Absorption summary

Mechanism of Pharmacokinetics

Biotransport mechanisms (Absorption process)

Bioavailability

Factors effecting bioavailability or absorption

Molecular weight, Ionization, Crystalline nature

Gastric emptying, GIT disorders, Presence of food and

Drug-drug interactions
BIOTRANSFORMATION
(METABOLISM)
????
Enzyme catalyzed chemical transformation of drug
(Microsomal and non-microsomal enzymes)
Sites

Liver
Kidneys
Intestine
Adrenal cortex
Lungs
Placenta
Skin
Process
Drug enters the liver

Form as metabolites
Drugs which
undergoes
biotransformation
reaction became less
Systemic circulation lipid soluble, hence
not be reabsorbed
from renal tubules
and get excreted
Site of action
Contd.

Drug which undergoes biotransformation reactions

may have three consequences

1. Inactive drug to active metabolite

2. Active drug to inactive metabolite

3. Active drug to active metabolite

 Inactive drug to active metabolite-

Ex-I-dopa (Prodrug) Dopamine

Talampicillin Ampicillin

Active drug to inactive metabolite

Ex- Pentobarbitone 5- hydroxy pentobarbitone
 Active drug to active metabolites

Ex- Diazepam Oxazepam

Imipramine Desimipramine
Propranolal 5-Hydroxy propranolol
Codeine Morphine
 First pass metabolism
Mean the drug get metabolized before enter the systemic
circulation

1. I.V administration of xylocaine used in combating

arrhythmias

2. Sublingual administration of isosorbide mononitrate in

angina
What are biotransformation reactions??

Phase 1 reactions Phase II reaction

Oxidation Conjugation
Reduction
Hydrolysis
Microsomal enzymes-
Glucuronyl transferase
Microsomal enzymes-
Cytochrome p-450 Non microsomal enzymes-
N-acetyl transferase,
Non microsomal enzymes- Glutathione S transferases
Monoamine oxidase
 Phase I reactions
Oxidation
Microsomal oxidation Non microsomal oxidation
(cyp-450, NADPH and oxygen)- (MAO, aldehyde dehydrogenase)

Epinephrine
Pentobarbital MAO
Hydroxypentobarbital vinyl mendalic acid
Morphine
Alcohol
Nor morphine
Codeine AD
Morphine acetaldehyde
 Reduction

Microsomal reduction Nonmicrosomal reduction

(cyt-c-reductase, NADPH)
Chloral hydrate
Chloramphenicol Trichlor ethanol
Arylamine metabolities

Cortisone
Hydroxycortisone
 Hydrolysis
Microsomal hydrolysis-
Esterase
Pethidine Pethidinic acid

Non microsomal hydrolysis (Proteases and peptidase)

Hydrolysis of Beta lactam ring of penicillin

Hydrolysis of procinamide
Phase II to reaction

Microsomal conjugation (Glucuronide cojugation)-

(UDPGA and Glucuronyl transferase)

Paracetamol
Aspirin
Sulfonamides

Drug + UDPGA Drug glucuronide + UDP

GA
 Non microsomal conjugation
N-acetyl conjugation or Acetylation(N-acetyl transferase
and acetyl coA)
Ex- Isoniazide, Dapsone, PAS

Glutathione conjugation (glutathione-S-transferase)

Ex- Ethacrynic acid

Many anti-cancer drugs also under non-microsomal

conjugation (Ribonucleoside synthesis)
Enzyme inducers and enzyme inhibitors
Several drugs after repeated administration will stimualte the
endoplasmic reticulum which induces enzyme activty and few
drugs will decrease enzyme activity

Enzyme inducer
Ex- Unwanted pregnancy can results even in the use of oral
contraceptive pills comitantly with phenytoin or rifampacin

Patient on enzyme inducing drug like barburates would need high

doses of anti-coagulantes like warfarin
Enzyme inhibitor
Unexpected nausea and vomiting due to

theophylline with concomitantly administered

chloramphenicol

Severe respiratory depression with morphine when

given with MAOIs
Factors affecting metabolism
Age- Neonates have low microsomal activity
because poor development of liver so
chloramphenicol is contraindicated in neonates
(Gray baby syndrome).

Genetic variation- Atypical pseudocholine esterase

in few people cant metabolise succinyl choline
(prolonged aponea)
 Disease state- Hepatic disorders like hepatitis, liver
cirrhosis leads to drug poisoning (poor
biotransformation process)

Drug- Drug interaction- Under points of enzyme

inducers and inhibitors