Antimuscarinic drugs used in the treatment of urinary incontinence
Tolterodine
(Detrol®)
Oxidation to
hydroxymethyl
Tolterodine
Non-selective
muscarinic antagonist
Active
Further oxidation to
Carboxylic acid
❖
Acts
on M2 and M3 subtypes of muscarinic receptors whereas most
antimuscarinic treatments for overactive bladder only act on M3
receptors making them more selective.
Known Side Effects:
Hyposalivation(Dry mouth)
Decreased gastric motility
(Upset stomach) Headache , Constipation , Dry eyes , Drowsiness
Half Life:
2-4 hrs
Oxybutynin
(Ditropan®)
Active
CYP3A4
Non-selective
muscarinic antagonist
Inactive
The (R)-enantiomer is a more
potent anticholinergic than the (S)-enantiomer, but marketed as
racemic mixture
Half Life : 2-5 hrs
—
Solifenacin
(Vesicare)
Half Life: 55 hrs
Metabolites:
4-hydroxy derivative (active),
N-glucuronide
N-oxide
4-hydroxy-N-oxide
Darifenacin(Enablex®)
CYP3A4
CYP2D6
Hydroxylation
Selective
M3
antagonist
Antimuscarinic
drugs used in the ^ treatment of bronchial asthma
Tiotropium
bromide
M3
receptors: Bronchiole
constriction
Therapeutic
use: block
cholinergic bronchiole constriction (anticholinergics) and allow
adrenergic bronchiole dilation to help overcome the pulmonary
constriction associated with asthmatic attack.
Ipratropium hydrobromide
N-isopropyl analogue of
Atropine
Quaternary cationic nature
makes it highly hydrophilic and poorly absorbed from the lungs
after inhalation via solution or aerosol, so bronchodilation
effect can be considered to be a local, site-specific effect
Ipratropium is indicated
primarily for the relief of bronchospasms
associated with COPD and
has seen little application for the treatment
of asthma
Reaches the circulation
minimally and is partially metabolized to inactive esterase products
Ipratropium Hydrobromide (Atrovent®)
Tiotropium
Bromide (Spiriva®)
Dithienyl
derivative of N-methyl scopolamine,
a quaternary analogue of naturally occurring scopolamine in Atropa
belladonna
Indicated primarily for the
relief of bronchospasms associated with COPD and can be considered
to be a site-specific, local medication to the lung.
Longer duration of action
than ipratropium (24 versus <4 hours, respectively).
Tiotropium is metabolized by
both CYP3A4 and CYP2D6, followed by glutathione conjugation to a
variety of metabolites
NICOTINIC
ANTAGONISTS
Cholinergics
Nicotinic
antagonists as neuromuscular blockers
й
Nicotinic
Antagonists
Compounds that bind to
cholinergic nicotinic receptors with no intrinsic efficacy
(competitive antagonists with Ach)
Two subclasses of nicotinic
antagonists
Skeletal
neuromuscular blocking agents and
Ganglionic blocking agents.
DONOT
confuse with skeletal muscle relaxants that produce their effects
through the CNS
