JNTU B.Pharmacy III PHARMACOLOGY-I Previous Question Paper (February-2022 - R17)

Routes of administration are the paths by which a drug is brought into contact with the body. They are broadly classified into enteral and parenteral routes.

1. Enteral Routes

These involve the gastrointestinal tract.

• Oral: The most common route. Advantages: Convenient, non-invasive, economical, and safe. Disadvantages: Slow onset of action, subject to first-pass metabolism, may cause gastric irritation, and cannot be used in unconscious patients.
• Sublingual/Buccal: Drug is placed under the tongue or in the cheek pouch. Advantages: Rapid absorption, avoids first-pass metabolism. Disadvantages: Limited to lipid-soluble drugs, may cause local irritation.
• Rectal: Used for systemic or local effects. Advantages: Useful in vomiting or unconscious patients, avoids partial first-pass metabolism. Disadvantages: Inconvenient, absorption can be irregular or incomplete.

2. Parenteral Routes

These bypass the gastrointestinal tract, providing faster onset.

• Intravenous (IV): Drug is injected directly into the vein. Advantages: Immediate onset, 100% bioavailability, suitable for large volumes. Disadvantages: Risk of infection/embolism, cannot be reversed once injected, requires skilled personnel.
• Intramuscular (IM): Injection into skeletal muscle. Advantages: Faster than oral, suitable for depot preparations. Disadvantages: Painful, risk of nerve damage, limited volume.
• Subcutaneous (SC): Injection into the loose connective tissue. Advantages: Self-administration possible (e.g., insulin). Disadvantages: Slower absorption than IM, limited to non-irritant drugs.

3. Other Routes

• Inhalation: Used for gaseous or volatile drugs. Advantages: Rapid absorption due to large surface area of alveoli. Disadvantages: Requires specialized equipment, risk of local irritation.
• Topical: Applied to skin or mucous membranes for local effect. Advantages: High local concentration, minimal systemic side effects. Disadvantages: Poor absorption through intact skin.
• Transdermal: Slow, sustained release through skin patches. Advantages: Constant plasma levels, avoids first-pass metabolism. Disadvantages: Slow onset, risk of contact dermatitis.

Drug metabolism, primarily occurring in the liver, is divided into Phase I (functionalization) and Phase II (conjugation) reactions to convert lipophilic drugs into more polar, water-soluble metabolites for excretion.

Phase I Reactions: These reactions introduce or expose a functional group (-OH, -NH2, -SH, or -COOH) on the drug molecule, making it slightly more polar and providing a handle for subsequent conjugation. The primary mechanism involves the Cytochrome P450 (CYP450) monooxygenase system located in the smooth endoplasmic reticulum.

• Oxidation: The most common reaction, involving the addition of oxygen. Examples include hydroxylation of aromatic rings, N-dealkylation, O-dealkylation, and S-oxidation.
• Reduction: Less common than oxidation, occurring typically under low oxygen tension. Examples include the reduction of azo groups or nitro groups.
• Hydrolysis: Mediated by esterases and amidases in the plasma and tissues, involving the cleavage of ester or amide bonds by the addition of water.

Phase II (Conjugation) Reactions: These reactions involve the covalent attachment of an endogenous polar molecule to the drug or its Phase I metabolite. This process generally results in pharmacologically inactive and highly water-soluble compounds that are readily excreted via urine or bile.

• Glucuronidation: The most important conjugation pathway, catalyzed by UDP-glucuronosyltransferases (UGTs), which transfer glucuronic acid from UDP-glucuronic acid to the drug.
• Sulfation: Catalyzed by sulfotransferases (SULTs), transferring a sulfate group from PAPS (3'-phosphoadenosine-5'-phosphosulfate) to hydroxyl or amino groups.
• Acetylation: Catalyzed by N-acetyltransferases (NATs) using Acetyl-CoA as a cofactor, common for drugs containing primary amino groups.
• Glutathione Conjugation: Catalyzed by Glutathione S-transferases (GSTs), this reaction is critical for the detoxification of reactive electrophilic intermediates, protecting cells from oxidative stress.
• Methylation: Catalyzed by methyltransferases, typically using S-adenosylmethionine (SAM) as the methyl donor; unlike other conjugation reactions, this often decreases the water solubility of the drug.

While Phase I reactions often activate or modify the drug, Phase II reactions represent the final detoxification step, ensuring the metabolite is sufficiently polar for renal or biliary elimination.