Pharmacology
Anaesthesia
Regarding muscle relaxant drugs, which of the following statements is CORRECT:
Answer:
The non-depolarising muscle relaxants do not cross the blood-brain barrier as they are water-soluble polar molecules and therefore have no effect on the central nervous system; they have no sedative or analgesic effects and are not considered to trigger malignant hyperthermia. Unlike the non-depolarising muscle relaxants, the effects of suxamethonium cannot be reversed with neostigmine, which in fact potentiates the neuromuscular block. Atracurium is a non-depolarising muscle relaxant which acts by competitively binding to and blocking acetylcholine receptors on the postsynaptic membrane.Muscle Relaxants
Pharmacology / Anaesthesia
Last Updated: 4th April 2019
Neuromuscular blocking drugs used in anaesthesia are also known as muscle relaxants. By specific blockade of the neuromuscular junction they enable light anaesthesia to be used with adequate relaxation of the muscles of the abdomen and diaphragm. They also relax the vocal cords and allow the passage of a tracheal tube. Their action differs from the muscle relaxants used in musculoskeletal disorders that act on the spinal cord or brain.
Patients who have received a neuromuscular blocking drug should always have their respiration assisted or controlled until the drug has been inactivated or antagonised. They should also receive sufficient concomitant inhalational or intravenous anaesthetic or sedative drugs to prevent awareness.
Non-Depolarising Agents
Non-depolarising muscle relaxant drugs e.g. atracurium compete with acetylcholine (ACh) molecules released from the presynaptic membrane at the neuromuscular junction (NMJ), by binding with the ACh receptors on the postsynaptic membrane of the motor endplate, blocking the action of ACh and preventing depolarisation and muscle contraction.
None of these drugs cross the blood-brain barrier as they are water-soluble polar molecules and therefore have no effect on the central nervous system; they have no sedative or analgesic effects and are not considered to trigger malignant hyperthermia.
Non-depolarising neuromuscular blocking drugs have a slower onset of action than suxamethonium chloride and can be classified by their duration of action as short-acting (15 - 30 mins), intermediate-acting (30 - 40 mins) and long-acting (60 - 120 mins), although duration of action is dose-dependent.
Atracurium besilate is a benzylisoquinolinium neuromuscular blocking drug with an intermediate duration of action. It undergoes non-enzymatic metabolism which is independent of liver and kidney function, thus allowing its use in patients with hepatic or renal impairment. Cardiovascular effects such as flushing, tachycardia, hypotension and bronchospasm are associated with significant histamine release; histamine release can be minimised by administering slowly or in divided doses over at least 1 minute.
All non-depolarising drugs should be used with care in patients suspected to be suffering with myasthenia gravis or myasthenic syndrome, as patients with these conditions are extremely sensitive to their effects.
Neostigmine, an anticholinesterase, is used specifically for reversal of non-depolarising (competitive) blockade. It acts within one minute of intravenous injection and its effects last for 20 to 30 minutes; a second dose may then be necessary.
Depolarising Agents
Depolarising muscle relaxants produce what appears to be a "persistent" depolarisation at the NMJ by binding to ACh receptors and mimicking the effect of ACh but without dissociating from the receptors and being rapidly hydrolysed by acetylcholinesterase. Propagation of an action potential is prevented by the area of inexcitability that occurs around the ACh receptors. Suxamethonium is the only depolarising muscle relaxant with clinical usefulness, has the most rapid onset of action of any of the neuromuscular blocking drugs and is ideal if fast onset and brief duration of action are required.
Unlike the non-depolarising neuromuscular blocking drugs, its action cannot be reversed and anticholinesterases such as neostigmine actually potentiate the neuromuscular block. Recovery from suxamethonium is spontaneous; the drug is normally hydrolysed rapidly (5 - 10 mins) by plasma pseudocholinesterase. Reduced plasma cholinesterase synthesis in end-stage hepatic disease or congenital deficiency may increase the duration of action resulting in prolonged paralysis with apnoea.
Suxamethonium should be given after anaesthetic induction because paralysis is usually preceded by painful muscle fasciculations due to the initial endplate depolarisation; asynchronous muscle fibre twitches cause damage which can result in muscle pains the next day, and also potassium release and hyperkalaemia. While tachycardia occurs with single use, bradycardia may occur with repeated doses in adults and with the first dose in children. Premedication with glycopyrronium bromide or alternatively atropine sulfate, reduces bradycardia, excessive salivation and other muscarinic effects associated with suxamethonium use.
Malignant hyperthermia is a rare but often fatal complication in susceptible patients that results from a rapid increase in muscle metabolism. About 50% of patients are genetically predisposed. It is characterised by tachycardia and, among other manifestations, intense muscle spasm that results in a rapid and profound hyperthermia.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
