Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

97 Cards in this Set

  • Front
  • Back
How are the Cholinoceptor Agonists classified pharmacologically?

How are they further classified?
By receptor action
1. Muscarinic
2. Nicotinic

Direct-acting & Indirect-acting
How do Direct-acting cholinomimetic agents act?

How do Indirect-acting agents act?
directly bind & activate Muscarinic or Nicotinic agents

Inhibit Acetylcholinesterase
-reduce hydrolysis of ACh
-increase Endogenous ACh conc. in synaptic clefts
List the 2 groups of Cholinoceptors and the type of receptor they are
Muscarinic = G protein-linked

Nicotinic = Ion channel

**activated by ACh
Muscarinic receptors are G protein-linked receptors:
1. How many domains are there
2. How is it coupled to G proteins?
1. 7 Transmembrane domains

2. Third cytoplasmic loop is coupled to G proteins
Where are the Muscarinic receptors located? (3)
1. CNS
2. tissues targeted by PSNS
2. vascular Endothelium (BUT not innervated by PSNS!!!)
Describe the structure of Nicotinic receptors

Where are they located?
4 subunits form cation-selective ion channels

1. All ANS Postganglionic cells ("neuronal" type)
2. Muscles innervated by Somatic Motor fibers (NMJ type)
3. some CNS neurons ("neuronal type)

**there is a difference in the proteins that make up the "neuronal" type and "NMJ" type = allows for selective use of drugs
How are the Direct-acting Cholinoceptor Agonists classified?
1. Esters of Choline

2. Alkaloids (Muscarine & Nicotine)
Prototypical drug agent & endogenous transmitter that has effects on both Nicotinic and Muscarinic receptors
What renders Choline Esters relatively insoluble in LIPIDS?
Quaternary Ammonium group
Choline esters:
1. acetic acid ester of choline

2. Acetic acid ester of Methylcholine

3. Carbamic acid esters of the same alcohols
1. Acetylcholine

2. Methacholine

3. Carbachol & Bethanechol
T or F: Choline esters are well absorbed and are distributed good to the CNS
-poor absorption
-poor distribution to CNS
1. Choline Ester that is very rapidly hydrolyzed by AChE

2. Choline Ester that is more resistant to hydrolysis

3. Choline Esters that are very resistant to hydrolysis
1. Acetylcholine

2. Methacholine

3. Carbachol & Bethanechol
What 2 Choline esters that have NO potency at Nicotinic receptors? Why?
Methacholine & Bethanechol

due to their methyl group
Choline Ester (other than ACh) that is more penetrant into the CNS than others. Why?

b/c it has an Amine group instead of Methyl
List the 3 Tertiary natural Cholinomimetic alkaloids

List 2 properties relative to Choline Esters
1. Pilo-car-pine
2. Nicotine
3. Lobe-line

1. not susceptible to degradtion by AChE
2. better at penetrating CNS
What type of compound is Muscarine? What is it's source? Does it have CNS activity?
Quaternary amine

Amantia muscaria mushroom

CNS activity = YES!!!
2 agonists that are chiefly Nicotinic agonists

2 agonists that are chiefly Muscarinic agonists

List the activation pathway when Muscarinic receptors are activated
1. G-protein coupled
2. activates IP3, DAG cascade = increase in IC Calcium (in some tissues i.e. smooth muscle & glands)
3. activates Gi = inhibits Adenylyl Cyclase = opens K+ channels (occurs in other tissues i.e. heart = decreases HR)
What is the mechanism of action of the Nicotinic receptors?
1. ACh binds to alpha subunits
2. results in electrical & ionic changes
3. depolarization of the nerve cell or neuromuscular end plate membrane
What happens if you have "prolonged agonist occupancy" at Nicotinic receptors?
1. abolishes the effector response
2. "depolarizing blockade" = lose the electrochemical gradient across the cell membrane = cell unable to fire
3. can produe MUSCLE PARALYSIS
What are the Muscarinic cholinoceptor effects predicted from? (2)
1. effects of PARASYMPATHETIC nerve stimulation

2. distribution of Muscarinic receptors
What are the Nicotinic Agonist effects predictable from?
Physiology of the Autonomic ganglia & Skeletal Muscle Motor End Plate
What do Muscarinic Agonists produce in the Eye?
1. contraction of the Iris sphincter = Miosis

2. Contraction of Ciliary Muscle = Accommodation = for close-up vision

3. facilitates Aqueous Humor outflow = relief of Glaucoma
What are the Muscarinic Agonist effects on the Cardiovascular system?
1. reduce Peripheral Vascular resistance (by IV infusions of ACh)

2. DIRECT EFFECT = Slow Heart Rate
What will Intravenous Infusions of ACh cause?
Vasodilation and reduce blood pressure by binding to Muscarinic receptors on Endothelial Cells -> NO release -> Smooth Muscle relaxation
What is the DIRECT EFFECT of ACh on Muscarinic receptors on Vascular Smooth Muscle? What is this masked by? When can this effect be seen?
Vascular Smooth Muscle contraction

masked by effects of NO released by ENDOTHELIAL CELLS

In vasculature stripped of Endothelium
What does Muscarinic Vasodilation evoke? What can mask this?
SNS reflex = increase in Heart Rate

Give large doses of ACh to mask the reflex = Direct Bradycardia (Muscarinic receptors in Heart contain Gi receptors = inhibit AC -> opens K+ channels -> slows HR)
Muscarinic Effects:
1. Respiratory system
2. GI tract
3. GU tract
4. Secretory glands
1. Constricts Bronchiolar Smooth Muscle & glands of Mucosa are stimulated to secrete (often exacerbates symptoms of Asthma)

2. Increases secretions (salivary, gastric, pancreatic, intestinal) & increases Peristaltic activity (contraction of Longitudinal muscle; relaxation of sphincters)

3. Contracts Detrusor muscle; relaxes Trigone & Sphincter muscles

4. stimulation of secretion by Thermoregulatory sweat glands (**UNDER SYMPATHETIC CONTROL**)
What is the major site of action of Nicotinic agonists?
Autonomic ganglia
What predominant tone are present in the following:
1. Vasculature
2. Most other tissues
1. SNS

Does Nicotine have a greater affinity for neuronal or skeletal muscle nicotinic receptors?
What effects do Nicotinic agonists have on NMJ's?
1. produces Muscle Fasciculations

2. subsequent development of Depolarization blockade = Flaccid Paralysis

**Nicotinic overdose could lead to lack of respiration b/c of paralysis
Explain "Low" dose Acetycholine
-NO release = Vasodilation
How would you block the effects of "Low" dose Acetylcholine
Atropine = muscarine antagonist
What could happen if you administered "Low" dose Acetylcholine along with a Ganglionic Blockade?

**Ganglionic blockers would inhibit the REFLEX TACHYCARDIA provided by SNS
**only DIRECT effects are observed with Ganglionic Blockade - Endothelial Muscarinic receptors are not affected
Explain "High" Dose Acetycholine
1. Muscarinic receptors on Endothelial cells activated = NO = Vasodilation

2. Cardiac Muscarinic receptors are activated = direct BRADYCARDIA
-slows rate of diastolic depolarization of SA node
-slow AV conduction
-reduces force of Myocardial contractions
-shortened Atrial refractory period which can lead to atrial flutter

**Vasodilation + Bradycardia = bad combination
**some Sympathetic responses can be evoked by high dose ACh & may be readily apparent in the presence of Muscarinic Antagonists
Name of a Cholinesterase inhibitor that is a simple alcohol bearing a Quaternary Ammonium group
List 3 Cholinesterase Inhibitors that are Carbamic Acid Esters of Alcohols bearing Quaternary or Tertiary Ammonium groups (Carbamates)
1. Neostigmine (Quaternary)

2. Physostigmine (Tertiary)

3. Carbaryl (high lipid solubility = rapid CNS effects)
Carbamate Cholinsterase Inhibitor that has high lipid solubility and therefore has rapid CNS effects
List the 9 Organophosphate Cholinesterase Inhibitors
1. Echo-thio-phate
2. Soman
3. Sarin
4. Mala-thion
5. Para-thion
6. Isoflurophate
7. Di-isoflurophate
8. Donepezil
9. Tacrine

**2&3 are nerve agents
2 Organophosphate Cholinesterase Inhibitors that have to be converted into active Organophosphates; are insecticides b/c insects convert them more readily

Cholinesterase Inhibitors that have poor absorption and poor CNS distribution
Quaternary Carbamates = Neostigmine & Pyridostigmine

*permanent charge renders them relatively insoluble in lipids
Cholinesterase Inhibitors that are well absorbed, distribute into the CNS, and the duration of their effect is determined by stability of Inhibitor-Enzyme complex
Tertiary Amines = Physostigmine
All Organophosphate Cholinesterase Inhibitors are well absorbed topically and are distributed to all parts of the body, including the CNS...exept which one?
What is the primary target of the Cholinesterase Inhibitors?

**Butyrylcholinesterase is also inhibited
Cholinesterase Inhibitors that reversibly bind to the ACTIVE site; inhibition is short-lived (2-10 minutes)
Quaternary Alcohols

**there are 2 sites on AChE: Binding & Active
AChEI that is a great diagnostic agent in Myasthenia Gravis
Explain the mechanism of action of the Carbamate Ester AChEI's
Undergo a 2-step hydrolysis
-Covalently bind to ACTIVE site of AChE = Covalent bond of the Carbamoylated enzyme is resistant to hydration
-inhibition is 30 minutes - 6 hours
Explain the mechanism of action of the Organophosphate AChEI's
1. results in a phosphorylated AChE ACTIVE SITE
2. covalent phosphorous-enzyme bond is extremey stable = inhibition lasts hundreds of hours = outlast the lifetime of the enzyme protein
-"Aging" strengthens phosphorus-enzyme bond
Before aging of the Organophosphate-AChE bond, what can restore enzyme function?
Prali-doxime (2-PAM)
List the Symptoms of Cholinesterase Inhibitors

What is not affected?

1. Diarrhea
2. Urination
3. Miosis = constricted pupil
4. Bronchospasm
5. Bradycardia
6. Excitation of skeletal muscle
7. Lacrimation
8. Sweating
9. Salivation

Not affected = Vascular Smooth Muscle = no effect on Blood Pressure
What happens at the NMJ when low doses of AChEI are given?

High doses?
Low = increase force of contraction

High = depolarizing neuromuscular blockade = flaccid paralysis
What are Cholinesterase Inhibitors used for to treat in the Eye? Explain mechanism
Closed-angle Glaucoma
-ACh binds to Muscarinic receptor ➡ reduce intraocular pressure by causing contraction of the Ciliary Body (accommodation) ➡ facilitates outflow of Aqueous Humor
What clinical disorders are AChEI's used for in the GI and Urinary tracts?
Inactivity of Smooth Muscle disorders
1. Postoperative Ileus
2. Congenital megacolon
3. Urinary retention
4. Neurogenic bladder
5. Reflux Esophagitis
6. Insufficient salivary secretion
Drug class used to treat Myasthenia Gravis...why?
Cholinesterase Inhibitors

Will allow for more ACh in the synapse of NMJ's where Nicotinic receptors are insufficient or decreased
What drug would Cholinesterase Inhibitors be used to reverse their intoxication?
Atropine = Muscarinic Antagonist
When would Cholinesterase Inhibitors be used for treatment in the CNS?

What drug has both Anticholinesterase and Cholinomimetic actions that is used?
mild to moderate Alzheimer's disease

Mnemonic given in class for Cholinesterase Inhibitor toxicity

Urinary incontinence
GI cramps
Emesis = vomiting
What is the treatment for Cholinesterase Inhibitor Toxicity?
1. Atropine = Muscarinic Antagonist

2. Maintenance of vital signs (respiration)
3. Decontamination to prevent further absorption
4. Atropine parenterally in large doses

**therapy may also include Pralidoxime to "rescue" un-aged inhibited enzyme
Nicotinic Toxicity:
1. what is it usually produced by?
2. what is fatal dose?
1. Nicotine

2. 40 mg = amount in 2 cigarettes
-BUT most destroyed by burning
-ingestion usually followed by vomiting = limits absorbed dose
What are the effects of Nicotinic Toxicity?
1. CNS stimulation = convulsions, coma, respiratory arrest

2. Skeletal muscle end plate depolarization = RESPIRATORY ARREST

3. HTN & Cardiac Arrhythmias (SNS effects)
What is the treatment for Nicotinic Toxicity?
-Muscarinic antagonists
-mechanical respiration
What is the most significant toxicity that Nicotinic toxicity is due to?
Chronic smoking
List the 2 groups and corresponding agonists of DIRECT MUSCARINIC AGONISTS
Choline Esters

List the 2 Direct Nicotinic Agonists
1. Nicotine

2. Lobe-line
List the 7 Carbamate Cholinesterase Inhibitors

"Stigmine CAD's"
List the 9 Organophosphate Cholinesterase Inhibitors
Diisopropylfluorophosphate (DFP)

What 2 groups are the Nicotinic Antagonists divided into?
1. Ganglion blockers

2. Neuromuscular junction blockers = paralytics
What are the Tertiary compound Antimuscarinic drugs used for?

What are the Quaternary Amine Antimuscarinic used for?

Peripheral effects
Prototypical Antimuscarinic that causes REVERSIBLE, COMPETITIVE blockade

**not selective between M1, M2, & M3 subtypes
What are the Cholinoceptor-Blocking drug effects on the CNS?

What do toxic doses cause?

With what other drug & what disease are they used to treat?
1. Minimal stimulant effects on CNS

2. Agitation, Hallucinations, & coma

3. Dopamine precursor in Parkinson's disease
What effects would Atropine or any other Muscarinic Antagonist have on the EYE?
1. Mydriasis = dilated pupil

2. Paralysis of the Ciliary Muscle = Cycloplegia (loss of accommodation) = precipitates Acute Glaucoma in patients with Narrow Anterior Chamber Angle
What effects does Atropine have on the on the Cardiovascular System?
-SA node is under PSNS tone, which is sensitive to Muscarinic blockade

Antimuscarinics can cause Cutaneous Vasodilation (mechanism of unknown)
What are the effects of Atropine on the Respiratory System?
Bronchodilation and reduction of secretion

**anti-muscarinic drugs are not as useful as Beta-adrenoceptor stimulants in the treatment of Asthma
What effect does Atropine have on the GI tract?

What could it be used for?
Reduces motility & secretion in GI tract

Preoperative adjuvant before abdominal surgery
What effect does Atropine have on the GU tract?
can produce Urinary retention, especially with BPH
What effect does Atropine have on Sweat Glands?
suppresses Thermoregulatory sweating (which is under SNS control!!!, but still Muscarinic receptor)

Body Temperature can be elevated = "Atropine Fever"
What are the therapeutic applications Muscarinic Antagonists?
What are the symptoms of Atropine poisoning?
Dry mouth, Mydriasis (dilated pupil), Tachycardia, Flushed skin, Delirium

"Dry as a bone, blind as a bat, red as a beet, mad as a hatter"
What is the mnemonic for the effects that Atropine blocks?
Blocks SLUD
What would Atropine poisoning be treated with?
Physostigmine (Acetylcholinesterase inhibitor)
-penetrates CNS
What are the contraindications for giving Atropine?
1. Glaucoma (especially angle-closure glaucoma)

2. Prostatic Hyperplasia = will cause Urinary Retention

3. May increase Gastric Ulcer Symptoms
Define Ganglion-Blocking Drugs
block actions of ACh & other agonists at NICOTINIC receptors
-receptors located on both PSNS & SNS Autonomic ganglia
What type of compound are all Gangion-blocking drugs?

What was the 1st developed Gangion-blocker called?
Synthetic Amines

Tetra-ethyl-ammonium = short duration of action & used for HTN
What Ganglion-blockers lack CNS effects?
Quaternary Amines & Trimethaphan
Ganglion-blocker that readily enters CNS

What are the side effects?

Sedation, tremor, choreiform movements, mental aberrations
What are the effects of Ganglion-blockers on the EYE?
1. Ciliary muscle ➡ mostly PNS tone ➡ Cycloplegia = loss of accommodation

2. Pupil = under both PNS & SNS, but PNS dominates slightly = if PNS blocked = moderate DILATION
What effect do Ganglion-blockers have on Blood Vessels?
Vessels are under SNS tone
-vasoconstriction is blocked = DECREASE IN ARTERIOLAR AND VENOMOTOR TONE
-reduced Blood Pressure
-Orthostatic HTN = get out of bed & faint due to lack of SNS reflex
What effect do Ganglion-blockers have on the Heart?
removal of PNS tone at SA node = moderate TACHYCARDIA
What effect would Ganglion-blockers have on the GI tract?
Tone is PNS = reduced secretion and motility = CONSTIPATION
What effect do Ganglion-blockers have on the GU system?
1. Hesitancy or urinary retention (especially with Prostatic Hyperplasia)

2. Sexual function is impaired b/c requires both SNS and PNS
What effects do Ganglion-blockers have on Sweat glands?
blocks Thermoregulatory Sweating
Give an example of how Ganglion blockers inhibit Homeostatic reflexes (use NE as example)
Normal:NE is given ➡ Blood Pressure would increase ➡ reflex PSNS causes decreased HR to decrease CO & minimize BP

Ganglion-blockers: give NE ➡ Blood pressure rises ➡ reflex PSNS is inhibited = Heart Rate does not decrease
List the 6 Tertiary Amine Muscarinic Antagonists
Scopolamine = motion sickness
Pirenzepine (M1 selective)

List the 5 Quaternary Amine Muscarinic Antagonists
Atropine Methyl Nitrate
List the 3 Ganlgionic-blockers