Pharma General Principles Flashcards
permeation depends on
- solubility (ionized are water soluble, unionized are lipid soluble)
- conc gradient (only FREE and UNionized contribute)
- SA and vascularity
some weak acid drugs
- aspirin (ASA, acetyl salisylic acid)
- penicillin
- cephalosporins
- loop & thiazide diuretics
some weak base drugs
- morphine
- local anesthetics
- amphetamines
- PCP (angel dust)
in which environment is a weak acid lipid soluble?
a weak acid is lipid soluble in an acidic environment (AH)
in which environment is a weak base lipid soluble?
a weak base is lipid soluble in a basic environment (B)
What forms of drug are filtered through the kidney?
- both ionized and nonionized forms filtered but the drug MUST be FREE and UNBOUND
- also note than ionized form is trapped in the filtrate b/c it’s NOT lipid soluble (whereas unionized can be reabsorbed or secreted b/c it is lipid soluble)
if overdose on weakly basic drug (ex: amphetamine, PCP), what should do?
- acidify the urine to incr renal elimination (in an acid environ, a weak base is ionized and therefore water soluble and lipid insoluble)
- can give vitamin C, cranberry juice, or the fav NH4Cl (ammonium chloride)
if overdose on weakly acidic drug (ex: aspirin), what should do?
alkalinize the urine (with NaHCO3 or acetazolamide) to incr renal elimin
NH4+ is
ammmonium
NH3 is
ammonia
fastest route of absorption
inhalation
bioavailability of IV admin drug
100%
bioavailability calculation
f = AUCpo/AUCiv (AUC = area under curve, f = bioavailability, po = per oral)
which a stronger barrier to distribution - placenta or blood-brain barrier?
BBB
BBB is only permeable to . . .
- lipid soluble drugs
* very low mw drugs (ex: Li+, EtOH)
what kinds of drugs are safer during pregnancy?
- water-soluble (b/c can’t cross membranes)
- large
- protein-bound
(ex: choose PTU over methimazole b/c PTU more highly protein-bound; Phenobarbital safer anticonvulsant b/c highly protein-bound)
volume distribution
Vd = Dose/Co (Co = plasma conc at time=0)
note L vs. L/kg . . . don’t forget to multiple by pt wt
interpreting low v high volume distribution
- low - lots of drug bound to plasma protein
* high - lots of drug sequestered in tissues
effect of P450 inducers v. inhibitors
- inducer –> incr P450 enzymes –> decr drug level in plasma (for certain drugs) therefore may need to give more drug
- inhibitor –> decr P450 enzymes –> less metab –> risk of drug toxicity b/c incr drug level in plasma
some classic P450 inducers?
- phenobarbital
- phenytoin
- carbamazepine
- rifampin
- chronic alcohol
some classic P450 inhibitors?
- cimetidine (OTC med)
- marcrolides (esp erythro-) . . .(note azythromycin is not a P450 inhibitor)
- ketonconazole
- “avirs” - antivirals, proteases for HIV
- ACUTE alcohol
- grapefruit juice
Phase I Rxns
hydrolysis, oxidation (monoamine oxidase, CYP450), alcohol metabolism, reduction
Phase II Rxns
- conjugation rxns (endogenous compound is conjugated to a drug by a transferase)
- includes glucuronidation, acetylation, GSH conjugation
zero order kinetics
constant AMOUNT eliminated per unit time
* thus t1/2 is variable
ex: zero “peas” for me: phenytoin, EtOH, aspirin
first order kinetics
constant FRACTION eliminated per unit time
t0.5 is constant (t0.5 = 0.7/k
rate of elimination
rate of elimination = GFR + active secretion - reabsorption
Clearance defn
volume of blood cleared of drug per unit time
constant in 1st order kinetics
What is used to estimate GFR? Why?
inulin clearance (b/c inulin is neither secreted nor reabsorbed)
equations for Clearance
- Cl = free fraction x GFR (b/c protein-bound drug is NOT cleared)
same as saying Cl = (1-% protein-bound)xGFR
steady state
when rate in = rate out
What does steady state depend on?
steady state depends on half-life (t0.5) ONLY
It does not depends on dose size and freq admin
What does rate of infusion (Ko) determine?
plasma level at steady state (but NOT the time to reach steady state
how do calculate time to clinical steady state?
4 or 5 time t1/2
loading dose calculation
LD = (Cp x Vd)/f (Cp= conc in plasma, Vd= volume distribution, f=bioavailability)
t1/2 eqn
t1/2 = (0.7 x Vd)/Cl
infusion rate eqn
Ko = Cl x Css (Ko = infusion rate, Cl = clearance, Css = conc steady state)
maintenance dose eqn
MD = (Cl x Css x dosing interval)/f (f=bioavail)
