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61 Cards in this Set
- Front
- Back
Pharmacokinetics (definition)
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what the body does to the drug (study of the temporal pattern of absorption, distribution, and elimination of drugs)
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Pharmacodynamics (definitions)
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what the drug does to the body. (study of effects, actions, and mechanism of action of the drug)
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Toxicology (definition)
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how drug harms body (study of adverse effects, mechanisms of said effects, conditions of these effects)
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clinical pharmacology and pharmacotherapeutics
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how the drug cures the body I study of the clinical use of drugs for the prevention, dx, and tx of diseases)
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Active processes of transfer across cell membrane
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active transport (both primary and secondary) and endo/exocytosis
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Lipid Diffusion of Drugs across cell membranes
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-most frequent
-directly proportional to conc gradient of drug and area of diffusion -inversely proportional to thickness of membrane -determined mainly by oil/water partition coefficient of the drug -passive -nonselective |
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Aqueous Diffusion of drugs across cell membranes
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- through aquaporins (MW<100)
-directly proportional to number of channels and conc gradient of drug -passive -nonselective |
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-oil/water coefficient definition
-of nonionizable drugs -of ionizable drugs |
-index of relative solubility of drug in lipid and water
-related to physicochemical properties (lipophillic) -related to degree of ionization (hydrophillic) |
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-Lipid solubility of weak acid
-Water solubility " " " |
-non-ionized pKa>pH
-ionized pKa<pH |
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-Lipid solubility of weak base
-Water solubility of a weak base |
non-ionized pKa less than pH
ionized when pKa greater than pH |
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pKa-pH>3
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>99.9% non-ionized and lipid soluble if weak acid
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pKa-pH=3
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99.9% non-ionized and lipid soluble if weak acid
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pKa-pH=2
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99% non-ionized and lipid soluble if weak acid
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pKa-pH=1
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90% non-ionized and lipid soluble if weak acid
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pKa-pH=0.5
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76% non-ionized and lipid soluble if weak acid
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pKa=pH
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50% in each form
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ion trapping
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when lumen pH causes drug to tp penetrate cells and intracellular pH of cells does not allow it to exit so drug is trapped inside as ionized form
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facilitated diffusion
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-mediated by protein carrier
-passive -selective -saturable -subject to inhibition |
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active transport
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-mediated by protein carrier
-active -selective -saturable -subject to inhibition -primary (energy from direct breakdown of ATP) or secondary (energy stored in the form of ionic conc differences across membrane) |
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carrier-mediated drugs
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Levadopa in intestine
Antimetabolites anticancer drugs in intestine Penicillins in kidney Iodide in thyroid Drugs crossing BBB |
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Endo/Exocytosis
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-large molecules
-active can be specific/nonspecific (bacterial toxins, antibodies, and protein hormones) |
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bulk flow
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-move through intercellular pores
-directly proportional to pressure gradient -passive -nonselective |
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absorption (def)
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passage of drug from external environment to the systemic circulation
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bioavailability (def)
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the fraction of a drug dose reaching unchanged by the systemic circulation when administered by any route
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oral drug administration
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-systemic or sometimes local
-mainly absorbed in small intestine via lipid diffusion -generally slow -easiest for pt, safest, cheapest, can be hastened or delayed |
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first pass elimination
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fraction of drug that is metabolized it the gut wall or the liver and therefore lowering bioavailability
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sublingual drug administration
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-systemic or very rarely local effects
-rapid absorption via LD -no first pass or exposure to digestive enzymes |
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rectal drug administration
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-systemic or sometimes local effects
-slow LD absorption -no first pass, consciousness not required |
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cutaneous drug administration
TOPICAL |
-local effectts
-negligible absorption, high concentration, low systemic effects |
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cutaneous drug administration
TRANSDERMAL |
-systemic effects
-slow, LD absorption -better when bandaged -no first pass, no repeat admins |
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Mucous Membrane drug administration
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-local or very rarely systemic effects
-rapid ld absorption at target membrane -high conc |
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Pulmonary Drug Administration
INHALED AS GAS |
-systemic
-most rapid LD proportional to partial pressure of gas |
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Pulmonary Drug Administration
INHALED AS AEROSOL |
-local effects
-slow, LD absorption proportional to amount of drug reaching the alveoli |
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Subcutaneous and IM drug administration
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-bulk flow transfer
-IM rapid -SC slower -can be hastened or delayed -good onset, well absorbed, dosage control, no first pass |
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Intravenous Drug Administration
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-systemic effects
-onset of drug is most rapid -good control -OD issues |
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Intraartieral
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Localize effect in particular tissue/organ by delaying systemic distribution (diagnostic agents, anticancer drugs)
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Intrathecal
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-into CSF for drugs that can't cross BBB
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Intracardiac
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-used in cardiac emergencies
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Intrapleual, intraperitoneal, intraarticular, intravitreal
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localize drug at specific site by reducing systemic absorption
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Distribution
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-passage of drug from the systemic circulation to the body tissues
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Volume of distributrion (def and eq)
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-the volume of fluid that would be required to contain the total amount of drug in the body at the same concentration as in the plasma
-Vd=D/C0 (D = dose by Iv or dose x F) |
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Vd=3L
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Vascular compartment
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Vd = 13 L
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ECF
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Vd = 42 L
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distributed throughout TBW
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Vd>42l
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extensively stored in particular tissues or cells
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drug binding to plasma proteins
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-albumin if acidic or alpha1-acid-glycoportein if basic
-constant percentage bound, ninding is saturable -competition can occur |
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Drug Distribution in CNS
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- must cross cerebral capillaries or choroid plexus through occuding zonulae
- also, some drugs are actively transported out of CSF by P-glycoprotien in choroid |
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Clearance
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-measure of drug eliminiation by either biotransformation and excretion
-add up all body clearance to get total volume cleared per unity time |
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Biotransformation
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-makes drugs more water soluble for excretion.
-can inactivate, activate, or maintain some activity -Phase 1 - oxidations, reductions, or hydrolyses -Phase 2 - conjugations |
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Oxidation reaction
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-catalyzed by (non)microsomal enzymes (mainly NADPH-cyto P450 reductase and cyto P450)
-can make highly reactive intermediates that cause major problems |
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Glucuronidation
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-most common conj reaction
-glucuronic acid + R-OH, R-COOH, R-NHS, R-SH -in liver cat by UDP-glucuronosyltransferase -more water soluble and inactive |
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Microsomal Drug-Metabolizing Enzymes
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-in SER of liver
-low substrate specificity -mainly oxidations and glucuronidations -induced when synthesis of cyto P450 is increased |
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Inducers of cytoP450
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-barbituates
-rifampin -omeprazole -phenytoin -carbamazepine -corticosteroids |
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Inhibitors of cytoP450
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-cimetidine
-fluoroquinolones -macrolides -isoniazid -grapefruit juice -ssris -amiodarone -metronidazole -omeprazole -HIV protease inhibitors |
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Non-mircrosomal Drug Metabolizing enzymes
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-in cytosol, mitochondira, and ECF
-substrate specificity is variable -can be under genetic control -cat conjugations and canbe inhibited |
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Drug excretion
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-renal - most important
-intestinal - biliary or fecal -pulmonary - gases or volatile drugs -other secretions |
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Glomerular Filtration
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-filtration of unbound drugs dependent on hydrostatic pressure in capillaries.
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Tubular Reabsorption of Drugs
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-along bephron by LD depending on physicochemical properties and pH of tubular lumen
-can lead to trapping in urine |
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Tubular Secretion of Drugs
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-in proximal tubule my active transport
- 1 system for acids and 1 for bases -competition can occur within each system |
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Renal Clearance
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CLr=(F x Ud)/Pd
=100-150 - glomerular filtration >150 tubulare secretion <100 tubulare reabs or protein binding |
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Biliary Excretion
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-for anions, cations, and some nonionized molecules
-put in bile canaliculus from liver cells. -leave via feces (active), stay concentrated (active), or go through enterohepatic cycle (passive) |