Which of the following anaesthetic agent causes adrenal suppression aEUR'
Phase 2 blockade produced succinylcholine [Ref : Morgan's Anaesthesia 4/e p 112; Miller's Anaesthesia 6/e p 9851 Patients developing paralysis after prolonged and high dose of succinyl choline is highly suggestive of phase II succinyl choline block. Phase II block with succinylcholine occurs with prolonged and high dose of the drug. -(High dose for Sch is 7-10 mg/kg, 30-60 minutes of exposure is considered prolong). Morgan's Anaesthesia 4thie p. 112 The type of succinylcholine block may change into a non depolarizing block following prolonged administration of the drug (phase II block). Transition from a depolarizing to phase 11 block is gradual and usually occurs after administration of 7-10 mg/kg of succinylcholine. Recovery from a phase II block is much slower. Millers Anaesthesia 6thie p. 985 After administration of 7-10 mg/kg or 30-60 minutes of exposure to succinylcholine, nondepolarizing dual or phase II block occurs Prolonged paralysis with succinylcholine administration may also occur in pseudocholinesterase deficiency - But in pseudocholinesterase deficiency prolonged paralysis occurs with usual dose of succinylcholine. Succinylcholine is a noncompetitive muscle relaxant Normally muscles contract due to the action of acetylcholine released in the neuromuscular synaptic junctions Acetylcholine acts by activating its receptors present on motor end plate, and generates action potential Competitive Neuromuscular blockers act by blocking the action of acetylcholine and prevents the generation of action potential. On the other hand succinylcholine acts by depolarization of the motor end plate i.e. it activates the acetylcholine receptor present at the motor end plate. - At their, ,first application voluntary muscle contracts but as they are not destroyed immediately like acetylcholine the depolarization persist. It might be expected that this prolonged depolarisation would cause muscles to remain contracted but this is not so. - With prolonged administration, a depolarization block changes to competitive block. Succinykholine produces neuromuscular block by overstimulation so that the end plate is unable to respond to fuher stimulation. Neuromuscular block with succinykholine occurs in two sequential phases An initial depolarization of the endplate produces muscle action potentials and .fasciculations. Maintained depolarization past the threshold for .firing produces Na+ channel inactivation so that muscle action potentials cannot be generated. This is called phase I or depolarization block In the continued presence of succinylcholine, the membrane becomes repolarized. Na+ channel inactivation is reversed and muscle membrane excitability is restored Nonetheless, the neuromuscular block persists because of desensitization of Acetylcholine receptors This is known as phase II or desensitization block -The mechanism for phase 11 block is not completely understood, a series of allosteric transitions in Acetylcholine receptor is suspected. Succinylcholine phase I block changes to phase II block after prolonged administration of the drug usually following 7-10 mg/kg of the drug or 700 nzg drug. Pseudocholinesterase deficiency Succinylcholine is rapidly hydrolyzed by plasma cholinesterase to succinylmonocholine which is pharmacologically inactive. In ceain conditions metabolism of succinylcholine to the metabolically inactive succinylmonocholine cannot occur. These are : ? Genetic determined inability to metabolize succinylcholine -Small propoion of patients have genetically determined inability to metabolize succinylcholine. -1n these patients either the plasma cholinesterase is absent or there is an abnormal fornz of the enzyme present. - The metabolism of sucinylcholine is reduced and the patient have prolonged paralysis. - An impoant point to note is that this prolonged paralysis occurs even with usual doses of succinylcholine. Other endogenous and exogenous causes Plasma cholinesterase activity can be reduced by a number of endogenous and exogenous causes such as : -- Pregnancy - Liver disease - Uremia - Malnutrition - Burns - Plasma pheresis - Oral contraceptives These conditions usually lead to a slight clinically unimpoant increase in the duration of action of succinylcholine.
Etomidate
Thiopentone
Ketamine
Propofol