Download Autonomic Nervous System Anticholinergic Drugs

Autonomic Nervous System
Anticholinergic Drugs-6
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Objectives
At end of this lecture, the students should be able
to:
1- Identify nicotinic antagonists drugs.
2- Discuss ganglionic blocking drugs .
3- Discuss neuromuscular blocking drugs.
- At a level consistence with standards scientific curriculum
for the College of Medicine/ University of Mosul.
Nicotinic Antagonists
Antinicotinic agents
1- Ganglionic Blocking
agents
2-Neuromuscular Blocking
agents
Non Depolarizing
competitive
blocking
agents
Depolarizing
Non-competitive blocking
agents
1- Ganglionic Blocking Agents
- Hexamethionin, mecamylamine and other
ganglion-blockers were mainly used in the
treatment of hypertension.
- But unfortunately, the adverse effect of ganglion blocked are
so severe (both sympathetic and parasympathetic divisions
are blocked), so that patients are unable to tolerate long
term treatment with them.
1- Ganglionic Blocking agents
Trimethaphan
- It is the only Ganglion-blocker still in clinical use. Its
poorly lipid soluble.
- Inactive orally and has a short half-life.
- It is used IV to treat severe accelerated hypertension
(malignant hypertension).
Note:
Because the ganglion-blocking agents interrupts
sympathetic control of venous-pooling, so so these
drugs cause postural hypotension.
2- Neuromuscular Blocking
Drugs
- These drugs are important for producing complete skm relaxation in surgery, by specific blockade of the NM junction.
-They enable light level of anesthesia to be employed
with adequate relaxation of the muscles of the
abdomen and diaphragm.
- They also relax the vocal cords and allow the passage
of a tracheal tube.
Note:
- Patients who have received a M-relaxant should always
have their respiration assisted or controlled until the
drug have been inactivated or antagonized.
Non Depolarizing Competitive
N-M blocking agents
Action:
- Drugs of this group cause N-M block by competing with
Ach at the receptor site at the N-M junction so prevent
depolarization of muscle cell membrane and inhibit
muscle contraction so causing complete SK- M
relaxation.
PK:
- Most non depolarizing agents have relatively long
t1/2 ranging from 20 min to several hours.
- These drugs are given parentally (by injection).
Non Depolarizing Competitive
N-M blocking agents
Tubocurarine
- Is the prototype it produces a competitive block at
the at the motor endplate of the muscle causing
flaccid paralysis lasts 30-60 min.
- Tubocurarine blocks autonomic ganglia and causes an initial
transient drop in blood pressure & cause histamine release
which may induce bronchospasm.
Pancuronium, Atracurium are short acting non-depolarizing
agents.
Non Depolarizing Competitive
N-M blocking agents
Note:
The action of competitive N-M blocking drugs is
antagonized by anticholinesterases, like
Neostigmine which is usually given IV, and preceded by
atropine to prevent the parasympathetic autonomic effect
of Neostigmine (such as bradycardia and salivation).
Depolarizing Non competitive
N-M blocking agents
Suxamethonium (Succinylcholine)
Mechanism of action:
- It attaches to the nicotinic receptors and acts like Ach to
depolarize the N-M junction.
- Unlike acetylcholine, which is rapidly destroyed by
Achesterase, the depolarizing agent persists at high
concentrations in the synaptic cleft, remaining attached to
the receptor for a relatively long time & providing a
constant stimulation of the receptor. Initially this produces
short-lasting muscle fasciculation, followed within a few
minutes by muscle paralysis.
Suxamethonium (succinylcholine)
- The drug does not produce a ganglionic block, except in
high doses, although it does have weak histaminereleasing action.
- Normally, the duration of action of succinylcholine is
extremely short (Total paralysis last up to 4 min)
- succinylcholine It is particularly used during anesthesia
for brief procedures? such as tracheal intubations or
electroconvulsive therapy (ECT).
PK of Suxamethonium (succinylcholine)
- Succinylcholine is injected intravenously.
- Unlike the non depolarizing muscle relaxants
(tubocurarine), the succinylcholine action cannot
be reversed by other drug. Instead of this its brief
duration of action (several minutes) ended by
rapid hydrolysis by plasma pseudo cholinesterase
enzyme.
PK of Suxamethonium (succinylcholine)
- It is hydrolyzed by plasma pseudo cholinesterase and
its persistence in the body is increased by :
1- Neostigmine, which inactivate that enzyme.
2- In patient with hepatic disease or severe malnutrition,
whose plasma concentration of enzyme may be lower
than normal.
3- Procaine also is destroyed by this enzyme and so by
competing with suxamethonium for the enzyme, may
prolong its action.
4- There are persons with hereditary defects in amount or
kind of enzyme, who cannot destroy the drug as rapidly
as normal, so paralysis (Apnea) then prologed for hours.
- Here treatment consist of ventilation until recovery,
and may need fresh blood transfusion.
Adverse effects of Succinylcholine
1- Hyperthermia:
When halothane is used as an anesthetic,
administration of succinylcholine has occasionally caused malignant
hyperthermia (with muscular rigidity and hyperpyrexia) in genetically
susceptible people.
- Treated by rapidly cooling the patient and by administration of dantrolene
which blocks release of Ca++ from the sarcoplasmic reticulum of
muscle cells, and so reducing heat production and relaxing muscle
tone.
2- Apnea: A genetically related deficiency of plasma
cholinesterase or presence of an atypical form of the
enzyme can lead to apnea due to paralysis of the
diaphragm.
Adverse effects of Succinylcholine
3- Cardiovascular:
a- Repeated injections of suxamethonium can cause
bradycardia and even cardiac arrest these probably
due to activation of cholinoceptors in the heart and
this can be prevented by atropine.
b- It causes release of K from muscle which can be
enough to cause cardiac arrest in patients with
already hyperthermia.
Adverse effects of Succinylcholine
4- Muscle pain lasting 1-3 days due to
muscle fasciculation preceded the paralysis by
Suxamethonium.
- The pain can largely prevented by a small dose of a
competitive N-M blocking agent (tubocurarine) before
giving succinylcholine.
5- High dose can stimulate the uterus and can
cause premature labour in pregnant patient.
Contraindication of succinylcholine
1- Hypersensitivity to suxamethonium.
2- Severe liver disease. ??
3- Burned patient.
??
4- Pregnancy.
??
Uses of N-M blocking agents
- The main use of these drugs is the producing
complete skeletal muscle relaxation in surgery.
Other uses:
1- Control Ventilation:
- In respiratory failure due to obstructive airway disease.
2- Treatment of convulsion:
- By decrease peripheral manifestation of convulsion (As
these drugs not cross BBB so has no effect on the central
processes involved).