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Flashcards in Cholinergic Agonists Deck (41)
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1
Q

Cycle of ACh

A

1) made from acetyl-CoA+choline
2) ACh stored in neruons (quanta)
3) Release of ACh when neruons stimulated by an action potential
4) bind to ACh receptors
5) AChE breaks down ACh
6) acetyl-CoA and choline are recycled

2
Q

Two types of receptors that bind ACh

A

Muscarinic receptors

nicotinic receptors

3
Q

Muscarinic Receptors

A

are at the effector organ level of parasympathetic nervous system
no muscarinic receptors on the sympathetic side

4
Q

Nicotinic Receptor

A

at the ganglionic level of the parasympathetic side and sympathetic side of autonomic NS

bind ACh released from pre-ganglionic and pass to post ganglionic neurons

no inhibitory capabilities-only relay efferent messages sent from CNS

5
Q

2 Roles of ACh at Muscarinic Receptors in Parasymathetic NS

A

1) ACh is released that ACTIVATES muscarinic receptors on target organs (alters organ function by creating a positive stimulus ex contraction of muscle)
2) ACh is released and binds to receptors on nerve terminals to inhibit release of other NT’s (alters organ function by creating negative stimulus (ex relaxation of muscle)

6
Q

Role of ACh at Nicotinic Receptors in the Somatic NS

A

nicotinic receptors present at neruomuscular jxn of skeletal muscles

ACh (or agonist) binding=depolarization of nerve cell=positive stimulus (muscle contraction)

Prolonged binding to receptor causes postganglionic neuron to stop firing=skeletal muscle relxes and prevents further depolarization=muscle paralysis (negative stimulus)

7
Q

Cholinomimetic Agnet

A

Nonacetylcholine compound that mimics actions of ACh

8
Q

Cholinomimetic Agents as stimulants (direct agonists)

A

directly bind to ACh receptors (mimic ACh and bind to receptors)

9
Q

Cholinomimetic Agents as AChE inhibitors (indirect agonists)

A

indirect cholinergic action by inhibiting break down of ACh, ACh will stay in synapse longer and will continue to produce cholinergic action….same action as if you gave more ACh

10
Q

Types of Muscarinic Receptors

A

M1, M2, M3, M4, M5

M1, M3, M5–>cellular excitation (+ response)
M2, M4–>inhibit cellular excitability (-response, relaxation)

compounds will bind as either agonists or antagonists (agonsits will get effect you want plus side fx)

11
Q

Where are Muscarinic receptors founds

A

Mainly on autonomic effector organs

heart, smooth muscle, brain, exocrine glands

12
Q

Types of Nicotinic Receptors

A

Nm–neuromuscular junction

Nn–nicotinic receptors in any other location (CNS, adrenal medulla, autonomic ganglia)

13
Q

Direct Acting Cholinomimetics

A

Esters of Choline
Ex: acetylcholine

Alkaloids (compounds often taken from plants)
ex:muscarin and nicotine

14
Q

Choline Esters-Quarternary Ammoniums

A

makes insoluble lipid (quarternary nitrogen notrogen, wont get to the brain, cant cross BBB–dont usually have CNS problems)

15
Q

Characteristics of Quarternary Ammoniums

A

Hydrophilic (stay in soln and go where blood goes)

Hydrolyzed by AChE–affects their 1/2 life

Variations of structure alter binding affinity to receptors and susceptibility to hydrolysis by AChE

16
Q

Cholinomimetic Alkaloids

A

Tertiary Amines–CAN cross the BBB and cause CNS effects because it’s neutral charged

4 examples of cholinomimetic alkaloids:
Tertiary:
pilocarpine, nicotine, lobeline
Quarternary:
Muscarin (so it cant cross BBB cuz its + charge)
17
Q

Characteristicts of Cholinomimetic Alkaloids

A
  • well absorbed orally
  • lipid soluble–> allows for larger volumes of distribution
  • Not susceptible to AChE
18
Q

Indirect Acting Cholinomimetic

A

act by inhibiting AChE

19
Q

Types of AChE inhibitors

A

simple alcohols– quarternary ammonium (edrophonium) able to inhibit AChE.

Carbamate esters– of alcohols with quarternary or tertiary ammonium (neostigmine, physostigmine, pyridostigmine)

Organophosphates (pestisides) (echothiophate, isofluorophate)

20
Q

Binding DIfferences Between AChE Inhibitors

A

Simple alcohols–> bind weakly and reversibly to AChE=shorter half-life of less than 10 mins

Carbamate Esters-bind reversibly but tighter to AChE=Prolonged half-life 30 minutes to 6 hours

Organophosphates–>covalent binding,extremely stable (nearly irreversible)= very long half-life of hundreds of hours

21
Q

Cholinomimetic Effects on Eye

A

contraction of iris sphincter smooth muscle=miosis (pupillary constriction)

contraction of ciliary muscle=responsile for focusing/accomidation

facilitate flow of aqueous humor out of anterior chamber so that you dont have buildup of aqueous fluid in posterior chamber–tx glaucoma

22
Q

Cholinomimetic Effect on Respiratory System

A

contraction of smoother muscle in bronchial tree, stimulates secretions from tracheobronchial mucosa

23
Q

Cholinomimetic Effects on the GI Tract

A

Increase secretory and motor activity- stimulates salivary and gastric gland secretions

increase peristalsis, relaxes GI sphincters allowsing GI contents to pass along tract

used to tx–>post op ileus congenital megacolan

24
Q

Cholinomimetic Effects on GU tract

A

stimulates detrusor muscle (contracts), and relaxation of trigone and sphincter muscles of bladder–> triggers voiding

tx urine retention (use bethanecol, neostigmine)

25
Q

Direct Cholinomimetics effects on Cardiovascular System (muscarinic agonists)

A

REDUCE PERIPHERAL VASCULAR RESISTANCE–> vasodilation reduces BP which causes an indirect reflex to increase HR (body’s compensatory mechanism)

also can decrease HR and reduces C/O

difficult to predict what it will do so ACh agonists aren’t used often in CV system

26
Q

Indirect Cholinomimetics effects on Cardiovascular System

A

AChE inhibitors=increase cholinergic activity in synapse

see same effects you see in muscarinic agonist
Negative chonotropic-bradycardia
Negative Inotropic-drop in C/O

modest drop in Bp

27
Q

Cholinomimetic Effect on Secretory glands

A

exaggerated muscarinic activity–> sweaty, tearing, increased mucous production/discharge from nose

28
Q

Direct Cholinomimetics on CNS: Nicotinic Receptors

A

induce tremor, stimulate emesis (vomiting), stimulate respiratory center

29
Q

Direct Cholinomimetics on CNS: Muscarinic Receptors

A

muscarin can’t cross the BBB, but there are muscarin receptors in the brain and muscarinic LIKE compounds can get to brain and trigger them

induce tremor, hypothermia, interfere w/nociception (ability of body to recognize toxin)

30
Q

Indirect Cholinomimetics effects on CNS

A

low concentration causes little effect

high concentration causes convulsions, coma, respiratory arrest

ex: exposure to organophosphates

31
Q

Use of Cholinomimetics for Alzheimers

A

AD=not enough receptors, soo tx with AChE inhibitors
AChE inhibitors–>ACh will hang around longer in the synapse and bind to more receptors
not curing but will slow progression

Ex:
tacrine, donepezil, galantamine, rivastigmine

32
Q

Use of Cholinomimetics with Smoking Cessation

A

Varenicline (chantix)–> direct nicotinic agonist, it will bind to nicotinic receptors in brain, decreases cravings and pleasurable effects of cigs

33
Q

Indirect Cholinomimetic Effects on Peripheral Nervous System

A

will cause discharge of sympathetic and parasympathetic nervous systems

Sympathetic–tachycardia or vagal induced bradycardia

Parasympathetic- GI, nausea, vomiting, diarrhea, urinary voiding

34
Q

ACh at Neuromuscular Junction

A

ACh is released and binds to NICOTINIC receptors on muscle fibers=depolarization=contraction of muscle

35
Q

Indirect Cholinomimetic effect on Neuromuscular Junction

A

AChE inhibitors
Low Dose-prolong effect of ACh=increased strenght

Medium Dose- muscle fibrillation=less effcitve use of muscle

High Dose= blocks muscle depolarization=paralysis

36
Q

Use of Cholinomimetics to Tx Mysthenia Gravis

A

increase muscle fxn
Mysthenia Gravis- antibodies bind to receptors and block ACh binding…give AChE inhibitor that allows ACh to have more time in synapse and find receptors to bind to that aren’t being blocked by antibody

doesnt cure but improves muscle fxn

37
Q

Use of Cholinomimetics Reverse Neuromuscular Paralysis

A

neostimine

38
Q

Use of Cholinomimetics to Tx Anticholinergic Intoxification

A

excessive anticholinergics–>dont eleict response they just sit on the receptor and block it–>cause arrhythmias

give AChE inhibitors like physostigmine to increase tje amnt of ACh at receptor sites

39
Q

Toxicity of Direct Muscarinic Agonists

A

N/V/D, urinary urgency. salivatiom, sweating, cutaneous vasodilation, bronchial constriction

tx with atropine and anticholinergics

40
Q

Toxicity of Direct Nicotinic Agonists

A

ex acute nicotine toxicity–>CNS stimulation, convulsions, coma, respiratory arrest, skeletal muscle depolarization, leading to blockade, respiratory paralysis. Htn and cardiac arrhythmias.

41
Q

Toxicity of Cholinesterase Inhibtors

A

Organophosphates and carna,ate cholinesterase inhibitors
symptoms–muscarinic excess (miosis, salivation, sweating, bronchial eonstriction, diaphragm paralysis, vomiting, diarrhea, convulsions)

Tx-antidote-parenteral atropine pr pralidoxime