Curare skeletal muscle relaxants

Drugs discussed in this chapter are used to decrease muscle excitability and contraction via an effect at the spinal cord level, at the neuromuscular junction, or within the muscle cell itself. Some texts also classify neuromuscular junction blockers such as curare and succinylcholine as skeletal muscle relaxants. However, these drugs are more appropriately classified as skeletal muscle paralytics because they eliminate muscle contraction by blocking transmission at the myoneural synapse. This type of skeletal muscle paralysis is used primarily during general anesthesia using neuromuscular blockers as an adjunct in surgery was discussed in Chapter 11. Skeletal muscle relaxants do not typically prevent muscle contraction they only attempt to normalize muscle excitability to decrease pain and improve motor function. 

Bisbenzylisoquinolines (macrocyclic or linear, formed by 2 benzylisoquinolines) (+)-tubocurarine (macrocyclic) (acetylcholine (nicotinic) receptor antagonist and skeletal muscle relaxant major component of Chondrodendron species (Menispermaceae) pareira bark-derived curare arrow poison) dauricine (linear) (Menispermaceae curarelike anaesthetic) rodiasine (macrocyclic) (Ocotoea venenosa (Lauraceae) curare-like skeletal muscle relaxant) cepharanthine (macrocyclic) (Stephania species (Menispermaceae) anti-mycobacterial active against leprosy and tuberculosis). 

Curare is sol in water and in dil alcohol. Stable aq solns (in ampuls) are standardized to contain 20 units per ml. therap Cat Skeletal muscle relaxant. therap CAT (vet) Muscle relaxant. 

The principle is fairly plain, even an old one. In 1939, the active ingredient of curare—an ancient plant toxin weapon still in use by Indians—was isolated for the first time. In 1943, it was introduced successfully into anesthesiology. Curare provided adequate muscle relaxation without the depressant effect of deep anesthesia induced by ether or chloroform. Over the last 20 years, physicians have used curare to ease the stiffened muscles caused by polio and to treat such diverse conditions as lockjaw, epilepsy, and cholea (a nervous disorder characterized by uncontrollable muscle movements). Eventually, more effective treatments were found for these illnesses, but the active ingredient of curare, d-tubocurarine, led to the skeletal muscle relaxant Intocostrin, which has been used in surgery ever since. Synthetic analogs of d-tubocurarine are used tens of thousands of times per day in the operating room [309]. 

Mecfianism of Action A cinchona alkaloid that relaxes skeletal muscle by increasing the refractory period, decreasing excitability of motor end plates (curare-like), and affecting distribution of calcium with muscle fiber. Antimalaria Depresses oxygen uptake, carbohydrate metabolism, elevates pH in intracellular organelles of parasites. Therapeutic Effect Relaxes skeletal muscle produces parasite death. Pharmacokinetics Rapidly absorbed mainly from upper small intestine. Protein binding 70%-95%. Metabolized in liver. Excreted in feces, saliva, and urine. Half-life 8-14 hr (adults), 6-12 hr (children). 

The development and use of muscle relaxants, to allow a reduction in the level of anesthesia during surgery, follows entirely from studies of South American arrow poisons (44)and particularly from the isolation by King (45) of pure D-tubocurarine (29) in the 1930s, from tube curare. Another of the South American blowpipe poisons, calabash curare, was used for similar purposes and developed (46,47), to give alcuronium (30) from the alkaloid C-toxiferine 1 (31). Both types of curare paralyze skeletal muscle by a similar mechanism, antagonizing the effect of acetylcholine at the neuromuscular junction (48). 

Curare is often used as a general term to describe a wide variety of highly toxic plant extracts. Curare was originally used by South American Indians as an arrow poison that caused paralysis of skeletal muscle of prey being hunted. Curare was first used medically as a muscle relaxant in 1912. An extract from Chondrodendron tomentosum has been used clinically to reduce spasms in patients with tetanus and those treated with shock therapy, and to treat muscular rigidity and spastic paralysis. Curare is also used as an adjunct to general anesthesia. 

Aceclidine is mostly used in ophthalmology for constriction of the pupil and reduction of intraocular pressure in glaucoma. Oxylidine is being used as a tranquilliser in patients with neurotic states and early states of hypertension. It is also recommended for the treatment of cerebral atherosclerosis. Its oral dose is 0.02—0.5 g. Qualidile is a curare-like drug used in general anaesthesia. The preparation is injected intravenously at a dose of 1 mg kg S muscle relaxation lasts for 10 minutes, slight inhibition of respiration being observed. A dose of 2 mg kg produces complete relaxation of the skeletal muscles, accompanied by apnoea. In spite of the fact that the review is well documented, it is difficult to form an idea about the clinical merits of these compounds. Some clinical information has been published recently a comparison of Qualidile with NiV -diallyl-bisnortoxiferine or tubocurarine chlorides loc. cit.) would be of special interest. 

Historically, Bernard (1851, 1856) demonstrated that curare (from arrow poisons used by South American Indians) blocked nerve impulse transmission at the junction of the nerve and skeletal muscle. It was later shown that many alkaloids, such as morphine, atropine, nicotine, and even strychnine and brucine (the latter two normally causing convulsions), will become muscle relaxants when quaternized by methylation. It soon became apparent that a great many quaternary ammonium compounds qualitatively share the ability to produce neuromuscular blockade. In fact, the onium ion need not be a nitrogen atom. Thus sulfonium (/ 3S+), phosphonium (/ 3P+), and arsonium (/ 3As+) ions have been shown to be curariform , although of lesser activity than ammonium ions. 

Pharmacological studies of curare were initiated in the middle of the nineteenth century by the French physiologist Claude Bernard (1813— 1878). The dominant pharmacological effect of curare is the paralysis of the whole skeletal muscle in both warm- and cold-blooded animals. The sequence of the paralytic effects of the skeletal muscle is well defined. At first, the eyes, ears, and toes are affected, and next the muscles of the arms and legs. Paralysis of the muscles of the neck then occurs, and finally the respiratory muscles are affected, resulting in suffocation in warm-blooded animals. The muscle relaxant activity of curare is strengthened by diethylether. Because curare can release stored histamine in the tissues, it may cause hypotension and excessive secretion in the trachea. 

Curare is a muscle relaxant drug, originally used as an arrow poison by Amazonian Indians. The traditional curare is prepared by a secret recipe thought to involve a number of plant species (Plotkin 1993). Plant sources of curare include Strychnos castelnaei and species in the Loganaceae family and Chondodendron tomentosum in the Menispermaceae family. Tubocurarine, a benzylisoquinoline dimer, is the major alkaloid in the curare plants. It exhibits paralysing effects on skeletal muscles, and is used as a muscle relaxant in surgical procedures. It controls convulsions caused by the toxic alkaloid strychnine. 

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