Dantrolene causing

In addition to its use in managing an acute attack of malignant hyperthermia see above), dantrolene has been used in the treatment of spasticity and hyperreflexia. Dantrolene causes a generalized weakness thus, its use should be restricted to nonambulatory patients with severe spasticity. Hepatotoxicity has been reported with continued use, requiring hver function tests. 

Toxicity The sedation produced by diazepam is significant but milder than that produced by other sedative-hypnotic drugs at doses that induce equivalent muscle relaxation. Baclofen produces less sedation than diazepam. Dantrolene causes significant muscle weakness but less sedation than either diazepam or baclofen. Tizanidine may cause drowsiness and hypotension. 

The skeletal muscle relaxants are contraindicated in patients with known hypersensitivity. Baclofen is contraindicated in skeletal muscle spasms caused by rheumatic disorders. Carisoprodol is contraindicated in patients with a known hypersensitivity to meprobamate. Cyclobenzaprine is contraindicated in patients with a recent myocardial infarction, cardiac conduction disorders, and hyperthyroidism, hi addition, cyclobenzaprine is contraindicated within 14 days of the administration of a monoamine oxidase inhibitor. Oral dantrolene is contraindicated in patients with active hepatic disease and muscle spasm caused by rheumatic disorders and during lactation. See Chapter 30 for information on diazepam. 

The answer is e. (Kat ung, pp 428-429J Although a rare occurrence, halothane and other inhaled gas anesthetics may cause malignant hyperthermia Apparently, this occurs in genetically susceptible individuals Its onset may be accelerated by the concomitant use of succinylcholine. Immediate treatment includes administration of dantrolene. 

Dantrolene is a drug that causes spastic muscle contraction. Unlike other muscle relaxants, it has a direct effect on the contractile mechanism by interfering in the process of calcium ion release from the sarcoplasmic reticulum. This results in a lack of coordination in the mechanism of excitation—contraction of skeletal muscle, which has a greater effect on fast muscle fibers than on slow muscle fibers. Dantrolene is used for controlling the onset of clinical spasticity resulting from serious clinical cases such as wounds, paralysis, cerebral palsy, and disseminated sclerosis. Synonyms of this drug are dantrium and danlen. 

If symptoms of hepatitis accompanied by liver function test abnormalities or jaundice appear, discontinue therapy. If caused by dantrolene and detected early, abnormalities may revert to normal when the drug is discontinued. See Warning Box. 

A rare interaction of succinylcholine with volatile anesthetics results in malignant hyperthermia, a condition caused by abnormal release of calcium from stores in skeletal muscle. This condition is treated with dantrolene and is discussed below under Spasmolytic Drugs and in Chapter 16. 

Baclofen is at least as effective as diazepam in reducing spasticity and causes less sedation. In addition, baclofen does not reduce overall muscle strength as much as dantrolene. It is rapidly and completely absorbed after oral administration and has a plasma half-life of 3-4 hours. Dosage is started at 15 mg twice daily, increasing as tolerated to 100 mg daily. Adverse effects of this drug include drowsiness however, patients become tolerant to the sedative effect with chronic administration. Increased seizure activity has been reported in epileptic patients. Therefore, withdrawal from baclofen must be done very slowly. 

Dantrolene sodium (Dantrium] Adult 25 mg/d initially increase up to 100 mg 2, 3, or 4 times per day as needed maximum recommended dose is 400 mg/day. Children (older than 5 yr of age] initially, 0.5 mg/kg body weight BID increase total daily dosage by 0.5 mg/kg every 4-7 days as needed, and give total daily amount in 4 divided dosages maximum recommended dose is 400 mg/d. Exerts an effect directly on the muscle cell may cause generalized weakness in all skeletal musculature. 

Chapter 8).2,58 In this situation, dantrolene inhibits skeletal muscle contraction throughout the body, thereby limiting the rise in body temperature generated by strong, repetitive skeletal muscle contractions.58 Dantrolene is not prescribed to treat muscle spasms caused by musculoskeletal injury. 

Muscle relaxation is caused by various mechanisms, such as depression of ACh synthesis (e.g, hemicholinium), storage (vesamicol) and release (magnesium, botulinum toxin) and depression of muscle activity by drugs such as dantrolene and baclofen,... 

Dantrolene interacts with verapamil and with diltiazem, causing myocardial depression and cardiogenic shock (SEDA-16,199). 

Deafness occurred after 5 days treatment with dantrolene 25 mg/day in a patient who was also taking long-term baclofen and diazepam (8). This may have been coincidental, but the authors suggested that dantrolene may have caused the effect by interfering with the release of calcium from the sarcoplasmic reticulum. It is therefore interesting that one hypothesis that explains the ototoxicity of aminoglycoside antibiotics involves disturbance of calcium ion binding and phosphorylation processes (SED-11, 549). 

Fatal lymphocytic Ijmphoma has been described during high-dose dantrolene therapy (600 mg/day over 3 years) (9). Although the association was only circumstantial, another hydantoin derivative, phenjhoin, is known to cause pseudolymphoma. 

Skeletal muscle relaxants fall into three major categories those that reduce spasticity, those that cause neuromuscular blockade and those that work at the cellular level. Spasmolytic agents (e.g. metho-carbamol, guaifenesin) act centrally whereas neuromuscular blockers (e.g. succinylcholine (suxamethonium), pancuronium, atracurium) act at the neuromuscular end plate to produce muscular relaxation. Dantrolene falls into the third category and acts within the muscle cell itself to produce relaxation. 

Dantrolene has a direct action on skeletal muscle to cause relaxation baclofen inhibits transmission at the spinal cord by acting on inhibitory presynaptic gamma-aminobutyric acid B (GABAb) receptors benzodiazepines cause muscle relaxation by some central action and tizanidine is an a2 adrenoreceptor agonist presumably with a central action. 

All of these anaesthetics (and suxamethonium, see page 235) have the potential to cause malignant hyperthermia. This is a rare but potentially lethal complication of anaesthesia. It is characterized by a rapid rise in body temperature, due to excessive muscle contractions, together with increased heart rate and acidosis. It is treated as an emergency with dantrolene, which causes muscle relaxation. 

Dantrolene, which is chemically related to the nitrofuran antibacterials (Chapter 7), was introduced as a myorelaxant with a unique direct action on skeletal muscle that reduces contractility by effecting Ca2+ release from the sarcoplasmic reticulum of certain muscle fibers. The CNS is not involved. The drug can control spasticity caused by spinal cord injuries, multiple sclerosis, cerebral palsy, and even strokes, but it is not indicated for arthritis or local acute spasms. 

Musck Halothane causes some relaxation of skeletal muscle via its central depressant effects and potentiates the actions of nondepolarizing muscle relaxants (curariform drugs see Chapter 9), increasing both their duration of action and the magnitude of their effect. Halothane and the other halogenated inhalational anesthetics can trigger malignant hyperthermia this syndrome frequently is fatal and is treated by immediate discontinuation of the anesthetic and administration of dantrolene. 

Cyclobenzaprine is likely to diy oropharyngeal secretions and to decrease gut motility Dantrolene has little effect on calcium release in cardiac muscle Diazepam causes sedation at most doses required to reduce muscle spasms Intrathecal use of baclofen is effective in some refractory cases of muscle spasticity... 

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