METABOLISM Flashcards
How can the drug be eliminated:
- Metabolism
- Excretion
- Redistribution
Metabolism synonyms
Biotransformation
Metabolism definition
Chemical alteration of the drug in the body. It is needed to inactivate the drug by making it ionized, water-soluble
Sites of metabolism
- Liver
- Lung
- Kidney and skin
- GIT
- Plasma cholinesterase (ChE)
Which drug is metabolised in the lung:
Nicotine
Which drug is metabolised in the kidney and skin
Vitamin D
Which drug is metabolised in the GIT:
Tyramine
Which drug is metabolised by the plasma cholinesterase
Succinylcholine
Types of metabolism in the liver
Phase I (non-synthetic) Phase II (Synthetic, conjucation)
What reactions happen in phase I
- Oxidation
- Reduction
- Hydrolysis
What reactions happen in phase II
- Glucuronic acid
- Acetylation
- Methylation
- Glycine
- Sulfation
Example of oxidation reaction
Ethyl alcohol —> acetaldehyde —-> acetic acid + H2O + CO2 + water
Example of reduction reaction
Chloral hydrate —-> trichloroethanol
Example of hydrolysis
Acetylcholine —-> acetic acid + choline
Example of drugs metabolised by glucuronic acid:
Asprin
Morphine
Chloramphenicol
Example of drugs metabolised by acetylation
Isoniazid
Procainamide
Hydralazine
Example of drugs metabolised by methylation
Noradrenaline
Example of drugs metabolised by addition of glycine
Asprin
Example of drugs metabolised by sulfation
Steroids
Results of phase I metabolism:
- Inactivation of drug
- Activation of inactive drug (prodrug)
- Maintain activation of the drug
- Toxication
Results of phase II metabolism
Usually inactivation except morphine-6-glucuronide
Most drugs enter Phase I then phase II while some drugs enter phase II directy like …..
Isoniazide
Types of cellular enzymes
- Microsomal enzymes
- Non-microsomal enzymes
Site of microsomal enzymes
In the sER or liver, kidney, lung and intestinal mucosa
Sites of non-microsomal enzymes
Cytoplasm and mitochondria in all tissue
Example of microsomal enzymes:
Monooxygenases, cytochrome P450, UGTs, epoxide hydrolases
Examples of non-microsomal enzymes
The esterases, amidases, some flavoprotein oxidases and most conjugases
What reactions does microsomal enzymes do?
Catalyze oxidation, reduction (phase I) and glucuronidation only (phase II)
What reactions does non-microsomal enzymes do?
Oxidation, reduction, hydrolysis (phase I)
All phase II except glucuronidation
Microsomal enzymes are inducible by ……..
drugs, diet and genetics
Non-microsomal enzymes are not inducible but
shows genitic variation
Factors affecting hepatic microsomal enzymes
- Hepatic microsomal enzyme inducers
- Hepatic microsomal enzyme inhibitors
- Age
- Disease
- Genetic defect
- Sex
Hepatic microsomal enzyme inducers action
Increase metabolism of other drugs , decrease their action
Increase their own metabolism, causes tolerance
Hepatic microsomal enzyme inducers examples
Phenobarbitone, phenytoin, carbamazepine, rifampicin, androgen and tobacco smoke
Hepatic microsomal enzyme inhibitors types
Specific/Direct
Non-specific/ Indirect
Specific hepatic microsomal enzyme inhibitors examples
Estrogen, cimetidine (ramitidine), valproic acid, erythromycin, ciprofloxacin, chloramphenicol.
Non-specific hepatic microsomal enzyme inhibitors examples
Hepatotoxic drugs and drugs decreasing hepatic blood flow as propranolol and cimetidine.
