3rd lecture - parasympathomimetics

Question 1

another term for parasympathomimetics

Answer 1

cholinomimetics

Question 2

What is required for synthesis of acetylcholiine?

Answer 2

Inflow of choline and glucose is required for synthesis.

Question 3

acetylcholine is broken down by?

Answer 3

acetylcholinesterase

Question 4

acetylcholine is a mediator between

Answer 4

nerve endings and innervated cells of autonomic ganglia, parasympathetic neuroeffector junction, some sympathetic neuroeffector junctions, the adrenal medulla and certain regions of the CNS.

Question 5

Cholinoreceptors are called (2)

Answer 5

M – Muscarinic (Multiple subtypes (5), clinical relevance not clear.)

N – nicotinic

Question 6

Nicotinic responsive sites are present in (3)

Answer 6

autonomic ganglia,
adrenal medulla chromaffin cells
and neuromuscular junctions of the somatic nervous system.

Question 7

Muscarinic receptors are located at

Answer 7

postganglionic parasympathetic neuroeffector junctions,
also in some blood vessels.

Question 8

Cholinomimetic drugs are divided into 2 main groups.

Answer 8

1) Direct-acting - act on the receptor. Acetylcholine, muscarine, pilocarpine, nicotine and arecoline.

2) Indirect-acting – act through acetylcholine metabolism. They are also referred to as cholinesterase inhibitors.

Question 9

acetylcholine analogues

Answer 9

Choline esters: bethanechol and methacholine, carbachol.

Question 10

Cholinomimetic effect is aimed at

Answer 10

the gastrointestinal tract, urinary tract and cardiovascular system.

Question 11

Cholinomimetic effect on the gastric, intestinal and salivary glands

Answer 11

Increase in the secretion and motility

Question 12

Cholinomimetic effect on bronchi

Answer 12

Bronchial contraction

Question 13

in which species are sweat glands regulated by the parasympathetic system?

Answer 13

horses

they can sweat profusely when cholinergic receptors are stimulated

Question 14

Cardiovascular effects of Cholinomimetics

Answer 14

Slowing of heart rate (activation of muscarinic receptors of blood vessels).

blood pressure decrease

at larger doses atrio-ventricular block, atrial fibrillation or flutter or even cardiac arrest.

Question 15

what is methacholine

Answer 15

also known as acetyl-β-methylcholine, is a synthetic choline ester that acts as a non-selective muscarinic receptor agonist in the parasympathetic nervous system.

Methacholine is primarily used to diagnose bronchial hyperreactivity, which is the hallmark of asthma and also occurs in chronic obstructive pulmonary disease.

Question 16

Carbachol causes

Answer 16

profuse salivation and an increase in peristaltic movements of the gut resulting in increased fluidity of feces and defecation (muscarinic receptors).

Carbachol and bethanecol are relatively more active on the GI and urinary tracts.

Question 17

carbachol effect on uterine muscles

Answer 17

Uterine muscles are contracted by Carbachol, should not be used during pregnancy.

Question 18

Carbachol (and Ach) is a

Answer 18

mixed nicotinic-muscarinic agonist, parasympathomimetic that mimics the effect of acetylcholine on both the muscarinic and nicotinic receptors.

Stimulating effect on autonomic ganglia and cromaffin cells of the adrenal medulla.

Question 19

Carbachol Effect on adrenal medulla can cause

Answer 19

an increased discharge of epinephrine and norepinephrine, that could produce diffuse sympathomimetic effect.

Carbachol and ohter parasymathomimetics not used frequently in veterinary medicine.

Question 20

Pilocarpine is

Answer 20

a drug that acts as a muscarinic receptor agonis, so cholinergic/parasympathomimetic.

used mainly in ophthalmic clinical medicine as causes miosis (pupil contraction)

Question 21

How does pilocarpine stimulate the eye?

Answer 21

Pilocarpine stimulates the sphincter muscle of the iris and the ciliary muscle of the lens. Intraocular pressure first increases, followed by a persistent decrease. (Irritating!)

Nowadays mainly for stimulating tear production in case of specific oftalmologic pathologies (keratoconjunctivitis sicca, KCS)

Question 22

Side effects of parasympathomimetics (5)

Answer 22

Colic, diarrhea
Miosis
Shortness of breath (vasoconstriction of bronchial vessels)
Phlegm retention in respiratory tract
Hypotension/extreme bradycardia

Question 23

Contraindications of parasympathomimetics (5)

Answer 23

Gestation - risk of abortion.
Old and exhausted animals - inhibitory action on the heart.
Diseases of the respiratory organs
Heart diseases
Spastic colitis

Question 24

Indirect-acting cholinomimetics cause

Answer 24

the accumulation of acetylcholine at synapses and parasympathomimetic effects appear.

Cholinesterase inhibitors, also known as anticholinesterase agents, impact the action of acetylcholine at all cholinergic synapses across the entire organism.

Question 25

pharmacologic effects of Indirect-acting cholinomimetics (3)

Answer 25

Stimulation of postganglionic muscarinic receptors, resulting in typical parasympathomimetic activity. Stimulation of adrenal chromaffin cells to discharge catecholamines into the circulation. Initial stimulation and subsequent depolarization block of nicotinic receptors of autonomic ganglia and skeletal muscle fibers.

Question 26

examples of Reversible cholinesterase-inhibitors (5)

Answer 26

Physostigmine Neostigmine Edrophonium – synthetic Pyridostigmine bromide Ambenonium chloride Last three agents are used in management of myasthenia gravis and curare overdose (a muscle relaxant of plant origin, arrow poison).

Question 27

Mechanism of action of Indirect-acting cholinomimetics

Answer 27

Reversible inhibitors combine with cholinesterase and prevent the enzyme from hydrolyzing Ach. The interaction with cholinesterase is reversible, as the inhibitor-enzyme complex breaks down, the enzyme is reactivated.

Question 28

Neostigmine/a cholinesterase inhibitor is believed to directly stimulate

Answer 28

nicotinic receptors of skeletal muscle fibers.

Question 29

Contraindications, side effects of Indirect-acting cholinomimetics

Answer 29

gestation, obstruction of the intestine contra. Side effects: Diarrhoea, colic, vomiting, Muscle tremors, weakness, Shortness of breath, Bradycardia, decrease in blood pressure etc.

Question 30

Antidote to Indirect-acting cholinomimetics

Answer 30

atropine, a cholinoblocker

Question 31

Physostigmine can be used to produce what in the eye

Answer 31

is a a reversible cholinesterase inhibitor. so miosis of the pupil and reduces intraocular pressure in the treatment of glaucoma; (also to stimulate ruminal activity in cattle)

Question 32

massive doses of Indirect-acting cholinomimetics can cause

Answer 32

Large doses first stimulate and then depress CNS, massive doses can produce convulsions. Toxic doses produse skeletal muscle weakness, nausea, vomiting, colic, diarrhea, dyspnea, bradycardia, lowered blood pressure.

Question 33

example of a phos containing Indirect-acting cholinomimetic

Answer 33

organophosphorus substances Primarily used as pesticides, insecticides, have also been used as peroral anthelmintics and for extermination of ectoparasites.

Question 34

Mechanism of action of Organophosphorus substances

Answer 34

Binding cholinesterase irreversibly. Enzyme must be synthesised again in order to restore the normal function of the synapse. This takes weeks.

Question 35

how does atropine act as an antidote to organophosphates

Answer 35

competitive antagonist to acetylcholine Blocks muscarinic receptors, lessens severity of parasympathomimetic effects. Blocks muscarinic receptors, lessens severity of parasympathomimetic effects, increases the quantity of organophosphate required to produce death.

Question 36

what is pralidoxime

Answer 36

a Cholinesterase reactivator used as an antidote to toxic doses of indirect-acting parasympathomimetics. If atropine is given in conjunction with pralidoxime, the lethal dose is increased many more times.

Question 37

Clinical uses of organophosphates

Answer 37

Highly toxic to a wide variety of internal and external parasites.

Question 38

what type of mediator is acetylcholine?

Answer 38

its a mixed nicotinic-muscarinic cholinergic agonist. required to maintain the homeostasis of the body.