**Question:** Nitroglycerine cannot be administered by which of the following route:

A. Injection
B. Oral
C. Intranasal
D. Intravenous

**Correct Answer:** D. Intravenous

**Core Concept:** Nitroglycerin is a nitrate medication used to treat angina pectoris and hypertension. It is a vasodilator, meaning it dilates blood vessels, allowing blood flow to increase and reducing cardiac workload. Nitroglycerin is converted to its active form, nitric oxide (NO), which activates the cyclic guanosine monophosphate (cGMP) signaling pathway in vascular smooth muscle cells, leading to vasodilation.

**Why the Correct Answer is Right:** Nitroglycerin is most effective when administered directly into the bloodstream to ensure rapid absorption into the systemic circulation. Intravenous (IV) administration provides the quickest and most direct route for the drug to reach its target sites (vascular smooth muscle cells) and exert its vasodilatory effects.

**Why Each Wrong Option is Incorrect:**

A. Injection: While injection can be used, it is less efficient than IV administration due to slower absorption into the bloodstream.

B. Oral: Oral administration of nitroglycerin results in poor bioavailability and first-pass effect, reducing its efficacy and increasing the risk of side effects.

C. Intravenous: Intranasal administration is not as effective as IV due to poor absorption from the nasal mucosa, which leads to slower onset and reduced therapeutic effects.

**Clinical Pearl:** Nitroglycerin should be administered via the IV route in critical situations such as severe chest pain, hypertension, or cardiovascular emergencies. Oral, intranasal, and injection routes should be avoided due to lower bioavailability, slower onset, and increased risk of side effects.