4 Pharmacokinetics/dynamics Flashcards
Vd of a drug that is lipophilic v hydrophobic
Lipophilic= exceeds TBW >0.6L/kg. Hydrophilic= <0.6 L/kg
Clearance is directly related to 3
Bf to clearing organ, extraction ratio, drug dose
Clearance is inversely proportional to 2
Bf to clearing organ and drug conc in central compartment
When is steady state achieved
5 half times
Alpha phase
Central compartment (plasma) to peripheral (tissues).steep pt of slope, distribution,
Beta phase
Elimination from central compartment
Elim half life
Time for half of drug to be removed from body after IV injection
Elim half time
Time for half of drug to be removed from plasma during elim phase
Ionized: solubility, hepatic v renal elim, diff thru bbb/gi tract/placenta
Hydrophilic/lipophobic, renal elim, no diffusion
Non ionized: solubility, hepatic v renal elim, diffusion
Lipophilic/hydrophobic, more hepatic, diffusion across bbb/gi/placenta
How to tell if a drug is a weak acid
Usually w a positive ion like na, ca, or mg
How to tell if a drug is a weak base
Usually with a neg ion like cl or so4
When unionized fraction predominates
If molecule weak base and ph of sol > pka of drug. Or if its a weak acid and ph sol is
How to calc % change w drugs
(New value - old value) / old value. X 100
Albumin: carries ___ charge, binds ___ drugs mainly
Negative, acidic
A1 glycoprotein binds ___ drugs, beta globulin binds ___ drugs
Basic, basic
Conditions w dec albumin, effect
Decreased binding of acidic drugs: liver/renal disease, elderly, malnutrition, preg
A1 glycoprotein effect when inc, cond, effect when dec, cond
Inc= more basic drug binding: stress, mi, pain, RA, elderly. Dec= less basic drug binding, preg and neonates
Zero v first order kinetics
Zero= linear, constant amt per time. First order= log, constant fraction per time
Drugs that follow zero order kinetics
Asa, phenytoin, alcohol, warfarin, heparin, theophylline
Phase 1 reactions
Oxidation, reduction, hydrolysis
Phase 2 rxn.
Conjugation, adding on a polar/h20 soluble substrate to molecule to allow it to be excreted
Phase 3 metab
Elimination. ATP dep carrier proteins transport drugs across membranes in kidney, liver, and gi tract
Drugs w low hepatic Er 7
Roc, valium, Ativan, methadone, tpl, theophylline, phenytoin
Drugs w intermediate hepatic Er
Versed, vec, alfent, methohexital
Drugs w high hepatic Er
Fent, sufent, morphine, demerol, narcan, ketamine, prop, lido, bup, metop/propranolol/Alpren, nifedipine, dilt, verap
CYP 3A4: drug substrates affected by it
Opioids (fent, methadone), benzos, locals
Cyp 3a4 inducers
Etoh, rifampin, barbs, tamoxifen, carbamazepine, john wort
Cyp 3a4 inhib
Grapefruit juice, cimetidine, emycin, antifungals, ssris
Cyp 2d6 substrates
Codeine to morphine, oxycodone, hydrocodone
Cyp 2d6 inducers and inhib
Induce: disulfiram. Inhib: isoniazid, ssris, quinidine
Dynamics v kinetics
Dynamics= effect site conc and clinical effect. Kinetics= drug dose and plasma conc
Pharmacobiophasics
Plasma conc and effect site conc
Dose response curve: x axis, y axis, slope
X= potency, y= efficacy, slope= receptors occupied to elicit a clinical effect
Synergism v potentiation
Syn= 1+1= 3. Potentiation= 0+1=3. Pot= has one drug that enhances another drug that would’ve had no effect on its own
How to calculate therapeutic index
LD50 / ED50
Chirality
Carbon bonded to 4 diff atoms. 2 enantiomers
Enantiomer
Chiral molecules that are mirror images
Site with lowest bioavailability
Intrathecal
Vessel rich: % co, % total body mass
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