Professional Documents
Culture Documents
BIOTRANSFORMATION
PURPOSE
Major Purpose:
- Make the drug inactiveless toxic
- Remove it out of the body
How it is achieved?
- Phase 1 metabolism: inactivate.less souble.
- Phase 2: least soluble in lipid.excretable
How reducing lipid solubility helps in excretion?
- Glomerular filtration, tubular reabsorption
lipid soluble drugs diffuse back to blood
across tubular epithelium. Water soluble can
not!
prodrug
Inactive themselvesbecome active after
undergoing metabolism.
LDOPA
- Designed with a purpose in mind.
- DopamineparkinsonismBBB
- LDOPA crosses BBB. Converted to dopamine.
Esters..hydrolysisparent drug
Bacampicillin, talampicillinto ampicillin
Better absorbed better bioavailabilitylesser
frequency.better patient compliance
Lesser GI adverse effectssuper infection,
diarrhoea
Prodrug.
Metronidazole Benzoylate.
Metronidazole base is unpalatable.
Paediatric patientpoor acceptance.
Benzoylate is taste lessester..
Erthromycin base bitter ..esters
bland
Mandelamine (methenamine
mandelate).formaldehyde.acidic
pHrenal tubulesformalin itself
fixes cells! Urinary infectionurinary
antiseptic.
Cyp450? superfamily
Cyp450? Superfamily.
P450 =spectrophotometricpeak at the
wavelength of the absorption maximum
of the enzyme (450nm) when it is in the
reduced state and complexed withCO.
Based on the nature of the electron transfer
proteins CYPs can be classified into several
groups
- Microsomal P450 systems
- Mitochondrial P450 systems
- Bacterial P450 systems
- P450 onlysystems; CYP5(thromboxane
synthase),CYP8(prostacyclin synthase),
and CYP74A (allene oxide synthase).
Nomenclature
Genesencoding CYP enzymes, and the
enzymes themselves, are designated with the
abbreviationCYP followed by a number
indicating the gene family, a capital letter
indicating the subfamily, and another numeral
for the individual gene.
Italicise the name when referring to the gene.
Cyp 3A4 = enzyme
Cyp 3A4 = gene
3 = gene family, A= subfamily, 4 =
individual gene
TheHuman Genome Projecthas identified 57
humangenescoding for the various
cytochrome P450 enzymes.
CYP..
Enzyme inducers
Phenobarbitone
Phenytoin
Carbamazepine
Rifampicin
Alcohol
Tobacco smoke
Marijuana smoke
Onset 2 days, peak 2-3 weeks,
increase in smooth endoplasmic
reticulum
Rifampicin
Auto induction
Warfarin
Oral contraceptives
Phenobarbitone
Warfarin .stabilised on phenobarb,
if phenobarb withdrawn, fatal
hemorrhage.
- Oral contraceptives
Enzyme induction.
Phenytoin
Warfarin
Theophylline
Carbamazepine
Auto induction
Warfarin
But inhibits phenytoin metabolism
Smoking
Theophylline
Imipramine
Pentazocin
propranolol
Enzyme induction.
ETHANOL
- Chronic alcoholism, liver disease,
abnormal drug metabolism
- Acute ethanol administration
inhibit competition
Inhibit NADPH cytochrome P-450
reductase, the rate limiting step in
the oxidative biotransformation of
drugs; higher plasma levels of many
benzodiazepines;
also inhibit phase two reactions.
Enzyme induction.
Enzyme induction.