Metabolism Flashcards
Is the chemical transformation of the drug by the biological environment to form metabolites
Drug metabolism or biotransformation
Objective of drug metab is to convert xenobiotics to a (4)
less active
less toxic
polar
readily excretable form
Exception of drug metab (3)
Inactive (prodrug) to active form
Active to active metabolites
Non-toxic to toxic form
What is the active form of chloral hydrate
Trichloroethanol
Active metabolites of amitriptyline
Nortriptyline
Hepatotoxic metabolite of paracetamol
NAPQI
N-acetyl-p-benzo-quinone imine
Detoxification of paracetamol convert by glutathione into
Mercapturic acid
initial metabolism that happens before a drug reaches the systemic circulation
• These are drugs with high extraction ratio (ER) in the liver.
First-Pass Metabolism
drugs with high extraction ratio (ER) - significant portion will metabolize (5)
(PCMMP)
Propranolol
Catecholamines
Meperidine
Morphine
Pentazocine
Phase 1 reaction also called (2)
Functionalization
Asynthetic
Conversion of drugs to active form by
addition or unmasking of a functional group.
Attach small polar grp to drug structure
Phase 1
3 Chemical Reactions
Oxidation
Reduction
Hydrolysis
Redox reaction
(GEROA) (LEORA)
Oxidation-reduction
Gain electron = reduction, oxidizing agent
Lose electron = oxidation, reducing agent
Most common reaction in all metabolic process (phase 1 & 2 )
Oxidation
What do you call the family of oxidative enzyme
Mixed function oxidases (MFO)
Cytochrome P-450 subfamily that is predominant in pediatrics
CYP3A7
Cytochrome P-450 subfamily that is predominant to adults
CYP3A4
Cytochrome P-450 subfamily that metabolizes antidepressants
CYP2D6
Cytochrome P-450 substrate (drugs) with 1A2 subfamily (4)
Induced by (2)
Acetaminophen
Theophylline
Warfarin
Caffeine
Induced by:
Omeprazole
benzopyrene (charred meat)
Cytochrome P-450 substrate (drugs) with 2C9 subfamily (3)
Phenytoin
Tolbutamide
Warfarin
Cytochrome P-450 substrate (drugs) with 2C19 subfamily (2)
Propranolol
Omeprazole
Cytochrome P-450 substrate (drugs) with 2D6 subfamily (4D)
Debrisoquin
Thioridazine
Haloperidol
Dextrometorphan
Cytochrome P-450 substrate (drugs) with 3A4 subfamily (8)
(MATAGA CD)
50% of drugs:
Acetaminophen
Astemizole
Macrolides
Terfenadine
Grapefruite juice
Amiodarone
Cortisol
Diazepam
Subject to enzyme inhibition/induction
MAO A selective metabolizes what (2)
Tx for _____
Give ex of drugs: (2)
Norepi
Serotonin
Antidepressants
Florgiline
Meclobemide
MAO B selective metabolizes what (1)
Tx for _____
Give ex of drugs: (2)
Dopamine
Parkinstons Disease
Selegiline
Rosagiline
MAO nonselective drug ex (3)
(TIP)
Tranylcypromine
Phenelzine
Isocarboxazid
Alcohol dehydrogenase inbitor ex(drug)
Fomepizole
Aldehyde dehydrogenase inhibitor drug ex
Disulfiram (Antabuse)
Drug that undego nitro reduction
DOC for typhoid fever
Chloramphenicol
Drug that undego carbonyl reduction
It is antidote for opioid toxicity
Naloxone
(4) ester drug that undergo hydrolysis
It stays at_____
(PACE)
Procaince
Aspirin
Cocaine
Enalapril
Plasma
(3) amide drug that undergo hydrolysis
It stays at_____
(LIP)
Lidocaine
Indomethacin
Procainamide
DOC for Patent Ductus Arteriosus (PDA) in premature infants
Indomethacin
Reactions generally involved in the inactivation of a drug and formation of its polar form
Collect complex molar grp
Phase 2
Phase 2 also called (2)
Conjugation
Synthetic
Most abundant process in phase 2
Most abundant in adult
Least abundant in Neonates
Glucuronidation
Enzyme of Glucuronidation
UDP-glucuronosyltransferase
Most abundant process in neonates
Sulfate conjugation
Enzyme involved in Sulfate conjugation
Sulfotransferase
Enzyme involved in glycine conjugation
N-acyltransferase
Tripeptide involve in glutathione conjugation
Glutamine
Cysteine
Glycine
Enzyme involve in glutathione conjugation
Glutathione-S-transferase
Enzyme involve in acetylation ____
Give (4) ex of drug
N-acetyltransferase
(HIPS)
Hydralazine
Isoniazid
Procainamide
Sulfonamide
Enzyme involve in metylation ____
Give ex (1)
Methyltransferase
Catecholamines
ENZYME INDUCERS
( CrOP GPSs)
Carbamazepine
Chronic Alcoholism
Rifampicin
Omeprazole
Phenobarbital
Griseofulvin
Phenytoin
Smoking
St. John’s Wort
ENZYME INHIBITORS
(SIiCK FACES 3D CGV)
Sodium Valproate
Isoniazid
Indinavir
Cimetidine
Ketoconazole
Fluconazole
Alcoholism
Chloramphenicol
Erythromycin
Sulfonamides
Diltiazem
Disulfiram
Diphenhydramine
Ciprofloxacin
Grapefruit juice
Verapamil
Genetic polymorphism- enzyme expression that produce normal/adequate amount of enzymes
EM: Extensive Metabolizers
Genetic polymorphism- enzyme expression that produce more than the normal amount of enzymes
UM: Ultra-rapid metabolizers
Genetic polymorphism- enzyme expression produce less than the normal amount of enzymes
PM: Poor metabolizers
Races that has fast metabolism
Filipinos
Orientals
Eskimos
Races that has slow metabolism
Africans
Americans
Caucasians
