pharmacodynamics and pharmacokinetics

half life

time it takes to decrease concentration of a drug by half

volume of distribution (V_d)

theoretical measure of apparent space in the body available to contain a drug (amount in body/concentration)

clearance (Cl)

elimination of a compound from the blood (volume cleared/time)

bioavailability (F)

proportion of the dose that reaches systemic circulation

IV bioavailability

100%

IM bioavailability

75-100%

SubQ bioavailability

75-100%

oral bioavailability

5-100%

rectal bioavailability

30-100%

inhalation bioavailability

5-100%

transdermal bioavailability

80-100%

pharmacology definition

study of substances that interact with living systems through chemical processes

toxicology definition

branch of pharmacology that deals with the undesireable effects of chemicals in living system

schedule 1 drugs

no currently accepted medical use and high potential for abuse

schedule 2 drugs

drugs with high potential for abuse that can potentially lead to severe dependence

schedule 3 drugs

drugs with a moderate to low potential for dependence

schedule 4 drugs

low potential for abuse and low risk of dependence

schedule 5 drugs

drugs with lowest potential for abuse and consist of preparations containing limited quantities of certain narcotics

pharmacodynamics

what the drug does to the body

pharmacodynamics includes:

recepter interactions, dose-response phenomena, and mechanisms of therapeutic and toxic action

primary mechanism of pharmacodynamics

receptors binding to ligands

example of ligand gated ion channels

cholinergic nicotinic receptors

example of GPCR

alpha and beta adrenoreceptors

example of enzyme linked receptors

insulin receptors

example of intracellular receptors

steroid receptors

types of GPCR

Gs, Gi, Gq, Gt, Golf, G0

endogenous ligands

NT, tachykinins, peptides, glycoprotein hormones, arachidonic acid derivatives, odorants, tastants, endothelins, platelet-activating factor, cannabinoids, light

receptor tyrosine kinase steps

ligand binds, receptor dimerizes, and autophosphorylates

relationship of dissociation constant (Kd) and potency

inversely proportional

affinity

measure of propensity of a drug to bind a receptor or attractiveness of a drug and receptor

Emax

maximal response that can be produced by a drug

EC50

concentration of a drug that produces 50% max effect

Bmax

total concentration of receptor sites bound

efficacy

maximum effect of which a drug is capable

potency

molar concentration required to produce a specific intensity of effect determined by EC50

efficacy vs potency

efficacy: can it get to Emax

potency: how much concentration can be given

competitive inhibition

can add enough agonist to get to Emax by competing out receptors

noncompetitive inhibition

cannot add enough agonist to get to Emax or outcompete receptors

inverse agonists

stabilize receptors and shut them down as opposed to directly binding as a ligand

typical drug Kd

10^-7 to 10^-9

ED50

median effective dose at which 50% of the population manifests a given effect

TD50

median toxic dose at which 50% of population manifests a given toxic effect

LD50

lethal dose at which 50% of the population dies

therapeutic index

ratio of toxic/effective, range of effective dose up to lethal/toxic dose

pharmacokinetics

branch of pharmacology dedicated to determining the fate of substances administered to a living organism

basic pharmacokinetics definition

what the body does to the drug

what affects bioavailability

rates and extent of absorption

first-pass effect

drugs absorbed in the GI tract pass through the hepatic portal vein to be partially metabolized in the liver before entering circulation

absorption

process of a substance entering blood circulation and transport across cell membranes

most common method of drug absorption

passive diffusion

relationship of higher partition coefficient (Kp) and transfer across membranes

higher Kp = increased transfer

electrolyte diffusion

unionized forms pass more readily across membranes than ionized

partition theory

acids accumulate in basic compartments and bases accumulate in acidic compartments

pka

pH when a drug is 50% in ionized and 50% unionized form

result of lowering pH for acidic drug

increases concentration of uncharged species and increases transport

result of lowering pH for basic drug

increased concentration of charged species and decreases transport

for acids: if pH < pKa by 2 units

mostly unionized

apparent volume of distribution (V_d)

plasma volume into which a drug seems to distribute

C₀

plasma concentration at time zero after IV infusion

half lives for 94% elimination

4

phase I drug metabolism

catabolic, polar, water soluble metabolites that are broken down from the original substrate

phase II drug metabolism

anabolic, large, polar metabolites via adding endogenous hydrophilic groups to form water soluble inactive compounds to be excreted

phase III drug metabolism

chemical substance undergoes further metabolism

primary phase I metabolism enzyme

cyp450 in the liver

most commonly used cyp450 variation

CYP3A4

consequence of acetaminophen overuse

hepatotoxicity due to NAPQI accumulation

primary site for drug excretion

kidney/urine

glomerular filtration - renal excretion of drugs

low MW drugs pass from bloodstream to urine

active secretion - renal excretion of drugs

depends on endogenous carriers to move molecules from the bloodstream to urine

passive reabsorption - renal excretion

determines elimination rates of most drugs, passive movement from urine back to bloodstream

acidification of urine result

increased reabsorption and decreased excretion of weak acids, decreased reabsorption of weak bases

alkalinization of urine result

decreased reabsorption and increased excretion of weak acids, increased reabsorption of weak bases

compounds more concentrated in maternal milk

basic compounds

elimination constant

k

clearance

factor that predicts rate of elimination relative to drug concentration

total clearance

volume of plasma completely cleared of drug per unit time by all routes and mechanisms

time to reach steady state level

4 half lives

K₀

infusion rate

loading dose

given to achieve desired therapeutic effect quickly