Potency

Relative doses of 2+ agonists to produce the same magnitude of effect

(tell by how close the drug's curve is to the Y axis and drug that are compared can't cross)

Affinity

Ability of drug to bind to reeptor (comparing drugs of parallel curves the one closer to the Y axis)

Can only be compared when the drugs bind to the same receptor

Efficacy

Measure of how well a drug produces a response (maximal height reach by the curve)

Partial agonist

Incapable of eliciting a maximal response and are less effective.

If used together with a full agonist acts as an antagonist as it displaces the full agonist from the receptor and reduces the response

Pharmacologic antagonism

Competitve antagonist

2 drugs 1 receptor

Dose response curves shifted to the Right (decreases the potency of the agonist)

Pharmacologic antagonism

Noncompetitive antagonists

Nonparallel shift to the Right on the D-R curve

Irreversibly binds to the receptors so can only be partially reversed by the agonist

Decrease the efficacy of the agonist

Examples: phenoxybenzamine, dig, allopurinol, PPI's, ASA

Physiologic antagonism

2 drugs 2 receptors of opposite effect

Example a vasoconstrictor w/ vasodilator

Phenylephrine vs. nitro

Chemical antagonism

Complex formed b/n effector drug and another compound

Ex: protamine binds to heparin for reversal

potentiation

parallel shit toe the left on the D-R curve

Ex: benzos and GABA

Therapeutic Index

TI = TD50/ED50

Where TD50 is the toxic dose in 50% of the patients and ED50 is the effective dose in 50% of the pts (want TI to be > 2)

Examples of drugs w/ low TI's = theophylline, dig, warfarin, lithium

Intracellular receptors

Include steroid receptors (like glucocorticoids) where pharmacologic responses are elicited via modification of gene expression

Usu slower in onset but longer in duration

Receptors directly coupled to ion channels

Can mimick or antagonize the actions of endogenous ligands

Ex: the nicotinic receptor for Ach (found in much of the body)  

Gs proteins

activates cAMP production via stimulation of adenylyl cyclase

Ex receptors: β1,β2,DA1,glucagon,H2,prostacyclin 

Gi proteins

decrease cAMP production

Ex of receptors: α2, DA2, M2 (muscarinic)

Gq proteins

Activates PLC which releases IP3, and DAG. IP3 releases Ca2+ and DAG activates PKC

Ex receptors: M1,M3, α1, angiotensin II

cGMP receptor

2nd messenger that dephosphorylates myosin light chains preventing muscle contraction

NO activates guanylyl cyclase and increases cGMP in smooth muscle

Drugs that act via NO: Nitrates, M-receptor agonists, bradykinin, and histamine

Transmembrane enzymes

Tyrosine kinase that with binding of the ligand causes dimerization leading to phosphorylation of tissue specific substrate proteins

Ex: insulin

Cytokine receptors

Receptors are membrane spanning and on activation activate cytoplasmic tyrosine kinases (JAK/STAT)

Ex receptors: EPO, somatotropin, IFNs

Clinical testing

Phase 1: is it safe (done in small healthy pop)

Phase 2: does it work (100+ pts w/ target dz)

Phase 3: how well does it work and what are the common SE's (double blind w/ both kinds of pts)

Phase 4: post marketing surveillance of adverse drug effects

Teratogenicity

A (no risks = folic acid, thyroid hormones)

B (Zidovudine)

C ("unkown" b/c research hasn't been done = ASA)

D (only when benefits outweigh risks = ACEi, anticonvulsants)

X (absolute contratindication = Statins, OC's, high dose vit-A)