Glycopyrrolate

 

An anticholinergic drug (competitive muscarinic receptor antagonist) particularly useful because:

1. it is a quaternary (rather than tertiary) amine, thus charged and unable to cross the blood brain barrier
2. it’s onset and offset of action approximately mirrors neostigmine, helping to avoid myocardial demands of the tachycardia seen with atropine (onset of atropine is faster than neostigmine)

 

 

 

 

For

•  bradycardia
•  with acetylcholinesterase inhibitors for prevention of muscarinic effects
•  antisialogogue

Dose

•   0.2 – 0.4 mg IV or IM (4 – 5 mcg/kg, 4 – 8 mcg/kg in children) for bradycardias/anti-sialogogue
•   0.2 mg per 1 mg neostigmine for muscarinic antagonism (10 – 15 mcg/kg with neostigmine 50 mcg/kg in children)

 

Pharmaceutics

Clear colourless liquid in glass container as 0.2 mg/mL for IM, Subcut or IV injection.  Physically incompatible with thiopentone, methohexitone and diazepam.

 

Pharmacokinetics

•   poor oral bioavailability (<5%) as charged
•   vd 0.5L/kg
•   does not cross blood brain barrier due to its charge
•   some placental transfer occurs (can cause foetal tachycardia)
•   renal excretion, 80% unchanged
•   elimination half life 1 - 2.5h, clearance 12 mL/kg/min

 

Pharmacodynamics

 

•    competitive muscarinic receptor inhibitor, thus vagolytic
•    antisialogogue  - more potent than atropine, lasts ~ 8h post administration
•    reduces respiratory secretions
•    mild bronchodilation (increasing dead space)
•    tachycardia

 

Precautions

•    as glycopyrrolate does not cross the blood brain barrier, it has no sedation/amnestic effects, no anti-emetic effects, and        does not cause mydriasis
•    duration of action may be prolonged in renal impairment
•    should be avoided in neonates as it contains benzyl alcohol

 

Side effects  - anticholinergic!!

•     dry mouth
•     dry eyes, blurred vision
•     urinary retention
•     constipation
•     nausea and vomiting
•     dyspepsia, reduced gastric mobility
•     tachycardia, arrhythmias
•     fever (anhidrosis) – beware hyperthermia in children
•     reduced lower oesophageal sphincter tone
•     minimal reduction in gastric acid secretion
•     rash
•     flushed skin
•     anaphylaxis
•     headache
•     drowsiness

 

Contraindications

•      myasthenia gravis
•      GI obstruction or atony, urinary obstruction

 

Specific interactions (probably less relevant for one off dose)

Interacts with other drugs with anti-cholinergic activity including:

                                           i.       anti-Parkinsonian medications - amantadine, benzhexol, benztropine, biperiden

                                           ii.      psych drugs - amitriptyline, chlorpromazine, clozapine,

                                           iii.      bladder relaxants – oxybutynin, propantheline, tolterodine

                                          iv.      anti-arrhythmics – procainamide, quinidine

                                           v.      other anti-cholinergics – atropine, hyoscine, promethazine

                                          vi.      bronchodilators – ipatropium, tiotriopium (minimal systemic absorption thus less problematic)