Clinical data | |
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Trade names | Arfonad |
Routes of administration | Oral, IM, IV |
ATC code | |
Pharmacokinetic data | |
Excretion | Renal, mostly unchanged |
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CAS Number | |
PubChem CID | |
DrugBank | |
UNII | |
ChEMBL | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.000.633 |
Chemical and physical data | |
Formula | C22H25N2OS(free base) |
Molar mass | 365.52 g·mol−1 |
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Trimetaphan camsilate (INN) or trimethaphan camsylate (USAN), trade name Arfonad, is a sympatholytic drug used in rare circumstances to lower blood pressure.
Trimetaphan is a ganglionic blocker: it counteracts cholinergic transmission at 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 acts as a non-depolarizing competitive antagonist at the nicotinic receptor, is short-acting, and is given intravenously.
It was discovered by Leo Sternbach. [1]
Trimetaphan is a sulfonium compound and therefore carries a positive charge. Being charged, it cannot cross lipid cell membranes, such as those that comprise the blood–brain barrier. Due to this, trimethaphan does not have any effect on the central nervous system.
The ciliary muscle of the eye functions to round the lens for accommodation and is controlled mainly by parasympathetic system input. With administration of a ganglion-blocking drug, the ciliary muscle cannot contract (cycloplegia) and the patient loses the ability to focus their eyes.
Trimetaphan has a strong effect on the cardiovascular system. The size of blood vessels is primarily controlled by the sympathetic nervous system. Loss of sympathetic system input to the blood vessels causes them to get larger (vasodilation) which has the effect of lowering blood pressure. Postural hypotension is a common side effect of such drugs. Trimethaphan causes a histamine release which further lowers 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 is also blocking 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 it is unknown, as trimethaphan does not appear to block neuromuscular transmission, and respiratory arrest is not an expected consequence of ganglionic blockage. [2]
The therapeutic uses of trimetaphan are very limited due to the competition from newer drugs that are more selective in their actions and effects produced. It is occasionally used to treat a hypertensive crisis and dissecting aortic aneurysm, to treat pulmonary edema, and to reduce bleeding during neurosurgery.
A ganglion is a group of neuron cell bodies in the peripheral nervous system. In the somatic nervous system, this includes dorsal root ganglia and trigeminal ganglia among a few others. In the autonomic nervous system, there are both sympathetic and parasympathetic ganglia which contain the cell bodies of postganglionic sympathetic and parasympathetic neurons respectively.
Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.
The autonomic nervous system (ANS), formerly referred to as the vegetative nervous system, is a division of the nervous system that operates internal organs, smooth muscle and glands. The autonomic nervous system is a control system that acts largely unconsciously and regulates bodily functions, such as the heart rate, its force of contraction, digestion, respiratory rate, pupillary response, urination, and sexual arousal. This system is the primary mechanism in control of the fight-or-flight response.
The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.
The sympathetic nervous system (SNS) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of the autonomic nervous system, and sometimes considered an independent system.
Dysautonomia, autonomic failure, or autonomic dysfunction is a condition in which the autonomic nervous system (ANS) does not work properly. This may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels. Dysautonomia has many causes, not all of which may be classified as neuropathic. A number of conditions can feature dysautonomia, such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, Ehlers–Danlos syndromes, autoimmune autonomic ganglionopathy and autonomic neuropathy, HIV/AIDS, mitochondrial cytopathy, pure autonomic failure, autism, and postural orthostatic tachycardia syndrome.
Anticholinergics are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central and peripheral nervous system.
The myenteric plexus provides motor innervation to both layers of the muscular layer of the gut, having both parasympathetic and sympathetic input, whereas the submucous plexus provides secretomotor innervation to the mucosa nearest the lumen of the gut.
The pterygopalatine ganglion is a parasympathetic ganglion in the pterygopalatine fossa. It is one of four parasympathetic ganglia of the head and neck,.
The ciliary ganglion is a bundle of nerves, parasympathetic ganglion located just behind the eye in the posterior orbit. It is 1–2 mm in diameter and in humans contains approximately 2,500 neurons. The ganglion contains postganglionic parasympathetic neurons. These neurons supply the pupillary sphincter muscle, which constricts the pupil, and the ciliary muscle which contracts to make the lens more convex. Both of these muscles are involuntary since they are controlled by the parasympathetic division of the autonomic nervous system.
Hexamethonium is a non-depolarising ganglionic blocker, a neuronal nicotinic (nAChR) receptor antagonist that acts in autonomic ganglia by binding mostly in or on the nAChR receptor, and not the acetylcholine binding site itself. It does not have any effect on the muscarinic acetylcholine receptors (mAChR) located on target organs of the parasympathetic nervous system, nor on the nicotinic receptors at the skeletal neuromuscular junction, but acts as antagonist at the nicotinic acetylcholine receptors located in sympathetic and parasympathetic ganglia (nAChR).
Parasympathetic ganglia are the autonomic ganglia of the parasympathetic nervous system. Most are small terminal ganglia or intramural ganglia, so named because they lie near or within (respectively) the organs they innervate. The exceptions are the four paired parasympathetic ganglia of the head and neck.
Alcuronium chloride is a neuromuscular blocking (NMB) agent, alternatively referred to as a skeletal muscle relaxant. It is a semi-synthetic substance prepared from C-toxiferine I, a bis-quaternary alkaloid obtained from Strychnos toxifera. C-toxiferine I itself has been tested for its pharmacological action and noted to be a very long acting neuromuscular blocking agent For a formal definition of the durations of actions associated with NMB agents, see page for gantacurium. The replacement of both the N-methyl groups with N-allyl moieties yielded N,N-diallyl-bis-nortoxiferine, now recognized as alcuronium.
A ganglionic blocker is a type of medication that inhibits transmission between preganglionic and postganglionic neurons in the autonomic nervous system, often by acting as a nicotinic receptor antagonist. Nicotinic acetylcholine receptors are found on skeletal muscle, but also within the route of transmission for the parasympathetic and sympathetic nervous system. More specifically, nicotinic receptors are found within the ganglia of the autonomic nervous system, allowing outgoing signals to be transmitted from the presynaptic to the postsynaptic cells. Thus, for example, blocking nicotinic acetylcholine receptors blocks both sympathetic (excitatory) and parasympathetic (calming) stimulation of the heart. The nicotinic antagonist hexamethonium, for example, does this by blocking the transmission of outgoing signals across the autonomic ganglia at the postsynaptic nicotinic acetylcholine receptor.
The Bezold–Jarisch reflex involves a variety of cardiovascular and neurological processes which cause hypopnea, hypotension and bradycardia in response to noxious stimuli detected in the cardiac ventricles. The reflex is named after Albert von Bezold and Adolf Jarisch Junior. The significance of the discovery is that it was the first recognition of a chemical (non-mechanical) reflex.
In neurophysiology, a ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:
Neurocardiology is the study of the neurophysiological, neurological and neuroanatomical aspects of cardiology, including especially the neurological origins of cardiac disorders. The effects of stress on the heart are studied in terms of the heart's interactions with both the peripheral nervous system and the central nervous system.
The classification of peripheral nerves in the peripheral nervous system (PNS) groups the nerves into two main groups, the somatic and the autonomic nervous systems. Together, these two systems provide information regarding the location and status of the limbs, organs, and the remainder of the body to the central nervous system (CNS) via nerves and ganglia present outside of the spinal cord and brain. The somatic nervous system directs all voluntary movements of the skeletal muscles, and can be sub-divided into afferent and efferent neuronal flow. The autonomic nervous system is divided primarily into the sympathetic and parasympathetic nervous systems with a third system, the enteric nervous system, receiving less recognition.
Autonomic drugs can either inhibit or enhance the functions of the parasympathetic and sympathetic nervous systems. This type of drug can be used to treat a wide range of diseases, such as glaucoma, asthma, urinary, gastrointestinal and cardiopulmonary disorders.
Cholinergic blocking drugs are a group of drugs that block the action of acetylcholine (ACh), a neurotransmitter, in synapses of the cholinergic nervous system. They block acetylcholine from binding to cholinergic receptors, namely the nicotinic and muscarinic receptors.
This article includes a list of general references, but it lacks sufficient corresponding inline citations .(September 2018) |