1 / 11

DRUG METABOLISM OR BIOTRANSFORMATION 2

An introduction to pharmacy

Ndubueze
Download Presentation

DRUG METABOLISM OR BIOTRANSFORMATION 2

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. DRUG METABOLISM OR BIOTRANSFORMATIONCONTINUED Dr. Kenneth Orimma B.Sc., M.Sc., M.B.B.S, D.I.R, D.M(Doctor of Medicine) Psychiatry

  2. DRUG METABOLISM OR BIOTRANSFORMATION CYP2D6  • This is the next most important CYP isoenzymewhich metabolizes nearly 20% drugs including tricyclic antidepressants, selective serotonin reuptake inhibitors, many neuroleptics, antiarrhythmics, βblockers and opiates. • Inhibition of this enzyme by quinidine results in failure of conversion of codeine to morphine → loss of analgesic effect of codeine. • Human subjects can be grouped into ‘extensive’ or ‘poor’ metabolizers of certain drugs example metoprolol and debrisoquin. • The poor metabolizers have an altered CYP2D6 enzyme and exhibit low capacity to hydroxylate many drugs.

  3. DRUG METABOLISM OR BIOTRANSFORMATION CYP2C8/9  • Important in the biotransformation of >15commonly used drugs including phenytoin, warfarin which are narrow safety margin drugs, as well as ibuprofen and tolbutamide. CYP2C19  • Metabolizes > 12 frequently used drugs including omeprazole, lansoprazole. • Rifampicin and carbamazepine are potent inducers of the CYP2C subfamily.

  4. DRUG METABOLISM OR BIOTRANSFORMATION CYP1A1/2  • Though this subfamily participates in themetabolism of only few drugs like theophylline, it is more important for activation of procarcinogens. • Apart from rifampicin and carbamazepine, polycyclic hydrocarbons, and cigarette smoke are its potent inducers of this isoenzyme group. CYP2E1  • It catalyzes oxidation of alcohol and formationof minor metabolites of few drugs, notably the hepatotoxic benzoquinone mine from paracetamol; chronic alcoholism induces this isoenzyme.

  5. OTHER REACTIONS

  6. DRUG METABOLISM OR BIOTRANSFORMATION Reduction  • This reaction is the converse ofoxidation and involves cytochrome P450 enzymes working in the opposite direction. Alcohols, aldehydes, quinones are metabolized by reduction reaction. • Other drugs primarily reduced are chloralhydrate, chloramphenicol, halothane, warfarin.

  7. DRUG METABOLISM OR BIOTRANSFORMATION Hydrolysis  • This is cleavage of drug molecule by taking up a molecule of water catalyzed by enzyme esterase. • Ester + H2O ————→ Acid + Alcohol  • Similarly, amides and polypeptides are hydrolyzed by amidases and peptidases. • In addition, there are epoxide hydrolases which detoxify epoxide metabolites of some drugs generated by CYP oxygenase. • Hydrolysis occurs in liver, intestines, plasma and other tissues. Examples are choline esters, procaine, lidocaine, procainamide, aspirin, carbamazepine, epoxide, pethidine, oxytocin.

  8. DRUG METABOLISM OR BIOTRANSFORMATION Factors affecting in Drug metabolism • Many factors affect the rate and pathway of metabolism of drugs. • The major influences can be sub-divided into internal (physiological and pathological) and external (exogenous) factors • Internal: species, genetic, sex, age, hormones, pregnancy, disease. • External: diet, environment.

  9. DRUG METABOLISM OR BIOTRANSFORMATION Factors affecting in Drug metabolism 1-Genetic abnormality • Due to the difference genetically in amount of CYP 450 available in the liver, there is individual differences in drug metabolism 2- Enzyme induction or Inhibition Enzyme Inhibition • Enzyme inhibition is the most frequently observed result of CYP modulation and is the primary mechanism for drug–drug pharmacokinetic interactions. Enzyme Induction • Induction of drug-metabolizing activity can be due either to synthesis of new enzyme protein or to a decrease in the proteolytic degradation of the enzyme.

  10. DRUG METABOLISM OR BIOTRANSFORMATION 3- Age • Generally, older age is associated with increased blood concentrations of drugs and altered metabolism, reduced effectiveness, and increased risk of adverse reactions for many medications. • Impaired response to pharmacotherapeutic agents is a critical yet underemphasized aspect of older age, more especially with increased risk of comorbid conditions and need for polypharmacy with aging. 4- Pathological conditions • Pathological factors can modify drug response through effects on receptor sensitivity or changes in the concentration of active drug at receptors due to abnormalities in drug absorption, distribution or elimination. • The absorption of drugs injected either subcutaneously or intramuscularly is likely to be accelerated in patients with peripheral vasodilatation caused by exercise, fever, anemia, thyrotoxicosis, Paget's disease, hypercarbia, liver disease etc.

  11. THE END THANK YOU

More Related