Pharmacology - Autonomics II and III Flashcards Preview

MS 2 - Unit 2 > Pharmacology - Autonomics II and III > Flashcards

Flashcards in Pharmacology - Autonomics II and III Deck (61):
1

M1/M3/M5 receptors couple to:

phospholipase C

2

M2/M4 receptors couple to:

adenylyl cyclase and/or K+ channels

3

Are M2 autoreceptors excitatory or inhibitory?

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

4

Pilocarpine is a nonselective muscarinic ______.

agonist

5

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

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

6

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

Neostigmine
active NM nicotinic cholinoceptors in addition to blocking cholinesterase

7

Bethanechol is used for:

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

8

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

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.

9

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

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.

10

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

Negative chronotropy
HR down
M2

11

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

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

12

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

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

13

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

small decrease in contractile strength
M2

14

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

dilation via NO (EDRF)
constriction is high dose direct effect

15

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

contraction/bronchoconstriction

16

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

increase

17

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

relaxation

18

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

stimulation

19

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

contraction

20

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

relaxation

21

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

secretion (SLUDGE)
M3

22

Neostigmine
Tacrine
Donepezil
Edrophonium
Physostigmine
Pyridostigmine

These drugs are examples of:

cholinesterase inhibitors

23

Isoflurophate
Sarin
Echothiophate
Parathion
Paraoxon

These drugs are examples of:

Organophosphate cholinesterase inhibitors

Poisons, insecticides and nerve gases

24

Sarin gas poisoning can be reversed by pralidoxime because:

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

25

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

Increases ACh level

Under or overdoses in MG patients cause paralysis

26

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

Depolarizing block

Under or overdoses in MG patients cause paralysis

27

Major uses for cholinomimetics:

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

28

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

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

29

SLUDGE effects can be reversed by administering:

Atropine (and pralidoxime (PAM))

30

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

Respiratory collapse from CNS effects;
skeletal muscle paralysis;
bronchospasm

31

Duration of action:
Edrophonium - MG and Ileus

5-15 minutes

32

Duration of action:
Neostigmine - MG and Ileus

30 min to 2 hours

33

Duration of action:
Pyridostigmine - MG

3-6 hours

34

Duration of action:
Physostigmine - Glaucoma

30 min to 2 hours

35

Duration of action:
Echothiophate - Glaucoma

100 hours

36

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

Adrenal medulla;
Norepi nicotinic receptor;
ACh nicotinic receptor

37

Does atropine bind to nicotinic receptors?

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

38

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

penetrate the CNS better
have more central effects

39

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

Glycopyrrolate

40

0.5mg of atropine has what effects?

slight cardiac slowing
drymouth
inhibition of sweating (cholinergic)

41

5mg of atropine has what effects?

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

42

10mg and up of atropine has what effects?

hallucinations and delirium
coma

43

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

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

44

Effects of Muscarine BLOCKING drugs:
Eye
M3 receptors

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

45

Effects of Muscarine BLOCKING drugs:
Bronchi
M3 receptors

Bronchodilation, especially if constricted

46

Effects of Muscarine BLOCKING drugs:
GI
M1 and M3 receptors

relaxation
slowed peristalsis

47

Effects of Muscarine BLOCKING drugs:
GU tract
M3 receptors

relaxation of bladder wall
urinary retention

48

Effects of Muscarine BLOCKING drugs:
Heart

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

49

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

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

50

Effects of Muscarine BLOCKING drugs:
Glands
M1 and M3 receptors

reduction in salivation, lacrimation, sweating,

51

Effects of Muscarine BLOCKING drugs:
Skeletal muscle

NONE!!! This is NMJ

52

Hexamethonium
Mecamylamine
these drugs are:

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

53

NMJ blockers inhibit what kind of receptor?

Nm

54

Give an example of a nondepolarizing NMJ blocker.

Tubocurarine
Mivacurium
prevents opening of the end plate channel

55

Give an example of a depolarizing NMJ blocker.

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

56

Succinylcholine is made up of:

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

57

Uses for NMJ blockers:

surgery prep
intubation prep

58

Length of effects - Tubocurarine

30-60 min

Mivacurium is much shorter bc hydrolyzed more rapidly

59

Toxic effects of NMJ blockers:
Tubocurarine
Succinylcholine

respiratory paralysis
disturbance of autonomic function (Nn overlap effects)

60

Pancuronium used in:

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

61

Botulinim Toxin A degrades what protein?

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)