JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD B. Pharmacy II Year PHARMACOLOGY-I Previous Question Paper (July - 2021 - R17)

Routes of drug administration are broadly classified into two main categories: local routes and systemic routes.

Local Routes: These involve application at the site of action, such as topical (skin, mucous membranes), deeper tissues (intra-articular, retrobulbar), or arterial supply to a particular region.

Systemic Routes: These involve absorption into the systemic circulation to reach the site of action. They are further divided into:

• Enteral: Oral, sublingual/buccal, and rectal.
• Parenteral: Intravenous (IV), intramuscular (IM), subcutaneous (SC), and intradermal (ID).
• Inhalation: Gases or aerosols for systemic effect.
• Transdermal: Sustained release through the skin into the circulation.

Merits and Demerits of Parenteral Routes:

Parenteral administration refers to routes other than the alimentary canal, typically involving injection. The key advantages and disadvantages are:

Merits:

• Rapid Onset: Provides immediate action, especially via the IV route, which is critical in emergencies.
• High Bioavailability: Bypasses the first-pass metabolism in the liver and avoids degradation by gastric enzymes or acidic pH.
• Patient Compliance: Ideal for unconscious, vomiting, or uncooperative patients who cannot take oral medication.
• Precision: Allows for accurate titration of dosage and administration of drugs that are poorly absorbed or irritating to the gastrointestinal tract.

Demerits:

• Invasiveness: Requires sterile equipment and trained personnel; it is painful and can cause anxiety in patients.
• Infection Risk: Improper aseptic technique can lead to local abscesses or systemic infections.
• Irreversibility: Once injected, the drug cannot be retrieved, making it difficult to counter adverse reactions or toxicity.
• Cost and Convenience: Generally more expensive and less convenient for self-administration compared to oral dosage forms.
• Tissue Damage: Risk of nerve injury, hematoma, or tissue necrosis if the injection technique is incorrect or the drug is highly irritant.

Drug metabolism, or biotransformation, is the chemical alteration of drugs by the body, primarily in the liver. Its importance lies in converting lipid-soluble, non-polar drugs into more polar, water-soluble metabolites, which facilitates their excretion via kidneys or bile, thereby terminating their pharmacological action and preventing accumulation.

Metabolism occurs in two main phases:

Phase-I (Non-synthetic reactions): These reactions introduce or expose a functional group (-OH, -NH2, -SH, or -COOH) on the drug molecule, making it slightly more polar. These reactions are primarily catalyzed by the Cytochrome P450 (CYP450) enzyme system located in the endoplasmic reticulum. Key processes include:

1. Oxidation: The most common pathway, involving hydroxylation, dealkylation, or deamination.
2. Reduction: Less common, occurring under low oxygen tension, often involving azo or nitro groups.
3. Hydrolysis: Cleavage of ester or amide bonds by esterases or amidases, often occurring in the plasma or liver.

Phase-II (Synthetic or Conjugation reactions): If the Phase-I metabolite is not sufficiently polar for excretion, it undergoes conjugation. In this phase, an endogenous substrate is attached to the functional group created in Phase-I, resulting in a highly polar, pharmacologically inactive, and easily excretable conjugate. Key processes include:

1. Glucuronidation: The most significant pathway, involving the transfer of glucuronic acid from UDP-glucuronic acid by the enzyme UDP-glucuronosyltransferase.
2. Acetylation: Transfer of an acetyl group from Acetyl-CoA, catalyzed by N-acetyltransferase.
3. Sulfation: Transfer of a sulfate group from PAPS (3'-phosphoadenosine-5'-phosphosulfate) by sulfotransferases.
4. Glutathione conjugation: Important for detoxifying reactive electrophilic intermediates, catalyzed by Glutathione S-transferase.

While Phase-I reactions usually produce active or inactive metabolites, Phase-II reactions almost exclusively result in inactive, water-soluble compounds ready for renal elimination.