General Principles Flashcards
Pharmacokinetics
What the patient does to the drug
Pharmacodynamics
What the drug does to the patient
Drug
any substance that changes biologic fnx through chemical aciton
agonist
activating drug
inhibition
antagonist drug
-can be overcome by increasing dose
Hormones/Xenobiotics/Poisons
endogenous/exogenous/usually harmful effects
side effect
harm at therapeutic doses
toxicity
may refer to sideeffects or commonly to adverse effects related to supratherapeutic dosing
What are 3 drug principles?
- MW ~100-1000 g/mol
- receptor interaction through bonding (electrostatic, ionic or covalent)
- drug shape confers specificity (stereoisomers impt)
steroisomerism
- whenever C binds 4 diff groups there are two ways this can occus
1. handedness
2. chirality - drugs are manufactured and given as racemic mixtures–>one is more active than the other.
Which isomer is more active?
the one with the flat, hydrophobic reguins,
-less reactive isomer is the one with polar region
Allosteric interactions
- substances that bind to receptors, but not at the same site as drug agonist
- may inhibit or activate receptor
- cannot be overcome by increasing drug dose
Draw the dose response curve
Partial Agonist
Binds receptor and activates it to less degree of a full agonist
- less intrinsic efficacy–>increase dose does not overcome limitation
- seen clinically
What would happen if you have an partial agonist opiod to a patient already on a full agonist opioid medicine?
- partial agonist will act as an antagonist
- competes w/ full agonist for the receptor
- prevents full efficacy (bc doesn stabilize the activated form of the receptor)
Inverse agonist
-binds to receptor and decreases effect
(stabilized the inactive form of the receptor reducing activity below baseline)
- like an antagonist, but not
- ex. Antihistamines
Neutral Antagonist
“fixes” the ratio of active and inactive forms of receptor
prevents any effect of agonist drugs if present in sufficient quantity
-not used clinically
Dose response curve for Full, partial, and inverse agonist
Drug duration
generally as long as a drug occupies receptor,
covalent binding to R may require generation of new R to terminate action
Binding selectivity
many drugs selective for receptor, inert binding sites affect drug distribution
Action of drugs
- absorbed from site of administration
- Distributed through body tissues
- Metabolized
- Eliminated
What are the different types of drug permeation?
- aqueous diffusion
- lipid diffusion
- special carriers (esp. large molecules)
- Endo/exocytosis
Are drugs weak acids and bases?
yes,
carbaxylic acids, amine bases
-both protonated and unprotonated forms found at physiologic pH
What is the equation for the ratio of conjugate acid to conjugate base
log (protonated/unprotonated)= pka-pH
lower pH=more protonated
high pH=less protonated
-pka=pH where molecules is 1/2 dissociated
Explain Ion trapping
- generally only uncharged molecules diffuse passively across cell membranes
- can manipulate pH of body fluids by giving NH4Cl or NaHCO3 to trap drugs by keeping them ionized
Zero-Order
rate of drug elimination is constant regardless of drug concentration
When would you see zero-order elimination?
when metabolism/elimination pathways are saturated
ex. seen clinically w/ EtoH and aspirin
First Order Elimination
- rate of drug elimination is proportional to the drug concentraion
- Hyperbolic curve
- most drugs have 1st order elimination
1st order semi-log plot
- slope of line is related to half-life
- steeper=shorter 1/2 life
- half life concept only works for 1st order elimination kinetics
Half-Life
Time to eliminate 1/2 of the drug
