Basic pharmacology of anaesthesia-related drugs

Premedication Drugs
Premedication is defined as administration of medication prior to anaesthesia. Aims: Anxiolysis Analgesia Antisialagogue (drying of airway secretions) Anti-emetic Acid aspiration prophylaxis

Midazolam
It is a short acting benzodiazepine. It is the most common drug used for sedation and anxiolysis preoperatively

Perioperative indications are sedative,anxiolysis,amnesic,anticonvulsant Preoperatively midazolam can be given via intravenous or orally.

Midazolam

(continued)

Dose : Oral - 0.2mg/kg IV - 0.1-0.2mg/kg * should be given 20-40 min preop Side Effect: hypotension, respiratory depression, apnoea Caution: reduce dose in elderly ( very sensitive )

Diazepam

It is a long acting benzodiazepine Perioperative indication are sedation, termination of status epilepticus For preoperatively diazepam normally be given orally Dose: oral 0.1-0.2mg/kg Side effect : Sedation, circulatory depression

Morphine It is an opioid It be given before op as an analgesia Can be given via iv or sc Dose: 0.15-0.2mg/kg. Total dose 10 mg. Side effect of morphine are histamine release, hypotension, bronchospasm, nausea, vomiting, pruritus, dysphoria Should be used with caution as it can cause prolonged risk of respiratory depression.

Pethidine It is an synthetic opioid Used preoperatively as an analgesia (agent of choice in asthma) Can be used postoperatively for postoperative shivering Analgesic dose 1-1.5mg/kg IV/IM

Pethidine

(continued)

Side effect : Respiratory depression, hypotension, dysphoria Should be used with caution because it can cause seizure in high dosage - maximum daily dose 1 g/day ( 20 mg/kg/day) Contraindication in pt on MAOI

Atropine sulphate
Anticholinergic Uses: Preoperative: Antisialogogue, reduce incidence of laryngospasm and reflex bradycardia arrythmia during general anaesthesia Postoperative: Counteract muscurinic effects of anticholinergic agents used for reversal of neuromuscular blocking agents. Cardiac: Sinus bradycardia or asystole durig cardiopulmonary resuscitation or drug toxicity.

Dosage:
Administered IV/IM at a dose of 0.015-0.02mg/kg Antisialogogue:IV (0.3-0.6mg) 30 min before op . Bradyarrythmias: adult IV/IM 0.5-1 mg max 2mg. Child IV/IM 0.01-0.03 mg/kg max 0.6 mg

Side effects: Decrease secretions, decreses lower oesophageal sphincter tone, relaxes bronchial smooth muscle. Confusion in elderly. Obstructive uropathy Contraindications/Precautions: angle closure glaucoma, obstructive uropathy, obstructive disease of GIT.Caution in IHD, MI and fever.

Glycopyrollate
It is an anticholinergic agent Perioperative indication : Blockade of muscurinic effects of anticholinesterases, Potent antisialogogue Quaternary ammonium therefore cannot cross blood brain barrier Dose iv/im : 0.004-0.008mg/kg 30 min preop

Glycopyrollate

(continued)

Side effect : Paradoxical bradycardia in small doses. Reduces lower oesophageal sphincter tone. Caution in glaucoma and cardiovascular disease.

Promethazine
It is a phenothiazine group It has an antihistamine with sedative and antiemetic propertie Commonly used as pediatric sedation Dose 0.25-0.5mg/kg oral Side effect extrapyramidal reactions

Metoclopromide
A procainamide derivative. It is a prokinetic drugs . Act at the dopaminergc receptor. Increases gastric emptying and lower oesophageal sphinter tone . Dopaminergic anti-emetic Prescribes for premedication drug in patient at risk of acid aspiration. e.g: pregnancy, gastric outlet obstruction, obese,etc

Metoclopromide

(continued)

Dose : Oral/IM/IV 5-20mg Side effect: sedation,extrapyramidal/dystonic reactions. Caution with concomitant usage with neuroleptic and anticholinergic, patient with abnormal renal or liver function, elderly ..

Ranitidine
Gastric PH increasing drugs Histamine (H2) receptor antagonist Reduction in gastric acid secretion. Use as premedication drug in patient at risk of acid aspiration

Ranitidine

(continued)

Dose :- Adult : Oral - 150mg ON & morning IV - 50-100mg 1H preop Child : Oral - 2 mg/kg/dose 12 hourly or 4 mg/kg at night IV - 1mg/kg/dose slowly 6-8 hourly Side effect : Generally infrequent. Headache, malais, dizziness, thrombocytopenia (clinically insignificant ) No known contraindication . Caution in renal and hepatic dysfunction

Omeprazole
Proton pump inhibitor. Gastric PH increasing. Significantly reduces volume of gastric acid secretion but no effect on gastric emptying. Clinical usage: Treatment of peptic ulcer disease, peptic esophangitis , zollinger Ellison and can also be use in patient at risk of gastric acid aspiration.

Dosage: Oral:40mg ON & 2-3h preop IV :40mg over 30 min Side effect : In general well tolerated . Headache and diarrhoea, myalgia, rash and abdominal pain.

Na Citrate 0.3M
Gastric PH increasing drugs. Uses: Given as premedication drug for patient at risk of gastric acid aspiration in particular pregnancy Dose : Oral 10-30mls <30 min preop

Reversal Drugs
Includes reversal of :
Muscle relaxation Drug action ( antagonist )

Neostigmine
Anticholinesterase reversal of non-depolarizing muscle relaxant treatment of myasthenia gravis Dose: Reversal of muscle relaxant IV 0.04-0.05mg/kg in combination with anticholinergic agent

Adverse/Side effects: Muscurinic effects: nausea, vomiting, epigastric discomfort, abdominal cramps, increase salivation and bronchial secretions, bradycardia, miosis, hypotension. Nicotinic effects: Fasciculations, twitching, generalised weakness, respiratory depression, paralysis. Overdosage: CNS stimulation, agitation , fear, death

Naloxone
Opioid antagonist. Pure mu-receptor antagonist Uses: 1. Reversal respiratory depression due to opiods. 2.the diagnosis of opioid overdose. Dosage: Reversal of opioid: adult IV 1.5mcg/kg IV 0.1 mg increments at 2-3 minutes intervals to the desired effect. Child IV 0.005-0.1 mg/kg repeated every 2-3 min up to 3 doses if necessary

Adverse/ side effects:

Abrupt reversal of analgesia may produce a catecholamine surge resulting in tachycardia, hypertension, pulmonary oedema and cardiac dysrhythmias

Remarks: Beware of renarcotization if reversing long-acting opioid. Caution in opiod addicts-may precipitate acute withdrawal.

Flumazenil
Benzodiazepine antagonist

Uses: reversal of centrally sedative effects of benzodiazepines. Dose: IV 0.2 mg increments up to 1-2 mg
Contraindicated in patient known allergy. Mixed intoxications with benzodiazepine and cyclic antidepressants since toxic effect of the latter may emerge with the reversal of the benzodiazepine effect.

Caution in severe head injury or epileptic patient. Side effects: Arrythmias,seizures Remarks: Special precaution in benzodiazepine dependence because can cause acute withdrawal. Beware of resedation if long-acting benzodiazepine

Miscellaneous:
Other drugs that are commonly used in anaesthesia .

Vasopressor & inotropes Electrolyte replacement Antiarrythmias Antihypertension

Ephedrine
Direct and indirect sympathomimetic ( and adrenergic action ). Uses: Treatment of hypotension particularly following general, spinal or epidural anaesthesia. As a nasal decongestant. Dose:3-6 mg repeated ( dilute 30 mg in 10 mls saline)1 ml increments. IM: 30 mg

Caution in elderly, hypertension and CVS disease. Can cause tachyphylaxis. Avoid with MAOI and tricyclic antidepressants may increase alpha-adrenergic effects of ephedrine. Side effect: Increase heart rate and blood pressure, acute urinary retention, anxiety, palpitation.

Phenylephrine
Selective direct-acting adrenergic agonist. Peripheral vasoconstriction Uses: Treatment of hypotension. Dose: IV 0.1-0.5 mg increments. (10mg in 20 ml saline, 1 ml aliquots.) IM: 2-5 mg Infusion: 30-60 /min

Contraindication/precaution: MAOI. Caution in elderly or CVS disease Side- effects: Reflex Bradycardia, arryhmias

Adrenaline
Endogenous cathecolamine with alpha and beta action Uses: 1. Treatment of anaphylaxis 2. Bronchodilator 3. Positive inotrope 4. Given by nebulizer for croup

Dose: IV/IM/ETT: 1 ml aliquots of 1:10 000 up to 5-10 ml (0.51mg) infusion: 2-20 mcg/min(0.04-0.4 mcg/kg/min) nebulisation:5ml 1:1000 max dose for infiltration: 2 mcg/kg Dilution: 3mg/50ml=1ml/hr=1g /min Diluent: Normal saline / D5% Infusion range: 1.2-12+ ml/h Initial rate: 5ml/h

Caution in elderly. Can cause arrythmias especially with halothane. Side effects: Hypertension, tachycardia, anxiety, hyperglycaemia, arryhtmias. Reduces uterine blood flow

Remarks: should be administered via central catheter whenever possible.

Dopamine
Naturally occuring catecholamine with ,1, and dopaminergic activity. Uses: Inotropic agent, treatment for hypotension. Dose: 2-10 mcg/kg/min Dilution:200mg/50ml (4mg/ml) alternative regime: 3mg/kg/50ml = 1ml/h = 1g/kg/min Diluent: 0.9% saline, 5%dextrose Infusion rate: 2-9 ml/h

Contraindicated in phaeochromocytoma (due to noradrenaline release),tachyarrythmias and VF. Caution in patient with peripheral vascular disease

Remarks: Should be administered via central catheter.

Dobutamine
1 adrenergic agonist, positive inotrope and chronotrope. Use in cardiac failure Dose: 2.5-10 mcg/kg/min Dilution:250mg/50ml (5mg/ml)

Contraindicated in arrythmias and hypertension. Side effects: Tachycardia, decreased peripheral and pulmonary vascular resistance. Remarks: Can cause phlebitis, but can be administereed peripherally

Noradrenaline
Potent cathecolamine adrenergic agonist. Vasoconstriction. Uses: Treatment of hypotension Dose:2-20 mcg/min (0.04-0.4 mcg/kg/min) Dilution: 4 mg/40ml (100 mcg/ml) Diluent: 5% dextrose

Side effects: Reflex bradycardia, arrythmia, hypertension Remark: Administered via central catheter only. Potentiated by MAOI and tricyclic antidepressants

Vasopressin
-ADH. -vasoconstriction. Uses: Treatment of hypotension Treatment of diabetes insipidus Dose: 20 unit/ml in 40 ml NS (0.5 unit/ml) initial rate 2 ml/h ( diluent normal saline )

Extreme caution in coronary vascular disease Side effects: Pallor, coronary vasoconstriction.

Calcium gluconate
Uses: 1. Electrolyte replacement 2. Positive inotrope. 3. Treatment for hyperkalemia and hypermagnesaemia.

Description: Calcium gluconate 10% contains Ca2+ 220 mol/ml. Calcium chloride contains Ca2+ 680mol/ml

Dose: 2-5 ml 10% solution (10mg/kg, 0.07 mmol/kg) Side effects: Arrythmias, hypertension, hypercalcaemia Remarks: Less phlebitis than calcium chloride

Potassium chloride
Uses: Electrolyte replacement Dose: 10-20 mmol/h (max concentration 40 mmol/litre peripherally). With ECG monitoring: Up to 20-40 mmol/h via central line (Max 200 mmol/day) Dilution: 1 gm in 50mls run over 1 h

Remarks: Dilute solution before administration with 0.9% normal saline,Dextrose 5%. Rapid administration can cause cardiac arrest. High concentration can cause phlebitis.

Magnesium sulphate
Essential mineral used to treat: 1.Hypomagnesaemia 2.Eclamptic seizures. 3. Arrythmias Magnesium sulphate 50%=500mg/ml=2mmol Mg2+/ml. Normal plasma level Mg2+ 1.5-2.2mEq/litre.

Uses: 1. Hypomagnesaemia: 10-15 mg/kg over 20 min, then 1 g/h. 2. Arrythmias: 2g over 10 min. 3. Eclampsia: 4g over 10 min then 1 g/h for 24h.

Caution: Potentiate muscle relaxants. Monitoring of serum level essential during treatment. Can cause heart block
Side effects: CNS depression, hypotension

Sodium bicarbonate
Treatment for acidosis Dose: Wt(kg)x base deficit x 0.3) mmol Normally administered undiluted (8.4% solution) Remarks: 8.4%=1000mmol/litre. Given via central line if possible

Amiodarone
Mixed class IC and III antiarrhythmic useful in treatment of supraventicular and ventricular arrhythmias. Dose: Should be diluted with 5% dextrose only Loading infusion : 5 mg/kg over 1-2 H then 15mg/kg over 24h Maximum 1.2 g in 24H

Contraindication: CI in Sinoatrial heart block, thyroid dysfunction and pregnancy Side effects: Commonly causes thyroid dysfunction, reversible corneal deposits, prolongation of QT interval. Lung Fibrosis (rare) Remarks: administered via central catheter.

Esmolol
Short acting cardioselective beta-blocker. Metabolized by red cell esterases. Treatment of supraventricular tachycardia or intra-operative hypertension

Dose: SVT: 0.5 mg/kg over 1 min, then 50200g/kg/min. Hypertension: 25-100 mg then 50-300 g/kg/min Dilution: 2.5g/50ml (50 mg/ml)

Contraindication: Asthma, heart failure, AV block Side effects: Hypotension, bradycardia

Labetolol
Combined (mild) and adrenergic receptor antagonist. Blood pressure control without reflex tachycardia. Duration 2-4 h Dose: 5 mg increments up to 100 mg. Infusion: 20-160mg/h Contraindicated in asthma,heart failure, AV block. Side effects: Hypotension, bradycardia, bronchospasm

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