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69 Cards in this Set
- Front
- Back
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Drug Absorbtion
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Depending on which tissues or other anatomical sites are involved in the absorption process, the rate at which a drug enters blodd ranges from slow to rapid
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Passive Transfer
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No energy involved, depends on concentration gradient
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Passive Transfer:
Aqueous Diffusion (Filtration) |
Involves pores through which H2O, ions & small molecules can pass.
- Hydrophilic, water soluble Filtration decreases when MW begins to exceed 100-200 daltons, if molecule is too "bulky" reduce the ability of the drug to get across by filtration but it could still be water soluble |
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Passive Transfer:
Lipid Diffusion (Simple) |
Transfered after penetration of the predominantly lipoid cell membrane. Proportional to concentraion gradient of the nonionized form across membrane and lipid/water partitio coefficient of nonionized for of drug.
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What makes up the ratio of an ionized fraction?
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Dependent upon the ionization constant(pKa) of drug and pH pf body fluid. The pKa is the pH in which hald of the drug is ionized.
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What is the factor on rate of absorbtion with drugs that have similar pKa values?
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The ultimate factor influencing absorbtion is the lipid solubility of NONIONIZED form rather than the ratio of nonionized/ionized form. Possible to have differnt absorbtion rates even if HH says it wont.
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Ion Trapping
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Molecule is trapped in an area because it becomes ionzed/compartmentalized.
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What is the rate of equilibrium of nonionized molecules directly related to?
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It is directly related to its lipid solubility.
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Passive Transfer:
Carrier Facilitated Diffusion |
Substance form a complex with a carrier molecule (protein) which is contained within the biological membrane. Known as a "downhill" process.
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What is carrier facilitated diffusion limited by?
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# of binding sites on carrier molecule and the concentration gradient; will not go against a higher concentration.
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Active Transport
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similar to carrier facilitated diffusion but will go against a concentration gradient a "uphill" process.
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What ways will interfere with active transport?
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Non-competitive and Competitive inhibition.
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Non-Competitive Inhibition
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Non-competitive drugs we will never prescribe because they will knock out non specific energy of cell - poison.
Interferes with energy production of the cell (ex: decrease in cell metabolism) |
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Competitive Inhibitors
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Similar molecules compete for limited sites on carrier molecule. Some anti cancer drugs and some drugs for depression; serontonin uptake inhibitors.
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How do cancer drugs perform competive inhibition?
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Cancer cells rapidly growing and taking in the same building molecules that othr cells take in but at a higher rate. Cancer drugs compete with the naturally occurring substance and hopefully the cancer drug wins, slowing down or eliminating the cancer. Other rapidly growing areas will be impacted
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What is bioavailability?
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The rate (speed) and extent (amount) of absorbtion of unchanged (not biotransfered) drug from its dosage form into systemic circulation (blood). Largely determined by the ofrmulation of drug.
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What is rate of bioavailibility?
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How long does it take for a tablet to go into circulation
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What is the sequence for oral administration?
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Dosage (tablets), Disintegration, Dissolution, Absorbtion
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What is the major factor in controlling the amount of unmetabolized drug that enters the blood flowing oral administration?
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In the empty stomach and upper GI the RATE OF DISSOLUTION
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Generic Equivalence
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Often based upon a comparison of its dissolution rate with that of the brand name. Some drugs have a tight dose response curve (Lithium, Digoxin) and are not always reliable in generic form.
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What should generic equivalence be based on?
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SHOULD BE BASED upon comparison of bioavailabilities of generic product and standard drug.
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Chemical Equivalence
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Same amount of active ingredients
Certifying a generic drug as chemical equivalent to brand name DOES NOT insure that it is equally bioavailable. |
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Pharmaceutical Equivalence
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Same amount of active and inactive ingredients.
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Biological Equivalence (Bioequivalence)
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Same bioavailability of active ingredient.
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Therapeutic Equivalence
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Same effectiveness in treating target disorder. Should not differ if bioavalibilty is the same.
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What is the first pass effect?
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Prior to a drug enetering systemic circulation either PO or PR it will initially undergo biotransfermation (metabolism), and occurs either pre-hepatic or hepatic
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Pre-Hepatic
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Biotransfermation occurring in the intestinal wall by columnar epithelial cells after PO administration.
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Hepatic
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Most biotransformation occurs here. The drug is biotransformed into a water-soluble so that it can be easily excreted in urine. From both gastric & upper GI drug will enter the hepatic portal system and transported to liver. PR will have limited amount entering hepatic portal system via Sup. Rec. Vein. Therefor first pass effect is not as extensive as that after PO administration.
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What factors are related to the ultimate degree of hepatic clearance?
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Degree of binding to plasma proteins, rate of biliary secretion, rate of of hepatic biotransformation, rate of transport into liver cells.
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When should a patient receive a REDUCED dose of highly extractable drugs?
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Patients with hepatic dysfunction or some condition that decreases blood flow to liver. If not can readily produce adverse drug reactions.
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What are the major reasons for oral administration?
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Most convenient for self medication, Safest, Most economical, Does not have to be sterile.
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Oral Mucosa
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pH 6.8-7.2
Sublingual, absorbtion is rapid and can be as fast as SC or IM. Higher concentration of drug in blood b/c not circulated through liver;catabolic pathways are bypassed. And not subjected to destruction by GI or formation of unabsorbable complexes with food or meals. |
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Gastric Mucosa
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pH 1-3.5
Organic acids well absorbed since almost completly nonionized, ethyl alcohol (lipid soluble non-electrolyte) is also well absorbed, weak acids are predominitly non-ionized, bases administered via injection may accumlate in stomach by ion trapping. |
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Intestinal Mucosa
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surface where absorbtion takes place is pH 5.3
Weak bases more readily absorbed. MAJOR site of drug absorbtion (weak acid & base) b/c pf surface area and highly permeable epithelium. |
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Enteric Coating
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Prevents destruction of drug by gastric juices, and therefor gastric irritation, nausea & vomiting. Will NOT cause GI ulcerations.
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Sustained Release Formulations
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Release drug primarily wihtin intestinal tract.
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What will make the patient more compliant in taking medication?
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The longer the half-life of a drug.
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What will increasing the GI motility do to drug absorbtion?
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It will decrease drug absorbtion
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What will the presence of food do?
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It will reduce absorbtion of SOME DRUGS.
But some (very rare) it may increase absorbence by limiting liver degradation of drug b/c some of the liver enzymes are tied up with food. |
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When should oral route NOT be used?
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Drug causes nausea/vomiting due to gastric iritation, Patient is unwilling or unable to swallow drug, drug is destroyed by digestive secretions (INSULIN), Drug not absorbed by GI mucosa (Tubocurarine)
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Rectal Administration
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pH 7-8
Drug in form of suppository or retention enema. Similar absorbtion to oral but less predictable. Many drugs and Anisotonic sol'n cause irritation of rectal mucosa. Fluids administered rectaly should be isotonic with plasma. |
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Parenteral Administration
Advantages |
Bypass the intestinal tract.
Immediate to moderatly rapid response, more predictable (dose can be selected with precision), always available (unconscious, uncooperative pt.), not destroyed by gastric contents, & psychological benefit. |
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Parenteral
Disadvantages |
Technique (self administration is usually impractocal), Sterililty is required, discomfort, more hazardous (irritation, allergic rxn, effects of overdose more difficult ot ocntrol)
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Intravascular
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within a vessel
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Intravenous IV
Advantages |
Direct injection into bloodstream, immediatly enters circulation and rapidly distributed to tissues, permits titration of dose, can maintain fairly constant blood level, large quantities of fluid can be administered over prolopnged periods of time, irriatation can be reduced by buffering of blood. (Buffering of blood is not that good though)
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IV
Disadvantages |
Once drug is administered can NOT be withdrawn, injections made to rapidly can cause seriuous respiratory and circulatory problems. All are made slowly so if rxn occurs can be stopped
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Intra-Arterial IA
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Direct in Artery rarely used. Primarily for local perfusion of an organ (chemotherapy), injection of diagnostic substances.
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Intramuscular IM
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Absorbtion fairly quick Deltiod>Vastus lateralis> gluteus maximus. Aqeuous soln absorb 10-30 mins, small molecules absorbed directly into capillaries, larger (proteins), eneter via lymphatic channels.
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Depot Forms
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desighned to promote gradual absorbtion of drugs over a prolonged period. Slow to enter blood due to drug being poorly soluble at tissue pH or suspended in a relatively insoluble vehicle
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Subcutaneous SC
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Administration of water soluble non irritant drugs. Lower blood flow than skeletal muscle, generally slower absorbtion rate than IM but some as fast as IM. Not for an emergency situation b/c it is slower.
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What would you do if an adverse rxn developed rapidly for SC or IM
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You would reduce the rate of absorbtion by 1)immobilization of the limb 2) local cooling or vasconstrictors to decrease blood flow 3) application of tourniquet
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How would you increase absorbtion in SC?
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SC tissue is rather loose, however normal CT prevents spreading of soln. Hyaluronidase (enzyme) will increase spread of soln and the absorbtion rate; then insert SC needle.
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What is Hypordermoclysis?
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Term used for then administration of Hyaluronidase which is a carbolic enzyme for mucopolysaccharides of connective tissue mastrix which increases spread of soln and absorbtion rate. Used for asministratio of large fluid volumes when continous IV is a problem.
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Bone Marrow (Sternum)
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Almost equivalent to IV, employed when viens are inaccessible, such as extensive burns
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Intrathecal (Spinal or Intraspinal)
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Injection into subarachnoid space. Indroduces the drugs into the spinal fluid or permitting drug to flow via CSF to brain (antibiotics in meningitis) NOT into spinal cord.
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Intradermal ID
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Injection within dermal layers of hte skin; used in dermal testing of skin for alergies.
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Intracardiac
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Emergency treatment of cardiac arrest, e.g. epinephrine or isoproterenol
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Intraperitoneal IP
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Not used in humans, except for dialysis; danger of infection, adhesions, used in animals.
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Inhalation
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Alveoli of lungs present a large absorbing surface and an extensive capillary supply
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Gases
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Oxygen; general anesthetics N2O. General anesthtics equilbrate amost instantatneaoudl with blood in alveolar capilaries.
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Why does general anesthtics equilibrate almost instatntaneously?
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1) Relatively high L/W partition coefficients 2) very small molecular radii 3) readily permeable alveolar membranes
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Aerosols
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Very small liquid or solid particles. They remain suspended in air instad of settling under force of gravity.
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What size should paricles be in a nebulizer?
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Partilces larger then 2u in diameter probably do not rach alveolar sacs. Some discharge particles between 1u - 3u however for effective therapy the particle diameter should not be less then 1u. This is so that medicaiton penetrates to level of terminal bronchioles and alveolar ducts.
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How do you increase the deposition of aerolized particles?
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If patient holds their breath or by addion of hygroscopic susbstances which increase the abosorbtion of water (paperback book cover curling up)
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Skin topical application
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Most are intended for local effect.
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Transdermal Patch
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Intended for systemic effect. penetrate skin at rate controlled by size of pores in patch. Water-soluble ions are practically excluded. lipid soluble substances penetrate skin faster.
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How do you increase percutaneopus absorbtion?
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Incoporationinto a fatty vehicle, inunction, proir application of keratolytic (salicytic acid).
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Dimethyl Sulfoxide
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Promotes absorption of many chemical through skin, may involve disruption of biological membranes.
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What is used for the treatment of interstitial cystitis?
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RIMSO-50
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