Pharmacology

Pharmacology Definition

the study of drugs and their interactions with the human body

Drug definition

any chemical agent that affects living protoplasm

Adverse Drug Reaction (ADR)

any response to a drug which is harmful and unintended

occurs at doses used for prophylaxis, diagnosis, or treatment

side effects, drug allergies ,and drug interactions

Pharmacokinetics processes

the absorption, distribution, metabolism, and elimination of drugs

ADME

Absorption
Distribution
Metabolism
Elimination

pharmacokinetics definition

the action of the body on a drug

absorption is...

the movement of a drug from its site of administration into the central compartment and the extent to which this occurs

effects of solid capsules and absorption

solid dosage forms require dissolution of the capsule first, then absorption can occur

passive transport

diffusion from higher to lower concentration

active transport

against a concentration gradient, requires energy

absorption and stomach

some medications need an empty stomach for basic environment, some need an acidic environment

after absorption comes

distribution

distribution

drug is transported to a site where it reacts with various bodily tissues and/or receptors

what determines the rate of delivery and potential amount of drug distributed to tissues

cardiac output, regional blood flow, capillary permeability, and tissue volume

what organs receive most of the drug first

liver, kidney, brain, and other well-perfused organs

medicines that can cross blood-brain barrier

lipophilic medicines, good for getting into CNS

second distribution phase

slower, delivers to muscle, most viscera, skin, and fat

lipid soluble drugs have a high affinity for

adipose tissue where they are stored

examples of highly lipid soluble drugs

phenothiazines, benzodiazepines, barbiturates

metabolism function

to convert active lipid soluble compounds to inactive water-soluble substances to be primarily excreted by the kidney

phase 1 of metabolic process

hepatic microsomal enzymes oxidize, demethylate, and hydrolyze drugs

more significant DIs

phase 2 of metabolic process

large water-soluble substances are attached to the drug

for those who aren't water soluble enough to go through phase 1

may need to do a few times until it's hydrolyzed enough to exit

Hepatic Microbial Enzymes

phase 1

CYP450 isoenzymes

either induce or inhibit metabolism

CYP450 classification scheme

CYP # X #

enzyme inhibition and its effect on metabolism

decrease the rate of metabolism

enzyme inhibitors effect on concentration

increases the drug concentration

enzyme induction of CYP 450

stimulates the increase in CYP 450 enzyme activity

enzyme induction and clearance of drug

increases clearance of drug by increasing metabolic activity

enzyme induction and drug concentraion

decreases drug concentration by increasing metabolic activity

phenobarbital

the prototype inducer. induces all enzymes it goes through

precipitant definition

cause the enzymes to speed up or slow down

object drug

drug that has the action done upon it by the precipitant

excretion

process that removes the drug and its metabolites from the body. primarily through the urine

routes of excretion

urine, feces, lungs, skin

most important organ for excreting drugs

the kidney

substances excreted in the feces

unabsorbed orally ingested drugs or drug metabolites

excretion of drugs in breast milk

potential sources of unwanted pharmacological effects in the nursing infant

excretion from lungs

important for elimination of anesthetic gases

factors affecting the pharmacokinectic principles

age, sex, weight, disease states, genetic factors

pharmacodynamics

what the drug does to the body

mechanisms for drug interactions

synergism
antagonism
altered cellular transport
effects on receptor sites

parameters governing drug disposition

bioavailability
volume of distribution
clearance
elimination

bioabvailability

F
fraction of medicine that reaches where we want it to go

factors that decrease bioavailability

GI absorption
first-pass effect
metabolism

volume of distribution definition

V
the amount of drug in the body or the concentration of drug in the blood or plasma

potential problems with large volume of distribution

may go everywhere, more side effects

small volume of distribution

won't go into the rest of the system
i.e. injecting cortisone locally into a joint

half life

t1/2
the time it takes for the plasma concentration to be reduced by 50%

inhibiting metabolism and its effect on half life

if we inhibit metabolism, medication stays around longer and t1/2 increases

how many half lives to get to steady state

anywhere from 5 to 7 but usually 7 if there's enough time

steady state

rate in = rate out
constant concentration of the drug

drug interaction

DI
pharmacological result
the effect of one drug (object) is changed by another (precipitant)

precipitant and object

precipitant does the changing, object has the changing being done to it

classification of drug interactions

pharmacokinetic
pharmacodynamic

types of drug interactions

drug-drug
drug-food
drug-disease

pharmacokinetic

action of the body on the drug

inducer examples

cigarette smoking, Phenytoin

inhibitor examples

grapefruit juice, tagamet

grapefruit juice

can alter metabolism enzymes for 3 days
need to change timing of doses or eliminate consumption

Things that can effect absorption

pH of environment
binding
increase or decrease in motility
changes in GI flora

binding

chelating ions will bind to certain medications and make them inert

(unbound) free drug

free drug = active drug

bound drug

don't get a lot of action out of it

inhibitors and concentration

inhibitors increase concentration

inducers and concentration

inducers decrease concentration

elimination considerations

urinary pH
competition

effect of urinary pH on excretion

some drugs are held on to or excreted based on an acidic or basic urine

probenecid

blocks excretion of penicillin, increases the concentration of penicillin in the body

one way to avoid inhibitors

decrease dose

synergistic effects

additive effects
beer and valium
increases the total effect

antagonistic effects

opposing effects
tenormin and sudafed
decrease effect of both