Pharmacology

Max rate of reaction for given amt of enz; proportional to [enz[

Michaelis constant; [substrate] reqd to reach V50; inversely proportional to affinity (ie high Km=more substrate reqd to reach same rate=lower affinity of enz for substrate)

Y axis=V, X axis=[S]

Y axis=1/V, X axis=1/Km; Y intercept=1/Vmax, X intercept= -1/Km

Competitive=bind active site, similar to substrate, CAN overcome inhibition with higher [S], increases Km/decreases potency, same Vmax/efficacy
Non=bind allosteric site OR active site irreversibly, CANNOT overcome inhibition, decreases Vmax/efficacy, same Km/potency

Volume of distribution=total body amount of drug(mass)/plasma concentration of drug(mass/volume)
4-8L=blood, 12-14L=ECF, >TBW ~40L=fat, etc
**altered in hepatic/renal failure=decrease plasma proteins (dec synth/inc excr) which bind drugs and hold in vasculature

Clearance=elimination rate (mass/time)/plasma drug concentration (mass/volume)=(volume/time)
=Ke*Vd
renal=GFR*free fraction of drug (unbound)

Half life=0.7*V_d/Cl
refers to decrease with elimination or increase with infusion
4-5* t_1/2=t to achieve steady state (93.75-96.9%)

LD=Vd*plasma concentration/F
MD=Cl*plasma concentration/F
F=Bioavailability, IV=1

Zero order=constant AMOUNT/time
ex Peas and WHEATS: Phenytoin/Phenylbutazone, Warfarin, Heparin, Ethanol, Aspirin, Theophylline/Tobutamide, Salicylates
First order=constant FRACTION/time
ex most drugs

In liver; lipid soluble drugs->water sol for excr
Phase I
Cyp450-SER; reqs O2, NADP, ox/red
NonCYP450-MAO, hydrolysis
Phase II
Conjugation of func groups to nonpolar for excr, transferases

Remember: parallel=can compare potency AND efficacy
perpendicular=can only compare efficacy; potency dept on dose

Recall: to metabolize lipid soluble drugs to water soluble metabolites for excretion so:
induce=more excretion=lower Cp=higher dose needed
inhibit=less excretion=toxic accumulation=lower dose needed

Therapeutic Index=safety margin
=median toxic/lethal dose/median therapeutic/effective dose
=LD₅₀/ED₅₀

Autonomic nicotinic Ach Rs=ligand gated Na+/K+ channels; parasymp and symp postganglionic neurons

somatic muscular nAchRs at neuromuscular jxn (motor neuron direct to)