Chemistry:Trimetaphan camsilate
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| Trade names | Arfonad |
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| Routes of administration | Oral, IM, IV |
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| Pharmacokinetic data | |
| Excretion | Renal, mostly unchanged |
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| Formula | C22H25N2OS (free base) |
| Molar mass | 365.52 g·mol−1 |
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Trimetaphan camsilate (INN) or trimethaphan camsylate (USAN), sold under the trade name Arfonad, is a sympatholytic drug that is infrequently used to lower blood pressure.
Trimetaphan is a ganglionic blocker: it counteracts cholinergic transmission at the a specific type of nicotinic acetylcholine receptors in the autonomic ganglia and, therefore, blocks both the sympathetic nervous system and the parasympathetic nervous system. It functions as a non-depolarizing competitive antagonist at the nicotinic receptor, has a short duration of action, and is administered intravenously.
It was discovered by Leo Sternbach.[1]
Effects
Trimetaphan is a sulfonium compound and, as such, carries a positive charge. This charge prevents it from crossing lipid cell membranes, including those that comprise the blood–brain barrier. Consequently, trimethaphan has no effect on the central nervous system.
The ciliary muscle of the eye functions to round the lens for accommodation and is primarily controlled by parasympathetic system input. When a ganglion-blocking drug is administered, the ciliary muscle is unable to contract (cycloplegia), and the patient loses the ability to focus.
Trimetaphan has a significant effect on the cardiovascular system. Blood vessel size is primarily controlled by the sympathetic nervous system. Loss of sympathetic system input to the blood vessels causes them to dilate (vasodilation), which lowers blood pressure. Postural hypotension is a common side effect of these drugs. Trimethaphan causes histamine release, further decreasing blood pressure. Effects on the heart include a decreased force of contraction and an increase in heart rate (tachycardia). Reflexive tachycardia can be diminished or undetected because trimetaphan also blocks the sympathetic ganglia innervating the heart.
The motility of the gastrointestinal tract is regulated by the parasympathetic system, and blockage of this input results in diminished motility and constipation.
A rare side effect of trimethaphan administration is sudden respiratory arrest. The mechanism behind this is unknown, as trimethaphan does not appear to block the neuromuscular transmission, and respiratory arrest is not an expected consequence of ganglionic blockage.[2]
Therapeutic uses
The therapeutic uses of trimetaphan are limited due to the availability of newer drugs that are more selective in their actions and effects. It is occasionally used to treat a hypertensive crisis and dissecting aortic aneurysm, to treat pulmonary edema, and to reduce bleeding during neurosurgery.
References
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- ↑ Bause GS (1 August 2017). "From Coenzyme R to "Arfonad" and from Vitamin H to Hypotension". Anesthesiology 127 (2): 381. doi:10.1097/ALN.0000000000001771. ISSN 0003-3022.
- ↑ "Respiratory paralysis during treatment of hypertension with trimethaphan camsylate". Archives of Internal Medicine 136 (7): 816–8. July 1976. doi:10.1001/archinte.1976.03630070060018. PMID 938175.
Further reading
- "Controlled hypotension with arfonad in paediatric surgery". British Medical Journal 2 (4931): 103–4. July 1955. doi:10.1136/bmj.2.4931.103. PMID 14378656.
- "The influence of trimethaphan (Arfonad)-induced hypotension with and without spine distraction on canine spinal cord blood flow". Spine 11 (3): 219–24. April 1986. doi:10.1097/00007632-198604000-00007. PMID 3715622.
- "Renal and cardiovascular hemodynamic response to ganglionic blockade with pendiomide and a comparison with hexamethonium and arfonad". The Journal of Pharmacology and Experimental Therapeutics 113 (4): 383–92. April 1955. doi:10.1016/S0022-3565(25)11524-3. PMID 14368507. http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14368507.
- "The treatment of primary priapism with arfonad". The Journal of Urology 81 (2): 291–3. February 1959. doi:10.1016/S0022-5347(17)66009-9. PMID 13631819.
- "Trimethaphan (Arfonad) control of hypertension and tachycardia during electroconvulsive therapy: a double-blind study". Journal of Clinical Anesthesia 8 (2): 104–9. March 1996. doi:10.1016/0952-8180(95)00192-1. PMID 8695090.
- "The use of arfonad for the alleviation of cardio-vascular stress following electro-convulsive therapy". The Journal of Mental Science 103 (432): 636–44. July 1957. doi:10.1192/bjp.103.432.636. PMID 13449573.
- "Systemic and Coronary Hemodynamic Effects of Trimethaphan Camphorsulfonate (Arfonad) in the Dog". Anesthesiology 25 (2): 156–60. 1964. doi:10.1097/00000542-196403000-00008. PMID 14156542. http://anesthesiology.pubs.asahq.org/article.aspx?volume=25&page=156.
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