Drug Metabolism (Biotransformation)

Question 1

Biotransformation Definiton ?

Answer 1

molecular alternation of a drug to make it inactivate and suitable for excretion from the body

Page-103

Question 2

Why Drug metabolism is necessary?

Answer 2

Drug=Polar & water soluble =Renal excretion
most of the drug=lipid soluble so if they depend on only renal excretion the time of action will be prolonged /

so need of a alternative way —-
lipid soluble=more polar(more water soluble) =more readily excreted products

page-103

Question 3

Organs of biotransformatiuon ?

Answer 3

1. liver-99%
2. lung
3. kidney
4. skin
5. blood
6. brain
7. eye
8. adrenal gland
9. spleen
10. leukocuytes
11. cardiac muscles

103

Question 4

Aims and Objectives of Biotransformation ?

Important of Biotransformation

Answer 4

1.Reducing lipid solubility
2.Alternating biological activity

page-104

Question 5

Alternating biological activity HOW ??

Answer 5

1.Active drug ————–Inactive drug
Morphine—-M-3-Glucoronide
2.Inactivate drug ————Active drug
Levodopa—–Dopamine
Talampicillin——-Ampicillin
3.Toxic drug ——–Less toxic
Morphine—–M-3-Glucoronide
4.Non toxic——–Toxic drug
Parathione—–Paraxone
Malathione—–Malaxone
5.One active drug ——- another active drugs
Codeine——Morphine
Morphine—–M-6-Glucoronide
Digitoxin——–Digoxin
Diazepam——Oxazepam
Spironolactone ——Canrenone

Question 6

Importance of prodrug ?

Answer 6

1. inc absorption
2. inc bioavailability of drug at its receptor
3. inc the specificity of drug action

4.Modify duration of action
5.Modify route of administration

6.dec tissue damage
7.dec offensive odor of the drugs
8.dec first pass metabolism

105 page

Question 7

Prodrug -Example ?

Answer 7

1. Levodopa—Dopamine
2. Talampicillin—Ampicillin
3. alpha methyl dopa— alpha methyl noradrenaline
4. prednisone—prednisolone
5. cholecalciferol—1-alpha-Cholecalciferol
6. zidovudin—Z triphosphate

page-106

Question 8

Phase-I reaction ?

Answer 8

Parent drug + Functional group (-OH,-NH2,-SH) = More polar metabolite (Inactivate)
* catbolic
* lose of activity
* retain of activity
* gain of activity

1.Lipid solubility dec
2.Not eliminated

Question 9

Phase-I reaction examples?

Answer 9

1. Codein —morphine
2. cortisone—hydrocortisone
3. acetic acid–ethanal–ethanol
4. Ach—Acetate+Choline
5. Adrenaline — Vanillyl mandelic acid (VMA)

Question 10

Phase Reaction-II ?

Answer 10

parent drug / phase-I metabolite
+endogenous substance(H2SO4+Acetic acid +Amino acid + Glucoronic Acid ) —- Drug-Conjugate complex— Polar–Excreted

Question 11

phase-II Recation example?

all Conjugation

Answer 11

1. Glucoronic acid conjugation
2. acetyl conjugation
   3.methyl conjugation
   4.sulphate conjugation
   5.amino acid conjugation

107

Question 12

Enzyme Induction definition ?

Answer 12

its the process of increasing synthesis and activity of hepatic microsomal enzymes by repeated administration of inducing drug/agent

111

Question 13

Mechanism of enzyme induction ?

Answer 13

Enzyme+DNA=synthesis of microbial enzymes(CytP450+Glucoronyl Transferase)= inc drug metabolism

112

Question 14

Significance of Enzyme Induction ?

Answer 14

1. Therapeutic failure of primary drug
   OCP using women if take Rifampicin(AntiTB DRug) - due to enzyme induction there will be Contraception failure

2.Development of tolerance
Repeated administration = Autoinduction = Tolerance

3.Development of toxicity
Rifampicin=enzyme induction=inc metabolism =hepatic toxicity

4.Disease may result by induction
5.Metabolism of some endogenous substance maybe inc

page-112

Question 15

Enzyme inducing Drugs ?

Answer 15

1. Rifampicin
2. Phenobarbitone
3. Phenytoin
4. Griseofulvin
5. Testesterone
6. Hydeocarbon
7. Cimetidine
8. Chloramphenicol

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