Elimination of a Drug
Termination of drug effect > biotransformation > inactive > excreted
Organs of Excretion
Kidney, Liver.Lungs,Skin (sweat)
Kidney > Glom.Filtration,Tubular secretion Re-absorption by passive diffusion
o Glom. Filtration > passive process
o Removes mols. Size of small proteins
o Protein bound drug > less Glom.Filtration
o Free drug more filtration > rate approximates cratinine clearance
o Tubular secretion > actively secreted by proximal convoluted tubule
o Lipid membrane of nephron reabsorbs lipid soluble mol.
o Water soluble mol. excreted
Liver
o Actively secreted into bile after metabolism
o Enters G.I.T & may be reabsorbed into the blood > entero hepatic circulation
o E.g/ cardiac glycosides and some anti microbials
o Gastro Intestinal Tract > passive diffusion
o Drugs > blood>lipid membrane > lumen of G.I.T.
Clinical importance of excretion into lumen of gut
o Weakly basic drugs like morphine in high concentrations diffuses into acidic environment of stomach > poorly re absorbed as it is 100% ionized. Hence can be removed by gastric lavage.
o If not removed, it is re absorbed in the small intestine
Other organs of excretion
o LUNGS > Gaseous anaesthetics
o SWEAT
o SALIVARY GLANDS
o MILK
DRUG CLEARANCE
o Rate of elimination is relative to the conc. Of drug any biological fluid e.g. plasma, blood.
CL= Rate of elimination
Plasma conc.
o CL(renal) =
Rate of elimination(Kidney)
conc.in plasma (Cp)
o CL(liver) =
Rate of elimination(liver)
Cp
o Rate of elimination
o For an organ =QxC(in) – Qx C(o)
Q = rate of bl.flow
C(in) = amt of drug entering
C(o) = amt of drug leaving
o Bioavailability(F) = 1 – ER(extraction ratio)
o Dosing Rate = CL x Css (IV infusions)
o Half life proportional to VD & CL
o t1/2 =
0/693VD or 0.7VD
CL
Loading Dose = VD x Cpss
o Used for long t1/2 drugs > raise conc of drug to steady state value > amt. of drug in the body when steady state is reached
o E.g. If reqd. ss conc is 15microgms/ml and VD is 35L Then LD = 15 x 35 = 525mg
Dosage Regimen
o 1. Dose of drug
o 2. Route of administration
o 3. Dosing interval
o 4. Period of administration
o Clinical significance of dosing rate
o Eg. Desired Pl.conc of drug A is 15microgms/ml CL = 48ml/min/70Kg
o Dosing rate = 48 x 15 = 720mugm/min =0.72mg/min = 43.2mg/hour = rate of IV infusion
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