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Chapter:
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Source:
Drugs in Anaesthesia and Intensive Care (5 ed.)
Author(s):

Edward Scarth

and Susan Smith

DOI:
10.1093/med/9780198768814.003.0017

Salbutamol

Uses

Salbutamol is used in the treatment of:

  1. 1. asthma

  2. 2. chronic obstructive airways disease and

  3. 3. uncomplicated preterm labour.

Chemical

A synthetic sympathomimetic amine.

Presentation

As 2/4/8 mg tablets, a syrup containing 0.4/2.5 mg/ml, an aerosol delivering 100 micrograms/puff, a dry powder for inhalation in capsules containing 200/400 micrograms, a solution for nebulization containing 2.5/5 mg/ml, and as a clear, colourless solution for injection containing 1 mg/ml of salbutamol sulfate.

Main actions

Bronchodilatation and uterine relaxation.

Mode of action

Salbutamol is a beta-adrenergic agonist (with a more pronounced effect at beta-2 than beta-1 receptors) that acts by stimulation of membrane-bound adenylate cyclase in the presence of magnesium ions to increase intracellular cAMP concentrations. It also directly inhibits antigen-induced release of histamine and slow-releasing substance of anaphylaxis from mast cells.

Routes of administration/doses

The adult oral dose is 2–4 mg 6- to 8-hourly. One or two metered puffs of 200–400 micrograms of the powder may be inhaled 6- to 8-hourly; 2.5–5 mg of the nebulized solution may be inhaled similarly 6-hourly. The drug may also be administered subcutaneously or intramuscularly in a dose of 0.5 mg 4-hourly. Salbutamol should be administered intravenously as an infusion diluted in glucose or saline at a rate not exceeding 0.5 micrograms/kg/min. Bronchodilatation is observed 5–15 minutes after inhalation and 30 minutes after ingestion of the drug, and lasts for up to 4 hours.

Effects

CVS

In high doses, the beta-1 actions of the drug lead to positive inotropic and chronotropic effects. At lower doses, the beta-2 effects predominate and cause a decrease in the peripheral vascular resistance, leading to a decrease in the diastolic blood pressure of 10–20 mmHg.

RS

Bronchodilatation, leading to an increased peak expiratory flow rate (PEFR) and FEV1, occurs after the administration of salbutamol. This is additive to the bronchodilatation produced by phosphodiesterase inhibitors. The drug interferes with the mechanism of hypoxic pulmonary vasoconstriction; an adequate inspired oxygen concentration should be ensured when the drug is used.

GU

Salbutamol decreases the tone of the gravid uterus; 10% of an administered dose crosses the placenta and may lead to tachycardia in the fetus.

Metabolic/other

Salbutamol may decrease the plasma potassium concentration by causing a shift of the ion into cells. It may also cause an increase in the plasma concentrations of free fatty acids and glucose; insulin release is therefore stimulated.

Toxicity/side effects

Anxiety, insomnia, tremor (with no attendant change in motor strength), sweating, palpitations, ketosis, lactic acidosis, hypokalaemia, postural hypotension, and nausea and vomiting may occur, following the use of the drug.

Kinetics

Data are incomplete.

Absorption

10% of the dose administered by inhalation reaches the bronchial tree, the remainder being swallowed.

Distribution

Salbutamol is 8–64% protein-bound in the plasma; the VD is 156 l.

Metabolism

Salbutamol undergoes a significant first-pass metabolism in the liver; the major metabolite is salbutamol 4-O-sulfate.

Excretion

30% of the dose is excreted unchanged in the urine, the remainder in faeces, and as the sulfate derivative in the urine. The clearance is 28 l/hour, and the elimination half-life is 2.7–5 hours.

Special points

Salbutamol appears to potentiate non-depolarizing muscle relaxants.

Sevoflurane

Uses

Sevoflurane is used for the induction and maintenance of general anaesthesia.

Chemical

A polyfluorinated isopropyl methyl ether.

Presentation

As a clear, colourless liquid which is non-flammable; the commercial preparation contains no additives or stabilizers and is supplied in amber-coloured bottles. The molecular weight of sevoflurane is 200, the boiling point 58.6°C, and the saturated vapour pressure 22.7 kPa at 20°C. The MAC of sevoflurane is age-dependent and ranges from 1.4 in elderly patients to 3.3 in neonates (0.7–2.0 in the presence of 65% N2O); the blood:gas partition coefficient is 0.63–0.69, and the fat:blood partition coefficient is 52. The oil:gas partition coefficient is 47–54. Degradation of sevoflurane may occur by two pathways in the presence of warm, dessicated alkaline CO2 absorbants (potassium hydroxide > sodium hydroxide) at low fresh gas flows. The first pathway results in the loss of hydrogen fluoride, with the production of pentafluoroisopropenyl fluoromethyl ether (PIFE or ‘Compound A’) and trace amounts of pentafluoromethoxy isopropyl fluoromethyl ether (PMFE or ‘Compound B’). The second pathway results in the production of HFIP and formaldehyde. The latter may further degrade into formate and methanol. Formate can contribute to carbon monoxide production, whilst methanol may react with Compound A to form Compound B. Compound B may undergo further loss of hydrogen fluoride to produce trace amounts of Compounds C, D, and E.

Main action

General anaesthesia (reversible loss of both awareness and recall of noxious stimuli).

Mode of action

The mechanism of general anaesthesia remains to be fully elucidated. General anaesthetics appear to disrupt synaptic transmission (especially in the area of the ventrobasal thalamus). This mechanism may include potentiation of the GABAA and glycine receptors and antagonism at NMDA receptors. Their mode of action at the molecular level appears to involve the expansion of hydrophobic regions in the neuronal membrane, either within the lipid phase or within hydrophobic sites in cell membranes.

Routes of administration/dose

Sevoflurane is administered by inhalation; the agent has a pleasant, non-irritant odour. The concentration used for induction of anaesthesia is quoted as 5–8%. Maintenance of anaesthesia is usually achieved using between 0.5 and 3%.

Effects

CVS

Sevoflurane causes a dose-related decrease in myocardial contractility and mean arterial pressure; the systolic pressure decreases to a greater degree than the diastolic pressure. The drug does not affect the heart rate, and myocardial sensitization to catecholamines does not occur. The drug does not appear to cause the ‘coronary steal’ phenomenon in man.

RS

Sevoflurane is a respiratory depressant, causing dose-dependent decreases in the tidal volume and an increase in the respiratory rate. The drug depresses the ventilatory response to CO2 and inhibits hypoxic pulmonary vasoconstriction. Sevoflurane appears to relax bronchial smooth muscle constricted by histamine or acetylcholine.

CNS

The principal effect of sevoflurane is general anaesthesia. The drug causes cerebral vasodilation, leading to an increase in the cerebral blood flow; the cerebral metabolic rate is decreased. As with other volatile anaesthetic agents, sevoflurane may increase the intracranial pressure in a dose-related manner. Sevoflurane use is not associated with epileptiform activity.

GU

Sevoflurane reduces renal blood flow and leads to an increase in fluoride ion concentrations (12 micrograms/l to 90 micrograms/l in anaesthesia lasting 1 to 6 hours, respectively). There is no evidence that sevoflurane causes gross changes in human renal function. The drug causes uterine relaxation.

Metabolic/other

In animal models, the drug decreases liver synthesis of fibrinogen, transferrin, and albumin.

Toxicity/side effects

Sevoflurane may cause PONV. It is a trigger agent for the development of malignant hyperthermia. There are no reports of renal toxicity occurring in patients who have received the drug. Rapid emergence in paediatric patients may lead to agitation in approximately 25% of cases. Paediatric patients with Down’s syndrome receiving sevoflurane for inhalational induction may develop bradycardia in up to 52% of cases.

Kinetics

Absorption

The major factors affecting the uptake of volatile anaesthetic agents are solubility, cardiac output, and the concentration gradient between the alveoli and venous blood. Due to the low blood:gas partition coefficient of sevoflurane, it is exceptionally insoluble in blood; the alveolar concentration therefore reaches inspired concentration very rapidly (fast washin rate), resulting in a rapid induction of (and emergence from) anaesthesia. An increase in the cardiac output increases the rate of alveolar uptake and slows the induction of anaesthesia. The concentration gradient between the alveoli and venous blood approaches zero at equilibrium; a large concentration gradient favours the onset of anaesthesia.

Distribution

The drug is initially distributed to organs with a high blood flow (brain, heart, liver, kidney) and later to less well-perfused organs (muscle, fat, bone).

Metabolism

Sevoflurane is metabolized by the process of defluorination via cytochrome P450 (CYP) 2EI, producing HFIP, inorganic fluoride, and CO2. HFIP is rapidly conjugated with glucuronic acid and eliminated in the urine. Approximately 3–5% of an administered dose is metabolized. Cytochrome P450 2EI may be induced by chronic exposure to ethanol and isoniazid. It is not induced by exposure to barbiturates. Fluoride concentrations may increase significantly in the presence of increased CYP 2EI activity, although there are no reports from clinical trials regarding fluoride toxicity.

Excretion

Excretion is via the lungs, predominantly unchanged. Elimination of sevoflurane is rapid, again due to its low solubility, resulting in a fast washout rate. HFIP peak excretion occurs within 12 hours; the elimination half-life is 55 hours. Fluoride ion concentrations peak within 2 hours at the end of anaesthesia; the half-life is 15–23 hours.

Special points

Sevoflurane potentiates the action of co-administered depolarizing and non-depolarizing muscle relaxants to a greater extent than either halothane or enflurane.

As with other volatile anaesthetic agents, the co-administration of N2O, benzodiazepines, or opioids lowers the MAC of sevoflurane.

Drug structure

For the drug structure, please see Fig. 7.


Fig. 7 Drug structure of sevoflurane.

Fig. 7 Drug structure of sevoflurane.

Sodium bicarbonate

Uses

Sodium bicarbonate is used:

  1. 1. for the correction of profound metabolic acidosis, especially that complicating cardiac arrest

  2. 2. for the alkalinization of urine and

  3. 3. as an antacid.

Chemical

An inorganic salt.

Presentation

As 300 mg tablets and as a clear, colourless, sterile solution containing 1.26/4.2/8.4% w/v sodium bicarbonate in an aqueous solution. The 8.4% solution contains 1 mmol/ml of sodium and bicarbonate ions and has a calculated osmolarity of 2000 mOsm/l.

Mode of action

The compound freely dissociates to yield bicarbonate ions which represent the predominant extracellular buffer system. Each gram of sodium bicarbonate will neutralize 12 mEq of hydrogen ions.

Routes of administration/doses

The adult oral dose for the relief of dyspepsia is 600–1800 mg as required. For the alkalinization of urine, an oral dose of 3 g is administered every 2 hours until the pH of the urine is 7.

When administered intravenously for the treatment of profound metabolic acidosis, the dose required to restore the pH to normal is usually calculated from the formula:

Half this amount is administered before the acid–base status is reassessed.

Effects

CVS

Overenthusiastic correction of an acidosis will result in a metabolic alkalosis, which may result in myocardial dysfunction and peripheral tissue hypoxia due to a shift in the oxygen dissociation curve to the left.

RS

Metabolic alkalosis diminishes pulmonary ventilation by an effect on the respiratory centre.

CNS

The major clinical effect of metabolic alkalosis is excitability of the CNS, manifested as nervousness, convulsions, muscle weakness, and tetany.

AS

Oral administration of the drug results in the release of CO2 with subsequent belching.

Metabolic/other

Hypernatraemia, hyperkalaemia, and hypocalcaemia may all result from the intravenous administration of sodium bicarbonate.

Toxicity/side effects

Hypernatraemia and hyperosmolar syndromes may complicate the use of sodium bicarbonate. The compound is highly irritant to tissues when extravasated and may cause skin necrosis and sloughing.

Kinetics

Data are incomplete.

Metabolism

Bicarbonate ions react with hydrogen ions to yield CO2 and water.

Excretion

Occurs via renal excretion of bicarbonate and exhalation of CO2.

Special points

Sodium bicarbonate is physically incompatible with calcium salts (which it precipitates) and may cause inactivation of co-administered adrenaline, isoprenaline, and suxamethonium.

The use of sodium bicarbonate should be avoided in patients with renal, hepatic, or heart failure due to its high sodium content.

Hypertonic preparations of sodium bicarbonate appear to lower intracranial pressure in a manner similar to hypertonic saline.

Sodium chloride

Uses

Sodium chloride is used:

  1. 1. to provide maintenance fluid and extracellular fluid replacement

  2. 2. to replace sodium and chloride ions under circumstances of reduced intake or excessive loss

  3. 3. in the management of hyperosmolar diabetic coma

  4. 4. as a priming fluid for haemodialysis and cardiopulmonary bypass machines

  5. 5. for rehydration of neonates and infants (0.45% solutions)

  6. 6. in the management of severe salt depletion (1.8% solutions)

  7. 7. for the dilution of drugs

  8. 8. for interspinous ligament injection in the treatment of chronic neck and back pain (10% solutions) and

  9. 9. in the management of raised intracranial pressure (5% solution).

Chemical

An inorganic salt.

Presentation

As clear, colourless, sterile 0.45/0.9/1.8/5% solutions in bags of various capacities. The 0.9% solution contains 154 mmol of both sodium and chloride ions per litre. The pH ranges from 4.5 to 7; they contain no preservative or antimicrobial agents.

Main action

Volume expansion.

Routes of administration/doses

Hypertonic saline solutions should be administered via a central venous line.

Effects

CVS

The haemodynamic effects of sodium chloride are proportional to the prevailing circulating volume and are short-lived.

GU

Renal perfusion is temporarily restored towards normal in hypovolaemic patients transfused with the crystalloid.

Toxicity/side effects

The predominant hazard is that of overtransfusion, leading to hypernatraemia or pulmonary oedema. A hyperchloraemic metabolic acidosis may result from repeated administration of sodium chloride.

Kinetics

Absorption

Sodium chloride is rapidly and completely absorbed when administered orally.

Distribution

0.9% solution is isotonic with extracellular fluid; it is initially distributed into the intravascular compartment where it remains for approximately 30 minutes before being distributed uniformly throughout the extracellular space.

Excretion

In the urine.

Sodium nitroprusside

Uses

Sodium nitroprusside is used in the management of:

  1. 1. hypertensive crises

  2. 2. aortic dissection prior to surgery

  3. 3. left ventricular failure and

  4. 4. to produce hypotension during surgery.

Chemical

An inorganic complex.

Presentation

As an intravenous solution of 10 mg/ml of sodium nitroprusside for dilution prior to infusion; it must be protected from light.

Main actions

Vasodilation and hypotension.

Mode of action

Sodium nitroprusside dilates both resistance and capacitance vessels by a direct action on vascular smooth muscle. It appears to act by interacting with sulfhydryl groups in the smooth muscle cell membrane, thereby stabilizing the membrane and preventing the Ca2+ influx necessary for the initiation of contraction.

Routes of administration/doses

Sodium nitroprusside should be administered through a dedicated vein using a controlled infusion device at a rate of 0.5–6 micrograms/kg/min, titrated according to response. Invasive arterial pressure measurement during the use of the drug is considered mandatory. Onset of action is almost immediate; the desired response is usually achieved in 1–2 minutes.

Effects

CVS

In hypertensive and normotensive patients, infusion of the drug causes a decrease in the systemic blood pressure and a compensatory tachycardia; the cardiac output is usually well maintained. In patients with heart failure, cardiac output increases due to a decrease in both venous return and systemic vascular resistance. The myocardial wall tension is decreased, and myocardial oxygen consumption falls; the heart rate tends to decrease due to improved haemodynamics with the use of the drug. The blood pressure is usually well maintained under these circumstances. Myocardial contractility is unaltered by the drug.

RS

Sodium nitroprusside causes a reversible decrease in PaO2 due to attenuation of hypoxic pulmonary vasoconstriction; an increased inspired oxygen concentration may be necessary.

CNS

The drug causes cerebral vasodilation, leading to an increase in intracranial pressure in normocapnic patients; a ‘steal’ phenomenon may occur. The autoregulatory curve is shifted to the left.

AS

Sodium nitroprusside decreases to lower oesophageal sphincter pressure and may cause a paralytic ileus.

GU

The renal blood flow and glomerular filtration rate are well maintained during infusions of the drug.

Metabolic/other

A compensatory increase in plasma catecholamine concentration and plasma renin activity occurs during the use of the drug. A metabolic acidosis may also occur.

Toxicity/side effects

The major disadvantage of the drug is its liability to produce cyanide toxicity, the likelihood of which is increased by hypothermia, malnutrition, vitamin B12 deficiency, and severe renal or hepatic impairment. Cyanide ion toxicity is related to the rate of infusion of sodium nitroprusside, rather than to the total dose used; however, it is recommended that no more than 1.5 mg/kg of the drug is infused acutely and no more than 4 micrograms/kg/min is used chronically. The cyanide ion combines with cytochrome C and leads to impairment of aerobic metabolism; metabolic acidosis due to an increased serum lactic acid concentration may result. The signs of cyanide ion toxicity are tachycardia, dysrhythmias, hyperventilation, sweating, and the development of a metabolic acidosis; these occur at plasma cyanide ion concentrations in excess of 8 micrograms/ml. Treatment of cyanide ion toxicity involves curtailing the infusion of sodium nitroprusside, general supportive measures, and the administration of sodium thiosulfate or dicobalt edetate.

Additionally, profound hypotension produced by the drug may manifest itself as nausea and vomiting, abdominal pain, restlessness, headache, dizziness, palpitations, and retrosternal pain.

Kinetics

Pharmacokinetic data are difficult to obtain due to the very short duration of action of the drug.

Absorption

The drug is not absorbed orally.

Distribution

Sodium nitroprusside in the blood is confined essentially to the plasma; scarcely any is present within red blood cells. The VD is approximately the same as the extracellular space (15 l).

Metabolism

Occurs by two separate pathways. In the presence of low plasma concentrations of sodium nitroprusside, the predominant route appears to be by reaction with the sulfhydryl groups of amino acids present in the plasma. In the presence of higher plasma concentrations of the drug, rapid non-enzymatic hydrolysis occurs within red blood cells. Five cyanide ions are produced by the degradation of each molecule of sodium nitroprusside; one reacts with methaemoglobin to form cyanomethaemoglobin. The remaining four cyanide ions enter the plasma; 80% of these react with thiosulfate in a reaction catalysed by hepatic rhodanese to form thiocyanate. The remainder of the cyanide ions reacts with hydroxycobalamin to form cyanocobalamin (vitamin B12).

Excretion

Both thiocyanate and cyanocobalamin are excreted unchanged in the urine. The elimination half-life of the former is 2.7 days.

Special points

Sodium nitroprusside is removed by haemodialysis.

Sodium valproate

Uses

Sodium valproate is used in the treatment of:

  1. 1. primary generalized epilepsies, especially petit mal epilepsy, myoclonic seizures, infantile spasms, and tonic–clonic epilepsy

  2. 2. chronic pain of non-malignant origin.

Chemical

Sodium valproate is the sodium salt of valproic acid, a fatty (carboxylic) acid.

Presentation

As 100/200/500 mg tablets, a syrup containing 40 mg/ml, and in ampoules containing 400 mg of lyophilized sodium valproate for dilution in 4 ml of water.

Main action

Anticonvulsant.

Mode of action

The most likely mode of action is via GABA-ergic inhibition; sodium valproate increases brain GABA levels by inhibition of succinic semialdehyde dehydrogenase in the GABA shunt. Alternatively, it may:

  1. 1. mimic the action of GABA at post-synaptic receptors and

  2. 2. reduce excitatory inhibition (especially that due to aspartate).

Routes of administration/doses

The adult oral dose is 600–2500 mg daily in two divided doses. The intravenous dose is 400–2500 mg daily in divided doses. The effective plasma range is 40–100 mg/l.

Effects

CNS

The drug has anticonvulsant properties as described. Sodium valproate produces minimal sedation; an essential tremor may occasionally develop with the use of the drug.

Metabolic/other

Hyperammonaemia occurs infrequently.

Toxicity/side effects

Sodium valproate is generally well tolerated. Hepatic dysfunction, acute pancreatitis, gastrointestinal upsets, hair loss, oedema, and weight gain may occur, following administration of the drug. There are also reports of platelet disturbances (decreased platelet aggregation and thrombocytopenia) and coagulation disturbances (increased bleeding time, prothrombin time, and APTT) complicating the administration of sodium valproate.

Kinetics

Absorption

Sodium valproate is rapidly and completely absorbed; the oral bioavailability is virtually 100%.

Distribution

The drug is 90% protein-bound in the plasma, predominantly to albumin; the VD is 0.1–0.41 l/kg. Brain concentrations are 7–28% of plasma levels.

Metabolism

Sodium valproate is almost completely metabolized in the liver by oxidation and glucuronidation; some of the metabolites are active.

Excretion

1–3% is excreted unchanged in the urine. The clearance is 7–11 ml/kg/hour, and the elimination half-life is 8–20 hours.

Special points

High concentrations of sodium valproate displace thiopental from its binding sites in vitro and similarly displace diazepam in vivo. Platelet function may need to be monitored prior to surgery or epidural or spinal anaesthesia.

The drug is contraindicated in patients with acute liver disease, and liver function should be monitored during chronic therapy. The sedative effects of the drug are additive with those of other CNS depressants.

Sodium valproate is not removed by dialysis.

Spironolactone

Uses

Spironolactone is used in the treatment of:

  1. 1. congestive cardiac failure

  2. 2. hepatic cirrhosis with ascites and oedema

  3. 3. refractory oedema

  4. 4. hypertension

  5. 5. the nephrotic syndrome

  6. 6. in combination with loop or thiazide diuretics to conserve potassium and

  7. 7. in the diagnosis and treatment of Conn’s syndrome.

Chemical

A synthetic steroid.

Presentation

As 25/50/100 mg tablets of spironolactone. Fixed-dose combinations with hydroflumethiazide or furosemide are also available.

Main actions

Diuretic.

Mode of action

Spironolactone acts as a competitive antagonist of aldosterone at the latter’s receptor site in the distal convoluted tubule; consequently, Na+ reabsorption is inhibited, and K+ reabsorption is increased. The drug thus promotes saliuresis and also potentiates that produced by other diuretic agents.

Routes of administration/doses

The adult oral dose of spironolactone is 100–400 mg daily; the corresponding dose of potassium canrenoate is 200–800 mg, administered by slow intravenous infusion. The drug has a slow onset of action; the diuretic effect takes 3–4 days to become established.

Effects

CVS

The drug has an antihypertensive effect that may be mediated by alteration of the extracellular:intracellular Na+ gradient or by antagonism of the effect of aldosterone on arteriolar smooth muscle.

CNS

Spironolactone may produce both sedation and muscular weakness, presumably secondarily to electrolyte derangements.

GU

The principal effect of the drug is diuresis with retention of K+. The renal blood flow and glomerular filtration rate are unaffected, although the free water clearance may increase.

Metabolic/other

Spironolactone has an anti-androgenic effect due to inhibition of ovarian androgen secretion and interference with the peripheral action of endogenous androgens. The drug increases renal Ca2+ excretion and may also lead to a reversible hyperchloraemic metabolic acidosis and an increased plasma urea concentration.

Toxicity/side effects

The predominant side effect of spironolactone is hyperkalaemia, especially in the presence of renal impairment. The use of the drug is also associated with an appreciable incidence of nausea and vomiting and other gastrointestinal disturbances. Menstrual irregularities in the female and gynaecomastia in the male may result from the anti-androgenic effects of spironolactone.

Kinetics

Absorption

Spironolactone is incompletely absorbed when administered orally and has a bioavailability by this route of 70%; the drug undergoes extensive first-pass hepatic metabolism.

Distribution

The drug is 90% protein-bound in the plasma.

Metabolism

Spironolactone is rapidly and extensively metabolized by deacetylation and dethiolation; some of the metabolites, including canrenone, are active.

Excretion

The metabolites are principally excreted in the urine, with a small proportion undergoing biliary excretion. The elimination half-life of spironolactone is 1–2 hours.

Special points

Spironolactone decreases the responsiveness to co-administered pressor agents and increases the effects of co-administered cardiovascular depressants, including anaesthetic agents. The drug increases the serum concentrations of co-administered digoxin and may interfere with digoxin assay techniques.

SSRIs

Uses

Selective serotonin reuptake inhibitors (SSRIs) are used in the treatment of:

  1. 1. unipolar depression

  2. 2. obsessive–compulsive disorder

  3. 3. generalized anxiety disorder

  4. 4. social anxiety disorder

  5. 5. panic disorder

  6. 6. post-traumatic stress disorder and

  7. 7. bulimia nervosa.

Chemical

SSRIs have a variety of chemical structures.

Presentation

The following SSRIs are in common clinical use and are available in tablet or capsule form: fluvoxamine, fluoxetine, sertraline, paroxetine, citalopram, and escitalopram.

Main action

Antidepressant and anxiolytic.

Mode of action

SSRIs selectively inhibit the neuronal reuptake of serotonin by the pre-synaptic serotonin reuptake pump. In vitro, they exhibit very weak anticholinergic and histaminergic activity.

Routes of administration/doses

SSRIs are usually administered orally as a single daily dose in the mornings. The specific dose of an SSRI administered is dependent on the clinical indication, age of the patient, and particular agent being used.

Effects

CVS

SSRIs may cause an increase or decrease in the heart rate, together with a fall in the blood pressure which may be postural in nature.

CNS

The effects of SSRIs are to improve mood and decrease feelings of anxiety.

Metabolic/other

SSRIs may cause a decrease in plasma sodium concentration, possibly causing inappropriate ADH secretion. These drugs should be used with caution in patients concurrently receiving diuretics.

Toxicity/side effects

SSRIs cause dose-related gastrointestinal effects (nausea, abdominal pain, diarrhoea). Hypersensitivity reactions of all types may occur. Urogenital side effects have been reported, including reduced libido, anorgasmia, impotence, and urinary frequency or retention.

Kinetics

Absorption

SSRIs are well absorbed from the gastrointestinal tract. They undergo extensive first-pass metabolism, except for citalopram.

Distribution

Due to the lipophilic nature of SSRIs, these drugs have large volumes of distribution and consequently take some time to reach a steady-state concentration.

Metabolism

SSRIs undergo extensive hepatic metabolism via the cytochrome P450 system. In addition, the drugs are potent inhibitors of certain CYP isoenzymes, including CYP2D6. Fluoxetine is metabolized to the active metabolite norfluoxetine.

Excretion

Metabolites undergo renal elimination.

Special points

All SSRIs are associated with a withdrawal syndrome if treatment is discontinued abruptly. The commonest symptoms include: nausea, vomiting, headache, paraesthesiae, dizziness, sweating, sleep disturbances, and anxiety.

Concurrent administration of SSRIs to patients receiving MAOIs, lithium, L-tryptophan, sumatriptan, risperidone, or 3,4-methylenedioxy- methamphetamine (MDMA) may lead to serotonin syndrome. Serotonin syndrome is characterized by the acute onset of the following symptoms and signs: tachycardia, hypertension, hyperthermia, sweating, nausea, diarrhoea, agitation, pupillary dilatation, myoclonus, and hyperreflexia.

Statins

Uses

Statins are used in the treatment of:

  1. 1. hypercholesterolaemia

  2. 2. primary prevention of cardiovascular events

  3. 3. secondary prevention of cardiovascular events.

Chemical

Naturally occurring or synthetically derived inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCoA).

Presentation

Six agents are available in the UK for oral administration. Atorvastatin and simvastatin comprise approximately 85% of statins prescribed in the UK.

Main action

Reduction in total cholesterol.

Mode of action

Inhibition of HMGCoA reductase, leading to early blockade of conversion of HMGCoA to mevalonate, thereby preventing subsequent conversion to cholesterol and isoprenoids.

Routes of administration/doses

The specific dose of an agent administered is dependent on the clinical indication and particular agent being used. Statins are administered orally, usually at night.

Toxicity/side effects

The most important side effect of statin therapy is muscle pains which may be associated with a myopathy, with subsequent development of rhabdomyolysis, and acute renal failure secondary to myoglobinuria. Sleep disturbance, memory loss, sexual dysfunction, depression, and rarely interstitial lung disease have all been reported, following use of these drugs. Hepatic serum transaminases may become elevated during treatment.

Kinetics

Absorption

The bioavailability of statins is variable, depending on the specific agent. Atorvastatin has a bioavailability of 12% and simvastatin a bioavailability of 5%. Statins undergo extensive first-pass metabolism.

Distribution

Statins are highly protein-bound in the plasma (90–98%), apart from pravastatin which has protein binding of 43–67%.

Metabolism

The majority of statins are metabolized via the cytochrome P450 enzyme system. Atorvastatin and simvastatin are metabolized by CYP3A4. Atorvastatin is metabolized to orthohydroxylated and parahydroxylated metabolites during first-pass metabolism, which are pharmacologically active. Simvastatin is an inactive lactone that is metabolized during first-pass metabolism to the active metabolite beta-hydroxyacid.

Excretion

The half-life of atorvastatin is 15 hours and that of simvastatin 1.9 hours. Up to 20% of a dose may be excreted renally. The majority of metabolites undergo biliary excretion. Minimal enterohepatic circulation occurs.

Special points

There is growing evidence to suggest that statins act as inhibitors of the inflammatory process. Statins reduce leucocyte adhesion to endothelial cells during sepsis-driven leucocyte activation. The drugs also downregulate the production of the following pro-inflammatory cytokines: IL-6, IL-8, TNF-alpha, monocyte chemoattractant protein-1, and C-reactive protein (CRP). Statins also appear to reduce the procoagulant effects seen in sepsis and have anti-inflammatory effects mediated through upregulation of endothelial NO synthase activity, thereby enhancing NO production.

Co-administration of agents that act as CYP3A4 inhibitors may lead to increased drug levels of statins and a corresponding increased risk in the development of myopathy/rhabdomyolysis. The following agents require either discontinuation of statin therapy or dose reduction, depending on the specific drug(s) being used: itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, ciclosporin, diazole, amiodarone, verapamil, diltiazem, grapefruit juice.

Sucralfate

Uses

Sucralfate is used:

  1. 1. in the treatment of peptic ulcer disease and

  2. 2. for the prevention of stress ulceration in the critically ill.

Chemical

An aluminium salt of sulfated sucrose.

Presentation

As tablets containing 1 g sucralfate and a white, viscous suspension containing 200 mg/ml of sucralfate.

Main actions

Cytoprotection of the upper gastrointestinal tract.

Mode of action

At acid pH, sucralfate forms a viscous paste which adheres preferentially to peptic ulcers via ionic binding. It acts by providing a physical barrier to the diffusion of acid, pepsin, and bile salts and also by forming complexes with proteins at the ulcer surface, which resist peptic hydrolysis.

Routes of administration/doses

The adult dose for the prophylaxis of stress ulceration is 1 g 6-hourly.

Effects

AS

Sucralfate has weak intrinsic antacid activity. It has no effect on gastric emptying time. The drug increases gastric blood flow and enhances gastric epithelial proliferation via stimulation of gastric mucosal epidermal growth factor and fibroblast growth factor.

Metabolic/other

In uraemic patients, sucralfate increases aluminium absorption and therefore should be used with care. It acts as a phosphate binder which may induce hypophosphataemia.

Toxicity/side effects

Sucralfate is essentially non-toxic. Constipation occurs in 2%.

Kinetics

Absorption

Sucralfate is minimally (3–5%) absorbed after oral administration.

Distribution

85–95% of an oral dose remains in the gastrointestinal tract. The VD and percentage of protein binding are unknown.

Metabolism

No metabolism of the drug occurs in man.

Excretion

Predominantly unchanged in the faeces. The fraction that is absorbed is excreted primarily in the urine.

Sufentanil

Uses

Sufentanil is used for:

  1. 1. the induction and maintenance of general anaesthesia and has been used for

  2. 2. post-operative analgesia.

Chemical

A phenylpiperidine which is the thienyl derivative of fentanyl.

Presentation

As a clear solution containing 50 micrograms/ml of sufentanil citrate. The drug is not commercially available in the UK.

Main actions

Analgesia and respiratory depression.

Mode of action

Sufentanil is a highly selective mu-agonist; the MOP receptor appears to be specifically involved in the mediation of analgesia. Part of the analgesic effect of the drug may be attributable to stimulation of 5HT release. Opioids appear to exert their effects by increasing intracellular calcium concentration which, in turn, increases potassium conductance and hyperpolarization of excitable cell membranes. The decrease in membrane excitability that results may decrease both pre- and post-synaptic responses.

Routes of administration/doses

The intravenous dose is 0.5– 50 micrograms/kg, and the adult dose via the epidural route is 10–100 micrograms (the optimal post-operative dose being 30–50 micrograms). When administered intravenously, the drug acts in 1–6 minutes, and the duration of effect is 0.5–8 hours, dependent on the other components of the anaesthetic.

Effects

CVS

Sufentanil causes little haemodynamic disturbance. Heart rate and blood pressure tend to decrease immediately post-induction. Venous pooling may lead to orthostatic hypotension.

RS

The drug produces dose-dependent respiratory depression which may be delayed in onset. Chest wall rigidity (the ‘wooden chest’ phenomenon) may occur after the administration of sufentanil—this may be an effect of the drug on mu-receptors located on GABA-ergic interneurones.

CNS

Sufentanil is 2000–4000 times as potent an analgesic as morphine. The EEG changes produced by the drug are similar to those produced by fentanyl—initial beta activity is decreased, and alpha activity is increased; subsequently, alpha activity disappears, and delta activity predominates. The drug has no intrinsic effect on intracranial pressure. Miosis is produced as a result of stimulation of the Edinger–Westphal nucleus.

AS

Sufentanil appears to cause less nausea than fentanyl. The drug may cause spasm of the sphincter of Oddi.

Metabolic/other

The drug tends to obtund the stress response to surgery, although it does not completely abolish it. Sufentanil may cause histamine release and may have less effect on immune function than fentanyl.

Toxicity/side effects

Hypotension, tachycardia, bradycardia, nausea, and the ‘wooden chest’ phenomenon are the side effects most commonly reported with the use of sufentanil. Tonic/clonic movements of the limbs have also been reported.

Kinetics

Absorption

The drug is normally administered intravenously; the drug is, however, 20% absorbed when administered transdermally.

Distribution

Sufentanil is 92% protein-bound in the plasma, predominantly to alpha-1 acid glycoprotein. The drug is highly lipophilic; the VD is 1.74–5.17 l/kg.

Metabolism

The metabolic pathways are unknown in man, although two metabolites (norsufentanil and desmethylsufentanil) have been identified in the urine.

Excretion

60% of an administered dose appear in the urine and 10% in bile. The clearance is 11–21 ml/min/kg; the elimination half-life is 119– 175 minutes.

Special points

Sufentanil decreases the MAC of co-administered volatile agents by 60–70%. The drug should be used with caution in the presence of renal or hepatic failure, although the kinetics appears to be unaltered.

The drug increases the effect of non-depolarizing muscle relaxants to a similar extent to halothane.

Sugammadex

Uses

Sugammadex is used to reverse neuromuscular blockade induced by rocuronium or vecuronium.

Chemical

A modified gamma-cyclodextrin.

Presentation

As a clear, colourless or pale yellow solution for injection, available in 2 ml and 5 ml glass vials, containing 100 mg/ml of sugammadex sodium (equivalent to sugammadex 100 mg/ml), needing to be stored below 30°C. It has a pH of between 7 and 8 and an osmolality of between 300 and 500 mOsm/kg. One ml of solution contains 9.7 mg of sodium. The solution may also contain 3.7% hydrochloric acid and/or sodium hydroxide for pH adjustment.

Main action

Reversal of neuromuscular blockade induced by rocuronium or vecuronium.

Mode of action

Sugammadex acts by encapsulating the steroid portion of aminosteroidal molecules within its hydrophobic interior. The negatively charged carboxyl groups bind to the positively charged nitrogen atom on the aminosteroidal molecule. This binding of the NMB drug decreases the amount of free drug within the central compartment, thereby establishing a concentration gradient and resulting in movement of the NMB drug away from the effector site towards the central compartment. The resultant reduction in competitive antagonism of acetylcholine at nicotinic (N2) receptors at the post-synaptic membrane of the neuromuscular junction leads to successful binding of acetylcholine and rapid re-establishment of neuromuscular function.

Routes of administration/doses

The drug is administered intravenously as a single bolus injection in a variety of doses, depending on the extent of neuromuscular blockade present in a given patient. A dose of 4 mg/kg is recommended when recovery of neuromuscular function has reached at least 1–2 post-tetanic counts following administration of rocuronium or vecuronium (i.e. ‘deep’ neuromuscular block). The median time to recovery of the T4/T1 ratio to 0.9 is 3 minutes. A lower dose of 2 mg/kg is recommended when recovery of neuromuscular function has reached at least the reappearance of T2 (i.e. ‘shallow’ neuromuscular block), with a median time to recovery of the T4/T1 ratio to 0.9 of 2 minutes. The median recovery time is slightly faster in patients who have received rocuronium, compared to those receiving vecuronium. Sugammadex may also be administered immediately following the administration of rocuronium, as part of a modified rapid sequence induction (i.e. ‘rescue reversal’) when a ‘can’t intubate, can’t ventilate’ scenario has occurred. The recommended dose for ‘rescue reversal’ is 16 mg/kg. Following the administration of 1.2 mg/kg of rocuronium, if sugammadex is given 3 minutes later, the median time to recovery of the T4/T1 ratio to 0.9 is approximately 1.5 minutes. Sugammadex is not recommended for use in ‘rescue reversal’ following the administration of vecuronium. In the event of the re-establishment of neuromuscular block, a second dose of 4 mg/kg of sugammadex is recommended. The recommended dose for reversal in children aged between 2 and 17 years, when the recovery of neuromuscular function has reached at least the reappearance of T2, is 2 mg/kg. Use of the drug is not currently recommended in other reversal situations, including ‘rescue reversal’. Sugammadex is not currently recommended for use in newborns and infants.

Effects

CVS

Sugammadex has minimal cardiovascular side effects. There is no significant prolongation of the QT interval.

RS

The drug has no respiratory effects.

CNS

The drug has no effect on intracranial or intraocular pressure.

AS

Administration of the drug may lead to a bitter or metallic taste.

Toxicity/side effects

There has been one report of a patient developing symptoms of flushing, tachycardia, and palpitations, following the administration of 8.4 mg/kg of sugammadex. These symptoms were confirmed to be that of an allergic reaction and were self-limiting.

Kinetics

Distribution

Sugammadex and the sugammadex–NMB complex do not bind to plasma proteins or erythrocytes. The VD is 11–14 l, and the drug exhibits linear kinetics in the dosage range of 1–16 mg/kg.

Metabolism

The drug does not undergo metabolism within the human body.

Excretion

The clearance is 88–120 ml/min, and the elimination half-life is 1.8 hours. More than 90% of a given dose is excreted within 24 hours. Ninety-six percent of the dose is excreted in the urine, with up to 95% as unaltered drug. Excretion via faeces or expired air was <0.02% of the dose in clinical studies.

Special points

In patients with mild and moderate renal impairment, no alteration in dosage is required. In patients with severe renal impairment, the excretion of sugammadex and the sugammadex–NMB complex is prolonged, and use of the drug is not recommended. The clearance of sugammadex by haemodialysis is variable.

No dose reduction is recommended in elderly patients, although the time to recovery of the T4/T1 ratio to 0.9 may be slightly prolonged.

No dose alteration is required for patients with mild and moderate hepatic impairment. No data are currently available in patients with severe hepatic impairment, and the use of sugammadex is not recommended.

Dose calculation in obese patients should be made, based on the actual body weight.

Reoccurrence of neuromuscular block following the administration of sugammadex has been reported as usually being due to suboptimal dosing of the drug. However, administration of drugs in the immediate post-operative period that potentiate the effects of neuromuscular block may theoretically lead to reoccurrence of block and should be used in caution in patients who have received sugammadex. In addition, displacement of bound neuromuscular block from sugammadex may theoretically occur, leading to reoccurrence of neuromuscular blockade if the following drugs are administered within 6 hours of a patient receiving sugammadex: toremifene, flucloxacillin, fusidic acid.

If neuromuscular blockade is required following reversal with sugammadex, then a non-steroidal agent (e.g. suxamethonium or a benzoisoquinolinium agent) should be used due to the risk of reduced efficacy of standard doses of rocuronium or vecuronium in the presence of residual sugammadex. A delay of 24 hours is recommended prior to repeat administration of rocuronium or vecuronium, following the use of sugammadex.

Due to the steroid-binding ability of sugammadex, the drug may interact with hormonal contraceptive agents. Administration of the drug may lead to a decrease in progesterone exposure (34% decrease) equivalent to missing one daily dose. It is recommended that patients taking oral hormonal contraceptive agents should consult the ‘missed daily dose’ advice contained in the product information leaflet. Patients receiving non-oral hormonal contraceptive agents should be advised to use an additional non-hormonal contraceptive method for the following 7 days after administration of sugammadex.

There is some evidence that sugammadex may interfere with the following laboratory tests: serum progesterone, APTT, prothrombin time. Data suggest that interference with these tests occurs following a dose of 16 mg/kg of sugammadex. The clinical relevance of this is uncertain.

Sulfonylureas

Uses

Sulfonylureas are used in the treatment of non-insulin-dependent (type II) diabetes mellitus.

Chemical

An S-phenylsulfonylurea structure with substitutions on the phenyl ring and urea terminus.

Presentation

Three generations of sulfonylureas exist:

  1. 1. first-generation: tolbutamide

  2. 2. second-generation: gliclazide, glibenclamide

  3. 3. third-generation: glimepiride.

All are presented in tablet form. There is a modified-release preparation of gliclazide.

Main action

Hypoglycaemia.

Mode of action

Sulfonylureas act by liberating insulin from pancreatic beta-cells; they appear to act by binding to the plasma membrane of the beta-cell and producing prolonged depolarization, reducing the permeability of the membrane to potassium. This, in turn, leads to the opening of calcium channels; the resulting influx of calcium causes triggering of insulin release.

Routes of administration/doses

These agents are only available for oral administration. The specific dose and frequency of an agent administered are dependent on the clinical indication and particular agent being used.

Effects

Metabolic/other

Sulfonylureas cause a decrease in plasma triglyceride, cholesterol, and free fatty acid concentrations. Gliclazide decreases the incidence of microthrombosis by two methods, firstly by partial inhibition of platelet aggregation and adhesion and secondly by an action on the vascular endothelium fibrinolytic activity with an increase in tissue plasminogen activator activity. Glimepiride has extra-pancreatic effects. It increases the number of active glucose transport molecules, in addition to increasing the activity of the glycosyl phosphatidylinositol-specific lipase C, which may be correlated with drug-induced lipogenesis and glycogenesis in fat and muscle cells. The drug also inhibits hepatic gluconeogenesis by increasing the intracellular concentration of fructose-2,6-bisphosphate.

Toxicity/side effects

Hypoglycaemia is a common complication of sulfonylurea therapy. Gastrointestinal disturbances, cholestatic jaundice, and alterations in liver function tests may complicate the use of sulfonylureas. Leucopenia and thrombocytopenia have also been reported. Sulfonylureas are potentially teratogenic.

Kinetics

Absorption

Sulfonylureas are well absorbed from the gastrointestinal tract. Gliclazide and glimepiride have a 100% bioavailability.

Distribution

The VD of these agents is variable: gliclazide VD 0.42 l/kg, glibenclamide VD 0.15 l/kg, glimepiride VD 0.12 l/kg. Protein binding is high, with 95–99% of agents bound to albumin.

Metabolism

Sulfonylureas undergo extensive hepatic metabolism via CYP2C9 to inactive metabolites.

Excretion

30–50% of an administered dose is excreted in the urine, the remainder in the faeces. Clearance and elimination half-lives of the individual drugs vary—the half-life of gliclazide is 12–20 hours, and that of glibenclamide is 1–2 hours and of glimepiride is 5–8 hours. The elimination of these agents is impaired in the presence of severe renal impairment.

Special points

The following drugs may potentiate the effect of sulfonylureas either by displacement from plasma proteins or by inhibition of their hepatic metabolism, resulting in hypoglycaemia: NSAIDs, salicylates, sulfonamides, oral anticoagulants, MAOIs, and beta-adrenergic antagonists. Conversely, the following drugs tend to counteract the effect of sulfonylureas and result in loss of diabetic control: thiazide and other diuretics, steroids, phenothiazines, phenytoin, sympathomimetic agents, and calcium antagonists.

The long-acting sulfonylureas should be stopped prior to anaesthesia for major surgery due to the risk of hypoglycaemia. Alternative methods of blood sugar control may need to be instituted.

Suxamethonium

Uses

Suxamethonium is used:

  1. 1. wherever rapid and profound neuromuscular blockade is required, e.g. to facilitate tracheal intubation and

  2. 2. for the modification of fits after electroconvulsive therapy.

Chemical

The dicholine ester of succinic acid (equivalent to two acetylcholine molecules joined back-to-back).

Presentation

As a clear aqueous solution containing 50 mg/ml of suxamethonium chloride; the preparation should be stored at 4°C.

Main actions

Neuromuscular blockade of brief duration in skeletal muscle.

Mode of action

Suxamethonium causes prolonged depolarization of skeletal muscle fibres to a membrane potential above which an action potential can be triggered.

Routes of administration/doses

The intravenous dose is 0.5– 2.0 mg/kg; the onset of action occurs within 30 seconds, and the duration of action is 3–5 minutes. Infusion of a 0.1% solution at 2–15 mg/kg/hour will yield 90% twitch depression. The intramuscular dose is up to 2.5 mg/kg. Equal doses on a mg/kg basis have a shorter duration of action in infants. The drug may also be administered sublingually at a dose of 2 mg/kg.

Effects

CVS

With repeated doses of suxamethonium, bradycardia and a slight increase in mean arterial pressure may occur.

RS

Apnoea occurs subsequent to skeletal muscle paralysis.

CNS

The administration of suxamethonium may initially cause fasciculations which are then followed by a phase I depolarizing block. The characteristics of this during partial paralysis are:

  1. 1. well-sustained tetanus during stimulation at 50–100 Hz

  2. 2. the absence of post-tetanic facilitation

  3. 3. train-of-four ratio >0.7 and

  4. 4. potentiation by anticholinesterases.

With repeated administration or a large total dose, a phase II block may develop. The characteristics of this during partial paralysis are:

  1. 1. poorly sustained tetanus

  2. 2. post-tetanic facilitation

  3. 3. train-of-four ratio <0.3

  4. 4. reversal by anticholinesterases and

  5. 5. tachyphylaxis.

Intracranial and intraocular pressures are both raised, following the administration of suxamethonium.

AS

The intragastric pressure increases by 7–12 cmH2O; the lower oesophageal sphincter tone simultaneously decreases with the use of suxamethonium. Salivation and gastric secretions are increased.

Metabolic/other

Serum potassium concentration is briefly increased in normal individuals by 0.2–0.4 mmol/l.

Toxicity/side effects

Bradycardia and other dysrhythmias may occur with single or repeated dosing. The hyperkalaemic response is markedly exaggerated in patients with burns or major denervation of muscle and acute or chronic renal failure; this may lead to cardiac arrest. Post-operative muscular pains are common, especially in women, the middle-aged, and those ambulant early in the post-operative period. Intraocular pressure is transiently raised, following the use of suxamethonium—the drug should be used with caution in patients with penetrating eye injuries. Suxamethonium is a potent trigger agent for the development of malignant hyperthermia and may cause generalized contractures in those patients exhibiting myotonia. Prolonged apnoea may occur in susceptible individuals. There have been many reports of fatal anaphylactoid reactions with the administration of suxamethonium. Cross-sensitivity exists with many of the non-depolarizing drugs, following administration of suxamethonium.

Kinetics

Distribution

An initial rapid redistribution phase may contribute to the brief duration of action of the drug. Suxamethonium appears to be protein-bound to an unknown extent.

Metabolism

The drug is hydrolysed by plasma cholinesterase (EC 3.1.1.8) to succinylomonocholine (which is weakly active) and choline; the former is further hydrolysed by plasma cholinesterase to succinic acid and choline. Eighty percent of an administered dose is hydrolysed before it reaches the neuromuscular junction.

Excretion

2–10% of an administered dose is excreted unchanged in the urine. The in vivo hydrolysis rate is 3–7 mg/l/min, and the half-life 2.7– 4.6 minutes.

Special points

The incidence of muscle pains after the administration of suxamethonium may be decreased by pre-treatment with:

  1. 1. low (0.2 mg/kg) dose of suxamethonium

  2. 2. small dose of a non-depolarizing relaxant

  3. 3. diazepam

  4. 4. dantrolene

  5. 5. aspirin or

  6. 6. vitamin C.

Plasma cholinesterase activity may be influenced by both genetic and acquired factors, leading to an altered pattern of response to suxamethonium. The normal gene encoding for plasma cholinesterase is EI u (usual); three abnormal genes also exist: EI a (atypical), EI s (silent), and EI f (fluoride-resistant).

Simple Mendelian genetics are involved; 94% of the population are heterozygous for the usual gene and are clinically normal in their response to suxamethonium. El a homozygotes comprise 0.03%, El s homozygotes 0.001%, and El f homozygotes 0.0003% of the population, and all remain apnoeic for 1–2 hours after receiving the drug and develop a phase II block during this period (fresh frozen plasma may be used to provide a source of plasma cholinesterase under these circumstances). All possible combinations of heterozygotes exist—they constitute 3.8% of the population and remain apnoeic for approximately 10 minutes after receiving suxamethonium.

In addition, plasma cholinesterase concentrations may be reduced in pregnancy, liver disease, cardiac or renal failure, hypoproteinaemic states, carcinomatosis, thyrotoxicosis, tetanus, muscular dystrophy, and in patients with burns, and suxamethonium may have a prolonged action in these states. Drugs which decrease the activity of plasma cholinesterase include ecothiopate, tacrine, procaine, lidocaine, lithium and magnesium salts, ketamine, pancuronium, the oral contraceptive pill, and cytotoxic agents. Suxamethonium does not appear to be potentiated by volatile agents, although phase II block may appear more readily in their presence.

Suxamethonium is pharmaceutically incompatible with thiopental. The effects of digoxin may be enhanced by suxamethonium, leading to enhanced ventricular excitability.

Total body weight should be used to calculate drug dosage in morbidly obese individuals.

Drug structure

For the drug structure, please see Fig. 8.


Fig. 8 Drug structure of suxamethonium.

Fig. 8 Drug structure of suxamethonium.

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