21. Antimuscarinic Drugs Flashcards
How do antimuscarinic drugs
work?
Antimuscarinic agents are competitive
antagonists of acetylcholine (ACh)
at muscarinic acetylcholine receptors (mAChR).
These are located in post-ganglionic target tissues innervated by the parasympathetic nervous
system (PNS)
and also in the
sympathetically innervated sweat glands.
> These drugs are also called
‘parasympatholytic’ agents because they
reduce the activity of the PNS.
What are the clinical uses of these agents?
Antimuscarinic agents have both
anaesthetic and non-anaesthetic uses:
1
> Premedication, e.g. hyoscine
Used to produce sedation and amnesia.
Hyoscine comes in two formulations: hyoscine hydrobromide, which crosses the blood–brain barrier (BBB) to produce central effects such as sedation, amnesia and anti-emesis; and hyoscine butylbromide (Buscopan®), which does not cross the BBB.
What are the clinical uses of
these agents?
cont.
2
> Bradycardia treatment, e.g. atropine
3 > Anti-sialogogue, e.g. glycopyrrolate. - Used prophylactically to reduce excessive secretions in procedures such as fibre-optic intubation.
- Hyoscine is used in palliative care to reduce excessive secretions
(death rattle).
4
> Bronchodilator, e.g. ipratropium bromide.
5 > Antiemetic, e.g. hyoscine - Used to treat motion sickness, post-operative nausea and vomiting, and opioid-induced nausea.
6
> Anti-spasmodic, e.g. hyoscine
- Used to treat colicky abdominal pain.
- Used to fascilitate upper gastrointestinal endoscopy.
7 > C o-administered with anticholinesterases, e.g. glycopyrrolate with neostigmine Used to attenuate the muscarinic effects of neostigmine.
8
> Anti-parkinsonian drug, e.g. benztropine, procyclidine and benzhexol.
9
> Mydriatic, e.g. tropicamide.
10
> Antidote to organophosphorus and nerve gas poisoning Troops at risk of chemical warfare carry mini-jets of atropine and obidoxime that can be injected into the thigh.
Can you describe the structure of hyoscine, atropine and
glycopyrrolate?
> Atropine and hyoscine
(also known as scopolamine) are naturally
occurring tertiary amines extracted
from plants of the deadly nightshade family.
They are formed from the
esters of tropic acid and tropine or
scopine respectively.
Being tertiary amines, these agents are able to cross
the
BBB and can produce central anticholinergic effects.
> Glycopyrrolate is a synthetic
quaternary amine that cannot readily cross
the BBB and
so central anticholinergic effects are
negligible with this
agent.
What are the major side effects of these agents?
The major side effects produced by
these agents result from their
antagonistic action on
the ‘rest and digest’ activity of glands,
smooth muscle
and cardiac muscle.
Therefore, their side effect profile can be worked out
logically and classified systematically:
> Neurological: - 3° amines can cross the BBB and produce an acute central anticholinergic syndrome. The central features of this syndrome include altered mental status, disorientation, hallucinations, agitation, ataxia, somnolence and coma.
The peripheral features of this syndrome include dry mouth, mydriasis, blurred vision, paralytic ileus, urinary retention, tachycardia, and hot, dry and vasodilated skin.
> Eye: Mydriasis causing photophobia and loss of accommodation (cycloplegia) resulting in blurred vision and diplopia
Dry eyes (xerophthalmia) due to reduced lacrimal secretion
Risk of raised intra-ocular pressure
in patients with closed angle
glaucoma
> Respiratory:
Increased anatomical dead space
> Cardiovascular:
Tachycardia
> Gastrointestinal: Decreased bowel movement Paralytic ileus Reduced lower oesophageal sphincter pressure – risk of exacerbating reflux in susceptible individuals.
> Genito-urinary: Reduced urinary tract peristalsis and detrusor muscle tone combined with increased sphincter tone to cause urinary retention.
> Skin:
Impaired sweating results in hot, dry and vasodilated skin.
Pyrexia may follow especially in children or in cases of overdose.
Compare and contrast hyoscine,
atropine and glycopyrrolate.
Table 21.1 The properties of hyoscine, atropine and glycopyrrolate compared
ATROPINE
Prep
Dose
MOA
ADME
Effects
Uses
Synthetic tertiary amine
• Solution: 0.6 mg/mL
• Tablets: 600 μg
DOSE
- 0.2–0.6 mg IV or IM (adult)
- 20 μg/kg (children)
MOA
• Competitive antagonist at muscarinic receptors
(‘vagolytic’)
CHEMICAL PROPERTIES
• Racemic mixture of D and L atropine
• Only L is active
METABOLISM
AND EXCRETION
• Hepatic metabolism
• Metabolised and
unchanged drug
excreted in urine
ABSORPTION/
DISTRIBUTION
• Well absorbed orally
• Oral bioavailability
10–25%
- Protein binding 50%
- VD 2–4 L/kg
USES
• Premed to decrease
secretions
• Treatment of
bradycardia
• In ALS algorithm
(PEA/asystole)
• Treatment of
organophosphate
poisoning
EFFECTS
CVS
• Tachycardia
• Effect last 2–3 hours
• May precipitate
arrhythmias by
decreasing AV
conduction time
RS
• Bronchodilation
• RR
CNS • Crosses BBB causing central anticholinergic syndrome • Antiemetic • Antiparkinsonian effects
GI
• Antisialagogue
• Tone lower
oesophageal sphincter
METABOLIC • Inhibits sweating may cause hyperpyrexia in children ANTIMUSCARINIC • Dry mouth • Urinary retention • Blurred vision Atropine
GLYCOPYRROLATE
Synthetic quaternary amine • Solution: 0.2 mg/mL • Mixed with neostigmine: 0.5 mg glyco + 250 mg neo/mL
DOSE
• 0.2–0.4 mg IV or IM (adult)
• 4–10 μg/kg (children)
MOA • Competitive antagonist at muscarinic receptors (‘vagolytic’)
• Does not cross BBB
METABOLISM AND EXCRETION • Minimal metabolism • Excreted unchanged in urine
ABSORPTION/
DISTRIBUTION
• Poor oral absorption
• Oral bioavailability 5%
USES • Premed to decrease oral secretions • To attenuate effects of anticholinesterases, i.e. when given to reverse non-depolarising muscle relaxants
- Bradycardia
- Hyperhydrosis
EFFECTS CVS • Tachycardia • Effect lasts 2–3 hours RS • Bronchodilation CNS
• Doesn’t cross BBB but
still causes headache
and sedation
GI
• Antisialagogue
METABOLIC
• Inhibits sweating
ANTIMUSCARINIC
• Dry mouth
• Urinary retention
• Blurred vision
