Trimethaphan
Encyclopedia
Trimetaphan camsilate or trimethaphan camsylate (USAN
), trade name Arfonad, is a drug that counteracts cholinergic
transmission at the ganglion type of nicotinic receptors of 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 acetylcholine
receptor, is short-acting, and is given intravenously.
compound and therefore carries a positive charge. Being charged, it cannot cross lipid
cell membrane
s, 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 vessel
s 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
.
, and to reduce bleeding during neurosurgery
.
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...
), trade name Arfonad, is a drug that counteracts cholinergic
Cholinergic
The word choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin...
transmission at the ganglion type of nicotinic receptors of the autonomic ganglia and therefore blocks both the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
and the parasympathetic nervous system
Parasympathetic nervous system
The parasympathetic nervous system is one of the two main divisions of the autonomic nervous system . The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously...
. It acts as a non-depolarizing competitive antagonist
Competitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...
at the nicotinic acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
receptor, is short-acting, and is given intravenously.
Effects
Trimetaphan is a sulfoniumSulfonium
A sulfonium ion, also known as sulphonium ion or sulfanium ion, is a positively charged ion featuring three organic substituents attached to sulfur. They have the formula [SR3]+...
compound and therefore carries a positive charge. Being charged, it cannot cross lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s, such as those that comprise the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. Due to this, trimethaphan does not have any effect on the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
.
The ciliary muscle
Ciliary muscle
The ciliary muscle is a ring of striated smooth muscle in the eye's middle layer that controls accommodation for viewing objects at varying distances and regulates the flow of aqueous humour into Schlemm's canal. It changes the shape of the lens within the eye not the size of the pupil which is...
of the eye
Human eye
The human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
functions to round the lens
Lens (anatomy)
The crystalline lens is a transparent, biconvex structure in the eye that, along with the cornea, helps to refract light to be focused on the retina. The lens, by changing shape, functions to change the focal distance of the eye so that it can focus on objects at various distances, thus allowing a...
for accommodation
Accommodation (eye)
Accommodation is the process by which the vertebrate eye changes optical power to maintain a clear image on an object as its distance changes....
and is controlled mainly by parasympathetic system input. With administration of a ganglion-blocking drug, the ciliary muscle cannot contract (cycloplegia
Cycloplegia
Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.-Anatomy:The iris is the heavily pigmented colored part of the eye. It has a contractile diaphragm in front of the lens with a central opening called the pupil...
) 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 vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...
s causes them to get larger (vasodilation
Vasodilation
Vasodilation refers to the widening of blood vessels resulting from relaxation of smooth muscle cells within the vessel walls, particularly in the large arteries, smaller arterioles and large veins. The process is essentially the opposite of vasoconstriction, or the narrowing of blood vessels. When...
) which has the effect of lowering blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
. Postural hypotension is a common side effect of such drugs. Trimethaphan causes a histamine release which further lowers blood pressure. Effects on the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
include a decreased force of contraction and an increase in heart rate (tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
). Reflexive tachycardia can be diminished or undetected because trimetaphan is also blocking the sympathetic ganglia innervating the heart.
The motility of the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
is regulated by the parasympathetic system, and blockage of this input results in diminished motility and constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
.
Therapeutic uses
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 edemaPulmonary edema
Pulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure...
, and to reduce bleeding during neurosurgery
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
.