9/10 required reading ch. 1 general principles of pharmacology

chemical antagonists

binds/reacts directly with the other substance → makes it inactive

osmotic agents

interact almost exclusively with water molecules, by pulling water towards itself

xenobiotics

chemical that is “foreign” to the body

Poisons

drugs that have almost exclusively harmful effects

Toxins

poisons of biologic origin, ie, synthesized by plants or animals

size of most drugs

between 100 and 1000 mw

larger sized drugs

administered directly in compartment where they effect, like intravenous or intra-arterial infusion

drugs interact with receptors by bonds

covalent, electrostatic, and hydrophobic

Covalent bonds

very strong and in many cases not reversible under biologic conditions

Electrostatic bonding

attraction between opposite electrical charges including ionic, H bonds, and van der waal

more common and weaker than covalent bonds

Hydrophobic bonds

when nonpolar/lipid-loving parts of a drug associate with nonpolar regions of membranes or receptor pockets

weaker

enantiomers of same drug

can have different effects on receptors due to chirality/stereoisomers

enzymes and drug transporters

can be stereoselective

drugs are mostly racemic mixtures

Because receptors are stereoselective, one enantiomer may bind better and be more active than the other

effector mechanism

final change in function for a drug to bind to a receptor to bring an effect

ex: effector complex, effector molecule, activation of coupling molecule

Pharmacologic antagonist drugs

by binding to a receptor, compete with and prevent binding by other molecules

Constitutive activity/basal activity

receptor has some activity even when no agonist is bound to it

intrinsic efficacy

How well a drug can activate a receptor after it binds to it

neutral antagonism

antagonist blocks an agonist from activating the receptor but does NOT change the receptor’s basal (constitutive) activity

inverse agonists

drugs that bind to a receptor and decrease its constitutive (basal) activity

two requirements for receptors

Must be selective and Binding must change the receptor's function

inert binding site

place in the body where a drug can bind, but the binding does not produce a biological response

prodrug

medication that is given in an inactive or less active form and then converted by the body into its active form

mechanisms for drug permeation

aqueous diffusion, lipid diffusion, special carriers, Endocytosis and exocytosis

Aqueous diffusion

drug moves through the body's watery fluids from an area of high concentration → low concentration

ex: Blood plasma → extracellular fluid → tissues

Lipid diffusion

drug moves through the lipid (fatty) cell membrane from an area of high concentration → low concentration

lipid:aqueous partition coefficient

determines how readily the molecule moves between aqueous and lipid media

-high value=good at lipid diffusion

Special carrier

transport protein in the cell membrane that helps certain drugs cross the membrane

-drugs that aren’t lipid-soluble

P-glycoprotein (multidrug resistance type 1 (MDR1) transporter)

special carrier protein that pumps drugs out of cells, can decrease how much drug gets into or stay inside cells

MRP (multidrug resistance-associated protein)

membrane transporter that pumps certain drugs and metabolites out of cells

Endocytosis and exocytosis

ways cells move large molecules or particles across the cell membrane using vesicles

-entering and exiting

Fick’s Law of Diffusion

how quickly a drug moves across a membrane by passive diffusion

Weak acids

Low pH (lots of H⁺) → HA dominates → uncharged

High pH (less H⁺) → acid gives up H⁺ → A⁻ dominates → charged

Weak bases

Low pH (lots of H⁺) → base picks up H⁺ → BH⁺ → charged

High pH (less H⁺) → B dominates → uncharged

Henderson–Hasselbalch equation

how much drug is ionized vs unionized at a particular pH

pKa is more than pH

protonated acid

pH is more than pKa

deprotonated acid

primary, secondary, and tertiary amines

undergo reversible protonation and vary their lipid solubility with pH, but quaternary amines are always in the poorly lipid-soluble charged form

prototype drugs

standard/example drug used to represent a whole class of drugs