Pharmacology of Neuromuscular and Ganglionic Blockers

Question 1

Nicotinic receptor antagonists are also known as

Answer 1

ganglionic blockers

Question 2

Reflexes blocked by nicotinic receptor antagonists/ganglionic blockers

Answer 2

baroreceptor reflex and pupillary reflex

Question 3

Two important ganglionic blocker drugs

Answer 3

Trimethaphan and mecamycalamine

Question 4

Trimethaphan

Answer 4

hypotension for surgery

Question 5

Mecamylamine

Answer 5

Tourette’s, smoking cessation, and severe hypertension

Question 6

In general which is stronger, the PANS tone or the SANS tone

Answer 6

the PANS tone, except for regulating the smooth muscles of the vascular system

Question 7

ganglionic blockade will result in

Answer 7

vasodilation and tachycardia

Question 8

What do neuromuscular blockers do?

Answer 8

locally antagonize nicotinic receptors on skeletal muscle in the somatic nervous system

Question 9

How do neuromuscular blockers block acetylcholine transmission pre-synaptically

Answer 9

decrease Ach formation/release, or increase metabolism

Question 10

How do neuromuscular blockers block acetylcholine transmission post-synaptically

Answer 10

block cholinergic receptors (Nm)

Question 11

Therapeutic use for neuromuscular blockers is primarily

Answer 11

to relax skeletal muscle: in surgery, orthopedic procedures, bronchoscopy and for artificial respiration/intubation

Question 12

How do you monitor neuromuscular blockade with TOF impulses

Answer 12

procedures are usually performed when the patient responds with 1-2 twitches, as long as 1 twitch responses is observed the blockade can be quickly reversed, no additional dose of blocker should be given if no twitches are observable

Question 13

Sequence of muscle paralysis by curare/neuromuscular blocker OD

Answer 13

muscles of the eye and those controlling speech are first to relax; fingers, toes then limbs become heavy; intercostals and diaphragm muscles are last; blockade of diaphragm muscles will lead to respiratory depression and eventual death

Question 14

depolarizing neuromuscular blockers

Answer 14

agonist nicotinic acetylcholine receptors; persistent depolarization makes the muscle fiber resistant to further stimulation by ACh

Question 15

Succinylcholine

Answer 15

depolarizing nicotinic acetylcholine receptor agonist - neuromuscular blocker

Question 16

When is succinylcholine used

Answer 16

used in trauma care for intubation; also used for electro-convulsant therapy

Question 17

What patients should you NOT give succinylcholine to?

Answer 17

patients with hyperkalemia as the additional release of potassium by the depolarizing agonist can cuase cardiac arrest

Question 18

How does succinylcholine (suxamethonium) work?

Answer 18

agonist of the NAchR, causing a persistent opening of the channel, thereby preventing repolarization and thus preventing further action potentials from occuring

Question 19

Non-depolarizing (curare-like) neuromuscular blockers

Answer 19

Pancuronium (Pavulon)
Vecuronium (Norcuron)
Atracurium (Tacrium)
Trimethaphan

Question 20

How does the endogenous neurotransmitter acetylcholine bind

Answer 20

as an agonist to nicotine acetylcholinergic receptors; thereby opening the channels are causing an influx of sodium ions

Question 21

Rocuronium

Answer 21

non depolarizing muscle relaxant and antagonist of the NAchR blocking acetylcholine induced activation and blocking nerve transmission

Question 22

how can you reverse the actions of rocuronium

Answer 22

using an Ache inhibitor like neostigmine, which will increase the levels of acetylcholine that can compete with rocuronium or using sugammedex which directly binds and sequesters/scavenges rocuronium

Question 23

Types of cholinesterases

Answer 23

Acetylcholinesterase (AChE) and Plasmacholinesterase (BuChE)

Question 24

Where is AChE and BuchE located?

Answer 24

AchE is located in synapses

BuchE is located in the plasma

Question 25

Classes of AchE inhibitors

Answer 25

carbamates, organophosphates, quarternary ammonium alcohols

Question 26

Describe carbamates

Answer 26

quaternary or teritary amine groups, temporary covalent modification to AChE, reversible and rapid

Question 27

Three important carbamate class AchE inhibitors

Answer 27

physostigmine, neostigmine, and pyridostigmine

Question 28

Describe physostigmine

Answer 28

tertiary amine and can enter the CNS

Question 29

What is physostigmine used for?

Answer 29

used for atropine OD, glaucoma and Alzheimer's disease

Question 30

What are neostigmine and pyridostygmine used to treat?

Answer 30

myasthenia graviis, reversal of neuromuscular blockers and post-operative ileus

Question 31

Why is pyridostygmine better than neostigmine?

Answer 31

pyridostygmine is orally available and has a longer duration of action and fewer side effects compared to neostigmine

Question 32

How do organophosphates bind

Answer 32

covalently but irreversibly to AchE

Question 33

How has the irreversible nature of organophosphates been exploited?

Answer 33

in their use as insecticides and as nerve gas (ex. sarin gas)

Question 34

How can insecticides cause problems in mammals?

Answer 34

although they are rapidly inactivated in mammals, high concentrations will still lead to paraysympathomimetic symptoms

Question 35

Primary antidote for organophosphate poisoning?

Answer 35

parlidoximine (2-PAM) in combination with atropine

Question 36

Explain why you have to use 2-PAM within a couple of hours after exposure to an organophosphate?

Answer 36

after an organophosphate has covalently bonding with AchE it will be further hydrolysed, once this has occured the bond is permanent and cannot be rescued anymore by 2-PAM, this hydrolysis process is known as aging

Question 37

Signs of AchE inhibitor overdose or poisoning

Answer 37

DUMBBELSS diarrhea, urination, miosis, branchospasms, bradycardia, excitation of skeletal muscle and CNS, lacrimation, sweating, salivation

Question 38

Describe edrophonium

Answer 38

AchE inhibitor

Question 39

How is edrophonium used?

Answer 39

used for the diagnosis of myasthenia gravis

Question 40

Myasthenia gravis

Answer 40

autoimmune disease in which antibodies attack nicotinic acetylcholine receptors at the postsynaptic neuromuscular junction

Question 41

Lambert Eaton induced myasthenia gravis

Answer 41

antibodies against vg calcium channels

Question 42

What happens when you exercise with myasthenia gravis?

Answer 42

exercise worsens muscle strength

Question 43

What happens when you exercise with Lambert Eaton induced myasthenia gravis?

Answer 43

exercise improves muscle strength

Question 44

What happens when you give a mysasthenia gravis patient edrophonium?

Answer 44

edrophonium improves muscle strength

Question 45

What happens when you give a lambert eaton MG patient edrophonium?

Answer 45

edrophonium has no effect/small increase in muscle strength

Question 46

What happens when you give edrophonium in a patient experiencing a cholinergic crisis?

Answer 46

edrophonium has no effect/small decrease in muscle strength

Question 47

What is a cholinergic crisis?

Answer 47

ex) overdose of Ache inhibitor | overstimulation -> paralysis -> weak muscles

Question 48

Contraindications to the use of parasympathomimetic drugs?

Answer 48

asthma/COPD; coronary deficiency; peptic ulcer; obstruction of the urinary or GI tract; epilepsy

Question 49

Cholinergic (Ach) centers in the CNS

Answer 49

nucleus basalis of meynert; medial septal nuclei; mesopontine tegmentum (brainstem)

Question 50

Adrenergic (NE) centers in the CNS

Answer 50

locus ceruleus (pons-brainstem)

Question 51

Degernation of the cholinergic cells in the nucleus basalis occurs in what?

Answer 51

dementia and PD (identified by Lewy bodies)

Question 52

Alzheimer's disease

Answer 52

most common cause of dementia after age 50; atrophy of the brain, widening of sulci and thinning of gyri; senile plaques, neurofibrillary tangles

Question 53

Reversible AchE inhibitors that are used in managing symptoms of Alzheimer's

Answer 53

donepezil, rivastigmine, galanthamine

Question 54

Rivastigmine

Answer 54

reversible carbamate AChE inhibitor, enhances cognitive ability in AD by increasing cholinergic function

Question 55

Galanthamine

Answer 55

reversible competitive AChE inhibitor; extract from daffodil bulbs; loses effectiveness as AD progresses