Sublingual nitroglycerine is effective because it is:

  # Sublingual nitroglycerine is effective because it is:

A. Ionic and has high lipid solubility

B. Ionic and has low lipid solubility

C. Non ionic and has high lipid solubility

D. Non ionic and has low lipid solubility

The correct answer is C. Non-ionic and has high lipid solubility.

Pharmacological Principle

For a drug to be absorbed rapidly across the sublingual mucosa, it must pass through the lipid bilayer of the epithelial cell membranes via passive diffusion.

• Non-ionic State: Drugs that are non-ionized (uncharged) are significantly more lipid-soluble than their ionized counterparts. Ionized molecules are polar and struggle to penetrate the hydrophobic core of the cell membrane.

• High Lipid Solubility: Nitroglycerine is a highly lipophilic (lipid-loving) molecule. This allows it to dissolve almost instantly into the membrane and enter the systemic circulation through the dense capillary network under the tongue.

Why Sublingual Administration?

In clinical practice, especially for acute angina pectoris, the sublingual route is preferred for Nitroglycerine because:

1. Bypassing First-Pass Metabolism: If swallowed, Nitroglycerine undergoes nearly 100% hepatic metabolism (first-pass effect) by the enzyme organic nitrate reductase, rendering it ineffective. The sublingual route allows the drug to enter the Superior Vena Cava directly.

2. Rapid Onset: Due to the high lipid solubility and thin mucosal membrane, therapeutic blood levels are reached within 1 to 3 minutes.

3. pH Environment: The pH of saliva (approximately 6.2 to 7.4) ensures that Nitroglycerine remains largely in its non-ionized, absorbable form.

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Comparison of Solubility Factors

Property	Effect on Absorption	Nitroglycerine Status
Ionization	Ionized = Low absorption; Non-ionic = High absorption	Non-ionic
Lipid Solubility	High lipid solubility = Rapid membrane crossing	High
Molecular Weight	Lower weight = Faster diffusion	Low (227.1 g/mol)