Test: General Pharmacology - 1 - NEET PG MCQ

• Amiodarone
• Terfenadine
• Astemizole
• Cisapride
• Cyclosporine
• Tacrolimus
• Lovastatin and other statins
• Calcium channel blockers
• Midazolam
• Protease inhibitors

Phenobarbitone is a barbiturate that originates from barbituric acid, a weakly acidic medication. Its elimination can be improved by alkalinising the urine.

Morphine, atropine, and amphetamines are classified as basic drugs.

• This indicates a potential interaction between these two medications.
• However, none of these enzymes were included in the options provided.
• It leaves us uncertain about what the examiner expects students to learn.
• Should students focus on clinically significant aspects or delve into the rarest details?

• After extensive searching, we discovered that this enzyme (CYP2C9) was formerly referred to as CYP2C10.
• Therefore, the correct answer from the available options should be CYP2C10.
• Nonetheless, we recommend remembering CYP2C19, as it holds greater clinical relevance.

Table 7-3 in Goodman and Gilman 12/e p159 clearly states that CYP2D6 is involved in the metabolism of beta blockers, while CYP3A4 is responsible for the metabolism of calcium channel blockers. The polymorphism of P-glycoprotein reduces the AUC of digoxin.

On page 1976 of Goodman and Gilman, it is noted that irreversible oxidative metabolites of simvastatin are formed by CYP3A enzymes. Another point that may confuse students is that simvastatin metabolites can undergo glucuronide conjugation.

• This is accurate, but the drug ceases to be simvastatin.
• The clinical significance of this is that if another drug or substance activates UGT glucuronyl transferase, it will not influence the activity of simvastatin.
• Conversely, if a drug is directly conjugated with glucuronide molecules, the inducers of the UGT enzyme will impact the drug's plasma concentration.

Metabolic reactions can be categorised into phase I (non-synthetic) and phase II (synthetic) reactions. Phase I reactions comprise:

• oxidation
• reduction
• hydrolysis
• cyclisation
• decylisation

In contrast, phase II reactions consist of:

• glucuronidation
• acetylation
• methylation
• sulfation
• glycine conjugation

Acidic medications primarily attach to albumin, while basic medications associate with alpha-1 acid glycoprotein. Drugs with a high protein plasma binding (PPB), such as sulfonamides, can displace other medications that are bound to the same site, potentially leading to toxicity.

Sex steroids connect to both steroid hormone binding globulin and albumin.

For poisonings caused by acidic drugs (such as barbiturates, salicylates, and methotrexate), agents that alkalinise urine are recommended. In contrast, for poisonings linked to basic drugs (including morphine, amphetamine, and atropine), agents that acidify urine are given.

• NADPH cytochrome P450 reductase is identical to flavin monooxygenase.
• Cytochrome oxidase plays a role in the respiratory chain but not in drug metabolism.
• CYP3A4 accounts for the metabolism of 50% of prescription medications processed by the liver.

Ionised molecules are unable to traverse biological membranes. Consequently, they are less probable to be absorbed.

The passage of these molecules through the blood-brain barrier and the blood-placental barrier is also limited.

Such drugs cannot be reabsorbed in the nephron, leading to their excretion by the kidneys.

pKa represents the pH level at which half of the drug exists in its ionised state. The ionisation of a drug shows the greatest variability around its pKa value. Phenobarbitone is classified as an acidic drug with a pKa of 7.2. Consequently, at a pH of 7.2, 50% of the drug is ionised while the other 50% remains un-ionised. In an acidic environment, a larger proportion will be un-ionised (due to its acidic characteristics). In plasma, with a pH of 7.4, a greater percentage will be ionised (60%) compared to those that are un-ionised (40%).

Acidic medications attach to albumin, while basic medications connect to α₁ acid glycoprotein. It is the unbound form of the medication that undergoes metabolism or excretion. The bound form is unavailable for either metabolic processes or excretion.

• Numerous medications can occupy the same plasma protein binding site, leading to displacement reactions.
• As plasma concentration rises, both free and bound forms of the drug will increase in the plasma.

All medications mentioned in the options are extensively bound to plasma proteins (>90%), while morphine exhibits a binding rate of only 35% to plasma proteins.

• Passive diffusion and filtration
• Specialised transport

• Active transport
• Facilitated diffusion

The significant protein binding of a medication restricts it to the vascular compartment, which consequently tends to reduce its volume of distribution. It acts as a long-acting drug since the bound fraction is not accessible for metabolism or excretion.

• Other elements that influence the duration of action of intravenous (IV) medications include:
• Clearance
• Half-life
• Volume of distribution, which is affected by:
  • Lipid solubility
  • Ionisation at physiological pH
  • Protein binding affinity of tissues
  • Regional blood flow

• Phenobarbitone
• Rifampicin
• Phenytoin
• Chloral hydrate
• Phenylbutazone
• Griseofulvin
• DDT
• Chronic alcohol consumption

• Lipid solubility of medications.
• Regional blood circulation.
• Ionisation at physiological pH.
• Fat to lean body mass ratio (which varies with age).
• Conditions such as CHF, uremia, and cirrhosis.
• Affinity for various tissues.
• Extent of plasma protein binding.

• When using the IV route, 100% bioavailability is observed.
• A sterile technique is essential for both I.V. and I.M. administration.
• In the case of the intradermal (ID) route, irritation and local tissue necrosis can occur.
• For the inhalational route, drug absorption occurs from the extensive surfaces of the alveoli, resulting in high bioavailability and very rapid action.