Fa: Pharmacology - Autonomic Drugs 1

Front 1

What types of NTs / receptors are involved in a parasympathetic pathway?

Back 1

- Preganglionic (long) releases ACh on Nicotinic receptor
- Postganglionic (short) releases ACh on Muscarinic receptor (eg, cardiac muscle, smooth muscle, gland cells, nerve terminals)

Front 2

What types of NTs / receptors are involved in a sympathetic pathway to sweat glands?

Back 2

- Preganglionic (short) releases ACh on Nicotinic receptor (sympathetic chain)
- Postganglionic (long) releases ACh on Muscarinic receptor

(same NTs and receptors as parasympathetic)

Front 3

What types of NTs / receptors are involved in a sympathetic pathway to cardiac muscle, smooth muscle, gland cells, and nerve terminals?

Back 3

- Preganglionic (short) releases ACh on Nicotinic receptor (sympathetic chain)
- Postganglionic (long) releases NE on α and β receptors

Front 4

What types of NTs / receptors are involved in a sympathetic pathway to renal vasculature and smooth muscle?

Back 4

- Preganglionic (short) releases ACh on Nicotinic receptor (sympathetic chain)
- Postganglionic (long) releases Dopamine on D1 receptors

Front 5

What types of NTs / receptors are involved in a pathway to the adrenal medulla?

Back 5

- Preganglionic releases ACh on Nicotinic receptor on adrenal medulla
- Adrenal medulla releases Epi and NE

Front 6

What types of NTs / receptors are involved in a somatic pathway to the skeletal muscle?

Back 6

Voluntary motor nerve releases ACh on Nicotinic receptor on skeletal muscle

Front 7

What nerve terminals does botulinum toxin affect?

Back 7

Botulinum toxin prevents release of Ach at all cholinergic terminals

Front 8

What are the types of ACh receptors?

Back 8

- Nicotinic ACh receptors
- Muscarinic ACh receptors

Front 9

What are the characteristics of a nicotinic ACh receptors?

Back 9

Ligand-gated Na+/K+ channels
- Nn - found in autonomic ganglia
- Nm - found in neuromuscular junction subtypes

Front 10

Which type of receptor is found in autonomic ganglia?

Back 10

Nn - Nicotinic ACh receptors, ligand-gated Na+/K+

Front 11

Which type of receptor is found in neuromuscular junctions?

Back 11

Nm - Nicotinic ACh receptors, ligand-gated Na+/K+

Front 12

What are the characteristics of muscarinic ACh receptors?

Back 12

G-protein coupled receptors that usually act through 2nd messengers

Front 13

What are the types of Muscarinic ACh receptors?

Back 13

- M1
- M2
- M3
- M4
- M5

Front 14

What are the types of G-protein receptors?

Back 14

- Sympathetic: α1, α2, β1, β2
- Parasympathetic: M1, M2, M3
- Dopamine: D1, D2
- Histamine: H1, H2
- Vasopressin: V1, V2

Front 15

What are the sympathetic G-protein receptors? Class?

Back 15

QISS and QIQ till you're SIQ of SQS (super qinky sex):
- α1: q
- α2: i
- β1: s
- β2: s

Front 16

What are the parasympathetic G-protein receptors? Class?

Back 16

QISS and QIQ till you're SIQ of SQS (super qinky sex):
- M1: q
- M2: i
- M3: q

"qiq" - "kickin' it" - chillin (PANS)

A - B - M - D - H - V

Front 17

What are the dopamine G-protein receptors? Class?

Back 17

QISS and QIQ till you're SIQ of SQS (super qinky sex):
- D1: s
- D2: i

A - B - M - D - H - V

Front 18

What are the histamine G-protein receptors? Class?

Back 18

QISS and QIQ till you're SIQ of SQS (super qinky sex):
- H1: q
- H2: s

A - B - M - D - H - V

Front 19

What are the vasopressin G-protein receptors? Class?

Back 19

QISS and QIQ till you're SIQ of SQS (super qinky sex):
- V1: q
- V2: s

A - B - M - D - H - V

Front 20

What G-protein class are α1 receptors? Major functions?

Back 20

"q"

- ↑ Vascular smooth muscle contraction
- ↑ Pupillary dilator muscle contraction (mydriasis)
- ↑ Intestinal and bladder sphincter muscle contraction

Front 21

What G-protein class are α2 receptors? Major functions?

Back 21

"i"

- ↓ Sympathetic outflow
- ↓ Insulin release
- ↓ Lipolysis
- ↑ Platelet aggregation

- ↓ aqueous humor production

Front 22

What G-protein class are β1 receptors? Major functions?

Back 22

"s"

- ↑ Heart rate
- ↑ Contractility
- ↑ Renin release
- ↑ Lipolysis

Front 23

What G-protein class are β2 receptors? Major functions?

Back 23

"s"

- Vasodilation and bronchodilation
- ↑ Lipolysis
- ↑ Insulin release
- ↓ Uterine tone (tocolysis)
- Ciliary muscle relaxation
- ↑ Aqueous humor production

Front 24

What G-protein class are M1 receptors? Location?

Back 24

"q"

- CNS and enteric nervous system

Front 25

What G-protein class are M2 receptors? Major functions?

Back 25

"i"

- ↓ HR
- ↓ Contractility of atria

Front 26

What G-protein class are M3 receptors? Major functions?

Back 26

"q"

- ↑ Exocrine gland secretions (eg, lacrimal, salivary, gastric acid)
- ↑ Gut peristalsis
- ↑ Bladder contraction
- Bronchoconstriction
- ↑ Pupillary sphincter muscle contraction (miosis)
- Ciliary muscle contraction (accommodation)

Front 27

What G-protein class are D1 receptors? Major functions?

Back 27

"s"

- Relaxes renal vascular smooth muscle

Front 28

What G-protein class are D2 receptors? Major functions?

Back 28

"i"

- Modulates transmitter release
- Especially in brain

Front 29

What G-protein class are H1 receptors? Major functions?

Back 29

"q"

- ↑ Nasal and bronchial mucus production
- ↑ Vascular permeability
- Contraction of bronchioles
- Pruritus
- Pain

Front 30

What G-protein class are H2 receptors? Major functions?

Back 30

"s"

- ↑ Gastric acid secretion

Front 31

What G-protein class are V1 receptors? Major functions?

Back 31

"q"

- ↑ Vascular smooth muscle contraction

Front 32

What G-protein class are V2 receptors? Major functions?

Back 32

"s"

- ↑ H2O permeability and reabsorption in the collecting tubules of the kidney (V2 is found in the 2 kidneys)

Front 33

Which receptors use the Gq receptor?

Back 33

H1, α1, V1, M1, M3

(HAVe 1 M&M)

Front 34

Which is the mechanism of activation of the Gq receptor?

Back 34

- Gq activation → Phospholipase C → PIP2 cleaved to DAG and IP3
- DAG → activates Protein Kinase C
- IP3 → ↑ [Ca2+]in → smooth muscle contraction

Front 35

Which receptors use the Gs receptor?

Back 35

β1, β2, D1, H2, V2

Front 36

Which is the mechanism of activation of the Gs receptor?

Back 36

Activate Gs → ↑ Adenylyl Cyclase → ↑ cAMP → PKA

- ↑ [Ca2+]in (heart)
- Myosin light chain kinase (smooth muscle)

Front 37

Which receptors use the Gi receptor?

Back 37

M2, α2, D2

MAD 2's

Front 38

Which is the mechanism of activation of the Gi receptor?

Back 38

Activated Gi → inhibits Adenylyl Cyclase → ↓ cAMP

Front 39

What modulates NE release from a sympathetic nerve ending?

Back 39

Modulated by NE itself, acting on pre-synaptic α2-autoreceptors, Ang II, and other substances

Front 40

What are the direct cholinomimetic agonists?

Back 40

- Bethanechol
- Carbachol
- Pilocarpine
- Methacholine

Front 41

What are the indirect cholinomimetic agonists (anticholinesterases)?

Back 41

- Neostigmine
- Pyridostigmine
- Physostigmine
- Donepezil, Rivastigmine, Galantamine
- Edrophonium

Front 42

What drug is used to treat post-operative ileus, neurogenic ileus, and urinary retention? Action?

Back 42

Bethanechol
- Direct cholinomimetic agent
- Activates Bowel and Bladder smooth muscle
- Resistant to AChE

"Bethany, call me directly if you want to activate your Bowels and Bladder"

Front 43

What drug is used to constricts pupils and relieve intraocular pressure in glaucoma?

Back 43

Carbachol
- Direct cholinomimetic agent

" direct CARBon copy of AcetylCHOLine"

Front 44

What drug is a potent stimulator of sweat, tears, and saliva and is used to treat open-angle and closed-angle glaucoma? Action?

Back 44

Pilocarpine
- Direct cholinomimetic agent
- Contracts ciliary muscle of eye (open-angle glaucoma), pupillary sphincter (closed-angle glaucoma)
- Resistant to AChE

"You cry, drool, and sweat on directly your PILOw"

Front 45

What drug is used to test for a diagnosis of asthma? Action?

Back 45

Methacholine
- Direct cholinomimetic agent
- Stimulates Muscarinic receptors directly in airway when inhaled

Front 46

What drug is used to treat post-operative and neurogenic ileus and urinary retention, in addition to myasthenia gravis and reversal of NMJ blockade (post-op)? Action?

Back 46

Neostigmine
- Indirect cholinomimetic (anticholinesterase)
- ↑ Endogenous ACh

Neo CNS = No CNS penetration

Front 47

What drug is used to treat myasthenia gravis (long acting)? Action?

Back 47

Pyridostigmine
- Indirect cholinomimetic agent (anticholinesterase)
- Does not penetrate CNS
- ↑ Strength

"pyRIDostiGMine = get RID of Myasthenia Gravis"

Front 48

What drug is used to treat anti-cholinergic toxicity? Action?

Back 48

Physostigmine
- Indirect cholinomimetic agent (anticholinesterase)
- Crosses blood-brain barrier → CNS
- ↑ Endogenous ACh

"PHYsostigmine "PHYxes" atropine overdose"

Front 49

What drugs are used to treat Alzheimer Disease? Action?

Back 49

Donepezil, Rivastigmine, and Galantamine
- Indirect cholinomimetic agent (anticholinesterase)
- ↑ Endogenous ACh

Front 50

What drug was historically used to diagnose myasthenia gravis? Mechanism?

Back 50

Edrophonium
- Indirect cholinomimetic agent (anticholinesterase)
- ↑ Endogenous ACh
- Extremely short acting

Front 51

What is used to diagnose Myasthenia Gravis now?

Back 51

Anti-AChR Ab (anti-ACh receptor antibody) test

Front 52

What do you need to watch for when giving cholinomimetic agents to patients?

Back 52

Watch for exacerbation of COPD, asthma, and peptic ulcers when giving to susceptible patients

Front 53

What can cause cholinesterase inhibitor poisoning? Action?

Back 53

Often due to organophosphates, such as parathion - irreversibly inhibits AChE

Front 54

What does cholinesterase inhibitor poisoning cause?

Back 54

DUMBBELSS:
- Diarrhea
- Urination
- Miosis
- Bronchospasm
- Bradycardia
- Excitation of skeletal muscle and CNS
- Lacrimation
- Sweating
- Salivation

Front 55

Who is likely to get cholinesterase inhibitor poisoning?

Back 55

Farmers because organophosphates are components of insecticides (these irreversibly inhibit AChE)

Front 56

How do you treat an irreversible inhibitor of AChE?

Back 56

- Atropine (competitive inhibitor) +
- Pralidoxime (regenerates AChE if given early)

Front 57

What are the clinical applications and actions of Bethanechol?

Back 57

Direct Cholinomimetic agent:
- Post-operative ileus, neurogenic ileus, and urinary retention
- Activates bowels and bladder smooth muscle
- Resistant to AChE

Front 58

What are the clinical applications and actions of Carbachol?

Back 58

Direct Cholinomimetic agent:
- Treats glaucoma, pupillary constriction, and relief of intra-ocular pressure
- Carbon copy of ACh

Front 59

What are the clinical applications and actions of Pilocarpine?

Back 59

Direct Cholinomimetic agent:
- Potent stimulator of sweat, tears, and saliva
- Treats open angle glaucoma (contracts ciliary muscle of eye)
- Treats closed angle glaucoma (contracts pupillary sphincter)
- Resistant to AChE

"You cry, drool, and sweat on your PILOw"

Front 60

What are the clinical applications and actions of Methacholine?

Back 60

Direct Cholinomimetic agent:
- Challenge test for diagnosis of asthma
- Stimulates muscarinic receptors in airway when inhaled

Front 61

What are the clinical applications and actions of Neostigmine?

Back 61

Indirect Cholinomimetic agent:
- Anticholinesterase
- ↑ Endogenous ACh
- Treats post-operative and neurogenic ileus and urinary retention, myasthenia gravis, and reverses NMJ blockade (post-op)

Front 62

What are the clinical applications and actions of Pyridostigmine?

Back 62

Indirect Cholinomimetic agent:
- Anticholinesterase
- ↑ Endogenous ACh
- Treats myasthenia gravis (long acting), ↑ strength
- Does not penetrate CNS

"pyRIDostiGMine gets RID of Myasthenia Gravis"

Front 63

What are the clinical applications and actions of Physostigmine?

Back 63

Indirect Cholinomimetic agent:
- Anticholinesterase
- ↑ Endogenous ACh
- Treats anti-cholinergic toxicity (crosses BBB → CNS)

"PHYsostigmine "phyxes" atropine overdose"

Front 64

What are the clinical applications and actions of Donepezil?

Back 64

Indirect Cholinomimetic agent:
- Anticholinesterase
- ↑ Endogenous ACh
- Treats Alzheimer Disease

Front 65

What are the clinical applications and actions of Rivastigmine?

Back 65

Indirect Cholinomimetic agent:
- Anticholinesterase
- ↑ Endogenous ACh
- Treats Alzheimer Disease

Front 66

What are the clinical applications and actions of Galantamine?

Back 66

Indirect Cholinomimetic agent:
- Anticholinesterase
- ↑ Endogenous ACh
- Treats Alzheimer Disease

Front 67

What are the clinical applications and actions of Edrophonium?

Back 67

Indirect Cholinomimetic agent:
- Anticholinesterase
- ↑ Endogenous ACh
- Historically used to diagnose Myasthenia Gravis (extremely short acting)

Front 68

What are the muscarinic antagonists?

Back 68

- Atropine, Homatropine, Tropicamide
- Benztropine
- Scopolamine
- Ipratropium and Tiotropium
- Oxybutynin, Darifenacin, and Solifenacin
- Glycopyrrolate

Front 69

Which muscarinic antagonists act on the eye? Applications?

Back 69

Atropine, Homatropine, Tropicamide
- Produces mydriasis (dilation) and cycloplegia (paralysis of ciliary muscle - loss of accommodation)

Front 70

Which muscarinic antagonists act on the CNS? Applications?

Back 70

- Benztropine → Parkinson Disease ("Park my Benz"); acute dystonia
- Scopolamine → Motion sickness

Front 71

Which muscarinic antagonists act on the Respiratory Tract? Applications?

Back 71

Ipratropium and Tiotropium
- COPD, asthma (I pray I can breath soon)

Glycopyrrolate:
- Parenteral administration: pre-operative use to reduce airway secretions

Front 72

Which muscarinic antagonists act on the Genitourinary Tract? Applications?

Back 72

Oxybutinin, Darifenacin, and Solifenacin

- Reduce bladder spasms and treat urge urinary

incontinence (overactive bladder)

(they inhibit M3, which is responsible for bladder muscle contraction)

Front 73

Which muscarinic antagonists act on the Gastrointestinal Tract? Applications?

Back 73

Glycopyrrolate:
- Oral administration: drooling, peptic ulcer