ANTICHOLINERGIC
AGENTS
ANTICHOLINERGIC
agents
Anticholinergic agents are substances that block the effects of
neurotransmitter acetylcholine (ACh) in the central and peripheral nervous
system.
Anticholinergics are divided into two categories in accordance with their
specific targets in the central and peripheral nervous system and at the
neuromuscular junction: 1.) antimuscarinic agents, and 2.) antinicotinic
agents (ganglionic blockers, neuromuscular blockers).
ANTIMUSCARINIC
AGENTS
ANTIMUSCARINIC
agents
Antimuscarinic agents also known as anticholinergic drugs are agents
that block primarily muscarinic receptors thus causing inhibition of
muscarinic functions.
ATROPI
NE
One of the most well known antimuscarinic agent.
Atropine's primary sites of actions are the following: eye, GI tract,
heart, salivary sweat and lacrimal glands.
ANTIMUSCARINIC
ACTIVITY OF
ATROPINE
EY
E
Results in relaxation of ciliary muscle which causes:
• Mydriasis - dilation of the pupil
• Cycloplegia - inability to focus visually,
• and unresponsiveness to light.
EY
E
Ophthalmic preparations of Atropine are used before an eye exam or
eye surgery as well as to treat certain inflammatory conditions of the
eye. However, because of its long duration of action, other
antimuscarinic agents such as Cyclopentolate and Tropicamide are
preferred over Atropine. While Cyclopentolate and Tropicamide can
produce mydriasis that lasts for hours, Atropine's effects can last for
days.
GI
TRACT
Atropine blocks M3 receptors in GI tract which results in reduction of
GI motility from stomach to colon that causes prolonged gastric
emptying and lengthen intestinal transit time.
Heart
At higher doses, Atropine can also effectively block M2 receptors on
the SA node (sinus node) and AV node (atrioventricular node) which
produces tachycardia. Heart rate may increase by as much as 30 to 40
beats per minute.
SALIVARY SWEAT AND
LACRIMAL GLANDS
By blocking muscarinic receptors on salivary sweat and lacrimal
glands, Atropine produces dry mouth, dry skin, and ultimately causes
body temperature to rise.
scopolamine
Scopolamine unlike Atropine has a much greater effect
on the CNS as well as longer duration of action.
Scopolamine is one of the most effective medications
used for prevention of motion sickness and post-
operative nausea and vomiting. It is available in a patch
formulation that provides effects lasting up to three days.
Ipratropium and
Tiotropium
Ipratropium and Tiotropium block muscarinic acetylcholine receptors without
specificity for subtypes resulting in decreased contractility of smooth muscle
in the lungs which in turn leads to bronchodilation and reduction of mucus
secretion.
Ipratropium and
Tiotropium
BRONCHODILATION
Ipratropium and
Tiotropium
Both are administered by inhalation for maintenance treatment of
bronchospasms in patients with COPD. Ipratropium also comes in a nasal
spray formulation which is often used for treatment of rhinorrhea which is
runny nose. The difference between Tiotropium and Ipratropium is;
Tiotropium is a long-acting agent that is dosed once daily, while Ipratropium is
a short-acting agent that typically requires a dose up to four times daily.
Tolterodine, Darifenacin, Solifenacin,
Oxybutynin, Trospium, and Fesoterodine
Tolterodine, Darifenacin, Solifenacin, Oxybutynin, Trospium, and
Fesoterodine are used for treatment of overreactive bladder. These agents have
varying selectivity for the M3 receptor which is the main receptor involved in
bladder function. However, the overall efficacy among all of these is very
similar.
Benztropine and
Trihexyphenidyl
These suppress central cholinergic activity and were found to be
very beneficial in treatment of Parkinson-like disorders.
ANTICHOLINERGIC
SIDE EFFECTS
ABCD
S
Anticholinergic side effects - ABCDs will help us to remember
anticholinergic adverse effects where A stands for agitation, B stands
for blurred vision, C stands for constipation and confusion, D stands
for dry mouth, and S stands for stasis of urine and sweating.
ANTINICOTINIC
AGENTS
GANGLIONIC
BLOCKERS
NICOTI
NE
The main agent of the group, which is a main component of cigarette smoke.
Nicotine is a cholinergic agonist and is also considered a functional antagonist
because of its ability to stimulate and then block cholinergic function. Nicotine
acts on the nicotinic receptors of both parasympathetic and sympathetic
autonomic ganglia. Effects of Nicotine result from increased release of
neurotransmitters such as dopamine serotonin and norepinephrine.
NICOTI
NE
Nicotine is nonselective. It stimulates and later depresses autonomic ganglia.
For example, Nicotine stimulates CNS which at high enough doses can lead to
convulsions and then it depresses CNS which can lead to respiratory paralysis.
NICOTI
NE
By stimulating the adrenal medulla and sympathetic ganglia, nicotine increases
blood pressure and heart rate, but at higher doses it can cause blood pressure to
fall. In GI system, nicotine increases the motility which can lead to nausea and
vomiting. Nicotine in any form can cause addiction due to CNS stimulation
that produces increased alertness and surge of well-being.
NICOTI
NE
NEUROMUSCULAR
BLOCKERS
NEUROMUSCULAR
BLOCKERS
Neuromuscular blockers lock the cholinergic transmission between motor
nerve endings and nicotinic receptors on the skeletal muscle.
NEUROMUSCULAR
BLOCKERS
NONDEPOLARIZING
AGENTS
Nondepolarizing agents are competitive antagonists they bind to acetylcholine
receptors but doesn’t induce ion channel opening. These agents prevent
depolarization of the muscle cell membrane and thus effectively inhibit muscle
contraction. In clinical practice these agents are used to facilitate mechanical
ventilation and tracheal intubation as well as to increase muscle relaxation
during surgery which allows for lower doses of general
anesthetics generally speaking nondepolarizing
NONDEPOLARIZING
AGENTS
Nondepolarizing agents must be injected usually intravenously. It is onset and
action is usually less than 2 minutes. Once administered these agents paralyze
small fast contracting muscle first that is eyes face fingers then larger muscles
of neck trunk and limbs and lastly diaphragm. These muscles recover in the
reverse manner that is diaphragm first then limbs trunk and so on and so forth.
Clinical duration
• Cisatracurium which has clinical duration of about 90 minutes.
• Pancuronium which also has clinical duration of about 90 minutes.
• Rocuronium with clinical duration of about 40 minutes.
• Vecuronium which also has clinical duration of about 40 minutes.
• Atracurium with 40 minute clinical duration.
Side effects:
• Atracurium causes histamine release which results in fall in blood
pressure flushing and Bronchoconstriction. It also has toxic metabolite called
laudanosine which can provoke seizures especially in patients with impaired
renal function. This is why Atracurium has been largely replaced by its isomer
Cisatracurium.
Side effects:
• Cisatracurium is often used in patients with multi-organ failure.
• Vecuronium and Rocuronium are metabolized by liver so their action
may be prolonged in patients with hepatic dysfunction but overall there are
safe and have minimal side effects.
• Pancuronium is excreted unchanged in urine and one of its main side
effects is increase in heart rate.
DEPOLARIZING
AGENTS
Depolarizing agents act as acetylcholine receptor agonists. They mimic the
acetylcholine however they are much more resistant to degradation by
acetylcholinesterase and therefore produce persistent depolarization now the
only depolarizing agent that's still used in clinical practice.
Succinylcholine
Succinylcholine binds to the nicotinic receptor and unlike the nondepolarizing
agents it causes the sodium channel to open which results in membrane
depolarization.
Succinylcholine
Phase-1 block – caused by prolonged depolarization which leads to a transient
fasciculations and finally flaccid paralysis because of the resistance of
Succinylcholine to acetylcholinesterase.
Phase-2 block - Sodium channel closes and membrane repolarizes due to
continued stimulation by Succinylcholine the receptor becomes desensitized to
acetylcholine thus preventing formation of further action potentials.
