skeletal muscle relaxants

• Baclofen is an agonist at GABA-B receptors, which inhibits the release of excitatory neurotransmitters.
• Dantrolene acts directly on skeletal muscle to reduce calcium ion sensitivity of actin-myosin interaction.
• Dantrolene acts directly on skeletal muscles to reduce calcium ion sensitivity by binding to the sarcoplasmic reticulum.
• Tizanidine is an alpha2 adrenergic agonist that reduces presynaptic norepinephrine release from sympathetic nerve terminals.
• Skeletal muscle relaxants are used to treat spasticity caused by upper motor neuron lesions or cerebral palsy.
• Tizanidine is an alpha2 adrenergic agonist that reduces motor neuron activity by decreasing presynaptic release of acetylcholine (ACh).
• Benzodiazepines are used as adjunctive therapy with other drugs or physical therapy for spasticity caused by upper motor neuron lesions.
• Skeletal muscle relaxants (SMRs) are drugs that reduce the muscle tone either by acting peripherally at the neuromuscular junction (neuromuscular blockers) or centrally in the cerebrospinal axis or directly on the contractile mechanism.
• Skeletal muscle relaxants are used to reduce the spasticity in a variety of neurological conditions and are also useful in surgeries.
• Curare, the active principle from which tubocurarine was identified, was used by the South American Indians as arrow poison for hunting wild animals because curare paralysed the animals.
• Tubocurarine (d-Tc) is the dextrorotatory quaternery ammonium alkaloid obtained from the plant Chondrodendron tomentosum and plants of the Strychnos species.
• Several synthetic agents have been developed as skeletal muscle relaxants.
• All these are quaternary ammonium compounds because of which they are not well absorbed, do not cross the BBB and are quickly excreted.
• Non-depolarising blockers bind to NMDA nicotinic receptors on the motor end plate and block the actions of acetylcholine by competitive blockade.
• These compounds slowly dissociate from the receptors and transmission is gradually restored, hence the action of d-Tc is reversible.
• Increasing the concentration of the agonist acetylcholine at the NMJ also overcomes the blockade, which can be done by the administration of anticholinesterases like neostigmine.
• On parenteral administration, tubocurarine initially causes muscular weakness followed by flaccid paralysis.
• Some people have an abnormal (atypical) pseudocholinesterase enzyme, a hereditary defect.
• In such people, SCh does not get metabolised and even the usual dose results in prolonged apnea and paralysis which may last for several hours.
• Artificial ventilation and fresh blood transfusion are needed to supply pseudo- cholinesterase.
• Postoperative muscle pain is a common adverse effect of SCh.
• Hyperkalemia: Succinylcholine can cause hyperkalemia due to sudden release of K+ from the intracellular sites which could be due to fasciculations.
• This can be dangerous particularly in patients with CCF.
• Hyperkalemia may result in cardiac arrest in patients with burns, nerve injuries and neuromuscular disease.
• Cardiac arrhythmias: Succinylcholine can cause cardiac arrhythmias.
• It stimulates the nicotinic receptors in the ganglia and cardiac muscarinic receptors.
• Malignant hyperthermia is a rare genetically determined condition where there is a sudden increase in the body temperature and severe muscle spasm due to release of intracellular Ca++ from the sarcoplasmic reticulum.
• Metabolic acidosis and tachycardia may be present.
• Certain drugs like halothane, isoflurane, sevoflurane and succinylcholine can trigger the process which can be fatal.
• Combination of these general anesthetics and SCh is the most common triggering factor.
• Intravenous dantrolene (1 mg/kg repeated if required) is life-saving in malignant hyperthermia.
• Oxygen inhalation, treatment of acidosis and immediate cooling of the body also help.
• Inappropriate use of peripherally acting SMRs can be fatal.
• Skeletal muscle relaxants are used as adjuvants to general anesthesia.
• Short- acting SMRs like succinylcholine are used during endotracheal intubation.
• The mechanism of action of succinylcholine involves the inhibition of acetylcholine esterase, leading to an increase in the concentration of acetylcholine.
• Autonomic Nervous System
• Botulinum toxin is produced by the anaerobic bacterium Clostridium botulinum.
• Small muscles of the eyes and fingers are the first to be affected, followed by those of the limbs, neck and trunk.
• Later the intercostal muscles and finally the diaphragm are paralysed and respiration stops.