PAST QUESTIONS – M02: Pharmacology of the Autonomic Nervous System (Click to Open)
SYLLABUS (Fourth Edition, 2023)
| LEVEL 1 | LEVEL 2 | LEVEL 3 |
|---|---|---|
| Antimuscarinic drugs | ||
| Atropine | ||
| Cholinesterase Inhibitors | ||
| Glycopyrrolate | Organophosphates | |
| Neostigmine | ||
N.B. The Syllabus tables used in out Pharmacopeia seem incomplete, but that is intentional because we have only included groups/classes/drugs which are mentioned directly in the syllabus or have been asked before in the exams.
TRAINEE EXPECTATIONS
- Trainees are expected to understand a drug’s pharmacology in the context of normal physiology, extremes of age (i.e., neonates, paediatrics, and the elderly), obesity, pregnancy (including foetal implications) and critical illness. An understanding of potential toxicity and relevant antidotes is also expected. Agents may be listed in more than one section when they are used for different indications.
- This is not an exhaustive list of all drugs relevant to or important in ICU practice. Each drug or classes of drugs have been assigned a details of understanding level outlined below. This is a guide to the minimum level of knowledge expected for that drug.
- For classes of drugs where examples are not specified, it is suggested a prototypical drug from the class be studied, as well as the relevant variations within the class exploring the major differences that exist between the agents in that class.
LEVELS OF UNDERSTANDING
| Level 1 | Level 2 | Level 3 |
|---|---|---|
| For these drugs, a detailed knowledge and comprehension of: | For these drugs a detailed knowledge of: | For these drugs a detailed knowledge of: |
| Class, Indications, and dose | ||
| Mechanism of Action | ||
| Pharmacodynamics and Adverse effects | ||
| Pharmacokinetics | Important pharmacokinetic differences or considerations when using in ICU | |
| Pharmaceutics | ||
CICMWrecks Tables (Click to Open)
| MASTER TABLE | ANS Drugs |
| INDIVIDUAL TABLES | Atropine vs Glycopyrrolate |
| Atropine |
MASTER TABLE
ANS DRUGS
Pharmacopeia - ANS Drugs
| NEOSTIGMINE | ATROPINE | GLYCOPYRROLATE Glycopyrronium bromide | Organophosphates | |
|---|---|---|---|---|
| GROUP | Cholinesterase Inhibitor | Antimuscarinic | Cholinesterase Inhibitor | Cholinesterase Inhibitors |
| CICM Level of Understanding | Level 2 | Level 1 | Level 2 | Level 3 |
| INTRODUCTION | ||||
| USES | - Reversal of NDMR (0.05mg/kg) - Myasthenia gravis (PO 15-30mg) - Urinary retention - Paralytic ileus | - Treatment of bradycardia - Counter muscarinic effects of anticholinesterase agents - Treatment of organophosphate poisoning - Tetanus - Treatment of occulocardiac reflex crises | - Protect against antimuscaranic effects when Acetylcholinesterase inhibitor used - Treatment of bradycardia - Hyperhydrosis - Symptom control in palliative care | |
| PHARMACEUTICS (PC) | ||||
| PC: Chemical | Carbamate ester Acetylcholinesterase inhibitor | Prototypical tertiary alkaloid | Quaternary amine derivative of atropine | |
| PC: Presentation | PO or IV (IV preparations may contain glycopyrolate) | Racemic mixture but only L-atropine is active Clear, colourless solution for injection (0.5 or 0.6mg/ml) | Clear solution for injection or in combination with neostigmine | |
| PHARMACODYNAMICS (PD) | ||||
| PD: Main Action | ||||
| PD: Mode of Action | reversible acid transferring cholinesterase inhibitor that binds to the esteratic site of AChE and is hydrolyzed but at a much slower rate than Ach. Leads to increase in Ach in the synapse. | Competitive antagonism of acetylcholine at muscarinic receptors. Little effect on nicotinic receptors except in high doses. | competitive antagonism at peripheral muscarinic receptors. More potent antagonism than atropine. Minimal anti-nicotinic effects, but more than atropine | |
| PD: Route & Doses | Onset in 2-4 min, duration of up to 3 hours | |||
| PD: Metrics (Onset/ Peak/ Duration) | ||||
| PD: Effects | CVS: Bradycardia. In high doses a central effect may precipitate hypotension Resp: Bronchoconstriction in asthmatic. Increased bronchial secretion Renal: Increased ureteric peristalsis leading to involuntary micturition GIT: - Salivation - Increased LOS tone and GIT motility (cramps) - N/V - Increased gastric acid output CNS: Miosis and failure to accommodate Other: Sweating and lacrimation | CVS - In low doses may produce a bradycardia (Bezold-Jarisch reflex, partial agonist at M2) followed by tachycardia (usual effect - Cardiac output is increased with little effect on blood pressure - Decreases AVN conduction time and may promote arrhythmias Resp - Bronchodilation with increase in physiological dead space - Bronchial secretions decrease - RR increased - Decreased laryngospasm has been reported CNS - Central depression or excitation may occur (anticholinergic syndrome)- characterized by hallucinations, agitation, confusion, dysarthria, ataxia, delirium - Has antiemetic and antiparkinsonian effects GIT - Decreased salivation - Decreased GIT motility - Antispasmodic in biliary tree - Decreased LOS tone GU- Tone and peristalsis in urinary tract decreased Metabolic/other - Sweating inhibited (children may develop pyrexia) - BMR increased - Suppresses ADH release | CVS: Tachycardia. Little effect on BP. Less arrhythmias than atropine. Vagolytic effects last 2-3 hours. CNS: Does not cross BBB. No effect on pupils. Resp: Bronchodilator. May increase dead space. Decreased bronchial secretions. Renal: Difficulty micturition GIT: Decreased salivation (8 hours). Decreased LOS. Other: Inhibition of sweating but generally no effect on body temperature. | |
| PD: Side Effects / Toxicity | (SLUDGE-BM) - Salivation - Lacrimation - Urination - Diaphoresis - GI upset - Emesis - Bradycardia and bronchoconstriction - Miosis - Prolongs suxamethonium duration of action | - Painful IM - Dry mouth - Central anticholinergic syndrome in the elderly - Hyperpyrexia in children (inhibition of sweating) - Urinary retention - Glaucoma from ocular (but not intravenous or intramuscular) administration. | - Tachycardia - Dry mouth - Urinary retention - Inhibition of sweating | |
| PHARMACOKINETICS (PK) | ||||
| PK: Absorption | Poorly absorbed orally (bioavailability 1%) | Rapidly absorbed orally but bioavailability is 10-25% | poor oral absorption F 5% | |
| PK: Distribution | Highly ionized so does not cross BBB | Crosses BBB and placenta | Rapid redistribution (90% disappears from plasma at 5 min) - Crosses placenta - Does not cross BBB | |
| Protein binding (PK: Distribution) | 10% PB | 50% PB | ||
| Volume of distribution (PK: Distribution) | Vd 0.5-1L/Kg | Vd 2-4L/kg. | Vd 0.2-0.6L/Kg | |
| PK: Metabolism | - Predominantly plasma esterases - Some hepatic metabolism with biliary excretion | Hydrolyzed in liver and tissues to tropine and tropic acid | Limited | |
| PK: Excretion | 65% renally excreted | 94% excreted in urine in 24 hours | 85% urine, 15% bile (80% unchanged) | |
| - Clearance (PK: Excretion) | ||||
| - Half Life (PK: Excretion) | T1/2= 15-80min (increased in renal failure) | T1/2 is 2.5hours | T1/2 of 1 hour | |
| SPECIAL POINTS |
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INDIVIDUAL TABLES
ATROPINE vs GLYCOPYRROLATE
Pharmacopeia - ANS Drugs
| ATROPINE | GLYCOPYRROLATE Glycopyrronium bromide | |
|---|---|---|
| GROUP | Antimuscarinic | Cholinesterase Inhibitor |
| CICM Level of Understanding | Level 1 | Level 2 |
| INTRODUCTION | ||
| USES | - Treatment of bradycardia - Counter muscarinic effects of anticholinesterase agents - Treatment of organophosphate poisoning - Tetanus - Treatment of occulocardiac reflex crises | - Protect against antimuscaranic effects when Acetylcholinesterase inhibitor used - Treatment of bradycardia - Hyperhydrosis - Symptom control in palliative care |
| PHARMACEUTICS (PC) | ||
| PC: Chemical | Prototypical tertiary alkaloid | Quaternary amine derivative of atropine |
| PC: Presentation | Racemic mixture but only L-atropine is active Clear, colourless solution for injection (0.5 or 0.6mg/ml) | Clear solution for injection or in combination with neostigmine |
| PHARMACODYNAMICS (PD) | ||
| PD: Main Action | ||
| PD: Mode of Action | Competitive antagonism of acetylcholine at muscarinic receptors. Little effect on nicotinic receptors except in high doses. | competitive antagonism at peripheral muscarinic receptors. More potent antagonism than atropine. Minimal anti-nicotinic effects, but more than atropine |
| PD: Route & Doses | Onset in 2-4 min, duration of up to 3 hours | |
| PD: Metrics (Onset/ Peak/ Duration) | ||
| PD: Effects | CVS - In low doses may produce a bradycardia (Bezold-Jarisch reflex, partial agonist at M2) followed by tachycardia (usual effect - Cardiac output is increased with little effect on blood pressure - Decreases AVN conduction time and may promote arrhythmias Resp - Bronchodilation with increase in physiological dead space - Bronchial secretions decrease - RR increased - Decreased laryngospasm has been reported CNS - Central depression or excitation may occur (anticholinergic syndrome)- characterized by hallucinations, agitation, confusion, dysarthria, ataxia, delirium - Has antiemetic and antiparkinsonian effects GIT - Decreased salivation - Decreased GIT motility - Antispasmodic in biliary tree - Decreased LOS tone GU- Tone and peristalsis in urinary tract decreased Metabolic/other - Sweating inhibited (children may develop pyrexia) - BMR increased - Suppresses ADH release | CVS: Tachycardia. Little effect on BP. Less arrhythmias than atropine. Vagolytic effects last 2-3 hours. CNS: Does not cross BBB. No effect on pupils. Resp: Bronchodilator. May increase dead space. Decreased bronchial secretions. Renal: Difficulty micturition GIT: Decreased salivation (8 hours). Decreased LOS. Other: Inhibition of sweating but generally no effect on body temperature. |
| PD: Side Effects / Toxicity | - Painful IM - Dry mouth - Central anticholinergic syndrome in the elderly - Hyperpyrexia in children (inhibition of sweating) - Urinary retention - Glaucoma from ocular (but not intravenous or intramuscular) administration. | - Tachycardia - Dry mouth - Urinary retention - Inhibition of sweating |
| PHARMACOKINETICS (PK) | ||
| PK: Absorption | Rapidly absorbed orally but bioavailability is 10-25% | poor oral absorption F 5% |
| PK: Distribution | Crosses BBB and placenta | Rapid redistribution (90% disappears from plasma at 5 min) - Crosses placenta - Does not cross BBB |
| Protein binding (PK: Distribution) | 50% PB | |
| Volume of distribution (PK: Distribution) | Vd 2-4L/kg. | Vd 0.2-0.6L/Kg |
| PK: Metabolism | Hydrolyzed in liver and tissues to tropine and tropic acid | Limited |
| PK: Excretion | 94% excreted in urine in 24 hours | 85% urine, 15% bile (80% unchanged) |
| - Clearance (PK: Excretion) | ||
| - Half Life (PK: Excretion) | T1/2 is 2.5hours | T1/2 of 1 hour |
| SPECIAL POINTS |
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ATROPINE
Pharmacopeia - ANS Drugs
| ATROPINE | |
|---|---|
| GROUP | Antimuscarinic |
| CICM Level of Understanding | Level 1 |
| INTRODUCTION | |
| USES | - Treatment of bradycardia - Counter muscarinic effects of anticholinesterase agents - Treatment of organophosphate poisoning - Tetanus - Treatment of occulocardiac reflex crises |
| PHARMACEUTICS (PC) | |
| PC: Chemical | Prototypical tertiary alkaloid |
| PC: Presentation | Racemic mixture but only L-atropine is active Clear, colourless solution for injection (0.5 or 0.6mg/ml) |
| PHARMACODYNAMICS (PD) | |
| PD: Main Action | |
| PD: Mode of Action | Competitive antagonism of acetylcholine at muscarinic receptors. Little effect on nicotinic receptors except in high doses. |
| PD: Route & Doses | Onset in 2-4 min, duration of up to 3 hours |
| PD: Metrics (Onset/ Peak/ Duration) | |
| PD: Effects | CVS - In low doses may produce a bradycardia (Bezold-Jarisch reflex, partial agonist at M2) followed by tachycardia (usual effect - Cardiac output is increased with little effect on blood pressure - Decreases AVN conduction time and may promote arrhythmias Resp - Bronchodilation with increase in physiological dead space - Bronchial secretions decrease - RR increased - Decreased laryngospasm has been reported CNS - Central depression or excitation may occur (anticholinergic syndrome)- characterized by hallucinations, agitation, confusion, dysarthria, ataxia, delirium - Has antiemetic and antiparkinsonian effects GIT - Decreased salivation - Decreased GIT motility - Antispasmodic in biliary tree - Decreased LOS tone GU- Tone and peristalsis in urinary tract decreased Metabolic/other - Sweating inhibited (children may develop pyrexia) - BMR increased - Suppresses ADH release |
| PD: Side Effects / Toxicity | - Painful IM - Dry mouth - Central anticholinergic syndrome in the elderly - Hyperpyrexia in children (inhibition of sweating) - Urinary retention - Glaucoma from ocular (but not intravenous or intramuscular) administration. |
| PHARMACOKINETICS (PK) | |
| PK: Absorption | Rapidly absorbed orally but bioavailability is 10-25% |
| PK: Distribution | Crosses BBB and placenta |
| Protein binding (PK: Distribution) | 50% PB |
| Volume of distribution (PK: Distribution) | Vd 2-4L/kg. |
| PK: Metabolism | Hydrolyzed in liver and tissues to tropine and tropic acid |
| PK: Excretion | 94% excreted in urine in 24 hours |
| - Clearance (PK: Excretion) | |
| - Half Life (PK: Excretion) | T1/2 is 2.5hours |
| SPECIAL POINTS |
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