Basic pharm Flashcards
Michaelis Menten graph and key variables
Velocity vs. substrate, MM = hyperbolic curve
Km = inversely related to enzyme’s affinity for substrate, is equal to [substrate] at 50% Vmax) ie as affinity increases, [substrate] needed to reach 50% decreases!
Vmax = directly proportional to enzyme concentration
Lineweaver-Burk plot and intercept meanings
1/V vs. 1/S
used to show relationships of inhibitors
y-intercept = 1/Vmax (therefore, incr. y-intercept = decr. Vmax) x-intercept = 1/Km (therefore, closer to 0 = incr. Km = decr. affinity)
Inhibitors and their effects on Vmax and Km
Competitive, reversible: no change on Vmax, incr. Km
leads to decr. potency of a drug
Comp., irreversible: decr. Vmax, no change on Km
leads to decr. efficacy of a drug
Noncompetitive: decr. Vmax, no change on Km
leads to decr. efficacy
Volume of distribution
give formula for Vd
- for protein-bound drugs, this volume can be affected by liver or renal disease (decr. protein binding = incr. volume)
- Vd = amount of drug in body / plasma drug concentration
Clearance of a drug
give formula
volume of plasma cleared of drug per unit time. IT’S A VOLUME!
CL = rate of elimination / plasma drug concentration = Vd x Ke (elim constant)
Half-life
4-5 half-lives to reach steady state
3.3 half-lives to reach 90% steady state
Dosage calculations
Loading dose, maintenance dose
Loading dose = Cp x Vd / F
Maintenance = Cp x CL x r / F
F = bioavailability (100 for IV dose) Cp = target plasma concentration r = dosage interval (time)
Zero-order elimination
constant rate of elimination (no effect of target plasma conc.), therefore linear decrease in conc. with time
aka. capacity dependent
Ex: phenytoin, ethanol, aspirin
First-order elimination
rate of elimination is proportional to drug concentration, therefore exponential decrease in conc. with time
aka. flow dependent
Weak acid overdose
ex. phenobarbital, methotrexate, ASPIRIN
Get trapped in basic environment (when they are ionized), therefore treat with bicarbonate
Weak base overdose
ex. amphetamines
Trapped in acidic environment, therefore treat with ammonium chloride
Drug metabolism Phase 1 (modification)
Reduction, oxidation, hydrolysis with cytochrome p450
Yields slightly polar, still-active metabolites
Lost first in old people
Drug metabolism Phase 2 (conjugation)
Glucoronidation, Acetylation, Sulfation
Yields very polar, inactive metabolites (renally excreted)
Definition of efficacy
maximal effect a drug can produce
represented by Vmax
partial agonists < full agonists
Definition of potency
amount of drug needed for a given effect
represented by EC50 (effective concentration)
Competitive antagonist effects
Decreased potency
Overcome by increasing concentration of agonist substrate
Noncompetitive antagonist
Decreased efficacy
Partial agonist
Lowers the maximal effect of the full agonist
Note: potency is an independent variable, though generally, a partial agonist is designed to have a higher potency
Therapeutic index
TD50/ED50 = median toxic dose/median effective dose
Safe drugs have higher TI values (means there is more wiggle room between the efficacious dose and possibly going up to the toxic dose)
Nicotinic Ach receptors
Ligand-gated Na/K channels
Muscarinic Ach receptors
G-protein coupled receptors that act through 2nd messengers
What is special about the sweat glands and adrenal medulla vs. all other autonomic nervous systems organs?
They are innervated by the SYMPATHETIC nervous system, but are innervated by CHOLINERGIC (sweat glands have muscarinic receptors, but adrenal medulla has nicotinic)
