3rd lecture - parasympatholytics Flashcards
another 2 terms for parasympatholytics
Anticholinergic agents
Cholinoblockers
parasympatholytics are broadly divided into (2)
1) Antimuscarinic agents
2) Antinicotinic agents
this division is not rigid
Skeletal muscle relaxants (neuromuscular blocking agents) are typically what type of drug
Antinicotinic agents.
Parasympatholytic drugs prevent
ACh from producing its characteristic effects in structures innervated by postganglionic parasympathetic nerves and prevent ACh effects on smooth muscle cells.
Typical natural representatives of Antimuscarinic agents are
alkaloids of plants belonging to the Solanaceae family such as:
Deadly nightshade (Atropa belladonna)((source of Atropine))
Jimsonweed (Datura stramonium)((source of Atropine))
Black henbane (Hyoscyamus niger) - scopolamine
duration of the effect of atropine is
long, particularly in the event of a topical route of administration (2-3 days in the eye).
Pharmacokinetics of atropine
Atropine absorbs well in case of all routes of administration and is evenly distributed in the organism.
Hydrolysis occurs slowly due to the effect of carboxylesterase.
classic example of a parasympatholytic
atropine
atropine Mechanism of action
blockade of postsynaptic receptors in competition with acetylcholine.
Atropine binds the receptor active centre and the mediator will be unable to access the receptor.
The blockade will be temporary and the effect will pass when the substance is eliminated.
Cholinesterase inchibitors eliminate the effect of atropine by
inducing the accumulation of acetylcholine at nerve endings which makes it able to compete with atropine.
Other cholinomimetics have no effect.
Although cholinoblockers act on all postganglionic cholinergic nerve endings, this block is not
equally effective throughout the body.
Salivary and chlolinergic sweat glands are susceptible.
GI and urinary tract smooth muscle less sensitive.
Difficult to achieve a selective action on targeted structures without concurrently inducing side effects on other sites.
atropine effect on the GI tract
Inhibitory effect of atropine on secretion already at low doses. It inhibits the function of lacrimal, sweat, salivary, bronchial and intestinal glands.
Atropine causes relaxation of GI smooth muscle by inhibiting contractile effects of cholinergic nerve impulses.
Helpful in treatment of intestinal spasm and hypermotility.
effect of atropine on bronchioles
Atropine decreases secretion and increases luminal diameter of the bronchioles.
especially valuable in counteracting constriction of bronchioles following overdosage of parasympathomimetic drug.
effects of atropine on the Cardiovascular system
Does not technically directly impact blood pressure, is a positive inotrope as atropine eliminates the vagus nerve’s depressing effect on the heart resulting in tachycardia. ‘
Large doses of atropine are actually directly depressant to the myocardium and also causes cutaneous dilation as a result of a direct vascular smooth muscle effect.
The basis of the effect of mydriasis by atropine
is the paralysis of the ciliary muscle of the eye lens and sphincter pupillae muscle, the pupil dilates and does not react to light. This is accompanied by an increase in internal eye pressure.
Effect lasts in the eye for days.
effect of atropine on the CNS
Atropine does not cause central nervous system side effects in therapeutic doses;
humans experience hallucinations in large doses, animals in large doses experience mania, irritable behaviour, increase in motor activity until coma.
What is scopolamine?
is a natural or synthetically produced tropane alkaloid and anticholinergic drug that is used as a medication to treat motion sickness and postoperative nausea and vomiting. It is also sometimes used before surgery to decrease saliva.
Large doses of scopolamine cause
delirium in horses, dogs and cats, small doses cause mainly depression.
Antidote to atropine/parasympatholytics
Indirect-acting cholinomimetics
aka Cholinesterase inchibitors
Clinical uses of parasympatholytics such as atropine
Inhibition of the function of intestinal glands, antispasmodic medicine in the case of spasms of the intestinal tract,
uterus, urinary bladder or bronchial spasms.
Premedication before general anaesthesia, in order to reduce the secretion of glands, in order to strengthen heart function (to prevent or treat bradycardia).
Glycopyrrolate clinical uses
increases pressure by reducing parasympathetic tone
Tachycardia response lower.
In dogs diminishes the volume and acidity of gastric secretions, reduces intestinal motility, reduces secretions of the respiratory tract.
Its duration of action exceeds that of atropine.
N-butylscopolamine bromide is a
Anticolinergic, similar in action to atropine.
Spasmolytic.
Used in case of GI spasms in horses. Investigations confirm efficacy also in case of bronchoconstriction (acts as bronchodilator).
Propantheline Is used as a
smooth muscle relaxant. Also acts as an autonomic ganglionic blocker (n-colinoblocking effect). Propantheline bromide is an antimuscarinic agent.
Most likely it contributes to the antispasmodic effect on GI smooth muscle.
Antinicotinic agents are
(neuromuscular blocking agents)
Peripheral muscle relaxants
Substances that block the impulse transmission from the motor nerve ending to the striated muscle. Curare-like substances.
Antinicotinic agents (neuromuscular blocking agents) / curare-like substances cause muscle paralysis in the following order:
Extraocular and face muscles
Muscles of the neck and tongue
Limb muscles
Trunk
Intercostal muscles, diaphragm.
Cause of death is respiratory paralysis, the animal will remain fully conscious until the end.
Mechanism of action of nondepolarizing muscle relaxants.
effects inhibit the nerve-muscle transmission, compete with acetylcholine, inhibit acetylcholine-induced membrane depolarization.
Indirect-acting cholinomimetics can be used to increase the amount of acetylcholine in postsynapse, impulse transmission will be restored (antidotes).
Substances with depolarizing effect induce
membrane depolarization by themselves similar to acetylcholine and compete with acetylcholine. Paralysis is preceded by muscle fibre contraction induced by depolarization.
There is no antidote in case of depolarizing substances.
In case of nondepolarizing substances the antidote is
cholinesterase inhibitors. This is also referred to as decurarization.
