Pharmacology - Autonomics II and III

Question 1

M1/M3/M5 receptors couple to:

Answer 1

phospholipase C

Question 2

M2/M4 receptors couple to:

Answer 2

adenylyl cyclase and/or K+ channels

Question 3

Are M2 autoreceptors excitatory or inhibitory?

Answer 3

Inhibitory
utilize signaling pathways identical to M2 receptors in the heart - cAMP reduction and K+ channel activation
*decreases HR

Question 4

Pilocarpine is a nonselective muscarinic ______.

Answer 4

agonist

Question 5

Direct-acting cholinomimetic agents bind to and directly activate muscarinic or nicotinic receptors. The indirect agents act by:

Answer 5

inhibiting the action of acetylcholinesterase –> increase endogenous ACh in the synaptic clefts and neuroeffector junctions

Question 6

Some cholinesterase inhibitors have a moderate direct action, for example some quaternary carbamates like ____

Answer 6

Neostigmine

active NM nicotinic cholinoceptors in addition to blocking cholinesterase

Question 7

Bethanechol is used for:

Answer 7

postoperative and neurogenic ileus and urine retention
relieves paralysis of GI/GU tract
carbamic acid ester

Question 8

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Eye - sphincter muscle of iris

Answer 8

contraction (miosis)

muscarinic agonists can reduce intraocular pressure by causing contraction of the ciliary body so as to facilitate outflow of aqueous humor and perhaps also its rate of secretion…Pilocarpine, a well-absorbed, tertiary amine, can be used for this.

Question 9

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Eye - ciliary muscle

Answer 9

contraction for near vision

muscarinic agonists can reduce intraocular pressure by causing contraction of the ciliary body so as to facilitate outflow of aqueous humor and perhaps also its rate of secretion…Pilocarpine, a well-absorbed, tertiary amine, can be used for this.

Question 10

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Heart - SA node

Answer 10

Negative chronotropy
HR down
M2

Question 11

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Heart - Atria

Answer 11

decrease in contractile strength - negative inotropy
_______ in refractory period
M2

Question 12

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Heart - AV node

Answer 12

decrease in conduction velocity - negative dromotropy
increase in refractory period
M2

Question 13

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Heart - ventricles

Answer 13

small decrease in contractile strength

M2

Question 14

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Arteries and veins

Answer 14

dilation via NO (EDRF)

constriction is high dose direct effect

Question 15

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Bronchial muscle

Answer 15

contraction/bronchoconstriction

Question 16

Direct muscarinic effects of direct-acting choliniceptor stimulants:
GI tract - motility

Answer 16

increase

Question 17

Direct muscarinic effects of direct-acting choliniceptor stimulants:
GI sphincters

Answer 17

relaxation

Question 18

Direct muscarinic effects of direct-acting choliniceptor stimulants:
GI secretion

Answer 18

stimulation

Question 19

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Urinary bladder - detrusor muscle

Answer 19

contraction

Question 20

Direct muscarinic effects of direct-acting choliniceptor stimulants:
Urinary bladder - Trigone and sphincter

Answer 20

relaxation

Question 21

Direct muscarinic effects of direct-acting choliniceptor stimulants:
sweat, salivary, lacrimal, nasopharyngeal

Answer 21

secretion (SLUDGE)

M3

Question 22

Neostigmine
Tacrine
Donepezil
Edrophonium 
Physostigmine
Pyridostigmine

These drugs are examples of:

Answer 22

cholinesterase inhibitors

Question 23

Isoflurophate
Sarin
Echothiophate
Parathion
Paraoxon

These drugs are examples of:

Answer 23

Organophosphate cholinesterase inhibitors

Poisons, insecticides and nerve gases

Question 24

Sarin gas poisoning can be reversed by pralidoxime because:

Answer 24

Pralidoxime (PAM) is a strong nucleophile that regenerates acetylcholinesterase

**must work before “aging” which makes acetylcholinesterase permanently/irreversibly inactive

Sarin gas takes only 2 minutes to age, so administer quickly

Question 25

Explain the effect of Neostigmine on muscle strength at LOW doses.

Answer 25

Increases ACh level Under or overdoses in MG patients cause paralysis

Question 26

Explain the effect of Neostigmine on muscle strength at HIGH doses.

Answer 26

Depolarizing block Under or overdoses in MG patients cause paralysis

Question 27

Major uses for cholinomimetics:

Answer 27

diseases of the eye ie glaucoma; GI and urinary tension (is post-surgical atony, neurogenic bladder, impaired salivation); NMJ issue ie MG, reversal of non-depolarizing blocker-induced neuromuscular paralysis; cognitive enhancement in Alzheimer's

Question 28

What drug can be used as a diagnostic tool for confirming MG in patients?

Answer 28

Edrophonium | transiently increases muscle strength, can be given IV to test

Question 29

SLUDGE effects can be reversed by administering:

Answer 29

Atropine (and pralidoxime (PAM))

Question 30

SLUDGE plus what symptoms characterize major cholinomimetic toxicity (as with suicide attempts)?

Answer 30

Respiratory collapse from CNS effects; skeletal muscle paralysis; bronchospasm

Question 31

Duration of action: | Edrophonium - MG and Ileus

Answer 31

5-15 minutes

Question 32

Duration of action: | Neostigmine - MG and Ileus

Answer 32

30 min to 2 hours

Question 33

Duration of action: | Pyridostigmine - MG

Answer 33

3-6 hours

Question 34

Duration of action: | Physostigmine - Glaucoma

Answer 34

30 min to 2 hours

Question 35

Duration of action: | Echothiophate - Glaucoma

Answer 35

100 hours

Question 36

What are the sites of action of the ganglionic blockers, Nn?

Answer 36

Adrenal medulla; Norepi nicotinic receptor; ACh nicotinic receptor

Question 37

Does atropine bind to nicotinic receptors?

Answer 37

No, while it is structurally similar to ACh, it binds only at muscarinic GPCRs.

Question 38

In general, tertiary amines are better absorbed and _______ than quaternary amines

Answer 38

penetrate the CNS better | have more central effects

Question 39

Give an example of a quaternary amine that has local effects but is too big to diffuse and affect the CNS.

Answer 39

Glycopyrrolate

Question 40

0.5mg of atropine has what effects?

Answer 40

slight cardiac slowing drymouth inhibition of sweating (cholinergic)

Question 41

5mg of atropine has what effects?

Answer 41

``` rapid HR palpitations market drymouth dilation of pupil (mydriasis) --> "belladonna" blurring of near vision ```

Question 42

10mg and up of atropine has what effects?

Answer 42

hallucinations and delirium | coma

Question 43

Effects of Muscarine BLOCKING drugs: CNS --muscarinic subtypes unknown

Answer 43

``` sedation anti-motion sickness action anti-Parkinsonian action amnesia delirium ```

Question 44

Effects of Muscarine BLOCKING drugs: Eye M3 receptors

Answer 44

Cycloplegia - paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation; mydriasis

Question 45

Effects of Muscarine BLOCKING drugs: Bronchi M3 receptors

Answer 45

Bronchodilation, especially if constricted

Question 46

Effects of Muscarine BLOCKING drugs: GI M1 and M3 receptors

Answer 46

relaxation | slowed peristalsis

Question 47

Effects of Muscarine BLOCKING drugs: GU tract M3 receptors

Answer 47

relaxation of bladder wall | urinary retention

Question 48

Effects of Muscarine BLOCKING drugs: | Heart

Answer 48

initially slight bradycardia at low doses - block of inhibitory presynaptic receptors then tachycardia - block M2 receptors at SA node

Question 49

Effects of Muscarine BLOCKING drugs: Blood vessels M3 receptors on endothelium

Answer 49

block muscarinic vasodilation with NO | will not manifest unless a muscarinic agonist is present

Question 50

Effects of Muscarine BLOCKING drugs: Glands M1 and M3 receptors

Answer 50

reduction in salivation, lacrimation, sweating,

Question 51

Effects of Muscarine BLOCKING drugs: | Skeletal muscle

Answer 51

NONE!!! This is NMJ

Question 52

Hexamethonium Mecamylamine these drugs are:

Answer 52

Ganglion-blocking drugs not really used therapeutically anymore used to be used to prevent bleeding out by dropping BP on the battlefield Ganglionic blockers competitively inhibit Nn receptors at both sympathetic and parasympathetic ganglia. Lack of selectivity --> side effects

Question 53

NMJ blockers inhibit what kind of receptor?

Answer 53

Nm

Question 54

Give an example of a nondepolarizing NMJ blocker.

Answer 54

Tubocurarine Mivacurium prevents opening of the end plate channel

Question 55

Give an example of a depolarizing NMJ blocker.

Answer 55

Succinylcholine "desensitize" the end plate by causing persistent depolarization flaccid paralysis

Question 56

Succinylcholine is made up of:

Answer 56

2 molecules of acetylcholine linked AGONIST of NMJ (initial contractions) **action is brief - 5-10 min Hydrolyzed by butyrylcholinesterase in the plasma en route to site of action

Question 57

Uses for NMJ blockers:

Answer 57

surgery prep | intubation prep

Question 58

Length of effects - Tubocurarine

Answer 58

30-60 min Mivacurium is much shorter bc hydrolyzed more rapidly

Question 59

Toxic effects of NMJ blockers: Tubocurarine Succinylcholine

Answer 59

respiratory paralysis | disturbance of autonomic function (Nn overlap effects)

Question 60

Pancuronium used in:

Answer 60

lethal injection. It's a NMJ blocker | used with sodium thiopental and potassium chloride

Question 61

Botulinim Toxin A degrades what protein?

Answer 61

SNAP-25 which mediates fusion of synaptic vesicles with the presynaptic terminal membrane --> AP can't get ACh released useful in treating diseases with pathologic muscular tone (locally injected) - ie achalasia, strabismus, oromandibular dystonia (spasms of face/jaw/neck)