Lecture 19

Question 1

What is the protypical muscarinic antagonist drug? Which modern drugs replace it?

Answer 1

Atropine

Glycopyrrolate

Question 2

What is the primary action of muscarinic antagonists on smooth muscle (5 examples)?

Answer 2

Relaxation of smooth muscle: Decreased GI motility, bladder, bronchi, biliary, eye (midriasis)

Question 3

Describe the effects of muscarinic antagonists like atropine in the eye.

Answer 3

They cause dilation of the pupils by preventing contraction of the ciliary muscles. They also impair near vision.

Question 4

How do exocrine glands respond to muscarinic antagonists (examples)?

Answer 4

Muscarinic antagonists reduce secretions from glands.

Examples: salivary glands, sweat glands, lacrimal glands, and bronchial secretions.

Question 5

Cardiovascular effects of atropine are dose dependent. Explain how and why.

Answer 5

At low doses, atropine increases vagal tone on the heart causing bradycardia.
At high doses, it blocks muscarinic AChR, causing slight tachycardia.

Question 6

What is the direct effect of atropine on blood pressure (trick question)?

Answer 6

It has no direct effect on blood pressure because there is nothing to antagonize (no parasympathetic innervation to vasculature).

Question 7

Explain 6 potential clinical uses of muscarinic antagonists (atropine and its derivatives)?

Answer 7

Atropine: dilate pupils for eye exam; reduce salivary and bronchial secretions during surgery (pre-anesthetic); decrease GI motility and bladder tone during surgery (anti-spasmodic); reduce vagal tone on the heart (prevent bradycardia); antidote for cholinergic toxicity; bronchodilation.

Question 8

What are adverse effects and symptoms of muscarinic antagonist toxicity?

Answer 8

Tachycardia, dry mouth, photophobia, constipation, urine retention, elevated temperature, restlessness

Question 9

What kind of drugs may be used as potential antidotes of muscarinic antagonist toxicity?

Answer 9

Acetylcholine Esterase Inhibitors

Question 10

What are 3 examples of other drug classes with anti muscarinic activities?

Answer 10

Antihistamines/anti-emetics (diphenhydramine)

Tricyclic Antidepressants (amitryptyline)

Phenothiazine tranquilizers (acepromazine)

Question 11

Name two ganglionic stimulants (what are they)?

Answer 11

Nicone and Acetylcholine

nACh stimulants that favor the neuronal AChR

Question 12

What are signs of acute nicotine poisoning and how do symptoms change if toxicity persists?

Answer 12

They originally present with stimulatory/excitatory signs such as excitement, hyperpnea, pulse rate irregularities, diarrhea, and then depressive signs come on such as tachycardia, ataxia, dyspnea, coma and death.

Question 13

What are the two classes of neuromuscular junction blockers?

What are drug examples of each class?

Answer 13

Non-depolarizing (competitive antagonists) and depolarizing.

Depolarizing: Succinylchoiline

Non-depolarizing: Atracurium, pancurium, curare

Question 14

Explain how depolarizing NMJ blockers work.

Answer 14

They overstimulate the ACh receptors at the NMJ with ACh until they become desensitized.

Question 15

What are the clinical uses of NMJ blockers?

Answer 15

Relax smooth muscles for surgery (easier intubation)

Question 16

What is an important ethical problem with NMJ blockers? What about pain relief?

Answer 16

They only paralyze the muscle, they do not provide pain relief. Their effects are enhanced by volatile anesthesia.

Question 17

What is a side effect of atracurium and tubocurarine but not succinylcholine?

Answer 17

Histamine release

Question 18

What is the cause of death in NMJ blocker overdose toxicity?

Answer 18

Paralysis of the diaphragm causing inability to breath

Question 19

Discuss cholinesterase inhibitors as antidotes for depolarizing versus non-depolarizing NMJ blocker toxicity.

Answer 19

AChE inhibitors can work as antidotes for non-depolarizing NMJ blockers because they are competitive antagonists to the ACh receptors in the NMJ. The AChE inhibitors will put more strain on the system for depolarizing blockers since they work by overstimulating the receptors until they desensitize.

Question 20

What 3 factors may enhance a non-depolarizing neuromuscular block?

Answer 20

Volatile anesthetics, hypokalemia, hypocalcemia, hypomagnesemia, aminoglycoside antibiotics.

Question 21

Are ACh esterase inhibitors useful for reversing succinylcholine activity?

Answer 21

No

Question 22

How can succinylcholine indirectly cause cardiac arrhythmia?

Answer 22

It’s muscle depolarization properties causes an increase in plasma K+ levels.

Question 23

What are other side effects of succinylcholine?

Answer 23

Malignant hyperthermia.
Intraocular and intracranial pressure.
Painful muscle contraction.
Potential for muscarinic activation resulting in bradycardia and increased bronchial salivary secretion.

Question 24

What is important about the use of depolarizing NMJ blockers in birds?

Answer 24

It will KILL them. Their receptors don’t desensitize and the sustain muscle contraction.

Question 25

Explain how depolarizing neuromuscular junction blockers are used as nematocides.

Answer 25

They same way they are used in mammals.

Question 26

What are the risks associated with these nematocides? What is the therapeutic window?

Answer 26

They work on nematodes the same way they work on mammals so you have to be careful with the dose so that you only have a toxic effect on the worms and not the host. There is a narrow therapeutic window.

Question 27

Name 4 examples of acetylcholinesterase inhibitors?

Answer 27

Neostigmine Edrophonium Demecarium Physostigmine

Question 28

What is the main effect of ACh esterase inhibitors at the cellular level?

Answer 28

Increase concentration of ACh at the synapse to stimulate muscle contraction or activation of ACh receptor.

Question 29

Which of the ACh esterase inhibitors act more on NMJ or neuronal postganglionic sites?

Answer 29

Neostigmine and edrophonium are more active at the NMJ. | Demercarium and physostigmine act more on neuronal postganglionic sites.

Question 30

On which synapses will ACh esterase inhibitors work most effectively?

Answer 30

The synapses that are active (have a high tone)

Question 31

What is 2-PAM and how does it work?

Answer 31

It’s and antidote to organophosphate poisoning. It works by binding to the AChE inhibitor, causing it to let go of the AChE enzyme.

Question 32

What are three clinical cholinesterase inhibitor effects?

Answer 32

Enhance muscarinic effects, enhance ACh at the synapse, CNS effects.

Question 33

What are 5 clinical uses of cholinesterase inhibitors?

Answer 33

1. Improve muscle contraction in myasthenia gravis patients 2. Improve GI motility 3. Improve bladder contraction 4. Reduce intraocular pressure in glaucoma patients 5. Antidote for organophosphate poisoning.

Question 34

Explain how edrophonium is used to diagnose myasthenia gravis (and what is MG).

Answer 34

Myasthenia gravis is an autoimmune disease where autoantibodies are directed against acetyl choline receptors. Edrophonium is and AChE inhibitor that causes a high concentration of ACh to remain at the NMJ, increasing saturation of functioning AChR. If the animal has myasthenia gravis and is administered edrophonium, they will regain muscle tone and functionality for a short period of time (10 minutes).

Question 35

Describe how neostigmine can be used as an antidote and to counteract what poison?

Answer 35

Neostigmine can counteract Belldonna (atropine) poisoning. Atropine (and belladonna) are muscarinic antagonists. By flooding synapses with ACh (2* to AChE inhibition), you can out compete atropine binding to mAChR.

Question 36

What are adverse effects of cholinesterase inhibitors (7)?

Answer 36

1. Miosis 2. Bradycardia 3. Muscle twitching or weakness 4. Bronchoconstriction and increased secretions 5. Diarrhea 6. Increased secretions 7. Ureter constriction

Question 37

What conditions require extreme caution when administering cholinesterase inhibitors?

Answer 37

Urinary obstruction, GI onbstuction, asthma/bronchoconstriction, pneumonia, cardiac arrhythmias

Question 38

What is an effective antidote to accidental cholinesterase inhibitor overdosing?

Answer 38

Atropine