Drugs Acting on Cardio-vascular & Respiratory

• Attainment of Steady-State Plateau: When a fixed dose of a drug is repeatedly administered at intervals equal to its elimination half-life ($t_{1/2}$), the steady-state (plateau) plasma concentration is reached after 4 to 5 half-lives.
• Accumulation Dynamics:
• After 1 half-life: $50\%$ of steady state
• After 2 half-lives: $75\%$
• After 3 half-lives: $87.5\%$
• After 4 half-lives: $93.75\%$
• After 5 half-lives: $96.88\%$ (clinically and mathematically considered steady state).

Correct option: (3) 4-5 half lives

• Henderson-Hasselbalch Ionization Calculation:
• For a weak organic base ($B$) with conjugate acid cation ($BH^+$), the ionization equilibrium is given by:

$$\text{pH} = \text{pK}_a + \log\left(\frac{[\text{Unionized Base}]}{[\text{Ionized Conjugate Acid}]}\right)$$ $$\log\left(\frac{[\text{Ionized}]}{[\text{Unionized}]}\right) = \text{pK}_a - \text{pH} = 9.2 - 1.0 = 8.2$$ $$\frac{[\text{Ionized}]}{[\text{Unionized}]} = 10^{8.2} \approx 1.585 \times 10^8 \approx 160,000,000$$

• Interpretation: In the highly acidic gastric juice (pH 1.0), dextromethorphan is almost completely protonated ($\gt 99.999999\%$ ionized), with only approximately 1 in every 160,000,000 molecules remaining in the lipid-soluble unionized form (Option 1).

Correct option: (1) Approximately 1 of every 160,000,000 molecules in the unionized form

• Pharmacokinetics of Weakly Acidic Drugs:
• Weakly acidic drugs (e.g., phenobarbital, aspirin, phenylbutazone) exist in equilibrium between unionized ($HA$) and ionized ($A^-$) states governed by the Henderson-Hasselbalch equation.
• Ion Trapping in Alkaline Urine: When urine is made alkaline (e.g., via sodium bicarbonate administration), weak acids ionize rapidly into lipid-insoluble conjugate bases ($A^-$). Because ionized species cannot cross renal tubular lipid bilayers, tubular reabsorption is blocked, and the drugs are excreted significantly faster in alkaline urine (Option 4).

Correct option: (4) Are excreted faster in alkaline urine