Cholinergic Transmission

Question 1

During depolarization, which channels open? What is the result?

Answer 1

Sodium channels open, large influx of sodium ions causes membrane potential to rise.

Question 2

What happens during repolatization?

Answer 2

K channels open, K ions move out

Question 3

What happens during hyperpolarization?

Answer 3

Lowered membrane potential is caused by closing of the potassium channels and efflux of potassium.

Question 4

Myasthenia Gravis, what is it and which drug can be indicated for the treatment?

Answer 4

Muscles under voluntary control get tired quickly. Normal dosage of nicotinic receptor stimulation would benefit these patients. Also reversible cholinesterase inhbitors such as neostigmine can be used.

Question 5

Pilocarpine- what is it- what is the oral and local indication?

Answer 5

It is a specific muscarinic R agonist, can pass BBB but not always, (so may have side effects) locally for eye miosis for closed angle glaucoma. Orally to treat extremely dry mouth

Question 6

Ach -what is it- indication?

Answer 6

It is a muscarinic Receptor agonist. Locally in ophtamologic surgery to induce miosis

Question 7

What is Carbachol and Betanetol

Answer 7

They are muscarinic Achetylcholine receptor agonists. They are permenantly + charged, therefore they cannot pass through BBB.

Question 8

How do we understand the difference between efficacy and affinity for a drug?

Answer 8

For affinty, lower EC50 value, higher affinity. For efficacy, see the plateau value.

Question 9

Verenicle- what is it- what are the indications. Compare efficacy and affinity with nicotine.

Answer 9

It is a partial agonist of nicotinic ACh receptor. Efficacy is lower than nicotine but the affinity is higher. It is indicated to stop smoking.

Question 10

Does verenicle have CNS related side effects?

Answer 10

YES

Question 11

What is edrophonium? What does it do? What are the indications?

Answer 11

It is a reversible cholinesterase inhibitor, it competes with Ach for anionic site of cholinesterase. It is used in myasthenia gravis diagnosis. In a few minutes, the patient should show improvement.

Question 12

What are neostigmine and pyridostigmine? What are their actions and indications?

Answer 12

They are reversible cholinesterase inhibitors, They disable enzyme activity for a longer time by binding to anionic site. They can be used for posoperative after a stomach-intestinal-bladder surgery or be used for myasthenia gravis treatmentç

Question 13

What is physostigmine, what is the action, can it pass BBB? What are the indications?

Answer 13

It is a reversible cholinesterase inhibitor, disables esterase site through carbamylester. IT CAN PASS BBB, It is indicated for closed angle glaucoma for miosis induction. Also it is antidote for atropine intoxication.

Question 14

What are some examples of irreversible AChE inhibitors?

Answer 14

Paration, sarin, soman, tabun, novichok

Question 15

What can be used to treat cholinesterase inhibitor intoxication.

Answer 15

General: End exposure through remove clothing, wash skin, gastric lavage, supporting measures for keeping BP from dropping, treating convulsions, preventing airway obstruction.
IV atropine. It is competitive inhibitor of nerve agent.
Oxims- breaks p bond, only effective before conformational change.
Praladoxime(cannot pass BBB), Diacetylmonoxime(can pass BBB) . DİAZEPAM CAN BE ALSO adminstered to stop seizures.

Question 16

What is tiotropium, (hint: same indication as ipratroprium)- why and how is it used.

Answer 16

They are muscaric receptor antagonists, namely anti-cholinergics. They are used by inhalation for asthma patients as they dont produce adverse effects on mucociliary clearance. In contrast to atropine. Their anticholinergic effects like bronchodilation can be exploited safely in airway disease treatment. They are used with inhalation of long acting B adrenergic receptor antagonists.

Question 17

Explain Pachycurares and Leptocurares

Answer 17

Pachycurares: nondepolarizing agent, competitive nicotinic receptor antagonist, prevents muscle contraction, activity can be cauntered by acetylcholinesterase inhibitors.
Leptocurares: continiously depolarizes, makes repolarization impossible and causes muscle paralysis. Used for anesthesia or other muscle relaxant purposes.

Question 18

What are some classes of drugs that can have anticholinergic side effects?

Answer 18

Tricyclylic antidepressants, Antipsychotics such as ferothiozines, Anti epileptics like carbamazepine, H1 antihistamines.

Question 19

Drugs used for closed angle glaucoma? How do they work?

Answer 19

Pilocarbin, Carbachol, Physostigmine. They induce miosis and improve intra ocular fluid drainage by increasing iris tension.

Question 20

What are drugs used for open angle glaucoma and what do they do?

Answer 20

They lower ocular pressure, B blocker timolol,
Physostigmine, Carbonyl anhydrase inhibitors, prostoglandines