Test: General Pharmacology - 2 - NEET PG MCQ

In elderly individuals, the volume of distribution (V_d) is elevated due to a higher total body fat percentage and reduced plasma protein binding of medications. In paediatric patients, there is also an increased volume of extracellular fluid, which results in a greater distribution volume for highly ionised drugs. Consequently, a larger initial dose may be necessary to reach the desired blood concentration. In obese patients, the V_d is increased because of an excess of adipose tissue. During pregnancy, blood volume rises by approximately 30-40%. Although the total protein levels increase, the concentration of plasma proteins decreases, which in turn affects the V_d.

• Prodrug Active form
• Enlapril
• Enalaprilat
• Dipivefrine
• Epinephrine
• Mercaptopurine
• Methylmercaptopurine

• Propranolol and lidocaine experience substantial first-pass hepatic metabolism.
• Theophylline is largely metabolised in the liver through demethylation and oxidation.
• Tricyclic antidepressants (TCAs) are also extensively broken down in the liver; for imipramine and amitriptyline, the primary metabolic pathway is demethylation, leading to the formation of active metabolites desipramine and nortriptyline, respectively.
• Ampicillin is partially excreted in bile, with enterohepatic circulation occurring.

The effect of a drug can be ended either through hepatic metabolism or renal excretion. Most medications are rendered inactive by metabolic processes. However, certain drugs can be converted from an inactive state (known as pro-drugs), and others may generate active metabolites. Additionally, some drugs can exert their effects beyond the bloodstream; for instance, digoxin exits the blood and enters the heart to perform its function.

The reduction in the quantity of a drug prior to its entry into the systemic circulation is referred to as first pass metabolism (commonly known as the first pass effect). In contrast, if the drug's amount diminishes after it has entered the systemic circulation, this process is termed elimination.

• Elimination encompasses both excretion and metabolism.

Inhalational anaesthetic agents, such as halothane, are utilised in clinical practice by adjusting the dosage based on the patient’s response.

Strong electrolytes (such as strong acids and strong bases) are completely ionised in all environments, regardless of whether they are acidic or basic. Weak acids, on the other hand, ionise in alkaline environments and are readily excreted.

Diclofenac is an acidic medication and remains non-ionised in the acidic environment of the stomach. As a result, it has the greatest likelihood of being absorbed from the stomach. The other medications provided in the options are basic substances that become ionised at gastric pH.

If a medication is significantly bound to plasma proteins, it is more prone to remain within the bloodstream. Therefore, its volume of distribution (V_d) will be reduced. Low ionisation promotes the dispersal of a drug, as unionised molecules are capable of traversing the membranes of blood vessels and tissues. Drugs that are more lipid soluble can readily cross these membranes and are more likely to be widely distributed.

After filtration through the glomerulus, a drug may experience two processes (tubular reabsorption and tubular secretion) prior to elimination from the body, known as renal clearance.

• If 100 mg of a drug is filtered by the glomerulus and the renal clearance is 150 mg, this indicates that an additional 50 mg originates from elsewhere, suggesting that tubular secretion must be occurring.
• However, we cannot conclude that reabsorption is absent, as it is possible for 20 mg to be reabsorbed while 70 mg is secreted, resulting in the same outcome.

• Conversely, if 100 mg of a drug is filtered and the renal clearance is only 50 mg, this implies that 50 mg must have been absorbed back, indicating that tubular reabsorption is indeed taking place.
• Again, we cannot assert that tubular secretion is not happening in this scenario.

• Lipid-soluble drugs tend to be reabsorbed,
• whereas water-soluble drugs are readily excreted.

Drugs that are highly soluble in lipids, such as thiopentone, are rapidly distributed to tissues with a rich blood supply, such as the brain. If the organ targeted also has a high blood flow, the action of the drug will occur very swiftly. This is true for general anaesthetics like thiopentone.

Subsequently, the drug will be distributed to less vascularised tissues, such as fat and muscle. The drug's movement away from the brain leads to the cessation of its effects. This phenomenon is referred to as redistribution.

The transdermal route is utilised for drugs that are highly lipid soluble and can penetrate intact skin. The dimensions of the pores in a transdermal patch are modified to ensure a consistent and smooth absorption of the drug. This results in a delayed and lower peak in plasma concentration. Since the drug enters the bloodstream directly, first-pass metabolism is circumvented.

When a medication is significantly bound to plasma proteins, it tends to remain in the bloodstream, resulting in a lower volume of distribution (V_d). Glomerular filtration is influenced by renal blood flow as well as plasma protein binding.

• Drugs that are highly bound to proteins are less likely to be filtered by the glomerulus.
• Because of non-specific binding sites on plasma proteins, these medications are prone to various drug interactions.

Most phase I reactions and glucuronide conjugation (Phase II reaction) are facilitated by microsomal enzymes. These enzymes can be either induced or inhibited by various drugs.

Acetylation is performed by N-acetyl transferase, which is a non-microsomal enzyme.

• It prolongs the effects of medications that are metabolised by these enzymes.

• Displacement from binding sites leads to an increase in the free drug, allowing for rapid metabolism.