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Neuro II Midterm > Cholinergic Drugs - Kruse > Flashcards

Cholinergic Drugs - Kruse Flashcards

1
Q

What are the neurotransmitters and receptors for parasympathetic?

A 
NT = ACH
Receptors = nAhR, mAChR
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2
Q

What are the neurotransmitters and receptors for sympathetic?

A

NT = NE >Epi (DA); Ach

receptors: a, b, (D), nAChR, mAChR

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3
Q

what neurotransmitters does sweat glands use?

A

Ach.

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4
Q

In general, which parasympathetic receptor has the higher affinity for the heart?

A

M2

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5
Q

In general, which sympathetic receptor has the higher affinity for the heart?

A

beta 1

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6
Q

which parasympathetic receptors are found on blood vessels?

A

M3.

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7
Q

In general, which sympathetic receptors are found on blood vessels?

A

a1, a2, b1, b2

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8
Q

Which sympathetic receptor is found on trachea and bronchi and what is the action?

A

beta 2, bronchodilation –> relaxation

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9
Q

Which parasympathetic receptor is found on tracheal and bronchial smooth muscle and what is the action?

A

M2 and M3 equally and they cause contraction

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10
Q

In the stomach explain what happens with sympathetic stimulation and parasympathetic stimulation to each of the following:

a. motility and tone
b. sphincters
c. secretion

A

a. symp = decrease; parasyp = increase
b. symp = constrcts; parasyp = relax
c. symp = inhibition; parasyp = stimulation

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11
Q

what sympathetic receptor causes a pregnant woman to contract and relax the uterus?

A

a1 = contraction

beta 2 = relaxation

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12
Q 
Explain where each of the following receptor are found and which GPCR it uses
M1
M2
M3
M4
M5
A 
M1 = nerve; Gq
M2 = heart, nerves, smooth muscle; Gi
M3 = glands, smooth muscle, endothelium; Gq
M4 = CNS; Gi
M5= CNS; Gq
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13
Q

which muscarinic receptor is predominant in most organs (or receptor abundnace is equal)

A

M3

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14
Q

M2 predominates in which organ?

A

heart

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15
Q

Mainly which muscarinic receptors are found on smooth muscle?

A

M2 and M3

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16
Q

What is the general MOA difference between direct and indirect cholinergic agonists?

A

Both direct and indirect mimic the actions of Ach on nAChR and mAChRs. Direct agonists acts directly on the receptor itself to mimic the action of Ach. and indirect acts indirectly to increase Ach concentration.

17
Q

in what two chemical forms do direct acting cholinergic drugs exist?

A

Alkaloids or Choline esters

18
Q

What is the MOA, charge status, absorption and distribution capacity, and metabolism of choline ester forms of direct acting cholinergic agonists

A

MOA: agonists binds to cholinergic receptors

  • Choline esters are permanently charged
  • poorabsorption and distribution to CNS
  • metabolized by AchE
19
Q

What are the direct acting choline esters and rank them in terms of affinity

A

Ach > Methacholine > carbachol > bethanechol

20
Q

Of the choline esters which one are not susceptible to cholinesterase?

A

Carbachol and bethanechol. Ach is the most susceptible.

21
Q

List the alkaloids of direct acting cholinergic agonists

A

muscarine and nicotine.

22
Q

How are alkaloids and choline esters different?

A

Alkaloids are uncharged tertiary amines and are well absorbed and thus can cross BBB to reach CNS. Example nicotine patches

23
Q

What are the three groups of AchE inhibitors and how are they different?

A
  1. Alcohols, reversible
  2. Carbamic acids esters, reversible but longer lasting than alcohols
  3. Organophosphates irreversible and thus with the use of organophasphate, the body needs to make more ACh to replenish. it’s often used as insecticide and weapon. They’re uncharged and lipophilic and thus can enter CNS
24
Q

List the charged AChE inhibitors and explain their PK

A

Charged AchE inhibitors are insoluble in lipids and does not cross BBB, poor PO absorption.
They include: edrophonium, pyridostigmine, neostigmine, echothiophate, ambenonium

25
Q

Give an example when you would use a charged AcheI vs neutral AChE I

A

charged: need to have local effect such as in the case of Myasthenia Graves.
Neutral: well distirbuted and thus can enter CNS such as histamine toxicity, or PD and AD

26
Q

Indicate the parasympathetic effect in each of the following organ:

  1. EYE: a. sphincter muscle of iris and b. ciliary muscle
  2. Heart: a. SA node; b. atria; c. AV node; d. ventricles
  3. Blood vessels
  4. Lung: a. bronchial smooth muscle; b. bronchial glands
  5. GI tract: motility, sphicters and section
  6. urinary bladder: Detrusor; trigone and sphincter
  7. Glands
A
  1. both contract
  2. a. decrease rate; b. decrease contracility; c. decease rate; d. small decrease in contractile strength
  3. Dilation via EDRF. constriction with high dose
  4. a. contraction; b. stimulation
  5. motility = increase; sphincters = relax; secretion = stimulation
  6. Detrusor; contract; trigone and sphincter = relax
  7. secretion
27
Q 
For each of the following Direct-acting cholinergic agonist indicate it's main approved use:
a. Acetylcholine
B. Bethanechol
C. Carbachol
D. Cevimeline 
E. Picocarpine
A

A. intraocular use during surgery and cause miosis (reduction in pupil size)
B. selective mAChR for urinary and GU tracts. used to treat urinary retention and heartburn
C. nonspecific agonist thats used for tx of glaucoma or to produce miosis during surgery or eye exam
D. dry mouth (PO) and pts with Sjogren syndrome
E. dry mouth (xerostomia) w/ Sjogrensyndrome; miosis, glaucoma. pure mAchR agonist

28
Q

What is the indication and MOA of Varenicline (Chantix). Give examples of adverse effects

A

Indication: smoking cessation
binds to a4, b2 and nACHRs (Nn)
MOA: stimulation and subsequent moderate, sustained release of mesolimbic dopamine = reduce craving and withdrawl symptoms associated with smoking cessation
Adverse effects: nausea and neuropsychiatric symptoms including suicidal ideation.

29
Q

What major disease of the eye and GI/GU disorders are direct-acting cholinergic agonists used for?

A

eye: glacoma, accomodative esotropia, esp in kids to fix accomodation,
GI/GU: postoperative ileus, congential megacolon, urinary retention, esophageal reflux, xerostomia, Sjogren syndrom

30
Q

What are some toxicity associated with use of direct acting cholinergic agonists?

A

Muscarinic stimulants: predictable - nausea, vomitting, diarrhea, urinary urgency, salivation, sweating, cutaneous vasodilation, bronchial constriction, increase glandular secretion (SLUDGE) . COntraindicated in: astham, hyperthryroidism, coronary insufficiency, acid-peptic disease

Nicotinic stimulants: nicotine poisoning, acute toxicity includes CNS stimulation, skeletal muscle end plate depolarization respiraoty paralysis, HTN, cardiac arrhythmias

31
Q

What are some clinical uses of indirect-acting cholinergic agonists?

A
  1. glaucoma
  2. dementia
  3. antidote to anticholingergic poisoning
  4. reversal of neuromuscular paralysis
  5. Myasthenia gravis
  6. ACHE inhibitor tox: SLUDGE symptoms, effects on NMJ. treatment includes atropine, maintenance of vital signs, decontamination, pralidoxime
32
Q

what is the prototype antimuscarinic agent?

A

atropine

33
Q

What is the main indication for scopolamine?

A

Scopolamine is an anticholingergic agent that is used to treat mainly motion sickness and ophthalmology

34
Q

What anticholinergic agents are used to treat GI disorders?

A

Atropine
Dicyclomine
Glycopyrrolate
Hyoscyamine

GI = GADH

35
Q

what anticholinergic drugs are used in opththalmology?

A

atropine and scopolamine

36
Q

What is ipratropium and tiotropium mainly used for?

A

Respiraotyr disorders. These are first line treatment for COPD

37
Q

What is the prototypical anticholinergic drug used for urinary disorders

A

Oxybutynin (treats leaky bladder)

38
Q

What drugs would be best used for cholingeric poisoning?

A

atropine + pralidoxime

39
Q

What anticholingergic drugs are used for movement disorders.

A 
these drugs can cross BBB readily and act in CNS to treat diseases like PD and AD
Benztropine
Biperiden
Orphenadrine
Procyclidine
Trihexyphenidyl

Neuro II Midterm (2 decks)

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