administration

liberation

absorption

distribution

metabolism

elimination

enteral (oral, sublingual, rectal); sublingual and rectal bypass GI tract and liver metabolism, enter veins directly

parenteral (IV, IM, subQ, IP, transdermal [easy admin], intrathecal, intraosseous [same as IV], intrapulmonary [endotracheal tube, no bicarb])

sustained release, sustained action, extended release, continuous release, etc.

pseudo increase half life --> less frequent dosing

mostly by simple diffusion

food slows down absorption (not clinically relevant) as drugs pass through cells

location depends on pH

low pH in stomach

weak bases (most drugs) ionized and poorly absorbed in stomach

weak acids will not be ionized and will be well absorbed (eg aspirin)

oral-->portal vein-->hepatocyte-->does not go to systemic circulation

especially pronounced in lidocaine (local anesthetic and antiarrhythmic)

Equieffective Dose: IV<IM<SC<Oral

Sign of increased FPE: oral dose>>IV dose

Onset of effect: IV>IM>SC>oral

IV drug dose is approx an order of magnitude smaller than oral dose

makes substances more water soluble

happens in liver, excreted by kidney

phase 1: oxidation, Child-Pugh dependent

phase 2: conjugation. Child-Pugh independent

50 different types

involved in phase 1 reactions

1A2: xanthine (caffeine)

3A4: erythromycin, most common

2C9: phenytoin (anti convulsant, gingival hyperplasia), 3rd most common

2C19: mephenytoin

2D6: debrisoquine, 2nd more common

most abundant, metabolizes 60% of drugs

most potent inducers: barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin, St. John's Wort

inhibitors: Azole antifungals, cimetidine, ciprofloxacin, erythromycin,nefazadone, grapefruit juice

filtration, absorption, secretion

cr = 1, filtered only

cr < 1, reabsorbed

cr > 1, secreted (weak acids, penicillin)

proximal tubule

multispecific transporters, transports both endogenous and exogenous anions

endogenous: cAMP, PG, bile salts, oxalate, hippurate, urate, thyroid hormone

exogenous:acetazolamide, chlorothiazide, furosemide,
penicillin, cephalosporine, probenicid,
hydrochlorothiazide, aspirin, cardiac glycosides

proximal tubule

endogenous: dopamine, epinephrine,
norepinephrine, creatinine

exogenous: Cimetidine, ranitidine, trimethoprim, diltiazem, triamterene, verapamil, atropine, isoproterenol,
morphine, quinine, quinidine, miloride,
procainamide, pramipexole

Cockcroft & Gault formula: converts SCr to CCr

M:Ccr = (140-age)(kg BW)/(72 Scr)
F: Ccr = (140-age)(kg BW)/(84 Scr)

Cr normal value is 0.8 to 1.4 mg/dL

Zero Order: constant amount of drug is eliminated per unit time, t1/2 is variable, eg ethanol, heparin @ high [], phenytoin, aspirin

First Order: constant fxn of drug eliminated per unit time, t1/2 constant

Clearance = Vd x Ke

Ke = 0.7/(t1/2)

The time it takes for a drug to be half of the initial concentration

5 half lives until elimination/steady state

ionotropic (fast): GABA, NMDA, 5HT3

metabotropic (slow): α and β adrenergic, cholinergic, 5HT receptors

Direct agonist: substance that binds to an endogenous receptor and elicits a stimulatory response; eg epinephrine at the cardiac beta-1 adrenergic receptor

Indirect Agonist: substance that increases the level of the endogenous agonist; eg PDE inhibitors, cholinesterase inhibitors, transporter inhibitors such as SSRIs

increase cAMP

PDE III selective: -rinone

used to treat bradycardia

ACh inhibitor, decreases secretions

are not specific to one receptor

Carvedilol: beta & alpha blocker
Ranitidine: H2 blocker & ChE inhibitor
Amitryptyline: Ne & 5-HT transporter inhibitor, alpha blocker, muscarinic blocker, H1 blocker; dopamine affects D1 > beta1 > alpha 1

graph relating the amount of a drug to the response of the organism under study

logarithm of the dose is plotted on the X axis and the response is plotted on the Y axis the curve is sigmoidal, with the steepest portion in the middle

concentration of a drug which
induces a response halfway
between the baseline and
maximum. It is commonly used as
a measure of drug potency

OR

plasma concentration required for
obtaining 50% of a maximum
effect in vivo

comparison of the amount of a
therapeutic agent that causes the
therapeutic effect to the amount that
causes toxic effects.

LD50/ED50

a drug with a narrow therapeutic
range (i.e. with little difference
between toxic and therapeutic doses)
may have its dosage adjusted
according to measurements of the
actual blood levels achieved in the
person taking it. This may be
achieved through therapeutic drug
41 monitoring (TDM) protocols.

Efficacy = largest maximal effect

Potency = Less dosing (curve to left)