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Pharm SJSM > Block 2 (Cholinergic drugs) > Flashcards

Block 2 (Cholinergic drugs) Flashcards

1
Q

Parasympathetic effects include which changes?

A

Bradycardia (reduced HR & conduction)
Bronchoconstriction
More peristalsis
Urination (bladder contraction)
Miosis (pupil constriction)
More secretions

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2
Q

Bradycardia (reduced HR & conduction)
Bronchoconstriction
More peristalsis
Urination (bladder contraction)
Miosis (pupil constriction)
More secretions

Are all effects of which system activation?

A

Parasympathetic nervous system

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3
Q

Describe the MOA of direct M agonist cholinergic (parasympathomimetic) & what are the drugs?

A

Direct MOA:
A muscarinic agonist that mimics Ach to act on M receptors directly

Bethanechol
Carbachol
Methacholine
Pilocarpine

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4
Q

Describe the MOA of indirect anticholinergic M agonists (Antiparasympathomimetic)

A

Indirect MOA:
They inhibit acetylcholinesterase to stop Ach breakdown thereby increasing the available Ach in the synapse to activate M receptors

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5
Q

Receptors:

What signaling pathway is involved with muscarinic receptors

A

G-protein coupled receptors (widely distributed)

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6
Q

Receptors:

What signaling pathway is involved with nicotinic receptors

A

Ligand-gated ion channels (skeletal muscle & CNS)

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7
Q

M1 receptors effect which parts of the body?

A

CNS
Ganglia
Gastric parietal cells

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8
Q

CNS
Ganglia
Gastric parietal cells

Are effected by which receptor?

A

M1

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9
Q

M2 receptors effect which part of the body?

A

Heart

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10
Q

Heart
Is effected by which receptor?

A

M2

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11
Q

M3 effect which parts of the body?

A

Smooth muscle (bladder, Git, & secretory glands)

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12
Q

Smooth muscle (bladder, Git, & secretory glands)
Are effected by which receptor?

A

M3

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13
Q

Which receptors activate the Gq protein & what is the cascade effect?

A

H1, A1, M1, M3 activate Gq protein to increase the activity of phospholipase C to increase expression of IP3, DAG, & Ca2+ (increase smooth muscle contraction)

“HAVe 1 M&M”

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14
Q

Which receptors activate the Gi protein & what is the cascade effect?

A

M2A2D2 activate Gi which inhibits adenylate cyclase to reduce cAMP levels & protein kinase A thereby inhibition myosin light chain kinase (smooth muscle)

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15
Q

Which receptors activate Gs protein & what is the cascade effect?

A

B1, B2, B3, D1, H2, & V2 activate Gs to increase adenylate cyclase to increase cAMP & protein kinase A to increase the overall Ca2+ in the heart

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16
Q

Which drugs can cause Miosis?

A

1) Sympatholytic (a2 agonists)
2) Opioids (not meperidine)
3) Parasympathomimetics/cholinergic (pilocarpine & organophosphates)

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17
Q

1) Sympatholytic (a2 agonists)
2) Opioids (not meperidine)
3) Parasympathomimetics/cholinergic (pilocarpine & organophosphates)

All cause which effect through acting on the M3 receptors?

A

Miosis (pupil constriction

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18
Q

Describe the following for an open angle glaucoma:

What is it?

What causes it?

What are the symptoms?

What are the main treatment options?

A

Patho:
When fluid in the eye cannot drain properly resulting in more intraocular pressure

Causes:
More resistance from the trabecular meshwork/canal of Schlemm

Signs
1) Vision/peripheral vision loss (optic nerve damage)

Rx:

1) M3 agonists to increase the trabecular meshwork drainage
- Pilocarpine #1
- Carbachol

2) Prostaglandin agonists to increase drainage through the uvea & sclera
- Latanoprost #1
- Bimatoprost

3) B-blockers (timolol), a2 agonists (brimonidine), & carbonic anhydrase inhibitors (acetazolamide) all reduce aqueous humor production

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19
Q

Patho:
When fluid in the eye cannot drain properly resulting in more intraocular pressure

Causes:
More resistance from the trabecular meshwork/canal of Schlemm

Signs
1) Vision/peripheral vision loss (optic nerve damage)

Rx:

1) M3 agonists to increase the trabecular meshwork drainage
- Pilocarpine #1
- Carbachol

2) Prostaglandin agonists to increase drainage through the uvea & sclera
- Latanoprost #1
- Bimatoprost

3) B-blockers (timolol), a2 agonists (brimonidine), & carbonic anhydrase inhibitors (acetazolamide) all reduce aqueous humor production

Describes which treatment?

A

Open angle glaucoma

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20
Q

List the B-blockers involved in treating glaucoma’s & what is their MOA?

A

B-blockers include:
Timolol
Betaxolol
Carteolol

MOA:
They decrease the aqueous humor in the eye

“visionis TBC”

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21
Q

List the alpha agonists involved in treating glaucoma’s?

  • What are their MOA’s?
  • What are their side effects?
  • What condition should you avoid it in?
A

Epinephrine (a1)
Apraclonidine
Brimonidine (a2)

MOA:
They decrease the amount of aqueous humor in the eye & increase the outflow through the uveoscleral pathway.

  • Epinephrine does it via vasoconstriction
  • Apraclonidine & Brimonidine both reduce the synthesis of aqueous humor

Side effects:
Mydriasis
Blurry vision
Ocular hyperemia
Foreign body sensation
Ocular allergic reactions
Ocular pruritis

Avoid in:
- Closed angle glaucoma

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22
Q

List the diuretic involved in treating glaucoma’s & what is their MOA?

A

Acetazolamide

MOA:
It reduces aqueous humor synthesis by inhibiting carbonic anhydrase

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23
Q

List the prostaglandins involved in treating glaucoma’s?

  • What is their MOA?
  • What are the side effects?
A

Bimatoprost
Latanoprost
(PGF2a)

MOA:
They increase the outflow of aqueous humor by reducing the resistance to flow in the uveoscleral pathway

Side effects:
Darkens the iris (browning)
Increases eyelash growth

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24
Q

List the cholinomimetics (direct & indirect) involved in treating glaucoma’s

  • What is their MOA?
  • What are the side effects?
A

Direct: Pilocarpine (#1 in open-angle glaucoma) & Carbachol

Indirect: Physostigmine & ecothiopate

MOA:
They increase the outflow of aqueous humor by contracting the ciliary muscles & opening the trabecular meshwork

Side effects:
Miosis
Cyclopsams

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25
Q

What are the effects of Gq activation on M3 receptors (IP3, DAG, & Ca2+) on the body?

A

Bronchoconstriction
Peristalsis & increased insulin release
Urination (contraction)
Miosis (constriction)
Peripheral vasodilation

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26
Q

Atropine, Homatropine, & Tropicamide are muscarinic antagonists that produce which effect?

A

Mydriasis (dilation) & cycloplegia

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27
Q

Which drugs result in mydriasis & cycloplegia? (3)

A

Anticholinergics:
1) Atropine
2) Homatropine
3) Tropicamide

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28
Q

Which muscarinic antagonists are used to treat Parkinson’s symptoms & acute dystonia (aka extrapyramidal symptoms)?

A

Benztropine
Trihexyphenidyl (preferred for parkinsons)

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29
Q

Describe the pathway for cholinergic neuroeffector effects at the synapse

A

1) Uptake of choline (synthesize Ach)

2) Vesicles take up Ach (protect from degeneration)

3) Release of Ach

4) Ach binds M receptor

5) Acetylcholinesterase breaks Ach down

6) Choline is recycled & re-uptaken

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30
Q

1) Uptake of choline (synthesize Ach)

2) Vesicles take up Ach (protect from degeneration)

3) Release of Ach

4) Ach binds M receptor

5) Acetylcholinesterase breaks Ach down

6) Choline is recycled & reuptaken

At what point in the pathway do the following drugs take effect?

1) Botulinum
2) Hemicholinium
3) Spider venom
4) Acetylcholinesterase

A

1) Botulinum (Inhibits Ach release)

2) Hemicholinium (inhibits choline uptake)

3) Spider venom (Increases Ach release)

4) Acetylcholinesterase (inhibits acetylcholinesterase)

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31
Q

Describe the following for pilocarpine:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

What are its adverse effects?

A

Drug:
Cholinergic/parasympathomimetic

MOA:
It’s a direct M agonist that mimics Ach’s effect on M receptors to activate them & produce parasympathetic effects

Clinical uses:
1) Urine retention
2) Open angle glaucoma
3) Xerostomia (aka dry mouth in Sjogren syndrome)

Side effects:
Worsens COPD
Peptic ulcers

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32
Q

Drug:
Cholinergic/parasympathomimetic

MOA:
It’s a direct M agonist that mimics Ach’s effect on M receptors to activate them & produce parasympathetic effects

Clinical uses:
1) Urine retention
2) Open angle glaucoma
3) Xerostomia (dry mouth)
4) Sjogren syndrome

Side effects:
Worsens COPD
Peptic ulcers

Describes which drug?

A

Pilocarpine

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33
Q

Describe the following for Bethanechol:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

What are its adverse effects?

A

Drug type:
Cholinergic/parasympathomimetic

MOA:
It’s a direct M agonist that mimics Ach’s effect on M receptors to activate them & produce parasympathetic effects. It’s resistant to acetylcholinesterase & it doesn’t activate nicotinic receptors!

Clinical uses:
1) Urinary retention
2) Ileus (obstructed bowel)

Side effects:
1) Reflex tachycardia
2) Diarrhea
3) Sweating
4) Cyclopsams
5) Urinary urgency
6) Vasodilation

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34
Q

Drug type:
Cholinergic/parasympathomimetic

MOA:
It’s a direct M agonist that mimics Ach’s effect on M receptors to activate them & produce parasympathetic effects. It’s resistant to acetylcholinesterase & it doesn’t activate nicotinic receptors!

Clinical uses:
1) Urinary retention
2) Ileus (obstructed bowel)

Side effects:
1) Reflex tachycardia
2) Diarrhea
3) Sweating
4) Cyclopsams
5) Urinary urgency
6) Vasodilation

Describes which drug?

A

bethanochole

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35
Q

Describe the following for Donepezil:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

What are its adverse effects?

A

Drug type:
Cholinergic/parasympathomimetic

MOA:
An indirect M agonist that inhibits acetylcholinesterase to increase the available Ach for M receptors

Clinical use:
1) Alzheimer’s

Side effects:
1) Nausea/vomiting

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36
Q

Drug type:
Cholinergic/parasympathomimetic

MOA:
An indirect M agonist that inhibits acetylcholinesterase to increase the available Ach for M receptors

Clinical use:
1) Alzheimer’s

Side effects:
1) Nausea/vomiting

Describes which drug?

A

Donepezil

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37
Q

Describe the following for Physostigmine:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

What are its adverse effects?

A

Drug type:
Cholinergic/parasympathomimetic

MOA:
An indirect M agonist that inhibits acetylcholinesterase to increase the available Ach to bind M receptors

Clinical use:
1) Glaucoma
2) Atropine poisoning aka anticholinergic OD
3) Belladona alkaloid poisoning (deadly nightshade)

Side effects:
1) Parasympathetic symptoms (nausea/vomiting/diarrhea/urine urg)
2) Seizures

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38
Q

Drug type:
Cholinergic/parasympathomimetic

MOA:
An indirect M agonist that inhibits acetylcholinesterase to increase the available Ach to bind M receptors

Clinical use:
1) Glaucoma
2) Atropine poisoning aka anticholinergic OD
3) Belladona alkaloid poisoning (deadly nightshade)

Side effects:
1) Parasympathetic symptoms (nausea/vomiting/diarrhea/urine urg)
2) Seizures

Describes which drug?

A

Physostigmine

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39
Q

Describe the following for Methacholine:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

A

Drug type:
Cholinergic/parasympathomimetic

MOA:
A direct M agonist that acts like Ach to produce parasympathetic effects

Clinical use:
1) To diagnose bronchial asthma “methacholine challenge”

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40
Q

Drug type:
Cholinergic/parasympathomimetic

MOA:
A direct M agonist that acts like Ach to produce parasympathetic effects

Clinical use:
1) To diagnose bronchial asthma

Describes which drug?

A

methacholine

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41
Q

Describe the following for Carbachol:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

What are the side effects?

A

Drug type:
Cholinergic/parasympathomimetic

MOA:
A direct M agonist that mimics Ach in the synapse to produce parasympathetic effects

Clinical use:
1) Open angle Glaucoma

Side effect:
1) Miosis

42
Q

Describe the following for Edrophonium:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

A

Drug type:
Cholinergic/parasympathomimetic

MOA:
An indirect M agonist that inhibits acetylcholinesterase to indirectly raise available Ach

Clinical use:
1) Diagnosing Myasthenia gravis

43
Q

Drug type:
Cholinergic/parasympathomimetic

MOA:
An indirect M agonist that inhibits acetylcholinesterase to indirectly raise available Ach

Clinical use:
1) Diagnosing Myasthenia gravis

Describes which drug?

A

Edrophonium

44
Q

Describe the following for Cevimeline:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

What are the side effects?

A

Drug type:
Cholinergic/parasympathomimetic

MOA:
A direct acting M agonist that targets M1 & M3 specifically (M1 increases secretory glands) & M3 (Increases SM contraction & secretions)

Clinical use:
1) Xerostomia (in Sjogren syndrome)

Side effects?
1) Sweating
2) Nausea
3) Rhinitis
4) Sinusitis
5) URI

45
Q

Drug type:
Cholinergic/parasympathomimetic

MOA:
A direct acting M agonist that targets M1 & M3 specifically (M1 increases secretory glands) & M3 (Increases SM contraction & secretions)

Clinical use:
1) Xerostomia (in Sjogren syndrome)

Side effects?
1) Sweating
2) Nausea
3) Rhinitis
4) Sinusitis
5) URI

Describes which drug?

A

Cevimeline

46
Q

Describe the following for Latanoprost:

What is it ?
- drug type

How does it work?
- MOA

What are its clinical uses?

What are the side effects?

A

Drug type:
Prostaglandin analog (PGF2)

MOA:
It increases the outflow of aqueous humor by reducing the resistance to flow through the uveoscleral pathway

Side effects:
1) Darkens the iris (browning)
2) Eye lash growth
3) Macular edema in aphasiacs (plp w/o eye lens)
4) Reactivation of uveitis

47
Q

Drug type:
Prostaglandin analog (PGF2)

MOA:
It increases the outflow of aqueous humor by reducing the resistance to flow through the uveoscleral pathway

Side effects:
1) Darkens the iris (browning)
2) Eye lash growth
3) Macular edema in aphasiacs (plp w/o eye lens)
4) Reactivation of uveitis

Describes which drug?

A

Latanoprost

48
Q

Describe which receptors effect which parts of the body?

M1
M2
M3
M4 & M5
N(n)
N(m)

A

M1= Gastric ganglia & CNS

M2= Heart (AV/SA nodal conduction) & CNS

M3= Eyes, GiT, Bladder, Bronchus, glands, & CNS

M4 & M5= CNS only

N(n)= Ganglia & adrenal medulla

N(m)= Neuromuscular junction

49
Q

List the direct cholinergic drugs that are considered choline esters

A

Acetylcholine
Carbachol
Bethanechol
Methacholine

50
Q

Acetylcholine
Carbachol
Bethanechol
Methacholine

Are all considered..

A

direct cholinergic drugs that are considered choline esters

51
Q

List the direct cholinergic drugs that are considered alkaloids

A

Pilocarpine
Nicotine
Lobeline

52
Q

Pilocarpine
Nicotine
Lobeline

Are considered what?

A

direct cholinergic drugs that are considered alkaloids

53
Q

These Indirect cholinesterase drugs have a very long duration of action

A

Organophosphates
- Malathion
- Parathion
- DFP
- Chlorpyrifos
- Ecothiophate
- Nerve gases (Tabun, Sarin, & Soman)

54
Q

Organophosphates
- Malathion
- Parathion
- Dyflos
- Chlorpyrifos
- Ecothiopate
- Diazinon
- Nerve gases (Tabun, Sarin, & Soman)

Have a ________ duration of action

A

Very long

55
Q

These Indirect cholinesterase drugs have a long duration of action?

A

Carbamates
Physostigmine
Neostigmine
Pyridostigmine
Rivastigmine
Donepezil

56
Q

Carbamates
Physostigmine
Neostigmine
Pyridostigmine
Rivastigmine
Donepezil

Have a _______ duration of action?

A

Long

57
Q

These Indirect cholinesterase drugs have a short duration of action?

A

Edrophonium

58
Q

Edrophonium has a ______ duration of action

A

Short

59
Q

What are the 3 drugs used to treat Alzheimer’s? & which is most preferred/why?

A

Rivastigmine (#1 because it has fewer drug interactions)

Donepezil

Galantamine

60
Q

Rivastigmine (#1 because it has fewer drug interactions)

Donepezil

Galantamine

Are used to treat which condition?

A

Alzheimers

61
Q

How would you treat poisoning by anticholinergic drugs, esp atropine OD?

A

Physostigmine (preferred because it can cross the BBB)

62
Q

Which drug is given before atropine in post op decurarization?

A

Neostigmine

63
Q

What would you give steve irwin if he said he’s just been bitten by a cobra?

A

Neostigmine then atropine

64
Q

What is the difference between a cholinergic & myasthenic crisis

What happens if you with both Edrophonium?

A

Cholinergic crisis is due to an excessive dose of anti-ChE drug, Edrophonium makes it worse

Myasthenic crisis is due to inadequate anti-ChE drug dose, Edrophonium makes it better

65
Q

What is organophosphorus poisoning?

Who gets it?

How do you treat it?

A

Usually from insecticides the organophosphates inversely inhibits AChE, (typically seen in farmers) causing Dumbbeelss symptoms:

Diarrhea
Urination
Miosis
Bradycardia
Bronchoconstriction
Emesis
Excitation (CNS/muscle)
Lacrimation
Salivation
Sweating

Rx:
1) Atropine (lifesaving reverse muscarinic effects)

2) Pralidoxime (reverse nicotinic effects by regenerating AChE)

66
Q

How does atropine reverse the muscarinic effects in organophosphorus poisoning?

A

It’s a competitive inhibitor that can cross the BBB & antagonize the M receptors (reduce parasympathetic effects)

67
Q

How does pralidoxime reverse the nicotinic effects in organophosphorus poisoning?

A

It regenerates AChE by dephosphorylation if it’s given early enough

68
Q

(Oximes)
Pralidoxime chloride (PAM)
Obidoxime chloride
Trimedoxime bromide
Diacetyl monoxime (DAM)

A

Cholinesterase Reactivators (Reactivate the enzyme AChE)

69
Q

What are Cholinesterase Reactivators (Oximes) used for clinically?

A

Organophosphate poisoning

70
Q

What are the adverse effects of cholinomimetics (parasympathomimetic”

DUMBBEELSS

A

Diarrhea
Urination
Miosis
Bradycardia
Bronchoconstriction
Emesis
Excitation (CNS/muscle)
Lacrimation
Salivation
Sweating

71
Q

N(n) receptor in the adrenals causes what response?

A

Secretion (epi & norepi)

72
Q

What type of receptors are nicotinic receptors?

A

Ligand-gated ion channels

73
Q

Edrophonium

What is the DOA?
What is it’s main clinical use?

A

DOA:
Short-acting

Clinical use:
Myasthenia gravis Rx

74
Q

DOA:
Short-acting

Clinical use:
Myasthenia gravis Rx

A

Edrophonium

75
Q

Physostigmine

What is a characteristic of the drug?
What is it’s main clinical use?

A

Characteristic:
Tertiary amine (enters CNS)

Clinical uses:
1) Glaucoma
2) Antidote in atropine OD

76
Q

Characteristic:
Tertiary amine (enters CNS)

Clinical uses:
1) Glaucoma
2) Antidote in atropine OD

A

Physostigmine

77
Q

Neostigmine & Pyridostigmine

What is a characteristic of the drug?
What is it’s main clinical use?

A

Characteristic:
Quaternary amines (no CNS entry)

Clinical uses:
1) Ileus
2) Urinary retention
3) Myasthenia gravis
4) Reversing NM blockers

78
Q

Characteristic:
Quaternary amines (no CNS entry)

Clinical uses:
1) Ileus
2) Urinary retention
3) Myasthenia gravis
4) Reversing NM blockers

A

Neostigmine & Pyridostigmine

79
Q

Donepezil & Rivastigmine

What is a characteristic of the drug?
What is it’s main clinical use?

A

Characteristic:
Lipid soluble (enters CNS)

Clinical uses:
Alzheimer’s (R is preferred)

80
Q

Organophosphates
What is a characteristic of the drug?
What is it’s main non-clinical use?

A

Characteristic:
Lipid-soluble & irreversible inhibitor

Uses:
Insecticides
Nerve gas (sarin)

81
Q

Characteristic:
Lipid-soluble & irreversible inhibitor

Uses:
Insecticides
Nerve gas (sarin)

A

Organophosphates

82
Q

Belladona poisoning use

A

Physostigmine

83
Q

Glaucoma use

A

Pilocarpine
Physostigmine
Ecothiophate

84
Q

Xerostomia in Sjogren’s use

A

Pilocarpine
Cevimeline

85
Q

Post op for paralytic ileus use

A

Bethanechol
Neostigmine

86
Q

Post op for Urinary retention use

A

Bethanechol
Neostigmine

87
Q

Diagnosing Myasthenia gravis vs cholinergic crisis use

A

Edrophonium

88
Q

Myasthenia gravis use

A

Neostigmine
Pyridostigmine

89
Q

Cobra bite use

A

Neostigmine
Pyridostigmine

90
Q

To reverse muscle relaxants use

A

Neostigmine
Pyridostigmine

91
Q

To diagnose bronchial hyper-reactivity use

A

Methacholine

92
Q

Which drug types decrease aqueous humor secretion in glaucoma?

A

B-blockers
A2 agonists
Carbonic anhydrase inhibitors

93
Q

Acetazolamide (oral)
Dorzolamide (topical)
Brinzolamide

are all which drug type that have what effect in glaucoma’s?

A

Carbonic anhydrase inhibitors that reduce aqueous humor secretion

94
Q

Brimonidine
Apraclonidine
(all topical)

are all which drug type that have what effect in glaucoma’s?

A

A2 agonists that reduce aqueous humor secretion

95
Q

Bethaxolol & Levo-betaxolol (cardio selective)

Timolol
Levobunolol
Carteolol
(All topical)

are all which drug type that have what effect in glaucoma’s?

A

B blockers that reduce the secretion of aqueous humor

96
Q

Which drug types increase aqueous humor outflow via trabecular outflow in glaucoma?

A

Miotics
A1 agonists

97
Q

Which drug types increase aqueous humor outflow via uveo-scleral outflow in glaucoma?

A

Latanoprost
Bimatoprost

98
Q

Latanoprost
Bimatoprost
(all topical)

are all which drug type that have what effect in glaucoma’s?

A

Prostaglandin analogs (PGF2) that increase outflow through the uveo-scleral pathway

99
Q

Pilocarpines
Physostigmine
(all topical)

are all which drug type that have what effect in glaucoma’s?

A

Miotics (direct & indirect cholinergics) that increase trabecular outflow

100
Q

Dipivefrine (topical)

are which drug type that have what effect in glaucoma’s?

A

A1 agonist, that increases trabecular outflow

Pharm SJSM (23 decks)

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