Drugs

Drug name:	MORPHINE SULPHATE
Phial size	1ml, 10mg/ml, usually diluted into 10ml with saline makes 1mg/ml
Dose	0.1 mg/kg
Pharmacokinetics (what the body does to the drug)	Peak action IV - in 10 minutes, IM in 30 mins. Duration of 3-4 hours. Liver and kidneys metabolise it, active metabolites accumulate in renal failure
Pharmacodynamics (what the drug does to the body)	70% First pass metabolism if taken orally.
Mechanism of action	Agonist at opiate receptor type mu-1 (analgesia, meiosis, euphoria) and mu-2 (respiratory depression, bradycardia, inhibits gastric motility). Receptors are pre-synaptic and activate Gi proteins leading to inhibition by increased K conductance and consequent hyperpolarization of the cell membrane.
Contraindications
Side Effects	Respiratory depression Nausea and vomiting (Chemotactic Trigger Zone effect) CNS sedation, euphoria, dysphoria Bradycardia and hypotension due to histamine release and reduced sympathetic tone, no effect on myocardial contractility Decreased gut motility from increased tone of sphincters Bronchospasm and hypotension from histamine release, improved if slow administration Pruritus Muscle rigidity rarely. Meiosis, reversed by atropine Endocrine - inh. ACTH, PRL and FSH/LH, Inc. ADH can lead to hyponatraemia Urinary retention from inc. detrusor and sphincter tone

Drug name:	ALFENTANIL
Phial size	2ml, 500mcg/ml - 1mg in the phial. Or a large phial has 10ml of same concentration. Can come in 5mg/ml concentration.
Dose	5-25 mcg/kg, typically 500mcg on induction, 250mcg boluses at time of painful stimulation intraop. Can be used as an infusion - longer duration of action
Elimination	In Liver CYP3A3/4, by N demethylation. Same enzyme as midazolam so they work synergistically.
Mechanism of action	Synthetic phenylpiperidine derivative. Mu agonist. Lower lipid solubility than fentanyl pKa = 6.4 therefore at pH 7.4,89% unionised and cross cell membranes contrast to fentanyl. pKa = 8.4, so only 9% unionised at pH of 7.4
Contraindications
Side Effects	Very potent respiratory depressant.

Neuromuscular blockade

Drug name:	ATRACURIUM, "Trac"
Phial size	5ml, 10mg/ml - 50mg in a phial. Also comes in 2.5ml.
Storage	Kept in fridge.
Dose	Short acting relaxant which is rapidly broken down by the body. Very predictable as it wears off rapidly compared to the longer acting relaxants. A dose of 0.3-0.6mg/kg will provide relaxation for 20-40 minutes. Intubation dose 0.5mg/kg. Supplemental doses should be 5-10mg
Pharmacokinetics	Atracurium is broken down to inactive metabolites by (minor) ester hydrolysis and spontaneous Hoffman degradation (major pathway) to Laudanosine. This metabolite has been shown to cause seizures in animal models >17mcg/ml). There is little change in its effects in patients with renal or liver failure. When used for long operations it is very predictable
Mechanism of action	Inhibit action of ACh at NMJ by competitively binding to the Alpha subunit of the nicotinic ACh receptor on the post junctional membrane.
Contraindications	Atracurium precipitates in an alkaline pH and it should never be mixed with thiopentone. Always flush the vein with saline if using the two drugs at induction.
Side Effects	Although atracurium produces few direct circulatory effects the absence of vagal blocking activity makes the patient vulnerable to bradycardias during anaesthesia. Histamine release may occur with doses of atracurium greater than 0.6mg/kg. Histamine may also be released if atracurium precipitates in the syringe or vein. This may occur if atracurium is injected immediately after thiopentone

Drug name:	VECURONIUM "Vec"
Phial size	5ml, 2mg/ml - 10mg in a phial.
Storage
Dose	IV dose of 0.1mg/kg will produce relaxation for 15-30 minutes and supplemental doses should be 1-2mg.
Pharmacokinetics	Excreted both in bile and urine. Its action is slightly prolonged in renal impairment. In the liver, vecuronium undergoes deacetylation to the active metabolites 3- and 17-hydroxy and 3,17-dihydroxyvecuronium
Mechanism of action
Contraindications
Side Effects	Are minimal although the potential problems listed under atracurium apply. Histamine release is not a feature. Little cardiovascular depression. Placental transfer is minimal

Drug name:	SUXAMETHONIUM "Sux"
Phial size	2ml, 50mg/ml - 100mg in a syringe.
Storage	Kept in fridge.
Dose	Suxamethonium is a short acting muscle relaxant. The main uses in anaesthesia are 1. to allow rapid intubation of the trachea and short periods of neuromuscular blockade 2. for the modification of fits after electroconvulsive therapy 1-2mg/kg for intubation. The muscle paralysis can be continued with intermittent intravenous boluses, using about 25% of the initial dose. The total dose should not exceed 6-8 mg/kg
Elimination
Mechanism of action	The dicholine ester of succinic acid (two acetylcholine molecules joined back-to-back).The drug causes prolonged depolarisation of skeletal muscles to a membrane potential above which an action potential can be triggered. The onset of muscle relaxation will be rapid after intravenous injection (30-60 seconds), and lasts 5-10 minutes. . In an emergency suxamethonium may be administered intramuscularly, but the onset of action is slower and less predictable than when given intravenously
Contraindications	Suxamethonium is contraindicated in patients with recent burns (ok in first 24 hours) or spinal cord trauma causing paraplegia (can be given immediately after the injury, but should be avoided from approximately day 10 to day 100 after the injury), raised potassium levels, severe muscle trauma, or a history of malignant hyperpyrexia. Suxamethonium should be used with caution in patients with atypical plasma cholinesterase, or with muscle diseases. There may be prolonged paralysis or dangerous rises in potassium levels.
Side Effects	Cardiovascular: suxamethonium can cause bradycardia, especially if second or further doses are given. This can be prevented by the prior administration of atropine. Children develop this complication more commonly than adults. • Metabolic: the potassium level in the serum will rise by about 0.2-0.4mmol/L in normal patients and by much more in patients with recent burns, paraplegias or severe muscle trauma. • Raised intracranial and intraocular pressure: there is a transient rise in intracranial and intraocular pressure after suxamethonium. This is of no importance in patients without eye or intracranial disease, but the drug should be avoided in patients with these conditions if possible. • Prolonged paralysis: this can occur in patients with abnormal plasma cholinesterases; if suxamethonium is given in excessive doses e.g. by repeat injections or infusion; in patients having certain drugs e.g. some antibiotics. SUX APNOEA • Anaphylaxis: suxamethonium can cause allergic reactions, which range in severity from minor flushing of the skin to cardiac arrest and severe bronchospasm. • Malignant hyperthermia: suxamethonium can trigger the onset of malignant hyperthermia in those patients who have this genetic muscle disorder. Muscle pains: the fasciculations seen before the onset of muscle paralysis can cause muscle pain post-operatively, especially in women, the middle-aged and those ambulant early in the post-operative period

SUX APNOEA

Suxamethonium is metabolised by an enzyme in the blood called plasma cholinesterase. Metabolism is normally complete within 5-10 minutes. Some patients lack this enzyme or have an altered enzyme that does not metabolize the suxamethonium as rapidly.

These patients may remain paralysed for many hours after a standard dose of suxamethonium, and must be kept anaesthetised and ventilated until the suxamethonium has been eliminated by other slower methods.
The normal gene encoding for plasma cholinesterase is E1u (usual).
There are three abnormal genes: E1a (atypical), E1s (silent) and E1f (fluoride-resistant)

94% of the population are heterozygous for the usual gene (hence normal response to suxamethonium), E1a homozygotes occur in 0.03% of the population, E1s homozygotes in 0.001% and E1f homozygotes in 0.0003% of the population. All remain apnoeic for 1-2 hours.

Anti-emetics

Induction agents

Drug name:	ETOMIDATE
Phial size	10ml, 2mg/ml - 20mg in phial.
	Imidazole derivate and an ester
Dose	0.3 mg/kg for induction. 70kg ~ one 10ml phial
Elimination	75% bound to albumin, actions terminated by redistribution, metabolised in liver and excreted in urine
Mechanism of action
Contraindications	Can trigger porphyric crisis
Side Effects	Least cardiovascular disturbance Less common hypersensitivity reactions Suppresses adrenocortical function, only clinically significant if used for sedation on ITU Pain on injection, Excitatory movement, Increased PONV

Drug name:	THIOPENTONE
Phial size	Make up to 20ml with water. 500mg in 20 ml. 25mg/ml
Classification
Dose	Induction 3-5mg/kg bolus
	Rapid onset, short duration of action. One arm-brain time to onset. Highly lipophilic and cross BBB readily. Distribution half-life of 4 mins
Mechanism of action	A Barbiturate.
Contraindications	Porphyria
Side Effects	Excitatory activity on induction 4% Extravasation injury due to alkaline medium Intra-arterial injection causes severe tissue damage due to the drug precipitating out of solution into crystals. How to manage... Venous thrombosis in 3-4% Unusual taste in mouth prior to sleep Hypotension
	Empty syringe. Light yellow liquid. Usually in 20ml syringes.

If intra-arterial injection:

Stop injection
Normal saline into same place
Local anaesthetic and/or vasodilator into same place (5ml 1% lignocaine, Phenoxybenzamine 0.5mg)
Papaverine systemically 10-20ml of 0.4% solution
Consider sympathetic block
IV heparin
Consider IA steroids
Postpone surgery if possible

Drug name:	KETAMINE
Phial size	10, 50, 00 mg/ml available
Storage
Dose	1-2mg/kg induction IV, 5-10mg/kg IM Takes up to 90 seconds to work
Elimination
Mechanism of action	NMDA antagonist within CNS. Complex action of opioid receptors.
Contraindications
Side Effects	Sympathetic activation - causing increase HR and BP and inc. myocardial O2 demands. Not arrhythmogenic Respiratory stimulant not depressant. Patent airway usually maintained Causes bronchodilation so may be useful for asthma Dissociative state. Confusion, hallucination on induction and emergence Increased O2 consumption, CBF and intracranial pressure Muscle tone increased and jerking movements occur PONV and salivation common

Co-induction agent

Emergency drugs

Aramine = Metaraminol, 10mg in 1ml, dilute down into 20ml = 0.5mg per ml, give in 0.5ml boluses = 0.25mg.

Aminophylline. 250mg in 10ml, dilute into 100ml with saline and put in burette, run over 1 hour.

Midazolam infusion for sedation, 1/2/3/4 mg/hr. Put 60mg in 60 ml and put on pump. If with morphine infusion also.

Propofol for TIVA, 10mg/kg/hr, down to 8, down to 6 at 10 minute intervals, if too deep - stop infusion for 2 mins.

Drug name	FENTANYL
Phial size / storage	2ml, 50mcg/ml - 100mcg in a phial
Chemistry	A anilo-piperidine opioid
Pharmacokinetics (what the body does to the drug)	Distribution and Elimination
Pharmacodynamics (what the drug does to the body)



	Dose 1mcg per kg Typically 100mcg at induction