Nicotine

Class	Cholinergic
Chemistry	Pyridine derivative alkaloid
Routes of administration	Oral, IV, IM, inhaled
Absorption	Well absorbed through mucosal surfaces; oral bioavailability is around 44%
Solubility	Nicotine has two pKa values, the pyrrolidine ring has a pKa of 8.10 and the pyridine ring has a pKa of 3.41. It is lipophilic but water-miscible; about 69% ionized and 31% unionized at physiological pH.
Distribution	VOD = 2.6 L/kg, less than 5% protein-bound
Metabolism	Extensively metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6)
Elimination	minimal renal elimination
Time course of action	Half life is ~ 2 hrs
Target receptor	Muscarinic receptors (M1-M5), which are mainly Gq-coupled receptors, and nicotinic receptors, which are cation channels and of which there are numerous subtypes, the ones specifically responsible for the desirable effects being β2 subunit-containing receptors localized on dopamine-containing cell bodies within the ventral tegmental area
Mechanism of action	Direct nicotinic receptor agonist. At the postganglionic cholinergic neurons, nicotine has a parasympathomimetic effect, mediated by downstream muscarinic receptors. At the postganglionic sympathetic neurons, by acting on acetylcholine-gated nicotinic cation channels, nicotine depolarises sympathetic postganglionic fibres, resulting in noradrenaline release. This effect also mediates systemic adrenaline and noradrenaline release from chromaffin cells of the adrenal medulla
Clinical effects	The net clinical effects are mostly sympathomimetic: - Increased blood pressure and heart rate - Cutaneous vasoconstriction - Increase in plasma free fatty acids - Hyperglycemia Also: - Increased gastric acid secretion - Bronchoconstriction - Intestinal sphincter relaxation - Increased bowel motility
Literature reference	McKinney & Vansickel, 2016
CICM details of understanding	Not specifically listed in the CICM syllabus
Mentioned around Deranged Physiology
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