General Principles Of Drug Action

Front 1

Pharmacokinetics (definition)

Back 1

what the body does to the drug (study of the temporal pattern of absorption, distribution, and elimination of drugs)

Front 2

Pharmacodynamics (definitions)

Back 2

what the drug does to the body. (study of effects, actions, and mechanism of action of the drug)

Front 3

Toxicology (definition)

Back 3

how drug harms body (study of adverse effects, mechanisms of said effects, conditions of these effects)

Front 4

clinical pharmacology and pharmacotherapeutics

Back 4

how the drug cures the body I study of the clinical use of drugs for the prevention, dx, and tx of diseases)

Front 5

Active processes of transfer across cell membrane

Back 5

active transport (both primary and secondary) and endo/exocytosis

Front 6

Lipid Diffusion of Drugs across cell membranes

Back 6

-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

Front 7

Aqueous Diffusion of drugs across cell membranes

Back 7

- through aquaporins (MW<100)
-directly proportional to number of channels and conc gradient of drug
-passive
-nonselective

Front 8

-oil/water coefficient definition
-of nonionizable drugs
-of ionizable drugs

Back 8

-index of relative solubility of drug in lipid and water
-related to physicochemical properties (lipophillic)
-related to degree of ionization (hydrophillic)

Front 9

-Lipid solubility of weak acid
-Water solubility " " "

Back 9

-non-ionized pKa>pH
-ionized pKa<pH

Front 10

-Lipid solubility of weak base
-Water solubility of a weak base

Back 10

non-ionized pKa less than pH
ionized when pKa greater than pH

Front 11

pKa-pH>3

Back 11

>99.9% non-ionized and lipid soluble if weak acid

Front 12

pKa-pH=3

Back 12

99.9% non-ionized and lipid soluble if weak acid

Front 13

pKa-pH=2

Back 13

99% non-ionized and lipid soluble if weak acid

Front 14

pKa-pH=1

Back 14

90% non-ionized and lipid soluble if weak acid

Front 15

pKa-pH=0.5

Back 15

76% non-ionized and lipid soluble if weak acid

Front 16

pKa=pH

Back 16

50% in each form

Front 17

ion trapping

Back 17

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

Front 18

facilitated diffusion

Back 18

-mediated by protein carrier
-passive
-selective
-saturable
-subject to inhibition

Front 19

active transport

Back 19

-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)

Front 20

carrier-mediated drugs

Back 20

Levadopa in intestine
Antimetabolites anticancer drugs in intestine
Penicillins in kidney
Iodide in thyroid
Drugs crossing BBB

Front 21

Endo/Exocytosis

Back 21

-large molecules
-active
can be specific/nonspecific (bacterial toxins, antibodies, and protein hormones)

Front 22

bulk flow

Back 22

-move through intercellular pores
-directly proportional to pressure gradient
-passive
-nonselective

Front 23

absorption (def)

Back 23

passage of drug from external environment to the systemic circulation

Front 24

bioavailability (def)

Back 24

the fraction of a drug dose reaching unchanged by the systemic circulation when administered by any route

Front 25

oral drug administration

Back 25

-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

Back 26

fraction of drug that is metabolized it the gut wall or the liver and therefore lowering bioavailability

Front 27

sublingual drug administration

Back 27

-systemic or very rarely local effects
-rapid absorption via LD
-no first pass or exposure to digestive enzymes

Front 28

rectal drug administration

Back 28

-systemic or sometimes local effects
-slow LD absorption
-no first pass, consciousness not required

Front 29

cutaneous drug administration
TOPICAL

Back 29

-local effectts
-negligible absorption, high concentration, low systemic effects

Front 30

cutaneous drug administration
TRANSDERMAL

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-systemic effects
-slow, LD absorption
-better when bandaged
-no first pass, no repeat admins

Front 31

Mucous Membrane drug administration

Back 31

-local or very rarely systemic effects
-rapid ld absorption at target membrane
-high conc

Front 32

Pulmonary Drug Administration
INHALED AS GAS

Back 32

-systemic
-most rapid LD proportional to partial pressure of gas

Front 33

Pulmonary Drug Administration
INHALED AS AEROSOL

Back 33

-local effects
-slow, LD absorption proportional to amount of drug reaching the alveoli

Front 34

Subcutaneous and IM drug administration

Back 34

-bulk flow transfer
-IM rapid
-SC slower
-can be hastened or delayed
-good onset, well absorbed, dosage control, no first pass

Front 35

Intravenous Drug Administration

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-systemic effects
-onset of drug is most rapid
-good control
-OD issues

Front 36

Intraartieral

Back 36

Localize effect in particular tissue/organ by delaying systemic distribution (diagnostic agents, anticancer drugs)

Front 37

Intrathecal

Back 37

-into CSF for drugs that can't cross BBB

Front 38

Intracardiac

Back 38

-used in cardiac emergencies

Front 39

Intrapleual, intraperitoneal, intraarticular, intravitreal

Back 39

localize drug at specific site by reducing systemic absorption

Front 40

Distribution

Back 40

-passage of drug from the systemic circulation to the body tissues

Front 41

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)

Front 42

Vd=3L

Back 42

Vascular compartment

Front 43

Vd = 13 L

Back 43

ECF

Front 44

Vd = 42 L

Back 44

distributed throughout TBW

Front 45

Vd>42l

Back 45

extensively stored in particular tissues or cells

Front 46

drug binding to plasma proteins

Back 46

-albumin if acidic or alpha1-acid-glycoportein if basic
-constant percentage bound, ninding is saturable
-competition can occur

Front 47

Drug Distribution in CNS

Back 47

- must cross cerebral capillaries or choroid plexus through occuding zonulae
- also, some drugs are actively transported out of CSF by P-glycoprotien in choroid

Front 48

Clearance

Back 48

-measure of drug eliminiation by either biotransformation and excretion
-add up all body clearance to get total volume cleared per unity time

Front 49

Biotransformation

Back 49

-makes drugs more water soluble for excretion.
-can inactivate, activate, or maintain some activity
-Phase 1 - oxidations, reductions, or hydrolyses
-Phase 2 - conjugations

Front 50

Oxidation reaction

Back 50

-catalyzed by (non)microsomal enzymes (mainly NADPH-cyto P450 reductase and cyto P450)
-can make highly reactive intermediates that cause major problems

Front 51

Glucuronidation

Back 51

-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

Back 52

-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

Front 54

Inhibitors of cytoP450

Back 54

-cimetidine
-fluoroquinolones
-macrolides
-isoniazid
-grapefruit juice
-ssris
-amiodarone
-metronidazole
-omeprazole
-HIV protease inhibitors

Front 55

Non-mircrosomal Drug Metabolizing enzymes

Back 55

-in cytosol, mitochondira, and ECF
-substrate specificity is variable
-can be under genetic control
-cat conjugations and canbe inhibited

Front 56

Drug excretion

Back 56

-renal - most important
-intestinal - biliary or fecal
-pulmonary - gases or volatile drugs
-other secretions

Front 57

Glomerular Filtration

Back 57

-filtration of unbound drugs dependent on hydrostatic pressure in capillaries.

Front 58

Tubular Reabsorption of Drugs

Back 58

-along bephron by LD depending on physicochemical properties and pH of tubular lumen
-can lead to trapping in urine

Front 59

Tubular Secretion of Drugs

Back 59

-in proximal tubule my active transport
- 1 system for acids and 1 for bases
-competition can occur within each system

Front 60

Renal Clearance

Back 60

CLr=(F x Ud)/Pd
=100-150 - glomerular filtration
>150 tubulare secretion
<100 tubulare reabs or protein binding

Front 61

Biliary Excretion

Back 61

-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)