Drugs Affecting the Cholinergic System

Question 1

Carbachol

Answer 1

Receptor: Direct acting agonist;
Indication for use: Used locally for miosis and to decrease IOP (Glaucoma);
Clinical features: Less susceptible to cholinesterases and acts for longer.

Question 2

Pilocarpine

Answer 2

Receptor: Direct acting agonist;

Indication for use: acts on smooth muscle of eye – miosos and increases aqueous outflow leading to decrease in IOP.

Question 3

Bethanacol

Answer 3

Receptor: Direct acting agonist;

Indication for use: stimulates urinary and GI tract – treats urinary retention and lack of muscular tone in GIT;

Question 4

Edrophonioum

Answer 4

Receptor: Reversible indirect acting agonist;

Indication for use: used for diagnosing myasthenia gravis (Abs block ACh receptors – muscle weakness);

Question 5

Physostigmine

Answer 5

Receptor: Reversible indirect acting agonist;

Indication for use: stimulates M and N and intermediated acting agent so used in reversing overdose of anticholinergics.

Question 6

Neostigmine (Proserin[um])

Answer 6

Receptor: Reversible indirect acting agonist;
Indication for use: more polar and doesn’t absorb from GIT and doesn’t enter GIT so used to treat MG. Stimulates bladder and GIT and reverses effects of anaesthesia from NM blocking agents.

Question 7

Pyridostigmine

Answer 7

Receptor: Reversible indirect acting agonist;
Indication for use: more polar and doesn’t absorb from GIT and doesn’t enter GIT so used to treat MG. Stimulates bladder and GIT and reverses effects of anaesthesia from NM blocking agents.

Question 8

Donepezil

Answer 8

Receptor: Reversible indirect acting agonist;

Indication for use: Treatment of Alzheimer’s boosting cholinergic activity.

Question 9

Rivastigmine

Answer 9

Receptor: Reversible indirect acting agonist;

Indication for use: Treatment of Alzheimer’s boosting cholinergic activity.

Question 10

Galantamine

Answer 10

Receptor: Reversible indirect acting agonist;

Indication for use: Treatment of Alzheimer’s boosting cholinergic activity.

Question 11

Echothiophate

Answer 11

Receptor: Irreversible indirect acting agonist;
Indication for use: covalent bond with cholinesterase – treats open angle glaucoma but not used due to side effect profile. Reversed by atropine. Risk of cataracts.

Question 12

Scopolamine

Answer 12

Receptor: Anti-muscarinic;
Indication for use: CNS and longer duration of action (prevents motion sickness and postoperative vomiting and nausea). “When you are on a school trip and you use binoculars to scope out you surroundings; but because you’re on a coach you feel nauseous”.

Question 13

Ipitropium & Tiotopium

Answer 13

Receptor: Anti-muscarinic;
Indication for use: decreased contractility in lungs –> bronchodilation –> reduction in mucus secretion – treats bronchospasm in COPD treats rhinorrhea.

Question 14

Tolterodine

Answer 14

Receptor: Anti-muscarinic;

Indication for use: Selective for M3 used for bladder function (overactive bladder).

Question 15

Darifenacin

Answer 15

Receptor: Anti-muscarinic;

Indication for use: Selective for M3 used for bladder function (overactive bladder).

Question 16

Solifenacin

Answer 16

Receptor: Anti-muscarinic;

Indication for use: Selective for M3 used for bladder function (overactive bladder).

Question 17

Oxybutynin

Answer 17

Receptor: Anti-muscarinic;

Indication for use: Selective for M3 used for bladder function (overactive bladder).

Question 18

Trospium

Answer 18

Receptor: Anti-muscarinic;

Indication for use: Selective for M3 used for bladder function (overactive bladder).

Question 19

Fesoterodine

Answer 19

Receptor: Anti-muscarinic;

Indication for use: Selective for M3 used for bladder function (overactive bladder).

Question 20

Benztropine & Trihexphenidyl

Answer 20

Receptor: Anti-muscarinic;

Indication for use: Reduce central cholinergic activity and are beneficial in treating Parkinsonian disorders.

Question 21

Cisatricurium

Answer 21

Receptor: Neuro-Muscular blocker;
Indication for use: Used for mechanical ventilation and tracheal intubation increases muscle relaxation (lower doses of general);
Clinical features: not absorbed and must be injected IV, onset of action is two minutes, these paralyse small fast acting first then larger muscle.

Question 22

Pancuronium

Answer 22

Receptor: Neuro-Muscular blocker;
Indication for use: Used for mechanical ventilation and tracheal intubation increases muscle relaxation (lower doses of general);
Clinical features: not absorbed and must be injected IV, onset of action is two minutes, these paralyse small fast acting first then larger muscle.

Question 23

Rocuronium

Answer 23

Receptor: Neuro-Muscular blocker;
Indication for use: Used for mechanical ventilation and tracheal intubation increases muscle relaxation (lower doses of general);
Clinical features: not absorbed and must be injected IV, onset of action is two minutes, these paralyse small fast acting first then larger muscle.

Question 24

Vecuronium

Answer 24

Receptor: Neuro-Muscular blocker;
Indication for use: Used for mechanical ventilation and tracheal intubation increases muscle relaxation (lower doses of general);
Clinical features: not absorbed and must be injected IV, onset of action is two minutes, these paralyse small fast acting first then larger muscle.

Question 25

Atracurium

Answer 25

Receptor: Neuro-Muscular blocker;
Indication for use: Used for mechanical ventilation and tracheal intubation increases muscle relaxation (lower doses of general);
Clinical features: not absorbed and must be injected IV, onset of action is two minutes, these paralyse small fast acting first then larger muscle.

Question 26

Succinylcholine

Answer 26

Receptor: Depolarising agents (neuromuscular);
Indication for use: Used for rapid tracheal intubation and muscle relaxation in electroconvulsive therapy;
Clinical features: Can lead to apnoea (prolonged);
Flow of K into intracellular fluid leading to hyperkalaemia which in people with tissue damage can lead to EKG changes and asystole as well as malignant hyperthermia.

Question 27

What are the general side effects of cholinergic drugs?

Answer 27

(DUMBBELS) Diarrhoea, Urination, Miosis / Muscle weakness, Bronchorrhea, Bradychardia, Emesis, Lacrimation, Salivation.

Question 28

What are the general side effects of anti-cholinergic drugs?

Answer 28

(ABCDS) Agitation, Blurred vision, Constipation and Confusion, Dry mouth and Stasis of urine and sweating.

Question 29

What are the contraindications of cholinergic drugs?

Answer 29

Pulmonary disease (COPD/bronchial asthma), Peptic ulcer disease (may use with caution), Arrhythmias (atrial fibrillation), Coronary vascular disease, Angle-closure glaucoma, Hyperthyroidism, Intestinal resection or anastomosis, Urinary obstruction, Orthostatic hypotension, Severe miosis.

Question 30

What are the contraindications of anti-cholinergic drugs?

Answer 30

Patients with autonomic neuropathy, hiatus hernia and
hepatic and renal impairment. They can worsen hyperthyroidism, coronary artery disease, congestive heart failure and arrhythmias. Myasthenia gravis, glaucoma, significant bladder outflow obstruction or urinary retention, severe ulcerative colitis and gastrointestinal obstruction.

Question 31

Where are M1 muscarinic receptors found and which GPCR do they activate?

Answer 31

They are found in the gastric glands and activate Gq receptors (increases IP3 and therefore muscle contraction).

Question 32

Where are M2 muscarinic receptors found and which GPCR do they activate?

Answer 32

Cardiac cells (Gi) - Gi –> decreased cAMP –> relaxation of smooth muscles;

Question 33

Where are M3 muscarinic receptors found and which GPCR do they activate?

Answer 33

They are found in smooth muscles in the eye, lungs, digestive tract and exocrine glands (sweat, salivary) and activate Gq receptors (increase IP3 and therefore muscle contraction).

Question 34

Atropine

Answer 34

Receptor: Anti-muscarinic;
Indication for use: Effects eye, GIT, heart and salivary, sweat and lacrimal glands. Relaxation of ciliary muscles (mydriases causing cycoplegia) long duration so shorter acting drugs like cyclopentoate and tropicamide are used;
Clinical features: blocks M3 receptors leading to reduced motility leading to prolonged gastric emptying and increased transit time; atropine can block M2 receptor on SA and AV node leading to tachycardia; blocks glands so dry mouth, dry skin and body temperature rises.

Question 35

Nicotine

Answer 35

Receptor: ganglionic agonist and antagonist (stimulates then blocks); acts at parasympathetic and sympathetic autonomic ganglia – this increases dopamine, serotonin and NE;
Clinical features: it is non selective stimulates CNS leading to convulsions but also depresses CNS leading to respiratory arrest; stimulates adrenal medulla and sympathetic ganglia increases BP and heart rate but at higher doses causes it to fall; GI increase motility leads to nausea and vomiting; causes addiction as due to CNS stimulation leads to alertness and searching for wellbeing.

Question 36

What causes the side effects of NM blockers?

Answer 36

Histamine release decreased BP and causes bronchoconstriction.

Question 37

What metabolite of NM blockers can cause seizures?

Answer 37

Laudanosine.

Question 38

Where are Rocuronium and Vecuronium metabolised? What is their contraindication?

Answer 38

They are metabolised by the liver and therefore contraindicated in patients with hepatic impairment.

Question 39

Which NM blocker causes increased heart rate?

Answer 39

Pancuronium.

Question 40

Explain the two phases of Succinylcholine action.

Answer 40

Phase 1: Binds to receptor and causes Na channel to open depolarisation. Resistant so prolonged opening leads to flaccid paralysis after transient fasciculations;
Phase 2: The channel closes and repolarises but becomes desensitised to ACh.

Question 41

What are the effects of parasympathetic activation (rest and digest)?

Answer 41

Pupil constriction, lacrimation, stimulation of salivary gland, inhibits heart and dilates arterioles, constricts bronchi, stimulates stomach and intestine motility, and relaxes bladder neck.