Cholinergic Drugs

Question 1

Cholinergic drugs are split into…

Answer 1

agonists (direct and indirect) and antagonists

Question 2

How do direct act?

Answer 2

bind and activate

Question 3

How do indirect act?

Answer 3

inhibit acetylcholinesterase

Question 4

Where are m receptors?

Answer 4

Parasym in cardiac and smooth muscle, only symp in sweat glands

Question 5

What are the direct effects of ACh?

Answer 5

Vasodilation (M3)
Decrease cardiac output (M2)
Decrease conduction in SA and AV M2
Decrease force in conduction (M2)

Question 6

Small dose of Ach?

Answer 6

reflex tachycardia

decrease PVR
decrease MAP
increase HR

Question 7

Large dose of Ach?

Answer 7

bradycardia

decrease PVR
decrease MAP
decrease HR

Question 8

Effects of Ach on various organs…

Answer 8

PARASYMPATHETIC

think of miosis, bronchial constrictions, decrease heart rate

Question 9

What happens if M receptors are blocked by atropine and you add large doses of Ach?

Answer 9

Nicotinic effects:
increase in BP and vasoconstriction

stimulation of symp and release of epinephrine from medulla

Question 10

Direct acting agonists

Answer 10

1. Esters of Choline (ABC-M)
   - Ach
   - Bethanechol
   - Carbachol
   - Methacholine
2. Alkaloids
   - Pilocarpine
   - Nicotine

Question 11

Choline esters

Answer 11

quaternary ammoniums
poorly absorbed in CNS
Ach rapidly hydrolyzed

Question 12

Acetylcholine

Answer 12

• rapidly hydrolyzed

- rapid miosis in cataract surgery

Question 13

Bethanechol

Answer 13

• Muscarinic agonist

- Atony of urinary bladder

Question 14

Carbachol

Answer 14

• Muscarinic and Nicotinic agonist

- Cataract surgery/miosis

Question 15

Methacholine

Answer 15

• Muscarinic agonist

- bronchial airway hyperreactivity in ppl who maybe have asthma

Question 16

Pliocarpine

Answer 16

• partial M agonist

- open angle glaucoma and dry mouth

Question 17

M agonist AE:

Answer 17

• sweating, flushing, low BP, diarrhea, AB pain

Question 18

Nicotine intersting fact:

Answer 18

depolarizes autonomic ganglia–> stimulation then paralysis

Question 19

Nicotine actions

Answer 19

Para and Symp

Mainly Para except CV system–> increase in BP and HR

Question 20

Nicotine poisoning

Answer 20

nausea, AB pain, cold swears, mental confusion

Question 21

Nicotine use

Answer 21

smoking cessation therapy

Question 22

Indirect Acting:

Answer 22

1. Edrophonium- reversible binding
2. Carbamates “stigmine”- covalent bond
   - Physostigmine
   - Neostigmine
   - Pyridostigmine
3. Organophosphates- phosphorylation
   - Echothiophate
   - Malathion
   - Sarin

Question 23

Organophosphates interesting fact:

Answer 23

phosphorylated enzyme goes through ageing to strengthen bond

Question 24

ANTICHOLINESTERASES:

ORGAN SYSTEM EFFECTS

Answer 24

CNS:
low- activation
high- convulsions

Most systems: PARA

CV: both para and symp

• in heart: mainly para
• increase resistance and BP

TLDR: bradycardia, decrease CO, increase vascular resistance and BP

Question 25

ANTICHOLINESTERASES interesting fact:

Answer 25

minimal effect in vascular smooth muscle

Question 26

Edrophonium

Answer 26

does not enter CNS | diagnosis of Myasthenia gravis

Question 27

Physostigmine

Answer 27

enter CNS | overdose of anticholinergic drugs

Question 28

Neostigmine

Answer 28

does not enter CNS | treatment of myasthenia gravis

Question 29

Pyridostigmine

Answer 29

does not enter CNS | treatment of myasthenia gravis

Question 30

Echothiophate

Answer 30

glaucoma RARELY used

Question 31

Malathion

Answer 31

insecticides

Question 32

Sarin

Answer 32

nerve agent: poison gas

Question 33

Ach inhibitors in Alzheimer disease

Answer 33

Galantamine Donepezil Rivastigmine

Question 34

Pralidoxime

Answer 34

split phosphorous-enzyme bond *used for organophosphate insecticide poisoning

Question 35

Cholinergic antagonists are split up to?

Answer 35

- M antagonists - N antagonists - Drugs that act presynaptically

Question 36

M antagonists -->

Answer 36

1. Natural alkaloids - Atropine - Scopolamine 2. Synthetic and semi synthetic drugs

Question 37

Atropine:

Answer 37

``` Eye: mydriasis, cycloplegia GI: reduces motility Urinary: reduces motility CV: low- bradycardia high- tachycardia ```

Question 38

Atropine intersting fact:

Answer 38

atropine flush- cutaneous vasodilation

Question 39

Atropine uses:

Answer 39

1. relax GI and bladder 2. antidote for cholinergic agonists 3. reduce respiratory secretions prior to surgery

Question 40

Atropine AE:

Answer 40

blurry vision, sandy eyes, constipation, tachycardia, urinary retention confusion, hallucinations

Question 41

Scopolamine

Answer 41

- similar to atropine but longer duration - can produce sedation - mydriasis and motion sickness****

Question 42

Synthetic and semi synthetic drugs:

Answer 42

1. Quaternary ammonium MA "pium" - Ipratropium and Tiotropium 2. Tertiary amine MA - Homatropine - Cyclopentolate - Tropicamide - Benztropine - Trihexyphenidyl

Question 43

Ipratropium and Tiotropium

Answer 43

COPD and asthma

Question 44

- Homatropine - Cyclopentolate - Tropicamide

Answer 44

Mydriasis

Question 45

- Benztropine | - Trihexyphenidyl

Answer 45

Parkinsons and effects of antipsychotic drugs

Question 46

Other M antagonists

Answer 46

Glycopyrolate Oxybutynin Tolterodine

Question 47

Glycopyrolate

Answer 47

- COPD - Peptic ulcer - drooling - reduce secretions

Question 48

Oxybutynin | Tolterodine

Answer 48

Overactive bladder

Question 49

Contraindications of Anti-M agents:

Answer 49

angle-closure glaucoma, prostatic hypertrophy and elderly

Question 50

Nicotinic receptor antagonists:

Answer 50

1. Ganglion blockers | 2. NMJ blockers

Question 51

Ganglion blockers:

Answer 51

both symp and para 2 mechanisms: 1. Prolonged depolarization- nicotine 2. Antagonism- Hextamethonium and mecamylamine

Question 52

Hextamethonium and mecamylamine

Answer 52

used for hypertension

Question 53

Ganglion blockers interesting fact:

Answer 53

remove dominant control of various organs a1- arterioles and veins M3- sweat glands will both become para (so dilation and no sweat) the rest by M2 and M3 will be symp

Question 54

NMJ blockers:

Answer 54

block on skeletal muscle 1. Competitive antagonists (non depolarizing) 2. Agonists (depolarizing)

Question 55

Competitive antagonists (non depolarizing)

Answer 55

Tubocurarine

Question 56

Tubocurarine

Answer 56

- reversible competitive - can be overcome by cholinesterase inhibitors like neostigmine or edrophonium - used for muscle relaxation during surgery in anaesthesia

Question 57

Agonists (depolarizing)

Answer 57

Succinylcholine

Question 58

Succinylcholine

Answer 58

- receptor desensitizes | used for: Rapid endotracheal intubation and ECT

Question 59

Succinylcholine AE:

Answer 59

- malignant hyperthermia dur to excess release of Ca+ from SR treated with: dantrolene

Question 60

Drugs that act presynaptically

Answer 60

1. inhibitors of synthesis - Hemicholinium-3 2. inhibitors of storage - Vesamicol 3. Inhibitors of release - Botox

Question 61

Hemicholinium-3

Answer 61

blocks CHT and prevents uptake of choline

Question 62

Vesamicol

Answer 62

blocks Ach-H antiporter (VAChT) needed for storage into vesicles

Question 63

Botox

Answer 63

inhibits Ach release