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Pharmacology Test #2 > Cholinergic Agonists > Flashcards

Flashcards in Cholinergic Agonists Deck (70):
1

Describe the Cycle of Acetylcholine

ACH is synthesized in the mitochondria of neurons catalyzed by choline O-acetyltransferase

ACh is stored and released in vesicles

Action potential stimulates the release of ACh into synaptic cleft

ACh binds to muscarinic or nicotinic acetylcholine receptors

ACh is broken down by AChE and components are recycled

2

What are the 2 types of receptors that bind ACh and where are they found

Muscarinic - effector organs

Nicotinic - ganglion of autonomic nervous system

3

What are the 2 key actions at muscarinic sites?

muscarnic receptors are activated on target organs and organ function is altered by positive stimulus

bind to receptors on nerve terminals to INHIBIT relase of other neurotransmitters; alters organ function by creating negative stimulus

4

What is the difference between positive and negative response?

positive response = activate; contraction or release of something

negative response = relaxation

5

Where are nicotinic receptors located?

ganglionic level of both parasympathetic and sympathetic sides of the autonomic nervous system

6

What do nicotinic receptors do?

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

7

Do nicotinic receptors have inhibitory capabilities?

No, only relay efferent message sent from CNS

8

Where are nicotinic receptors in the somatic nervous system located?

at the neuromuscular junction of skeletal muscle

9

What do the nicotinic receptors in the somatic nervous system do?

binding of ACh --> depolarization of nerve cell or neuromuscular end plate membrane --> positive stimulus (muscle contraction)

10

What happens if there is prolonged ACh binding to nicotinic receptors in the somatic nervous system?

postganglionic neuron will stop firing

skeletal muscle will relax

muscle paralysis; prevents further depolarization (negative stimulus)

11

What are the 5 types of muscarinic receptors?

M1 - M5

12

What do each of the muscarinic receptors do?

M1, M3, M5 --> cellular excitation

M2 and M4 --> inhibit cellular excitability

13

Where are muscarinic receptors found?

Effector Organs:

Heart

Smooth Muscle

Brain

Exocrine glands

14

What are the 2 types of nicotinic receptors?

Nm

Nn

15

Where are Nm receptors located?

neuromuscular junction

16

Where are Nn receptors located?

CNS

Adrenal Medulla

Autonomic Ganglia

**Nn = NON muscular

17

What are the 2 groups of direct acting cholinomimetics?

Esters of Cholines - acetylcholine

Alkaloids - muscarine and nicatine (comes from plants)

18

Are Choline Esters lipophilic? And what consequence does this have in the body?

No they're hydrophilic

Can't cross the BBB --> don't produce CNS side effects like sedation

19

How are choline esters classified chemically?

quarternary ammoniums

20

What are the characteristics of quaternary ammoniums?

Hydrophilic

Hydrolyzed by acetylcholinesterase (AChE)

Variations in chemical structure alter characteristics like potency and susceptibility to hydrolysis by AChE

21

How are cholinomimetic alkaloids classified chemically? What about Muscarine?

Tertiary amines

Muscarine = quarternary amines

22

What are the 4 examples of cholinomimetic alkaloids that are quaternary amines?

Muscarine

Pilocarpine

Nicotine

Lobeline

23

What are the characteristics of cholinomimetic alkaloids?

well absorbed after oral administration

lipid soluble --> larger volume of distribution; cross into BBB (even muscarine)

Not susceptible to acetylcholinesterase

24

What is the Mechanism of Indirect Acting Cholinomimetics

Act by inhibiting AChE

25

What is the consequence of inhibiting AChE

prolongs the presence and actions of ACh @ ALL ACh-R (muscles, neurons, neural muscular junction, brain)

26

What are the 3 types of AChE inhibitors, and what are some examples?

Simple alcohols w/ a quarternary ammonium - Edrophonium

Carbamate esters of alcohols with quaternary or tertiary ammonium - neostigmine, physostigmine, pyridostigmine

Organophosphates - Echothiophate, Isoflurophate

27

What is the binding affinity of simple alcohols and AChE?

weak affinity --> bind weakly

reversible

half life = short

28

What is the binding affinity of carbamate esters and AChE?

higher affinity for AChE than simple alcohols

still reversible

half life = 30 minutes - 6 hour half life

29

What is the binding affinity of organophosphates and AChE?

HIGH affinity --> bind covalently

very long half-life

can only be overcome with new production of AChE

30

Which effector organs do direct and indirect cholinomimetics have similar effects on?

Eye

Respiratory System

GI tract

GU tract

31

Which effector organs do direct and indirect cholinomimetics have different effects on?

CV system

Secretory Glands

CNS

Peripheral NS

Neuromuscular junction

32

What are the cholinomimetic effects on the eye?

Contraction of iris sphincter smooth muscle --> mitosis (pupillary constriction)

Contraction of Ciliary muscle --> accommodation (focusing on object; muscarinics = close objects)

33

What does the contraction of the iris sphincter smooth muscle and the ciliary muscle do in the eye?

facilitate flow of aqueous humor out of anterior chamber

alter amount and focus of light reaching retina

34

Which type of cholinomimetics is the eye sensitive to?

Muscarinic agonists

AChE inhibitors

35

What is the clinical use of cholinomimetics in the eye?

Glaucoma --> Pilocarpine, Physostigmine

36

What is the action of cholinomimetics on glaucoma?

Muscarinic agonists/AChE inhibitors increase outflow of aqueous humor --> reduce intra-ocular pressure

37

What are the actions of cholinomimetics on the respiratory system?

contraction of smooth muscle --> restrict airflow

stimulate secretions from tracheobronchial mucosa

**ACh agonists aren't used much in respiratory medicine

38

What are the cholinomimetic effects on the GI tract?

Increase secretory and motor activity in the gut

Stimulate salivary/gastric glands, pancreas, small intestine

increase peristalsis

relaxes most GI sphincters --> GI contents pass along freely

39

Clinically when would you use cholinomimetics for GI disorders?

When you want to correct depressed smooth muscle activity and increase motility

Post-op ileum (neostigmine)

Congenital mega colon

40

What are the cholinomimetic effects on the GU tract?

Trigger voiding of bladder

stimulate detrusor muscle (contraction) and relax trigone and sphincter muscles of bladder

41

When would you clinically use cholinomimetics for GU disorders, and name 2 drugs that are used?

treat urinary retention: post-op, post pardum; spinal cord injuries; neurogenic bladder

bethanecol, neostigmine

42

What are the direct cholinomimetic effects on the cardiovascular system?

reduce peripheral vascular resistance: vasodilation = reduced BP; drop in BP can cause indirect reflex increase in HR

Decrease heart rate: decrease SA node firing = bradycardia, reduces cardiac output

**ACh agonists not used a lot for CV medicine because their results are unpredictable**

43

What are the effects of indirect cholinomimetics on the Cardiovascular system?

Increase cholinergic activity

work on sympathetic and parasympathetic nerves:

negative chronotropic --> bradycardia

negative inotropic (squeeze of heart) --> drop in cardiac output

44

What are the cholinomimetic effects on secretory glands?

stimulates sweat gland production --> help regulate body temp

stimulate lacrimal glands

stimulate nasopharyngeal glands

REMEMBER: Tears, Sweat, Snot

45

What are the effects of direct cholinomimetics on the nicotinic receptors in central nervous system?

Induce tremor

stimulate emesis (vomitting)

stimulate respiratory center

46

What are the effects of direct cholinomimetics on the muscarinic receptors in central nervous system?

induce tremor

cause hypothermia

interfere w/ nociception (pain sensation)

47

What are the effects of indirect cholinomimetics on the central nervous system?

need high concentration to stimulate effect

convulsions

coma

respiratory arrest

48

What are 2 clinical uses of cholinomemetics in the CNS?

Alzheimer's

Smoking cessation

49

How would cholinomemetics help in Alzheimer's?

AChE inhibitors allow ACh to hang out in synaptic cleft for longer to reach receptors and produce effect

Pallative effect, not a cure

50

How do cholinomemetics help with smoking cessation?

Direct nicotinic agonists help to decrease cravings and pleasurable effects of cigarettes

51

How do cholinomimetic's indirectly effect the peripheral nervous system?

cause discharge of both sympathetic AND parasympathetic nervous systems

52

What are some of the indirect effects of cholinomemetics on the peripheral nervous system?

Increase BP

Sympathetic tachycardia or vagal induced bradycardia

Parasympathetic effects on GI tract --> nausea, vomitting, diarrhea, urinary voiding

53

Describe how ACh acts @ the neuromuscular junction

ACh is released from presynaptic neurons

ACh binds to nicotinic cholinergic receptors on the muscle fiber --> depolarization of muscle fiber --> contraction of skeletal muscle

54

What is the low dose effect of AChE inhibitors @ the neuromuscular junction?

prolong the effects of ACh --> increase strength of muscle contraction

55

What is the medium dose effect of AChE inhibitors @ the neuromuscular junction?

can cause muscles to fibrillate --> muscle = less effective

56

What is the high dose effect of AChE inhibitors @ the neuromuscular junction?

block muscle depolarization --> muscle paralysis

57

What is Myasthenia Gravis?

Autoimmune disorder; antibodies target nicotinic receptors --> block ACh binding

58

Which drug type is useful in treating Myasthenia Gravis and why is it an effective treatment?

AChE inhibitors are drug of choice

blocks AChE and allows ACh time to find and bind receptors that aren't blocked by antibodies

59

When would you use the drug neostigmine and what does it do?

following surgery, reverses neuromuscular paralysis

60

What are the consequences of excessive anticholinergic actions?

Can be lethal in kids

cause arrhythmias in adults

61

How would you want to treat anticholinergic intoxication?

AChE inhibitors

want to increase amount of ACh @ receptor site

62

What is the toxicity of cholinomimetics dependent on?

Receptor type: Muscarinic vs Nicotinic

Mechanism of Action: Direct cholinomimetic vs AChE inhibitor

63

What are some signs of direct muscarinic agonist toxicity?

Nausea

Vomitting

Diarrhea

Urinary urgency

Salivation

Sweating

Cutaneous vasodilation

Bronchial Constriction

64

How would you treat direct muscarinic agonist toxicity?

Anticholinergic --> Atropine

65

What are some of the signs of acute nicotine toxicity?

Infants = vomitting (ingestion of 2 cigarettes which contain fatal dose of nicotine)

Large doses:

CNS stimulation (convulsions, coma, respiratory arrest)

Skeletal muscle depolarization --> blockade/ respiratory paralysis

hypertension/cardiac arrhythmias

66

How would you treat acute nicotine toxicity?

supportive treatment until drug is metabolized (several hours)

67

What are some of the effects of chronic nicotine toxicity?

nicotine addiction

68

What is the most common cause of toxicity caused by cholinesterase inhibitors?

pesticide exposure

69

What are some of the symptoms of cholinesterase inhibitor toxicity?

Muscarinic excess:

Miosis (pupillary constriction)

Salivation

Sweating

Bronchial constriction

Diaphragm paralysis

Vomitting

Diarrhea

Convulsions

70

How would you treat cholinesterase inhibitor toxicity?

Monitor Vital Signs

Decontaminate if possible

Antidote w/ parenternal atropine or pralidoxime (2-PAM)

2-PAM reactivates inhibited AChE before full covalent bond forms through "aging"