METABOLISM OF DRUG

It inhibits microsomal enzymes

Ans. is ‘c’ i.e., More fat soluble metabolites are formed

• Biotransformation is needed to render nonpolar (lipid soluble) compounds polar (water soluble) so that they are not reabsorbed in the renal tubules and are excreted.

Ans. is ‘c’ i.e., Phenobarbitone

Remember

o All Barbiturates are enzyme inducers except secobarbital, which inhibits the enzyme.

o Acutely, ritonavir is an inhibitor, while with chronic (repeated) administration it acts as an inducer.

Ans. is ‘b’ i.e., Cytosine arabinoside

o Cytarabine is phosphorylated in the body to the corresponding nucleotide which inhibits DNA synthesis by inhibiting DNA polymerase.

Ans. is ‘a’ i.e., Reduction

Types of biotransformation reactions

• Biotransformation reactions (metabolism) of drugs can be classified :

A. Non-synthetic (phase I) reactions

• Metabolism brings about a change in the drug molecule by :

1. Oxidation
2. Hydrolysis
3. Decyclization
4. Reduction
5. Cyclization

• The new metabolite may retain biological activity or it may be an inactive metabolite.
• Oxidation is the most important metabolizing reaction.
• The most important enzyme for oxidation reaction is cytochrome P450.

B. Synthetic (phase H or conjugation) reaction

• Metabolism involves union of the drug with one of several polar (water-soluble) endogenous molecules that are products of intermediary metabolism, to form a water-soluble conjugate which is readily eliminated by kidney or, if the molecular weight exceeds 300, in the bile.
• Phase II metabolism almost invariably terminates biological activity, i.e. metabolites are usually inactive. o Reactions are

1. Acetylation
2. Glutathione conjugation
3. Neucleotide synthesis
4. Glucuronide conjugation
5. Sulfate conjugation
6. Glycine conjugation
7. Methylation

Ans. is ‘b’ i.e., Polar to less polar

Ans. is ‘d’ i.e., Products of phase II biotransformation reactions are mostly active drug metab liter

BIOTRANSFORMATION (METABOLISM)

• Most of the drugs are treated by the body as foreign substances (xenobiotics).
• Like other foreign substances (xenobiotics), body tries to eliminate drugs by various mechanisms for ridding itself of chemical intruders.
• Biotransformation means chemical alteration of the drug in the body.

Why drug transformation is necessary ?

• Kidney plays a pivotal role in terminating the activity of drugs.
• For renal excretion the drug tends to be polar (lipid insoluble/water soluble) so that it can not diffuse back from tubular lumen and can be excreted.
• But pharmacologically active organic molecules (drugs) tend to be lipophlic (nonpolar) and remains unionized or only partially ionized at physiological pH.
• Biotransformation is needed to render nonpolar (lipid soluble) compounds polar (water soluble) so that they are not reabsorbed in the renal tubules and are excreted.

Types of biotransformation reactions

• Biotransformation reactions (metabolism) of drugs can be classified :

A) Non-synthetic (phase I) reactions

• Metabolism brings about a change in the drug molecule by :

1. Oxidation
2. Hydrolysis
3. Decyclization
4. Reduction
   
5. Cyclization

• The new metabolite may retain biological activity or it may be an inactive metabolite.
• Oxidation is the most important metabolizing reaction.
• The most important enzyme for oxidation reaction is cytochrome P450.

B) Synthetic (phase II or conjugation) reaction

• Metabolism involves union of the drug with one of several polar (water-soluble) endogenous molecules that are products of intermediary metabolism, to form a water-soluble conjugate which is readily eliminated by kidney or, if the molecular weight exceeds 300, in the bile.
• Phase II metabolism almost invariably terminates biological activity, i.e. metabolites are usually inactive.
• Reactions are :

1. Acetylation
2. Glutathione conjugation
   
3. Neucleotide synthesis
4. Glucuronide conjugation
5. Sulfate conjugation
6. Glycine conjugation
7. Methylation

Ans. is ‘a’ i.e., Oxidation

Oxidation is the most important metabolizing reaction.

Ans:D.)Blocks Cytochrome enzyme P- 450.

The poisoning case shown in the picture above represents HCN poisoning as lividity shown is bright red(pinkish red) staining.

Ans. is ‘b’ i.e., Cytochrome p450 

• Cytochrome p450 enzymes are microsomal enzymes that are involved in phase I metabolism of many drugs. 
• Most of the drugs are metabolized by CYP 3A4 isoform.

Drug metabolizing enzymes

• The drug metabolizing enzymes are divided into two types :

1. Microsomal

• These are located on smooth endoplasmic reticulum primarily in liver, also in kidney, intestinal mucosa and lungs.
• Examples are monooxygenase, cytochrome P450, glucronyl transferase.
• They catalyze most of the oxidation, reduction, hydrolysis and glucuronide conjugation.
• They are inducible by drugs, diet and other agencies.

2.Non microsomal

• These are present in the cytoplasm and mitochondria of hepatic cells as well as in other tissues including plasma.
• Examples are flavoprotein oxidase, esterases, amidases and conjugases.
• They catalyze some oxidation and reduction, many hydrolysis and all conjugation except glucuronidation.
• They are not inducible but many show genetic polymorphism (acetyl transferase, pseudocholinesterase).