Test: General Pharmacology - 5 - NEET PG MCQ

Our goal is to reduce the plasma concentration of digoxin from 4 ng/ml to 1 ng/ml. This process will require two half-lives. Therefore, the time needed will be calculated as 2 × t_1/2, which equals 2 × 1.6, resulting in a total of 3.2 days.

When a medication is given less often, it results in significant fluctuations in plasma levels. In this scenario, the drug has a half-life of 6 hours. If we administer the dose every 6 hours, there will be a complete 100% variability in the plasma concentration.

Increasing the frequency of dosing will reduce the difference between the highest and lowest plasma concentrations. Given that the safety margin of this drug (as stated in the question) is quite narrow (with the maximum tolerable concentration being only 1.5 times the effective concentration), a continuous intravenous infusion is the most effective method.

For a medication that follows first-order kinetics, the increase in plasma concentration and the decrease in plasma concentration occur in a similar fashion. Once the steady state is reached and the drug administration ceases, it will be cleared from the body.

• 50% will be eliminated in one half-life.
• 75% in 2 half-lives.
• 87.5% (50 + 25 + 12.5%) in 3 half-lives.
• 93.75% (50 + 25 + 12.5 + 6.25%) in 4 half-lives.

When a constant intravenous infusion is given, the plasma concentration rises in a similar manner. At the end of one half-life, it will be at 50% of the steady state, and to achieve 93.75% of the steady state, 4 half-lives will be necessary. Since the half-life of this medication is 8 hours, around 32 hours (4 × 8) will be needed.

The half-life of this medication is 2 hours, and its plasma concentration is 3 mg/L after 4 hours (from 9 AM to 1 PM). This indicates that after 2 half-lives (4 hours), the plasma concentration remains at 3 mg/L.

It is understood that with continuous intravenous infusion, the plasma concentration reaches 75% of the steady state within 2 half-lives. Therefore, if 3 mg/L represents 75% of the steady state, the total would equate to 4 mg/L.

In this scenario, 80 per cent of the medication is removed via the renal pathway, while 20 per cent is eliminated through non-renal methods, comprising 10 per cent through hepatic metabolism and 10 per cent via biliary secretion. This patient exhibits 50 per cent renal functionality, with a GFR of 60 ml/min instead of the normal 120 ml/min. Consequently, the amount of the drug that can be eliminated by this individual is:

• 20 per cent (non-renal route) +
• 40 per cent (renal route; 50 per cent of 80 per cent) =
• 60 per cent.

Therefore, the required dose rate should be 60 per cent of the initial amount, meaning:

50 mg/hr × 60 per cent = 30 mg/hr.

The rate of elimination rises as the concentration in plasma increases.

• Half Life: Elimination of the first 50%
• Second 75% (50 + 25)
• Third 87.5% (50 + 25 + 12.5)
• Fourth 93.75% (50 + 25 + 12.5 + 6.25)

Following a dosage schedule, the concentration of the medication at which the input balances elimination is referred to as the steady state plasma concentration, C_pss. C_pss is attained after approximately 4 to 5 half-lives. The extent of variations in C_pss is influenced by the dosing interval in relation to t_1/2.

Notable medications that can induce a syndrome resembling SLE consist of:

• Sulfonamides
• Hydralazine
• Isoniazid
• Procainamide

Enzymatic receptors possess two distinct sites:

• The drug attaches to the extracellular site.
• The intracellular site exhibits enzymatic activity, primarily involving tyrosine kinase.

This enzyme can be triggered through the JAK-STAT pathway. Hormones such as insulin, growth hormone, prolactin, and various cytokines function through enzymatic receptors.

G proteins are named for their ability to bind the guanine nucleotides GDP and GTP. They consist of three different subunits, making them heterotrimers: G_α, G_β, and G_γ. In their inactive form, the G protein has GDP attached to its G_α subunit. When a hormone or another ligand attaches to the corresponding receptor (GPCR), GDP is replaced by GTP.

• The binding of GTP activates G_α, leading to its separation from G_βG_γ, which continues to exist as a dimer.
• Activated G_α subsequently triggers an effector molecule, such as adenylyl cyclase.
• This enzyme facilitates the conversion of ATP into the "second messenger" cyclic AMP.

Gs, Gi, and Gq represent various types of G proteins, distinguished by their different α-subunits. While Gs and Gq are stimulatory, Gi acts as an inhibitory G protein.

• S – Sulfonamides, such as dapsone
• H – Hydralazine
• I – Isoniazid
• P – Procainamide