Introduction
Welcome back to Unit III – Pharmacodynamics part 2 from the MSc Chemistry 4th Semester syllabus (BAMU University – Introduction to Medicinal Chemistry).
🖇In Part 1, we studied the Mechanism of Drug Action – including enzyme stimulation, enzyme inhibition, antimetabolites, membrane-active drugs, and chelation.
👉 Now in Part 2, titled Pharmacodynamics Notes: Drug Metabolism & Inactivation – Phase I & II Reactions | MSc Chemistry 4th Sem BAMU – Part 2, we will focus on the second half of this unit: Drug Metabolism and Inactivation.
This section explains how our body handles drugs after they enter — how they are broken down, activated or inactivated, and finally eliminated.
Understanding drug metabolism is very important because:
- It decides how long a drug works in the body
- Explains why the same drug dose can work differently in different people
- Helps avoid side effects and drug toxicity
- Is important for exams as well as research and pharma careers
📚 Topics Covered in This Blog:
Introduction
Drug metabolism and Inactivation
- Drug Metabolism (Biotransformation)
- Factors Affecting Drug Metabolism
- Pathways of Drug Metabolism (Phase I & Phase II Reactions)
- Microsomal Enzyme Systems
- Excretion of Drugs & Metabolites
- Drug Inactivation
FAQs
This post is written in simple, easy-to-understand language, especially for BAMU MSc Chemistry students, but it will also help anyone preparing for all universities and also CSIR NET, GATE, GPAT, or other competitive exams.
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📗Drug metabolism and activation:
Factor affecting drug metabolism [metabolicreation (phase 1) and conjugation reaction (phase 2)]
#Drug metabolism: (biotrasformation)
Drug metabolism is the process by which the body chemically modifies drugs to make them more water-soluble for easy elimination. It primarily occurs in the liver but also in the kidneys, lungs, and intestines.
Metabolism serves two major purposes:
💊Drug Inactivation: Most drugs lose their activity after metabolism.
💊Pro-drug Activation: Some drugs (pro-drugs) become active only after metabolism.
The body eliminates drugs and their metabolites through different pathways, mainly via urine, but also through bile, saliva, sweat, lungs, and milk.
📗Factor affecting on drug metabolism
Drug metabolism mainly occurs in the liver through enzyme-catalyzed reaction, converting drugs into water-soluble forms for elimination.
Several factor influence the rate and efficiency of metabolism which can be categorized into physical physiological, genetic. environmetal. and drug related factors.
1)Physiological Factors:
i) Age:
Newborns and elderly individuals have reduced enzyme activity leading to slower metabolism.
ii)Sex
Harmonal differences affect drug metabolism.
iii) Liver Function:
Liver diseases (cirrhosis, hepatits) reduce drug metabolism, increasing toxcity risks.
iv) Nutritional status:
Protein and vitamins deficiencies. impair enzyme activity
2)Genetic Factor:
i)Enzyme polymerphism:
Genetic variations affect enzyme efficiency making some individuals fast or slow metabolizers.Examples:slow acetylators metabolize isoniazid-Slowly increasing side effects.
ii) Ethanic variations:
Some populations metabolize drug differently due to genetic factors.
3)Environmental factors:
i)Drug Interactions:
• Enzyme Induction (eg rifampicin. Phenobarbital) speed up metabolism.
• Enzyme Inhibition: reg grapefruit juice cimetidine) slows down metabolism, increasing drug levels.
(ii)smoking and alcohol:
• chronic alcohol use & smoking induce liver enzymes, speeding up metabolism
• Acute alcohol use inhibits metabolism, leading to toxicity.
iii)Pollutants:
Exposure to pesticides and heavy metals alters enzyme activity
4)Drug-Related Factors:
i) Done and frequency:
High dose or frequent use can saturate enzymes, reducing metabolism efficiency.
ii)Route Ad ministration:
- oral drug undergo first-pass metabolism the liver, reducing drug activity.
- Ⅳ drug bypass the liver initially, leading to delayed metabolism.
iii) Drug Solubility:
Lipophilic drug need metabolism for excretion, while hydrophilic drugs excreted easily.
First-Pass Effect (Presystemic Metabolism)
✔ Some drugs are metabolized in the liver before reaching circulation.
✔ This reduces the drug’s bioavailability.
✔ Example: Nitroglycerin undergoes extensive first-pass metabolism.
📗Pathways of Drug Metabolism
Drug metabolism occurs in two phases:
Phase 1: Functionalization Reactions
- ✔ These reactions introduce or modify functional groups (-OH, -NH₂, -COOH, -SH) to make the drug more polar.
- ✔ They are mainly catalyzed by Cytochrome P450 (CYP) enzymes.
Types of Phase 1 Reactions:
🔸️ Oxidation:
Adds oxygen or removes hydrogen.
Example: Paracetamol → Hydroxylated metabolite.
🔸️ Reduction:
Adds hydrogen or removes oxygen.
Example: Warfarin → Reduced Warfarin.
🔸️Hydrolysis:
Breaks ester or amide bonds using water.
Example: Aspirin → Salicylic Acid.
🔸️Dealkylation of Ether & Thioether:
Removes alkyl groups from sulfur or oxygen, forming acetals or thioacetals.
👉 Purpose: Converts drugs into more reactive or slightly water-soluble metabolites, which are further processed in Phase II.
Phase 2: Conjugation Reactions
- ✔ In this phase, drugs or Phase I metabolites are combined with a hydrophilic molecule to enhance excretion.
- ✔ These reactions increase water solubility and inactivate the drug.
Types of Phase 2 Reactions:
🔸️ Glucuronidation:
Adds glucuronic acid (most common pathway).
Example: Paracetamol → Paracetamol-glucuronide.
🔸️Sulfation:
Adds sulfate group (SO₄²⁻).
Example: Paracetamol → Paracetamol-sulfate.
🔸️ Acetylation:
Adds acetyl group (-COCH₃).
Example: Isoniazid → Acetylated Isoniazid.
🔸️ Methylation:
Adds methyl (-CH₃) group.
Example: Epinephrine → Metanephrine.
🔸️Glutathione Conjugation:
Adds glutathione (detoxification).
Example: Detoxification of Paracetamol metabolites.
🔸️ Glycine Conjugation:
Adds glycine to form water-soluble metabolites.
👉 Purpose: Converts drugs into highly water-soluble, inactive metabolites for easy elimination.
📗Microsomal Enzyme Systems in Drug Metabolism:
✔ Microsomal Reduction:
Reduction of azo and nitro groups by microsomal enzymes.
Example: Nitrazepam → 7-amino derivative.
✔ Alcohol Dehydrogenase:
Converts ethanol to acetaldehyde.
✔ Hydrolysis Enzymes:
Break down esters and amides in liver, kidney, and blood.
💊Excretion of Drugs & Metabolites
Drugs and their metabolites are mainly excreted via urine. Other excretion routes include:
✔ Bile – Important for excreting large, conjugated drugs.
✔ Saliva – Some drugs are excreted into saliva and swallowed.
✔ Lungs – Used for volatile drugs like anesthetics.
✔ Sweat – Some drugs exit through sweat glands.
✔ Milk – Certain drugs pass into breast milk.
💡Clinical Importance of Drug Metabolism
- Determines drug duration and effectiveness.
- Prevents drug accumulation and toxicity.
- Explains individual differences in drug response.
- Guides dose adjustments in liver diseases and enzyme deficiencies
📗Drug Inactivation:
Drug metabolism often leads to drug inactivation, meaning the drug loses its therapeutic effect.
Mechanisms of Drug Inactivation:
1. Metabolic Transformation:
Conversion into an inactive metabolite.
Example: Lidocaine → Inactive metabolite by the liver.
2. Conjugation (Phase II Reactions):
Converts drugs into highly polar forms that are easily excreted.
Example: Morphine → Morphine-glucuronide (inactive).
3. First-Pass Metabolism:
Some drugs are rapidly metabolized in the liver before reaching circulation.
Example: Propranolol, Nitroglycerin (extensive first-pass metabolism).
4. Enzyme Induction
Some drugs increase CYP enzyme activity, leading to faster metabolism and reduced effect.
Example: Rifampicin induces CYP enzymes, inactivating Warfarin faster.
💡Summary
In this part, we explored the factors that affect drug metabolism. From age, genetics, and diet to liver function and other drugs we take, each factor plays a big role in how quickly or slowly medicines are broken down in our body.
Think of it like this: 🧪 our body is a chemical factory, but not all factories work at the same speed. Some people metabolize drugs very fast, while others process them slowly — that’s why the same medicine can work differently in two people.
Understanding these factors is not only important for exams but also for real-life pharmacy and medical applications.
Frequently Asked Questions (FAQs):
Q: What is drug metabolism in pharmacodynamics?
Drug metabolism is the process by which the body modifies drugs for easy elimination, mainly in the liver.
Q: What are Phase I and Phase II reactions?
Phase I adds or modifies functional groups, while Phase II conjugates drugs with hydrophilic molecules for excretion.
Q:What are the main factors that affect drug metabolism?
The main factors are age, genetics, diet, liver function, and drug interactions. These decide how fast or slow a drug is broken down in the body.
Q:Why does age affect drug metabolism?
In newborns and elderly people, the liver and kidneys don’t work as efficiently. That’s why drug metabolism is slower compared to healthy adults.
Q:How do genetics influence drug metabolism?
Some people inherit faster or slower enzyme activity from their parents. This is why the same medicine may work differently for two people.
Q: Can food and diet change drug metabolism?
Yes ✅. Some foods like grapefruit juice or alcohol can speed up or slow down metabolism, changing how effective a drug will be.
Q:Why is liver function important in drug metabolism?
The liver is the main site where drugs are broken down. If the liver is weak or damaged, drug metabolism slows down, which may cause side effects.
Q:How do drug interactions affect metabolism?
Taking two or more medicines together can either speed up or block drug metabolism. That’s why doctors always check your prescriptions carefully.
Q:Why do the same drugs act differently in different people?
Because factors like age, genes, diet, health, and lifestyle make each person’s metabolism unique.
Q: Why is drug metabolism important in MSc Chemistry?
It explains how drugs act in the body and is a key exam topic for medicinal chemistry and pharmacology.
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