle (acts on the lens) of the eye (open angle) and pupillary sphincter (narrow angle) and is resistnat to AChE degredation |
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VHY
What can Pilocarpine be used to treat besides glaucoma (increased intraocular pressure)? |
Xerostomia caused by Sjogrens syndrome
|
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|
What Direct muscarinic agonist can be used to challenge or make the diagnoses of asthma?
|
Methacholine (it induces asthma in an asthma patient)
|
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VHY***
This drug is used in postoperative ileus and urinary retention, myasthenia gravis, and reversal of nueromusclar junction blockade (postoperative)? What is the MOA Does it cross the BBB? |
Neostigmine (quantanary amine, + charge)
AChe inhibiotr (indirect agonist), reversible inhibiotor increasing endogenous ACh Does not cross the BBB, because of positive charge |
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VHY***
This drug does not cross the BBB and used in the treatment of myasthenia gravis? MOA |
Pyridostigmine (quantanary amine; positive charge)
increases endogenous ACh and strength by inhibiting AChE reversibly |
|
|
VHY**
This drug is used in the diagnosis of Myasthenia gravis and to distinguish it from a cholinergic crisis? |
Edrophonium (Tensilon test)
AChE inhibitor (increases endogenous ACh) t1/2 is 10min |
|
|
VHY**
This drug is used in the treatment of gluacoma and atropine overdoses, it crosses the BBB? MOA? |
Physostigmine (tertiary amine, lipid soluble)
AChE inhibitor, stops central and peripheral effects because it crosses the BBB |
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|
This drug is an organophosphate and is used the treatment of glucoma?
MOA, how is different from other drugs in its class |
Echothiophate
AChE inhibitor but it binds IRREVERSIBLEY |
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VHY*** (Always a question)
Farmer presents w/ Diarrhea (and cramping), Urination, Miosis, Bradychardia, bronchospasm (dyspnea), Lacrimation, Excitation of skeletal muscle and CNS, sweating and salivation what has happen? What is the TX? |
Insectiside posioning (e.g. Malathion, parathion, sarin(nerve gas)) all are organophasphates and irreversibley inhibit AChE
TX - Atropine (muscarinic agonist)and pralidoxime (antagonist used to regenerate AChE) To help remember the symptoms of insectiside posioning, DUMBELSS. |
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VHY
What is death due to in an insectiside poisoning? |
Permanent depolarization of Diaphram; inhibiting it.
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|
why would you use a AChe Inhibitor in an alzhiemers patient? What drug is used?
|
Loss of ACh neurons in the nucleus of Meynert
Donepazil or Tacrine (lipid soluble and enter the CNS |
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|
What is the clinical use of the durg atropine?
MoA of this drug, and what does it cause on application? What patient would you not use this in? |
Good to use in eye exams (except elderly, increase IOP)
MOA - cholinoreceptor blocker (muscarinic antagonist) Application - produces midriasis (dilates the eyes) and cycloplegia (no accomadation) NOTE: homatropine and tropicamide are just like atropine |
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|
Why can atropine enter into the CNS
|
tertiary amine, so it can cross the BBB
|
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|
What are the cholinoreceptor blockers?
|
Atropine (homatropine, tropicamide), Benztropine, Scopolamine, Ipratropium, Methscopolamine (oxybutin and glycopyrrolate)
|
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|
What is the clinical use of Benztropine and trihexyphenidyl?
MOA |
Used in treatment of parkisonism and in acute extrapyramidal symptoms caused by antipsychotics
MOA - muscarinic antagonist |
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|
WHat is the clinical use of scopolamine?
MOA |
MOTION sickness also causes sedation.
Enters the CNS MOA - muscarinic receptor antagonist |
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|
What is the clinical use of ipratropium?
MOA? |
Used in COPD and Asthma - does not enter CNS nor increase mucus viscosity
MOA - muscarinic antagonist |
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|
What is the clinical use of the drugs methscopolamine, oxybutin and glycopyrrolate?
MOA |
Treat urinary incontinence, reduce urgency in mild cystitis and reduce bladder spasms
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|
How do you treat an acute intoxication of atropine?
|
symptomatic + or - physostigmine
|
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|
describe ANS dominance
|
The PANS dominantes whenever there is a dual innervation like the AV node or GI And GU muscles
SANS is dominant only in terms of vascular tone (arterioles and veins) and thermoregulatory sweat glands |
|
|
Describe the most imporant effects of Atropine?
|
EYE - dilation, cycloplegia
Airway - dec. secretions Stomach - dec. acid secretion Gut - decrease motility Bladder - dec. uregency in cystitis In a nut shell it blocks SLUD: Salivation, Lacrimation, Urination and Defecation. |
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|
What are the side affects or toxicities of Atropine?
|
increase body temp; rapid pulse; dry mouth; dry, flushed skin, cycloplegia, constipation and disorientation.
REMEMBER: HOT as a hare, Dry as a bone, Red as a beet, Blind as a bat and Mad as a hatter |
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|
What can atropine cause the elderly, and infants
|
Elderly - closed angle glaucoma and urinary retention if they have prostatic hypertrophy
Infants - hyperthermia |
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|
What is the mechanism of action of Hexamethonium?
What is its used in? |
Nicotinic receptor antagonist
Gaglionic blocker. Used in experimental models to prevent the vagal reflex response to changes in blood pressure. (e.g. reflex bradycardia caused by NE) |
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|
It what situations will Hexamethonium prove ineffective?
|
It prevents reflex changes in HR caused by drugs that act on the vascualature but it cannot prevent changes in HR that are caused by drugs that act directly on the heart (B1 and M2 agonists)
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|
Summarize catecholamine synthesis, action and degredation in a sympathetic nerve terminal
|
Tryosine is recycled/obtained and is converted DOPA by tryosine hydroxylase (rate limiting)...DOPA becomes dopamine and is then converted to NE and both are packeged in vesicles...when the nerve is stimulated and calcium enters NE is released by exocytosis and diffuses through the synapse where it binds to an alpha or beta receptor...it is borken down by COMT...some is taken back up and added to the NE mobile pool...from there some will be broken down by MOA and some packaged back into vesicles
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|
What is the rate limiting step of NE synthesis or catecholamines for that matter
|
tyrosine hydorxylase
|
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|
What drug inhibits tryosine hydroxylase?
|
Methyl-p-tyrosine...leading to decrease NE
|
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|
What drug inhibts the packaging of NE and dopamine into vesicles?
|
Reserpine...dec. NE because DO and NE will get chewed up by MOA
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|
What drugs act to inhibit the fusion and release of NE containing vesicles?
|
Guanethidine (blocks exocytosis)
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|
What drug increases the release of NE by displacing NE from the mobile pool
|
AMPHETAMINES
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|
What drugs block the re-uptake of NE?
|
TCA and Cocaine
|
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|
Good example of a drug that increases NE release by blcoking MOA.
|
Phenelzine
|
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|
What are the 4 things that can happen to NE once it is in the presynaptic space?
|
1. bind to receptor
2. reuptake (short half life) 3. degraded 4. bind to alpha 2 receptor for negative feed back |
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|
What are the different release modulating receptors that are found on the presynaptic termainal of SANS nerve at its effector cell?
|
M1 - results in dec. NE release
angiotensin II receptor - causes more NE to be released (remember the effects of Angiotensin II) Alpha 2 receptor used for negative feedback to reduce release of NE |
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|
adrenergic receptors are either alpha or beta, which are more sensetive?
|
beta responses are dominant at low doses
alpha responses at higher doses especially in response to epinephrine since it is non selective |
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|
This durg is mostly an Alpha 1 agonist used as a pupil dilator, vasoconstrictor and as a nasal decongestant?
what may the increase in BP be caused by when using this drug? |
Phenylephrine alpha1>alpha2
DRUG causes increase in BP and TPR which may cause Relfex bradycardia |
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|
This drug is rarley used to treat AV heart block. It is an equal agonist of B1 and 2 receptors?
What are the ADRs |
ISOPROTERENOL
ADR - flushing and angina |
|
|
what are the drugs that are used in mild to moderate HTN especially w/ renal disease (don't decrease flow to the kidneys)? What is the MOA
|
clonidine and alpha-methyldopa
These two durgs act in the CNS predominantly at alpha 2 receptors as AGONISTS decreasing the sympathetic outflow? |
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|
This drug is a beta 1 > beta 2 agonist and is used in shock and acute heart failure
|
Dobutamine
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|
This drug is a selective B2 agonist and is used in asthma patients?
|
albuterol and terbutaline
|
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|
What drugs cause flushing
|
Isoproternol, vasodilators, Niacin and Those that cause histamine release (vancomycin, Morphine and amphotericin B)
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|
This drug is a selective beta 2 agonist and is used in premature labor?
|
Ritodrine
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|
This drug is used in asthma patients and is a selevtive beta2 agonist
|
albuterol and terbutaline
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|
What receptors does NE act on, what effect does this have?
|
alpha 1 and 2 receptors and B1 receptors
get a increase in TPR and BP (alpha 1) Increase in HR, SV and CO (B1) Potential for reflex bradychardia |
|
|
What is the clinical application for NE
|
Hypotension (but dec. renal perfusion)
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|
VHY**
How does Epinephrine differn from NE? |
DIRECT AGONIST (alph 1 and 2 and B 1 and 2 receptors)
at low doses acts like isoproterenol, beta receptors (actually get a dec. in systemic BP due to vasodilation w/ inc. HR) (see figure pg 61 Kaplan pharm book) At high doses acts like NE W/ alpha1 receptors involved and B1 right after (POTENTIAL RISK OF REFLEX BRADYCHARDIA) |
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|
What are the clinical uses of Epinphrine
|
Adjunct to local anesthetic
DOC in anaphylaxis also used in glucoma, asthma and hypothension |
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|
How do you reverse the effects of high dose Epinphrine?
|
alpha 1 blocker to reverse hypertension (phenoxybenzamine) Beta 2 response will take over and you get hypotension
|
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|
What can you use to treat a pheochromocytoma?
|
PHENOXYBENZAMINE
remember this tumor causes an increase in catecholamines, use alpha blocker to get epireversal |
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|
What are the indirect general adrenergic agonist drugs
|
Amphetamines, Tyramine and ephedrine
|
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|
This drug is a indirect general adrenergic agoinst, releases stored catecholamines.
Used to treat Narcolepsy, obesity and attention deficit disorder |
Amphetamine
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|
This indirect general adrenergic agonist indhibits MOA and can result in a HTN crisis, especially if eating chesse, meats red wine.
|
Tyramine
|
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|
This drug is an indirect general adrenergic agonist that results in release of stored catacholamines.
It is used clinically fro Nasal decongestion, sometimes urinary incontinence and hypotension |
Ephedrine
|
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|
What are the different types of MAO?
|
A - mainly in the liver but can be found anywhere (metabolizes, NE, 5HT and Tyramine)
B - Mainly in the Brain (Dopamine metabolism) |
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|
Which of the MOA inhibtitors does phenylzine and selegiline inhibit
|
Phenylzine inhibits Type A and B.
Selegiline - inhibits type B |
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|
This drug is a natural occuring catecholamine and is used in shock (high renal perfusion) and heart failure.?
|
Dopamine - acts on D1=D2>B>alpha
|
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|
This drug is an indirect general adrenergic agonist, it inhibits uptake of catecholamines.
IT causes vasoconstriction and local anesthesia? |
Cocaine
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|
WHat are the drugs that are the catecholamines (overview flashcard)
|
E (mixed agoist alpha and beta)
NE (mixed agonist), isoproterenol (beta agonist) dopamine (Dopamine and mixed) dobutamine (beta 1 agonist) |
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|
What are the alpha 1 and 2 agonists? (overvies flashcard)
|
1 - phenylephrine
2 - clonidine and alpha methyldopa |
|
|
What are the alpha-blocker drugs?
|
Non-selective: Phenoxybenzamine and phentolamine
Selective: alpha1 - Prazosin, terazosin, doxazin ALpha2 - Mirtazapine |
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|
What drug is used to treat pheochormocytoma, and what toxicity does it have?
|
Phenoxybezamine or phentolamine (non-selective alpha-blocker)
Tox - reflex tachycardia and orthostatic hypotension |
|
|
What drug is used to treat urinary retention in BPH and Hypertension?
What side effects does it have? |
SIN drugs (prazosin, terazosin, doxazosin and tamsolusin; only used in BPH acts on alpha 1a subtype)
Tox - 1st dose get orthostatic Hypotension, dizziness and headache` |
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|
VHY**
This drug is an alpha 2 blocker and is used treat Depression? What toxicities does it have |
Mirtazapine
causes sedation, inc. cholesterol and appetite |
|
|
How would the effects of an alpha blocker (phentolamine) on blood pressure differ when given after a dose of epinephrine Vs Phenylephrine?
|
Epinphrine high dose - change from net increase in BP (w/o alpha blocker from epi. alpha response) to a net dec. in BP (beta 2 response kicks in after alpha blocker was given)
Phenylephrine - its effects would be suppresed by the alpha blocker just like Epi. but w/o net decrease in BP becauase it is a "pure" alpha agonist and would have no Beta 2 response |
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|
What are the beta blockers that are beta 1 selective?
These drugs are saffer in what group of patients? |
A BEAM of B1 blockers
A - Acebutolol B - betoxolol E - Esmolol (short acting) A - Atenolol M - Metoprolol Diabetics and asthmatics (no B2 blocking), however any beta blocker can mask the prodrome of hypoglycemia (palpatations/inc. HR) |
|
|
What are the non selective Beta blockers?
|
N-Z olol durgs
propanolol timolol nadolol pindolol |
|
|
what are the two beta blockers that do not increase plasma lipid levels?
|
Acebutolol and pindolol
|
|
|
What are the uses of Beta-blockers?
For the 6 uses describe why it helps? |
1. HTN - dec. Co and renin
2. Angina pectoralis - Dec. HR and contractility resulting in dec O2 demand 3. MI - dec. mortality 4. SVT - dec. AV conduction velocity 5. CHF - slows progression of chronic failure 6. Glaucoma - dec. aqueous humor secretion |
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|
Which of the beta blockers are used to treat SVT?
|
propanolol and Esmolol
|
|
|
WHich of the beta blockers is used in glucoma?
|
Timolol (rembmer they dec. aqeuous humor formation)
|
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|
Which of the beta blockers is used in preformance anxiety (Stage fright) and essencial tremor
|
Propanolol
|
|
|
Which of the beta blockers are used in angina, HTN and post MI?
|
ALL of them
|
|
|
IF you need a beta blocker for a person w/ hyperlipidemia, asthma and diabetes what would be a good drug to use?
|
Acebutolol
|
|
|
What does chronic use of beta blockers lead to?
VHY what should you do when you are withdrawling a patient from a beta blocker? |
chronic use - upregulation
Withdrawl - taper the dose over time to avoid rebound |
|
|
what are the beta blocer toxicities?
|
impotence, exacerbation of asthma, cardiovascular ADR (bradycardia, AV block, CHF), CNS ADR (sedation, sleep, fatigue (most common) alterations), use w/ caution in diabetics
|
|
|
What do you treat a beta blocker overdose w/
|
Glucagon - positive inotropic and chrontropic effect are not through alpha 1 activation but glucagon receptors that are G-protein linked.
|
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|
What is open angle gluacoma?
Patient will have progessive painless loss of vision and if untreated blindness |
Decrease in the reabsorption of the aqueous humor (painless)
|
|
|
VHY
What are the stratagies in the treatment of gluacoma? |
beta blockers (timolol) to dec. formation of aqueous humor by ciliary epithelial cells
improve drainage throught the canals of schlemm by muscarinic activators |
|
|
What is closed angle gluacoma?
|
acute (painful) or chronic (genetic) increase in IOP due to blockage of the canal of schlemm
|
|
|
How do you treat emergent closed angle glaucoma
|
fast acting Rx's - pilocarpine (cholinergic agonist)or echothiophate, increases flow through the canal of schlemm by contraction of the ciliary muscle
carbonic anhydrase inhibitor (acetazolamide), dec. aqeous humor formation. |
|
|
what drugs are contraindicated in closed angle glaucoma?
|
alpha1 agonists and antimuscarinic drugs
|
|
|
What are the vision side affects of timolol, poilcarpine and echothiophate?
|
timolol - no pupillary of vision changes
Pilocarpine and echothiophate - Miosis and cyclospasm |
|
|
What is an autocoid present at high levels in the lungs, skin, and the GI tract and is released from mast cells and basophils by type I hypersensitivity rxns, drugs, venom, and traums.
|
Histamine
|
|
|
Describe histamine H1 activation?
|
Gq messenger -
increased capillary dilation - decrease BP increase capillary permeability-increase edema increase bronchial sm.muscle contrxn |
|
|
What type of activation is by a Gs 2nd messenger and increases gastric acid secretion - increasing GI ulcers.
|
Histamine H2 activation
|
|
|
What is a widely used OTC antihistimine that has properties of M block, sedation, and antimotion?
|
Diphenhydramine***
|
|
|
What antihistamine is highly effective in motion sickness?
|
Meclizine***
-also DOC for nausea and vomiting w/ pregnancy |
|
|
What are considered 2nd generation antihistimines that have no CNS entry and no sedation?
|
Loratidine (Claritin)***
Fexofenadine |
|
|
What stimulates acid production?
|
Gastrin
ACH Histimine |
|
|
What agents mechanism of action is to suppress secretory responses to food stimulation and nocturnal secretion of gastric acid by decreasing (indirectly) the activity of the proton pump?
|
H2 antagonists - ***
Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid) |
|
|
What are the uses for H2 antagonists?
|
PUD (less effective than proton pump inhibitors)
GERD Zollinger-Ellison syndrome |
|
|
What H2 antagonist has the SE's of being a major inhibitor of P450 system (DDI's w/ quinidine, phenytoin, TCAs, warfarin) and decrease androgens leading to gynecomastia and decrease libido?
|
Cimetidine***
|
|
|
What agents MOA are irreversible***, direct inhibitors of the proton pump(K/H antiport) in the gastric parietal cell?
|
"-prazoles"
-Proton Pump Inhibitors (PPIs) Omeprazole (Prilosec) |
|
|
What are the uses for PPI's?
|
PUD (more effective than H2 antagonists)
GERD and Zollinger Ellison Eradication regimen for H. pylori |
|
|
Omeprazole is an inhibitor of the P450 system decreasing the elimination of what drugs?
|
diazepam, phenytoin, and warfarin
|
|
|
What agent is ued selectively for NSAID induced GI ulcers?
|
Misoprostol***
a PGE analog that increases mucus and bicarb and decreases HCl secretion |
|
|
What agent forms a protective gel-like coating of ulcer beds?
|
Sucralfate
-requires acid pH*** |
|
|
What agents MOA is similar to sucralfate binding selectively to an ulcer, coating it, and protecting it from acid and pepsin?
|
Bismuth Subsalicylate
-combo w/ metronidazole and tetracycline to eradicate H. pylori (BMT regimen) |
|
|
What agents neutralize the protons in the gut (increase the pH of the stomach)?
|
Antacids -
SE's: AlOH3 - constipation CaCO3 - constipation MgOH2 - diarrhea NaHCO3 - gas |
|
|
Antacids decrease oral absorption of what drugs?
|
'azoles'
flouroquinilones tetracyclines warfarin -decrease absorption of weak acids |
|
|
True or False: Antacids increase oral absorption of weak bases.
|
True - example quinidine
They also decrease absorption of weak acids (see previous card). |
|
|
What laxative is a direct intestinal wall stimulant?
|
Bisacodyl
|
|
|
What laxative is a detergent - (stool softener)?
|
Docusate
|
|
|
What agents are opoids that are poorly absorbed?
|
Antidiarrheals -
Loperamide (Immodium) Diphenoxylate |
|
|
What drugs help w/ nausea and vomiting by blocking their receptors?
|
Antiemetics
|
|
|
What antiemetic is a 5HT3 antagonists used commonly for cancer chemotherapy?
|
odansetron ***
|
|
|
What DA antagonist is also used for cancer chemotherapy and is also prokinetic in GERD?
|
metoclopramide***
|
|
|
Other antiemetics
|
Cannabinoids - dronabinol
H1 antagonists - diphenhydramine, meclizine, promethazine Muscarinic antagonists - scopolamine NK1 receptor antagonist - aprepitant. |
|
|
What serotonergic drug is a partial agonist at the 5HT(1a) receptor?
|
Buspirone***
anxiolytic (generalized anxiery disorder) 5HT1(a-h) receptors found in CNS (usually inhibitory) and sm. muscle (excitatory or inhibitory) |
|
|
What serotonergic drug is DOC for acute migraine?
|
sumatriptan
-agonist at 5HT(1d) receptor in cerebral vessels (decreases migraine pain) |
|
|
What serotonergic drug decreases symptoms of psychosis?
|
Olanzapine
antagonist at 5HT(2a) receptor in CNS 5HT2(a-c) found in CNS (excitatory) |
|
|
What serotonergic drug is a 5HT2 antagonist used for carcinoid, GI tumors, and postgastrectomy; also for anorexia nervosa?
|
Cyproheptadine
|
|
|
What serotonergic drug is a 5HT3 antagonist that decreases emesis?
|
ondansetron "-setrons"
5HT3 MOA: activation opens ion channels (think vomit receptor)...so you want to block the vomit receptor. |
|
|
What drug acts as a partial agonist at both alpha1 and 5HT2 receptors in the vasculature and CNS?
|
Ergotamine***
potent vasoconstrictor used for migraines |
|
|
What two drugs target leukotrienes and are used in the treatment of asthma?
|
Zileuton - inhibits lipoxygenase (decreases leukotrienes)
Zafirlukast and (-lukasts) - leukotriene receptor antagonists |
|
|
Where is Cox2 expressed?
|
Cox2 is expressed in the brain, kidney and at sites of inflammation.***
|
|
|
Prostaglandins
What PGE1 drug is used in the treatment of NSAID induced ulcers and is also used to open a patent ductus arteriosus? |
Misoprostol***
|
|
|
What PGE1 drug is used in male impotence and also maintains a patent ductus arteriousus?
|
Alprostadil - vasodilation; can use w/ pt. on nitrates w/ erectile dysfxn.
|
|
|
What agent is used to CLOSE a patent ductus arteriosus?
|
Indomethecin***
|
|
|
What PGFa2 is used for the treatment of glaucoma?
|
Latanoprost - decreases intraocular pressure.
|
|
|
What drug is considered a platelet stablizer?
|
Epoprostenol (PGI2-Prostacyclin)
from endothelial cells (Gs) - decreases free Ca++. |
|
|
What drug is considered a platelet aggregator?
|
Thromboxanes (TXA's)
from platelets (Gq)- increases free Ca++. |
|
|
What agents are non-selective inhibitors of cyclooxygenases, acting on both COX1 and COX2 to decrease formation of PGs and thromboxanes?
|
NSAIDS - analgesic, antipyretic, and anti-inflamm w/ anti-platelet effects.
ASA is prototype of the group. |
|
|
What agent causes irreversible inhibition of COX?
|
ASA (acetylsalicylic acid)
|
|
|
What are the SE's of ASA?***
|
***Salicylism - tinnitus, vertigo, decreased hearing
***Bronchoconstriction - exacerbation of asthma (arachidonic acid takes leukotriene pathway) also GI distress, hypersensitivity, Reye syndrome, increased bleeding time. No specific antidote - gastric lavage (+/- activated charcoal) |
|
|
What are the two most toxic NSAIDS?
|
Indomethicin - thrombocytopenia, agranulocytosis and > CNS effects
Sulindac - Stevens Johnson syndrome, hematotoxicity |
|
|
What drug is more effective as an anti-inflamm agent than COX1 w/ less GI stress?
|
Celecoxib
rofecoxib, valdecoxib - now off the mkt |
|
|
What agent has no inhibition of COX in peripheral tissues and lacks significant anti-inflamm effects?
|
Acetominophen (Tylenol) - equivalent analgesic and antipyretic activity to ASA due to inhibition of COX in the CNS.
|
|
|
Compare acetominaphen w/ ASA?
|
No antiplatelet action
Not implicated in Reye syndrome No effects on uric acid Not bronchospastic GI distress is minimal |
|
|
What is the major SE w acetominaphen?
|
***Hepatotoxicity - N/V, abdominal pain, and ultimately liver failure due to centrolobular necrosis.
Chronic use of alcohol enhances liver toxicity via induction of P450. |
|
|
What is the management (antidote) of hepatoxicity?
|
N-acetylcysteine
|
|
|
What agents are known as Disease Modifying Antirheumatic Drugs (DMARDS)?
|
-Hydroxycholoroquine
-Methotrexate -Etanercept -Infliximab |
|
|
What agents are used for the ACUTE episodes of gout?
|
***Colchicine - binds to tubulin, decreases microtubular polymerization
|
|
|
What agents are used for the CHRONIC episodes of gout?
|
***Allopurinol (decreases uric acid in BOTH blood and urine)
SE's - inhibits 6-mercaptopurine (6-MP) metabolism (bone marrow suppression) ***Probenicid - decreases uric acid in blood, increases in urine) SE's - GI distress, ASA may decrease effects ***Both drugs target uric acid |
|
|
What agent is used as an antiinflammatory and immunosupressive agent and has good activity as a glucocorticoid and mineralocorticoid?
|
***Cortisol - short duration
|
|
|
What derivative of cortisol is a pure glucocorticoid w/ no aldosterone (mineralocorticoid) activity?
|
***Dexamethasone - long acting
|
|
|
What are the SE's assoc. with glucocorticoids?
|
-suppression of ACTH
-Hyperglycemia -Osteoporosis -Ulcers, GI bleeding |
|
|
What asthma drug is DOC for acute attacks?
|
***Beta 2 agonists - albuterol, metaproterenol, terbutaline.
-for relief of acute bronchoconstriction and exercise induced asthma |
|
|
What beta receptor agonist is used as prophylaxis only and may decrease nighttime attacks?
|
Salmeterol - not for acute attacks
|
|
|
What SE's are assoc. with beta receptor agonists?
|
-Anxiety, muscle tremors, and cardiovascular toxicity with overuse
|
|
|
What asthma drug is a mast cell stabalizer?
|
Cromolyn
|
|
|
What are considered the #2 drugs in asthma tx and may cause oropharyngeal candidiasis?
|
Flunisolide, triamcinaolone, beclomethasone
|
|
|
What agents are antagonists at LTD4 receptors used mainly as prophylactics for many forms of asthma, including antigen, exercise, or drug induced?
|
Antiluekotrienes
-Montelukast (Singulair) -Zafirlukast |
|
|
What anticoagulant catalyzes the binding of antithrombin III to factors IIa, IXa, Xa, and XIa, resulting in their rapid inactivation?
|
***Heparin (given parenterally)
|
|
|
How do you monitor Heparin?
|
PTT (partial thromboplastin time)
|
|
|
What is the antidote (antagonist) for Heparin?
|
Protamine sulfate***
|
|
|
What SE's are assoc w/ Heparin?
|
***Bleeding, osteoporosis, Heparin induced thrombocytopenia (HIT), hypersensitivity
|
|
|
What anticoagulant decreases hepatic synthesis of vitamin K-dependent factors II, VII, IX, X?
|
***Warfarin (given orally)
|
|
|
How do you monitor Warfarin?
|
***Prothrombin time (PT); INR
|
|
|
What are the SE's?
|
***Bleeding, drug interactions, teratogenic
Warfarin has extensive (but weak) binding; displaced by many drugs increasing free fraction and effects slow metab. via p450 system: inducers - decrease activity inhibitors - increase activity |
|
|
What clotbuster works on both bound and free plasminogen (not clot specific)?
|
Streptokinase
-is antigenic...may cause allergies |
|
|
What clot buster is specific, acting mainly on fibrin-bound plasminogen?
|
Alteplase (tPA)
|
|
|
What antiplatelet drug works by blocking ADP receptors on platelets?
|
Clopdogrel (Plavix) & Ticlopidine
|
|
|
What antiplatelet drug is an antagonist that binds to glycoprotein IIb/IIIa receptors which prevents the cross-linking reaction?
|
Abciximab
|
|
|
Platelet aggregation in a nutshell:
|
Platelet aggregation:
Increased by - ADP, 5HT, TxA2, thrombin, alpha2 agonists Decreased by: PGI2, cAMP, ASA, ticlopidine, clopidogrel, gp blockers IIb/IIIa blockers |
|
|
What diabetic medications can be used intravenously?
|
***Lispro and Regular
Fast acting insulins |
|
|
What basal insulin forms provide coverage between meals?
|
Lente and Ultralente
|
|
|
What form of insulin has no peak therefore less hypoglycemia?
|
Glargine
|
|
|
What drugs block K+ channels causing increased insulin release and decreased glucagon release?
|
***Sulfonylureas (insulin secretors)
1st generation: Chlorpropramide (long acting, SIADH/disulfiram rxns) 2nd generation: Glipizide - decr. dose in hepatic dysfxn. Glyburide - decr. dose in renal dysfxn |
|
|
What drug used in diabetes does not cause hypoglycemia and is synergistic w/ sulfonylureas?
|
Metformin***
|
|
|
What drug used in diabetes inhibits alpha-glucosidase and decreases formation of absorbable carbs?
|
Acarbose
-decreases postprandial glucose |
|
|
What drug used in diabetes are insulin sensitizers and increase insulin receptor numbers?
|
the glitazones...
Pioglitazone*** Rosiglitazone*** |
|
|
What drug used in diabetes stimulates insulin release from pancreatic beta cells?
|
Repaglinide
|
|
|
Endocrine uses of glucocorticoids (prednisone, dexamethasone) and mineralocorticoid (fludrocortisone):
|
-Addison dz
-Adrenal insuff -premature delivery to prevent Resp. distress syndrome (increase surfactant) -adrenal hyperplasia |
|
|
What steroid antagonist blocks aldosterone and androgen receptors?
|
Spironolactone***
|
|
|
What steroid antagonist blocks glucocorticoid and progestin receptors and is a abortifacient?
|
Mifepristone***
|
|
|
What steriod antagonists are synthisis inhibitors?
|
***Ketaconazole
Metyrapone |
|
|
What estrogen drug stimulates ovulation and is used as a fertility drug?
|
Clomiphene
|
|
|
What selective estrogen-receptor modulator is linked with a possible risk of endometrial cancer?
|
Tamoxifen***
|
|
|
What selective estrogen-receptor modulator is used as a prophylaxis of postmenopausal osteoporosis with no increased cancer risk?
|
Raloxifene
|
|
|
Oral contraceptives have decrease effectiveness when used with...
|
antimicrobials and enzyme inducers (p450 inducers).
|
|
|
What androgen antagonists are used for androgen receptor positive prostate cancer?
|
flutamide***
Leuprolide***-GnRH analog |
|
|
What androgen antagonist is a 5-alpha reductase inhibitor, preventing conversion of testosterone DHT?
|
Finasteride***
-used for BPH, male pattern baldness |
|
|
What two antithyroid agents are used for uncomplicated hyperthyroid conditions?
|
Propylthiouracil - safer in pregnancy
Methimazole |
|
|
What drugs are used in the treatment of carcinoid?
|
***Octreotide
Cyproheptadine Ondansetron |
|
|
What is the DOC for hyperprolactinemia?
|
***Bromocriptine
|
|
|
What anticancer drug is an alkylating agent, used for non hodgkins, ovarian, and breast cancer with SE's of hemorrhagic cystitis (Mesna) and hepatotoxicity?
|
***Cyclophosphamide
|
|
|
What anticancer agent has a SE of delayed CHF and radiation recall?
|
***Doxorubicin
|
|
|
What anticancer agent is assoc. with mucositis and leucovorin (folinic acid) rescue?
|
***Methotrexate
|
|
|
All cancer drugs are associated with bone marrow suppression except?
|
***Cisplatin, Bleomycin, Vincristine
|
|
|
What anticancer drug is assoc. w/ renal toxicity?
|
***Cisplatin
|
|
|
What anticancer drug is assoc. w/ pulmonary toxicity?
|
***Bleomycin
|
|
|
What anticancer drug is assoc. w/ cardiac toxicity?
|
***Doxorubicin
|
|
|
What anticancer drug is assoc. w/ neurologic toxicity?
|
***Vincristine
|
|
|
AChE inhibitor toxicty
signs/sx's: miosis, salivation, sweats, GI cramps, diarrhea, muscle twitches Antidote? |
***Atropine + pralidoxime
and respiratory support |
|
|
Atropine and muscarinic blockers toxicity
signs/sx's: increase BP/HR, hot dry skin, delirium, hallucinations Antidote? |
***Physostigmine
-also control cardio symptoms and hyperthermia |
|
|
Carbon monoxide toxicity
Sign/sx's: nausea/vomiting, dyspnea with hyperventilation, mydriasis, vertigo, decrease BP, syncope, increased HR, arrythmias Antidote? |
***Hyperbaric O2 and decontamination
|
|
|
CNS Stimulant toxicity
signs/sx's: anxiety, agitation, hyperthermia, mydriasis, increase BP/HR, psychosis, seizures Antidote? |
+/- Benzodiazipines or antipsychotics
|
|
|
Opioid analgesic toxicity
signs/sx's: lethargy, sedation, decreased HR/BP, hypoventilation, miosis, coma, respiration failure Antidote? |
***Naloxone
|
|
|
Salicylates (ASA) Toxicity
signs/sx's: confusion, lethargy, hyperventilation, hyperthermia, dehydration, hypokalemia, acidosis, seizures, coma Antidote? |
Urinary alkalization
also correct acidosis and electrolytes |
|
|
Sedative hypnotics and ethanol toxicity
signs/sx's: disinhibition, lethargy, ataxia, nystagmus, stupor, coma, hypothermia Antidote? |
Flumazenil if BZ's implicated and ventilatory support
|
|
|
SSRI's toxicity
signs/sx's: agitation, confusion, hallucination, muscle rigidity, hyperthermia, increased HR/BP Antidote? |
control hyperthermia and seizures; possible use of cyproheptadine and BZ's and antipsychotics
|
|
|
Acetaminophen poisoning...antidote?
|
Acetylcysteine***
|
|
|
AChE inhibitors (physostigmine, neostigmine, malathion, parathion)poisoning...antidote?
|
Atropine + pralidoxime***
|
|
|
Iron and iron salts poisoning...antidote?
|
Deferoxamine***
|
|
|
Digoxin poisoning...antidote?
|
Digoxin immune F(ab)***
|
|
|
Arsenic, gold, mercury, lead poisoning...antidote?
|
Dimercaprol (BAL)***
|
|
|
Theophyline and beta agonists poisoning...antidote?
|
Esmolol***
|
|
|
Methanol or ethylene glycol poisoning...antidote?
|
Ethanol, fomepizole***
|
|
|
Benzodizepines, zolpidem, zalepon poisoning...antidote?
|
Flumazenil***
|
|
|
Copper (Wilson dz) poisoning...antidote?
|
Penicillamine***
|
|
|
Anticholinergics: atropine, antihistimine, antiparkisonian poisoning...antidote?
|
Physostigmine***
|
|
|
Heparin poisoning...antidote?
|
Protamine***
|
|
|
Warfarin and coumarin anticoagulants poisoning...antidote?
|
Vitamin K***
|
|
|
Nonspecific, all oral poisonings except Fe, CN, Li, solvents, mineral acids, or corrosive poisoning...antidote?
|
Activated charcoal***
|
|
|
What herbal medicine should you use caution with when using with anticoagulants?
|
Gingko
|
|
|
What herbal medicine may be used to symptomatically treat BPH and is assoc. w/ GI pain, decreased libido, HA, hypertension?
|
Saw Palmetto
|
|
|
What herbal medicine has major drug interactions including serotonin syndrome with SSRI's?
|
St. Johns Wort
|
