Emergency drugs Flashcards
Propofol
Propofol
Uses: induction and maintenance of GA, sedation in ICU/RA, refractory N/V in CTx, Tx of status
Chemical: phenol derivative, 2,6-diisopropylphenol
Presentation: white oil-in-water emulsion (1% or 2%) w/v in soybean oil, purified egg phosphatide, NaOH. aqueous emulsions can support bacterial and fungal growth
Action: hypnotic
MoA: potentiates inhib effects of GABA & glycine
Routes/Dose: IV. Induction bolus (1.5-2.5mg/kg), maintenance infusion (4-12mg/kg/hr). +50% in children.
Effects:
- CVS: CO reduced by 20% as 15-25% decreased in BP & SVR without compensatory tachycardia
- RS: Bolus -> apnoea of varying duration and suppression of laryngeal reflexes. Infusion -> decrease TV, increase RR, decreased response to hypoxia & hypercarbia, bronchodilation (?action on smooth muscle). No increase intrapulmonary shunting, preserves hypoxic pulmonary vasoconstriction
- CNS: smooth, rapid induction with rapid and clear-ehaded recovery. Decreases ICP, CPP, cerebral O2 consumption. ?Anticonvulsant ?Antiemetic (?D2 antagonism)
- Metabolic/other: long term use ?-> hypertriglyceridaemia; free-radical scavenger
Toxicity/SEs:
- pain on injection 28%
- epileptiform movements, facial paraesthesia, bradycardia
- appears safe in porphyria and malignant hyperpyrxia
- ?increased mortality and neuro sequelae in long-term paeds
- quinol metabolites can cause green urine and hair
Kinetics:
- Distribution: 97% protein-bound, VD 700-150l. Distribution 1/2life 1.3-4.1mins
- Metabolism: rapid liver metabolism -> inactive gluconoride (49-73%) + sulphate and gluconoride conjugates of hydroxylated metabolite via P450. Not effected by renal/hepatic disease on metabolism
- Excretion: urine excretion of metabolites + 0.3% unchanged. Clearance = 18.8-40.3ml/kg/min. Elimination 1/2life 9.3-69.3min. Decreased in renal failure. Generally non-cumulative.
Other: may increase energy required for cardioversion; shortened seizure activity in ECT; physically incompatible with atracurium
Metaraminol
Metaraminol
Uses: adjunct in hypotension during GA/SpinalA; Mx of hypotension in cardiopulm bypass
Chemical: sympathomimetic amine
Presentation: metaraminol tartate 10mg/ml as a clear solution
Action: peripheral vasoconstriction
MoA: direct & indirect sympathomimetic, both A and B agonist activity (A»>B)
Routes/Dose: IV = dilute in saline, titrate to response, 0.5-5mg boluses; 1-2min onset, max effect 10min, lasts 20-60min. IM/SC = 2-10mg.
Effects:
- CVS: increase SCR -> sustained increase in SBP &DBP. Increased pulm VR. Reflex bradycardia. Positive inotrope properties. Sometimes increases CO. Indirectly increases coronary blood flow.
- RS: Slight decrease in RR and increase in TV
- CNS: reduces cerebral blood flow
- GU: reduces renal blood flow & contracts pregnant uterus
- Metabolic/other: hyperglycaemia due to increased glycogenolysis and inhibition of insulin release. Increased lipolysis. ?increases body temp and O2 consumption
Toxicity/SEs: headaches, dizziness, tremors, N/V. Reports of rapid increase in BP causing LVF and cardiac arrest. Extravascular injection can cause tissue necrosis and abscess formation
Kinetics: no data
Ephedrine
Ephedrine
Uses:
- Tx hypotention in anaesthesia (general, spinal, epidural)
- nocturnal enuresis
- narcolepsy
- diabetic autonomic neuropathy
- hiccoughs
- nasal decongestant
Chemical: naturally occuring sympathomimetic amine
Presentation: ephedrine sulphate as clear colourless solution for injection at 30mg/ml. Also as tablets at 15/30/60mg, elixir at 3mg/ml, nasal drops at 0.5/1%
Action: sympathomimetic
MoA: Directly - stimulating A and B andrenoreceptors. Indirectly - causing NA release from sympathetic nerve terminals
Routes/Doses: 3-30mg (parenterally) titrated to response, when IV cardiovascular effects are rapid and duration is ~1hr. Orally 30mg 8 hourly acting within 60min with 3-5hour duration. Nasally 1-2drops 4 hourly.
Effects:
- CVS: similar to adrenaline, more prolonged as nor broken down by MOA or catechol-O-chronotropic actions. Positive inotrope & chronotrope. Increased CO, cardiac work, mayocardial O2 consumption. Increased myocardial irritability. Increases coronary blood blow, SBP, DBP, pulm artery pressure. Post-capilliary vasoconstriction can increase circulating volume.
- RS: resp stimulant, bronchodilation
- CNS: stimulant (similar to amphetamine), incraesed cerebral blood flow. Mydriasis if used topically and some local anaesthetic properties.
- AS: Relaxes GI smooth muscle and -> splanchnic vasoconstriction
- GU: constricts renal blood vessels -> decreased renal flow & GFR. Contracts bladders sphinctor and relaxes detrusor muscle -> ?urinary retention. Decreases uterine tone
- Metabolic/other: increases rate of hepatic glycogenolysis, ?? central stimulation -> increase BMR and brain O2 consumption
Toxicity/SEs: insomnia, anxiety, headache, dysrhythmia, N/V, CP, mucous membrane irritant
Kinetics: incomplete data
Absorption: rapid and complete
Distribution: crosses placental barrier
Metabolism: resistant to MOA and catechol-O-methyl transferase. In the lives, small amount of oxidative metabolism, demethylation, aromatic hydroxylation, conjugation
Excretion: 87-99% unchanged in urine
Other: tachyphylaxis with prolonged use. More dysrhythmias when used with halothane. Clonidine premedication enhances pressor effects/
Glycopyrronium
Glycopyrronium
Uses: treat bradycardia in anaesthetised patients, premedication as an antisialogue, to protect against peipheral muscarinic effects of anticholinesterases, hyperhydrosis treatment (topically)
Given in combination with neostigmine to reverse non-depolarising neuromuscular blockage
Chemical: quarternary ammonium compound
Presentation: clear solution for injection at 0.2mg/ml, as a fixed-dose combination of 0.5mg/ml glycopyrronium and 2.5mg/ml neostigmine; also as powder for topical application
Action: anticholinergic, especially anti-secretory
MoA: competitive antagonism of acetylcholine at peripheral muscarinic receptors
Routes/Doses: IV adult 0.2-0.4mg, IV paeds 4-10ug/kg, peak effect at 3min
Effects:
- CVS: if >0.2mg to anaesthetised pt can cause tachycardia; protective against bradycardias from oculocardiac reflex and suxamethonium; vagolytic effect lasts 2-3hrs
- RS: significant long=lasting bronchodilator with increase in physiological dead space
- CNS: cannot cross BBB, no effect on pupil size or accommodation, however can cause headache and drowsiness, hastens post-anaesthetic recovery
- AS: powerful antisialogue lasting >8hrs (5x more potent than atropine); at 4hrs it can reduce gastric volume by 90% and reduces antral motility, and lower oesophageal sphincter tone
- GU: miturition difficulty
- Metabolic/other: inhibits sweat gland activity (little effect on T), weak LA
Toxicity/SEs: anticholinergic - dry mouth, micturition difficulty, sweating inhibition
Kinetics: incomplete data
Absorption: PO bioavailability 5%, poor and erratic absorption PO.
Distribution: rapid redistribution, >90% disappears from plasma in 5min; crosses the placenta and can induce foetal tachycardia; VD 0.2-0.64l/kg
Metabolism: little in humans; in animals both hydroxylation and oxidation in the liver
Excretion: 85% urine, 15% bile; 80% unchanged. Clearance 0.89l/min, elimination half-life 0.6-1.1hrs
Other: when given in combination with neostigmine it causes less initial tachycardia and less anti-cholinesterase-induced late bradycardia than atropine, as their time-courses are better matched. Physically incompatible with thiopentone, methohexitone and diazepam.
Atropine
Atropine
Uses:
- dry secretions prior to ether/chloroform anaesthesia, or for dry airway (paeds >1year intubation)
- to counter bradycardia due to increased vagal tone
- counter anticholinergic muscarinic effects
- in CPR, cycloplegic, in cold cures, organophosphorous poisoning, tetanus
Chemical: alkaloid from Atropia belladona, tertiary amine (ester of tropic acid and tropine). Commercially a racemic mixture of D- and I-hyoscamine (I-form is active)
Presentation: atropine sulphate - clear colourless solution for injection at 500/600ug/ml; also 600ug tablet
Action: anticholinergic
MoA: competitive antagonism of Ach at muscR (little effect at nicotinicR except at high doses)
Routes/Doses: IM/IV at 0.015-0.02mg/kg. PO adult 0.2-0.6mg. 3mg for complete vagal blockade in adults
Effects:
- CVS: low doses -> initial bradycaria (Bezold-Jarisch reflex) then tachycardia. Increase CO, little effect on BP. Decrease AV conduction time, can -> dysrhythmias. High doses -> facial capilliary dilatation.
- RS: bronchodilation with increased dead space, decreased bronchial secretions. Increased RR, decreased laryngospasm.
- CNS: central anticholinergic syn (excitation or depression) - somnolence, confusion, amnesia, agitation, hallucinations, dysarthria, ataxia, delirium. Also has anti-emetic and anti-Parkinsonian effects
- AS: reduces salivation, gastric secretion volume, gut tone & peristalsis, lower oesophageal tone. Mild antispasmodic on biliary tree
- GU: decreased tone and peristalsis in urinary tract
- Metabolic/other: cycloplegia, mydriasis, increased IOP. Sweating inhibition, BMR increse. Supresses ADH secretion and has LA properties.
Toxicity/SEs: painful IM, unpleasant dry mouth sensation. Central anticholinergic syn most likely in elderly. Lack of sweating can cause hyperpyrexia in children. Can ppt urinary retention.
ocular administration can lead to glaucoma.
Kinetics:
- Absorption: PO bioavailability 10-25%, rapidly absorbed from the gut
- Distribution: 50% protein bound in plasma. VD = 2-4l/kg. crosses placenta and blood-brain barrier
- Metabolism: hydrolysed in liver and tissue as tropine and tropic acid
- Excretion: 94% urinary exretion within 24hours, some unchanged. clearance = 70l/hr, elimination 1/2life 2/5hrs
Other: reduces incidence and morbidity of oculocardic crisis
Suxamethonium
Suxamethonium
Uses: for rapid and profound neuromuscular blockade (e.g. to facilitate tracheal intubation); for the modification of fits after ECT
Chemical: dicholine ester of succinic acid (two Ach molecules back to back)
Presentation: clear aqueous solution of 50mg/ml suxamethonium chloride - stored at 4C
Action: brief duration NM blockade of skeletal muscle
MoA: prolonged depolarisation of skeletal muscle fibres to a membrane potential above which an action potential can be triggered
Routes/Doses: IV 0.5-2mg/kg, onset within 30s, action duration 3-5min; infusion of 0.1% solution at 2-15mg/kg/hr -> 90% twitch suppression. IM up to 2.5mg/kg. shorter duration of action in children
Effects:
- CVS: repeated doses -> bradycardia and slight increase in MAP
- RS: skeletal muscle paralysis -> apnoea
- CNS: may initially cause fasciculations then phase I depolarising block. 1 well-sustained tetany at 50-100Hz. 2. absence of post-tetanic facilitation. 3. train-of-four ratio >0.7. 4. potentiation by anticholinesterases.
Repeated administrations/large total dose can -> phase II block. 1. poorly sustained tetanus. 2. post-tetanic fasciculation. 3. train-of-four ratio <0.3 4. reversal by anticholinesterases. 5. tachyphylaxis
raises ICP and IOP
- AS: increase in intragastric pressure by 7-12cmH2O with simultaneous decrease in lower oesophageal sphincter tone. Increase in salibation and gastric secretion
- Metabolic/other: brief increase in serum K by 0.2-0.4mmol/l
Toxicity/SEs: bradycardia/other dysrhythmias. Exaggerated hyperkalaemic response in burns, major muscle denervation, acute/chronic renal failure can -> cardiac arrest. Postop muscle pains (esp women or elderly, or early ambulants). Transient raised IOP NB penetrating eye injury pts. Malignant hyperthermia triggers. Contractures in myotonic pts. Prolonged apnoea. Anaphylaxis.
Kinetics: below
Distribution: protein bound - unknown extent; ?initial rapid redistribution -> short effect
Metabolism: hydrolysed by plasma cholinesterase to succinylmonocholine (weakly active); then further hydrolysed to succinic acid and choline. 80% hydrolysed before reaching NMJ
Excretion: 2-10% unchanged in urine. in vivo hydrolysis 3-7mg/l/min, 1/2life 2.7-4.6min
Other:
- Muscle pain incidence can be decreased with using a low dose 0.2mg/kg, small dose non-depolarising relaxant, diazepam, dantrolene, aspirin, vitamin C.
- plasma cholinesterase activity varies. E1U (normal gene) + E1a (atypical), E1s (silent), E1f (fluoride-resistant). Homozygotes of E1a/s/f remain apnoiec for 1-2hours (can use FFP to replace plasma cholinesterase). Heterozygotes approx 10 min apnoea.
- plasma cholinesterase conc can be reduced in pregnancy, liver/cardiac/renal failure, hypoproteinaemia, carcinomatosis, thyrotoxicosis, tetanus, muscular dystrophy, burns.
- drugs decreasing plasma cholinesterase activity: ecothiopate, tacrine, procaine, lignocaine, Li, Mg salts, ket, pancuronium, OCP, cytotoxics,
- not potentiated by volatile agents but ?more phase II block
- pharmaceutically incompatible with thiopentone
