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?

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

Block 2 (Cholinergic drugs) Flashcards by isabelle courtney

Parasympathetic effects include which changes?

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

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

Are all effects of which system activation?

Parasympathetic nervous system

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

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

Bethanechol
Carbachol
Methacholine
Pilocarpine

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Describe the MOA of indirect anticholinergic M agonists (Antiparasympathomimetic)

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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Receptors:

What signaling pathway is involved with muscarinic receptors

G-protein coupled receptors (widely distributed)

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Receptors:

What signaling pathway is involved with nicotinic receptors

Ligand-gated ion channels (skeletal muscle & CNS)

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M1 receptors effect which parts of the body?

CNS
Ganglia
Gastric parietal cells

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CNS
Ganglia
Gastric parietal cells

Are effected by which receptor?

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M2 receptors effect which part of the body?

Heart

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Heart
Is effected by which receptor?

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M3 effect which parts of the body?

Smooth muscle (bladder, Git, & secretory glands)

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

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

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

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

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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Which drugs can cause Miosis?

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

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

All cause which effect through acting on the M3 receptors?

Miosis (pupil constriction

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Describe the following for an open angle glaucoma:

What is it?

What causes it?

What are the symptoms?

What are the main treatment options?

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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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?

Open angle glaucoma

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

B-blockers include:
Timolol
Betaxolol
Carteolol

MOA:
They decrease the aqueous humor in the eye

“visionis TBC”

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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?

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

Acetazolamide

MOA:
It reduces aqueous humor synthesis by inhibiting carbonic anhydrase

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List the prostaglandins involved in treating glaucoma’s?

What is their MOA?
What are the side effects?

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

What is their MOA?
What are the side effects?

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

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

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

Mydriasis (dilation) & cycloplegia

Which drugs result in mydriasis & cycloplegia? (3)

Anticholinergics: 1) Atropine 2) Homatropine 3) Tropicamide

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

Benztropine Trihexyphenidyl (preferred for parkinsons)

Describe the pathway for cholinergic neuroeffector effects at the synapse

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

1) Botulinum (Inhibits Ach release) 2) Hemicholinium (inhibits choline uptake) 3) Spider venom (Increases Ach release) 4) Acetylcholinesterase (inhibits acetylcholinesterase)

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?

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

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?

Pilocarpine

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?

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

bethanochole

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?

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

Donepezil

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?

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

Physostigmine

Describe the following for Methacholine: What is it ? - drug type How does it work? - MOA What are its clinical uses?

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"

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?

methacholine

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?

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

Describe the following for Edrophonium: What is it ? - drug type How does it work? - MOA What are its clinical uses?

Drug type: Cholinergic/parasympathomimetic MOA: An indirect M agonist that inhibits acetylcholinesterase to indirectly raise available Ach Clinical use: 1) Diagnosing Myasthenia gravis

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?

Edrophonium

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?

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

Cevimeline

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?

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

Latanoprost

Describe which receptors effect which parts of the body? M1 M2 M3 M4 & M5 N(n) N(m)

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

List the direct cholinergic drugs that are considered choline esters

Acetylcholine Carbachol Bethanechol Methacholine

Acetylcholine Carbachol Bethanechol Methacholine Are all considered..

direct cholinergic drugs that are considered choline esters

List the direct cholinergic drugs that are considered alkaloids

Pilocarpine Nicotine Lobeline

Pilocarpine Nicotine Lobeline Are considered what?

direct cholinergic drugs that are considered alkaloids

These Indirect cholinesterase drugs have a very long duration of action

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

Organophosphates - Malathion - Parathion - Dyflos - Chlorpyrifos - Ecothiopate - Diazinon - Nerve gases (Tabun, Sarin, & Soman) Have a ________ duration of action

Very long

These Indirect cholinesterase drugs have a long duration of action?

Carbamates Physostigmine Neostigmine Pyridostigmine Rivastigmine Donepezil

Carbamates Physostigmine Neostigmine Pyridostigmine Rivastigmine Donepezil Have a _______ duration of action?

Long

These Indirect cholinesterase drugs have a short duration of action?

Edrophonium

Edrophonium has a ______ duration of action

Short

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

Rivastigmine (#1 because it has fewer drug interactions) Donepezil Galantamine

Rivastigmine (#1 because it has fewer drug interactions) Donepezil Galantamine Are used to treat which condition?

Alzheimers

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

Physostigmine (preferred because it can cross the BBB)

Which drug is given before atropine in post op decurarization?

Neostigmine

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

Neostigmine then atropine

What is the difference between a cholinergic & myasthenic crisis What happens if you with both Edrophonium?

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

What is organophosphorus poisoning? Who gets it? How do you treat it?

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)

How does atropine reverse the muscarinic effects in organophosphorus poisoning?

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

How does pralidoxime reverse the nicotinic effects in organophosphorus poisoning?

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

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

Cholinesterase Reactivators (Reactivate the enzyme AChE)

What are Cholinesterase Reactivators (Oximes) used for clinically?

Organophosphate poisoning

What are the adverse effects of cholinomimetics (parasympathomimetic" DUMBBEELSS

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

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

Secretion (epi & norepi)

What type of receptors are nicotinic receptors?

Ligand-gated ion channels

Edrophonium What is the DOA? What is it's main clinical use?

DOA: Short-acting Clinical use: Myasthenia gravis Rx

Edrophonium

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

Characteristic: Tertiary amine (enters CNS) Clinical uses: 1) Glaucoma 2) Antidote in atropine OD

Physostigmine

Neostigmine & Pyridostigmine What is a characteristic of the drug? What is it's main clinical use?

Characteristic: Quaternary amines (no CNS entry) Clinical uses: 1) Ileus 2) Urinary retention 3) Myasthenia gravis 4) Reversing NM blockers

Neostigmine & Pyridostigmine

Donepezil & Rivastigmine What is a characteristic of the drug? What is it's main clinical use?

Characteristic: Lipid soluble (enters CNS) Clinical uses: Alzheimer's (R is preferred)

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

Characteristic: Lipid-soluble & irreversible inhibitor Uses: Insecticides Nerve gas (sarin)

Organophosphates

Belladona poisoning use

Physostigmine

Glaucoma use

Pilocarpine Physostigmine Ecothiophate

Xerostomia in Sjogren's use

Pilocarpine Cevimeline

Post op for paralytic ileus use

Bethanechol Neostigmine

Post op for Urinary retention use

Bethanechol Neostigmine

Diagnosing Myasthenia gravis vs cholinergic crisis use

Edrophonium

Myasthenia gravis use

Neostigmine Pyridostigmine

Cobra bite use

Neostigmine Pyridostigmine

To reverse muscle relaxants use

Neostigmine Pyridostigmine

To diagnose bronchial hyper-reactivity use

Methacholine

Which drug types decrease aqueous humor secretion in glaucoma?

B-blockers A2 agonists Carbonic anhydrase inhibitors

Acetazolamide (oral) Dorzolamide (topical) Brinzolamide are all which drug type that have what effect in glaucoma's?

Carbonic anhydrase inhibitors that reduce aqueous humor secretion

Brimonidine Apraclonidine (all topical) are all which drug type that have what effect in glaucoma's?

A2 agonists that reduce aqueous humor secretion

Bethaxolol & Levo-betaxolol (cardio selective) Timolol Levobunolol Carteolol (All topical) are all which drug type that have what effect in glaucoma's?

B blockers that reduce the secretion of aqueous humor

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

Miotics A1 agonists

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

Latanoprost Bimatoprost

Latanoprost Bimatoprost (all topical) are all which drug type that have what effect in glaucoma's?

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

Pilocarpines Physostigmine (all topical) are all which drug type that have what effect in glaucoma's?

Miotics (direct & indirect cholinergics) that increase trabecular outflow

Dipivefrine (topical) are which drug type that have what effect in glaucoma's?

A1 agonist, that increases trabecular outflow