Jawaharlal Nehru Technological University Hyderabad B.Pharmacy II PHARMACOLOGY-I Previous Question Paper (March- 2022 - R17)

Metabolism (biotransformation) is the biochemical alteration of a drug within the body, primarily occurring in the liver. It involves converting lipid-soluble, non-polar drugs into more polar, water-soluble, and ionized metabolites to facilitate their excretion via the kidneys. This process involves Phase I reactions (oxidation, reduction, hydrolysis) and Phase II reactions (conjugation).

Enzyme Induction refers to the process where a drug or chemical increases the synthesis or activity of hepatic microsomal enzymes (specifically the Cytochrome P450 system). This leads to an increased rate of metabolism of the inducer itself or other co-administered drugs, often resulting in decreased pharmacological effect or therapeutic failure.

Key points of enzyme induction:

• Mechanism: Increased transcription of mRNA and synthesis of new enzyme protein.
• Consequences: Reduced plasma concentration of drugs, potential loss of therapeutic efficacy, and tolerance development.
• Examples: Phenobarbitone, Rifampicin, and chronic alcohol consumption induce CYP enzymes, accelerating the metabolism of drugs like oral contraceptives or warfarin.

Enzyme Inhibition refers to the process where a drug decreases the activity of hepatic microsomal enzymes. This leads to a reduced rate of metabolism of other drugs, causing their accumulation in the body, which can result in toxicity or exaggerated pharmacological effects.

Key points of enzyme inhibition:

• Mechanism: Competitive or non-competitive binding to the enzyme active site or destruction of the enzyme complex.
• Consequences: Increased plasma concentration of drugs, prolonged duration of action, and increased risk of adverse drug reactions.
• Examples: Cimetidine, Erythromycin, and Ketoconazole inhibit various CYP isoforms. For instance, Cimetidine inhibits the metabolism of Theophylline, potentially leading to theophylline toxicity.

Routes of administration are classified into three main categories: enteral, parenteral, and topical routes. Enteral routes include oral, sublingual, buccal, and rectal administration. Parenteral routes involve administration by injection, bypassing the gastrointestinal tract, and include intravenous (IV), intramuscular (IM), subcutaneous (SC), and intradermal (ID) routes. Topical routes include transdermal, inhalation, intranasal, and ophthalmic applications.

The parenteral route is defined by the direct injection of drugs into systemic circulation or tissues. Its advantages and disadvantages are as follows:

Advantages:

• Rapid onset of action: Particularly with intravenous administration, the drug reaches systemic circulation immediately, making it ideal for emergencies.
• High bioavailability: It avoids first-pass metabolism in the liver and degradation by gastric enzymes, ensuring 100% bioavailability for IV injections.
• Suitability for unconscious patients: It is the preferred route for patients who are vomiting, unconscious, or unable to swallow oral medications.
• Precise control: Dosage can be accurately titrated based on the patient's response, especially in continuous infusions.
• Drug stability: It allows for the administration of drugs that are poorly absorbed or inactivated by the gastrointestinal tract.

Disadvantages:

• Invasiveness and pain: The use of needles causes pain and discomfort, which may lead to poor patient compliance.
• Risk of infection: Improper sterilization or technique can introduce pathogens directly into the body, leading to sepsis or local abscesses.
• Irreversibility: Once administered, the drug cannot be retrieved or removed from the body, making it difficult to manage in cases of overdose or adverse reactions.
• Requirement for skill: Administration requires trained personnel, sterile equipment, and aseptic techniques, making it more expensive and less convenient than oral administration.
• Local tissue damage: Improper injection technique or the nature of the drug can cause local irritation, nerve damage, or tissue necrosis.