METABOLISM OF DRUG

METABOLISM OF DRUG

Q. 1 Regarding Phenytoin all the following are correct, Except:
 A It acts on voltage sensitive neuronal Na., channels
 B Used by slow IV injection in status epilepticus
 C Kinetics change from 1st order to 0 order over therapeutic range
 D It inhibits microsomal enzymes
Q. 1 Regarding Phenytoin all the following are correct, Except:
 A It acts on voltage sensitive neuronal Na., channels
 B Used by slow IV injection in status epilepticus
 C Kinetics change from 1st order to 0 order over therapeutic range
 D It inhibits microsomal enzymes
Ans. D

Explanation:

It inhibits microsomal enzymes


Q. 2

About biotransformation untrue is –

 A

Inactive metabolites are formed

 B

Active metabolites are formed

 C

More fat soluble metabolites are formed

 D

More Hp soluble metabolites are formed

Ans. C

Explanation:

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.

Q. 3 CYP-450 inducers are –

 A

Cimetidine

 B

Ketoconazole

 C

Phenobarbitone

 D

All

Ans. C

Explanation:

Ans. is ‘c’ i.e., Phenobarbitone

Drugs that induce microsomal enzymes

o Phenobarbitone o Rifampin

o Isoniazid

o Phenylbutazone o DDT

o Carbamezepine

o Clofibrate

o Ritonavir

o Chronic alcohol intake

o Cyclophosphamide

o Phenytoin

o Glucocorticoids

o Chloral hydrate o Griseofulvin

o Omeprazole

o Meprobamate

o Glutethimide

o Cigarette smoking

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.


Q. 4 An antimetabolite which undergoes biotransformation to form an inhibitor of DNA polymerase is –

 A

Vinablastine

 B

Cytosine arabinoside

 C

Methotrexate

 D

Chlorambucil

Ans. B

Explanation:

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.


Q. 5 Phase 1 biotransformation includes ‑

 A

Reduction

 B

Acetylation

 C

Sulfate conjugation

 D

Methylation

Ans. A

Explanation:

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 :

 – Oxidation

 – Hydrolysis

 – Decyclization

 – Reduction

 – 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 or conjugation) reaction

* Metabolism involves the 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

 – Acetylation

 – Glutathione conjugation

 – Nucleotide synthesis

 – Glucuronide conjugation

 – Sulfate conjugation

 – Glycine conjugation

 – Methylation


Q. 6 About biotransformation not true ‑

 A

Active metabolite generation

 B

Polar to less polar

 C

Less polar to more polar

 D

Generate active drug from prodrug

Ans. B

Explanation:

Ans. is ‘b’ i.e., Polar to less polar


Q. 7

All of the following are true about biotransformation except

 A

It means chemical alteration of the drug in body

 B The primary site for drug metabolism is liver

 C

Phase I biotransformation reactions are nonsynthetic

 D

Products of phase II biotransformation reactions are mostly active drug metabolites

Ans. D

Explanation:

Ans. is ‘D’ i.e., Products of phase II biotransformation reactions are mostly active drug metabolites

BIOTRANSFORMATION (METABOLISM)

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

Why drug transformation is necessary?

  • The 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 the tubular lumen and can be excreted.
  • But pharmacologically active organic molecules (drugs) tend to be lipophilic (nonpolar) and remain 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 the 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. Nucleotide synthesis
  4. Glucuronide conjugation
  5. Sulfate conjugation
  6. Glycine conjugation
  7. Methylation

Q. 8 Most common phase I biotransformation reaction is‑

 A Oxidation

 B

Hydrolysis

 C

Cyclisation

 D

Reduction

Ans. A

Explanation:

Ans. is ‘a’ i.e., Oxidation

Oxidation is the most important metabolizing reaction.


Q. 9

The Autopsy findings of a case of poisoning caused by inhalation of fumes for a few minutes in a person working in gold mining is represented in the picture below .Mechanism of action for poisoning is ? 

 A

Inhibition of acetylcholine

 B

Irreversible inhibition of selenoenzymes

 C

Inhibits protein syntheisis.

 D

Blocks Cytochrome enzyme P- 450.

Ans. D

Explanation:

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.

HCN poisoning

  • Acute hydrogen cyanide poisoning can result from inhalation of fumes from burning polymer products that use nitrile in their production, such as polyurethane, or vinyl.
    • Cyanides are used in many industries and thus are available to potential poisoners.
      • The main industries that use cyanides are:Mining of gold and Silver,Electroplating industry,pesticide industry
  • Cyanide poisoning is a form of histotoxic hypoxia because the cells of an organism are unable to create ATP, primarily through the inhibition of the mitochondrial enzyme cytochrome c oxidase.
  • Autopsy Findings
    • Hypostasis is said to be brick-red, due to excess oxyhaemoglobin (because the tissue are prevented from using oxygen) and to the presence of cyanmethaemoglobin.
    • There may be a smell of cyanide about the body, and a distinct odor of bitter almonds about the viscera especially in the skull cavity and the brain.
    • Internally the tissues may also be bright pink caused by the oxyhaemoglobin that cannot be utilized by the tissues – which is probably more common than the presence of cyanmethaemoglobin.
    • The stomach lining may be badly damaged and can present a blackened, eroded surface, by altered blood staining the stripped mucosa.The oesophagus may be damage, especially the mucosa of the lower third.
  CO poisoning Cyanide poisoning
Effect on ability of RBCs to transfer Oxygen Yes,it impairs No
Effect on mitochondria Effect not as much as Cyanide poisoning Complete and sustained blockade of cellular respiration inducing severe lactic acidosis
Type of Hypoxia Hypemic hypoxia is caused by the reduction of the oxygen carrying capacity of the blood.  
Histotoxic hypoxia because the cells of an organism are unable to create ATP, primarily through the inhibition of the mitochondrial enzyme cytochrome c oxidase.
Amount of exposure required Requires hours of exposure  Occurs within seconds or minutes of exposure
Post-mortem lividity Colour Cherry red Pinkish red
Treatment Oxygen Oxygen with Antidote like amyl nitrite,intravenous sodium nitrite, intravenous sodium thiosulfate and Hydroxocobalamin

Q. 10 Detoxification of drugs is controlled by ‑

 A

Cytochrome

 B

Cytochrome p450

 C

Cytochrome C

 D

Cytochrome A

Ans. B

Explanation:

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).


Leave a Reply

%d bloggers like this:
Malcare WordPress Security