2. Autonomic Pharmacology Flashcards Preview

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Flashcards in 2. Autonomic Pharmacology Deck (86):
1

Draw out the flow chart from sensory afferent input to final efferent output

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2

Draw out the synthesis of NE 

Phenylalanine to tyrosine (phenylalanine hydroxylase - deficiency = PKU)

Tyrosine to DOPA (Tyrosine hydroxylase)

DOPA to Dopamine (Amino acid decarboxylase)

Dopamine to NE (Dopamine-B hyroxylase)

 

*RLS is the first step

*NE to E occurs within the adrenal medulla

3

What blocks tyrosine hydroxylase?

What blocks dopamine entry into vesicles?

Metyrosine

Reserpine

4

How does NE enter nerve terminals?

Tyrosine enters a nerve terminal via Na channel and is converted into dopamine. Dopamine then enters a vesicle vai VMAT2 where it is converted into NE

5

What are the three fates of NE after being released into the synaptic cleft?

1) Binds to post-synpatic membrane

2) Binds to autoreceptor 

3) Reuptake into presynaptic neuron via NET

 

The three autoreceptors are

  • Alpha 2: Inhibits NE release
  • M2: Inhibits NE release
  • Angiotensin2: Stimulates NE release

6

How can you block NE reuptake? (i.e. NET)

Cocaine

TCA

7

What two enzymes metabolize NE?

Monoamine oxidase (oxidizes NE)

Cathechol-O-methyl transferase (methylates NE)

8

Why is taking dopamine orally not effective?

MOA and COMT are located within the liver and thus taking dopamine will result in significant metabolism

9

How is Ach synthesized?

Choline enters the nerve terminal via Na channels and is combined with acetyl Ca via the enzyme choline acetly transferase

10

What drug blocks packaging of Ach inside of vesicles?

Vesamicol

11

Name one toxin that stimulates Ach release and another that inhibits Ach release.

Stimulates Ach release: Black widow spider toxin (results in spastic paralysis)

 

Inhibits ACh release: Botulinum toxin (results in flaccid paralysis)

12

What causes NE and Ach to be released from their vesicles?

Depolarization resulting in Ca channels opening and Ca influx

13

What inhibits Ach release?

Botulism toxin

14

What enzyme metabolizes Ach?

Acetylcholinesterase

15

What are the two cholinergic receptors?

Nicotinic (ligand-channels)

Muscarinic (GPCR)

16

What are the adernergic receptros?

Alpha and beta

17

What NT is released from the CNS in

a. Somatic innervation to skeletal muscle

b. SNS innervation to organs

c. PNS innervation to organs

Somatic: Ach

SNS: Preganglion - Ach; Postganglion - NE

PNS: Preganglion - Ach; Postganglion - Ach

 

*Postganglion SNS release Ach only when targetting sewat glands

*Preganglion SNS release Ach (as expected) at ganglions or at the adrenal medulla to induce E formation

18

What receptor do each of the following hit?

 

a. Somatic innervation to skeletal muscle

b. SNS innervation to organs

c. PNS innervation to organs

Somatic: NM on skeletal muscle

SNS preganglion: NN at adrenal medulla or ganglion

SNS postganglion: Adrenergic (alpha/beta) at organs

SNS postganglion: M receptors at sweat glands

PNS preganglion: NN at ganglion

PNS postganglion: M receptors at organs

19

What effect does SNS have on the body?

Increase HR

Increase blood flow to skeletal muscles

Dilate bronchi and pupils

Sweat

20

What effect does PNS have on the body?

Decrease HR

Increase GI

Pupil constriction

Poop

21

What inhibits choline uptake into nerve terminals, which otherwise would have gone on to become Ach?

Hemicholinium

22

Muscarinic Receptor

*For each, name the receptor involved and the effect

Heart

  • SA Node
  • AV node
  • Atria
  • Ventricles

 

 

M2 receptor invovled

Heart

  • SA Node: Decrease HR
  • AV node: Decrase conduction
  • Atria: Decrease contractility
  • Ventricles: No effect

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23

Muscarinic Receptor

*For each, name the receptor involved and the effect

Blood vessels

  • Arterioles
  • Skeletal muscle
  • Veins

 

 

M3 receptor invovled

Blood vessels

  • Arterioles: No effect
  • Skeletal muscle: No effect
  • Veins: No effect

*While there is no PNS innervation, endothelium of blood vessels contain M3 receptors which if acted on by NO, cause vasodilation

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24

Muscarinic Receptor

*For each, name the receptor involved and the effect

Lung

  • Bronchiols
  • Glands

 

 

M3 receptor invovled

Lung

  • Bronchiols: Contraction (bronchospasms)
  • Glands: Secretion

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25

Muscarinic Receptor

*For each, name the receptor involved and the effect

GI

  • Motility/tone
  • Sphincters
  • Glands

 

M3 receptor invovled

GI

  • Motility/tone: Increase
  • Sphincters: Relax
  • Glands: Secretion

 

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26

Muscarinic Receptor

*For each, name the receptor involved and the effect

Eye

  • Radial muscle (dilator pupillae)
  • Circular muscle (sphincter pupillae)
  • Ciliary muscle

 

 

M3 receptor invovled

Eye

  • Radial muscle (dilator pupillae): No effect
  • Circular muscle (sphincter pupillae): Contract (miosis)
  • Ciliary muscle: Contract (accomodation near vision)

 

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27

Muscarinic Receptor

*For each, name the receptor involved and the effect

Urinary bladder

  • Detrusor
  • Trigone/sphincter

 

M3 receptor invovled

Urinary bladder

  • Detrusor: Contract
  • Trigone/sphincter: Relax

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28

Muscarinic Receptor

*For each, name the receptor involved and the effect

Glands

  • Salivary
  • Salivation
  • Lacrimation

M3 receptor invovled

Glands

  • Salivary: Secretion
  • Salivation: Secretion
  • Lacrimation: Secretion

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29

Muscarinic Receptor

*For each, name the receptor involved and the effect

Sphincters

M3 receptor invovled

Sphincters

Relaxation except for lower esophageal (contract)

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30

Muscarinic Receptor

*For each, name the receptor involved and the effect

Sex organ

M3 receptor invovled

Sex organ

Erection

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31

PNS acts mainly on M2 and M3 receptors.

Which organs are associated with each?

M2 - Heart

M3 - the rest

32

What are the 3 receptors of the CNS

Major receptors for the CNS

  1. NN receptor
    1. Found in PNS/SNS ganglions as well as on the adrenal medulla
  2. Nm

    1. Found on skeletal muscle motor end plate which are innervated by somatic motor neurons

  3. M1-3

    1. Found on organs that are innervated by the PNS as well as sweat glands which are innervated by SNS

 

 

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33

Where are the SNS and PNS ganglions located?

SNS: Within the paraventral chains adjacent to the 

PNS: Within their target organs 

34

What is the equation for BP and CO?

BP = TPR x CO

CO = HR x SV

35

Explain the body's ANS response to an increase in BP 

 

How might you you stop the baroreceptor reflex at the level of the ganglion and at the level of organ?

An increase in BP will cause the baroreceptors to discharge causing an increase in PNS and a decrease in SNS

*A decrease in BP would have the opposite effect

BP = TPR x CO

CO = TPR x CO

 

Level of the ganglion: Nantagonist

Level of the organ: Muscarinic antagonist

*To inhibit tachycardia reflex, you add a B1 antagonist

36

Explain the body's kidney response to an decrease in BP 

 

A decrease in BP would cause reduced blood flow at the level of the kidney. Reduced renal blood means reduced renal pressure. This causes the release of renin which promotes angiotensin II formation. Angiotensin II causes vasoconstriction (increase TPR) and increases aldosterone levels which acts on the kidney to retain salt and water, increasing blood volume (increase CO). This extra volume increases venous return to the heart

*An increase in BP would cause the opposite

BP = TPR x CO

CO = TPR x CO

 

37

Name 4 muscarinic agonists?

Ach

Bethanechol

Methacholine

Pilocarpine

38

Achetylcholine

1) What receptors does it bind to?

2) Will this be hydrolyzed by AChE?

3) What are its clinical uses?

1. M and N receptors

2. Yes

3. Half life is too short for any clinical uses

39

Bethanechol

 

1) What receptors does it bind to?

2) Will this be hydrolyzed by AChE?

3) What are its clinical uses?

1. M receptors

2. No (thus longer duration of action)

3. Treats ileus (disruption of GI motility - induced either by postop or neurogenic in origin) and urinary retention

 

 

*Urinary retention (inability to empty bladder)

40

Methacholine

1) What receptors does it bind to?

2) Will this be hydrolyzed by AChE?

3) What are its clinical uses?

1. M > N receptors

2. Slightly

3. Used to diagnose bronchial hyperreactivity (methacholine is inhaled to induce bronchoconstriction - by measuring the degree of constriction, you can diagnose bronchial hyperreactivity)

41

Pilocarpine

1) What receptors does it bind to?

2) Will this be hydrolyzed by AChE?

3) What are its clinical uses?

1. M

2. No

3. Treats glaucoma (topical) and xerostomia (dry mouth)

42

Name 7 AChE inhibitors

Edrophonium

Physostigmine

Neostigmine and pyridostigmine

Donepezil and tacrine

Organophosphates

43

What is edrophonium used for?

Used to differentiate myasthenia gravis from cholinergic crisis

 

*Myasthenia gravis is due to auto-Ig blocking Ach from binding to nicotinic receptors. This causes muscle weakness. Edrophonium, an AChE inhibitor, will increase the concentration of Ach and thus reduce the amount of weakness.

*Cholinergic crisis is when there is over-stimulation of the nicotinic receptors due to reduced or inhibition of AChE esterase. By increasing the pool of ACh, edrophonium should increase muscle weakness

44

What is physostigmine used for?

Teritary amine (uncharged) and thus can enter CNS

 

-Treats glaucoma 

-Treats atropine overdose


*Atropine is an Ach receptor antagonist used to dilate pupils (mydriasis) for cosmetic purposes and for urinary hypermotility. **Also results in an inability to focus on near vision and unresponsiveness to light. ***At low doses, atrophine binds to M1 and causes bradycardia. At high doses, it binds to M2 and causes tachycardia

45

What is neostigmine and pyridostigmine used for?

-Quaternary amine (thus no CNS entry)
-Treats ileus, urinary retention, myasthenia, reversal of nondepolarizing Nm blockers (such as muscle relaxants used during operations, e.g. Rocuronium)

46

What is donepezil and tacrine used for?

-Enter CNS

-Treats alzheimer disease

 

*Alzheimer is characterized by neurofibrillary tangles, amyloid plaques, and loss of ACh neurons - thus the use of AChE inhibitors

47

Organophosphates

-CNS entry

-Irreverisble inhibitors

-Treats glaucoma 

 

 

*Commonly used as an insecticide and as a nerve gas

48

What are two irreverisble AChE inhibitors that can treat glaucoma?

Organophosphates

Echothiophate

49

Excessive muscarinic and nicotinic stimulation causes toxicity.

 

What are the effects of muscarinic and nicotonic toxicity levels?

Muscarinic

-Diarrhea

-Urrination

-Miosis

-Bradycardia

-Bronchoconstriction

-Lacrimation

-Salivation

-Sweating

-CNS stimulation

 

Nicotinic

-Skeleta excitation 

-CNS stimulation

 

*Mnemonic - DUMBBELSS (E for excitation - refers to skeletal and CNS stimulation)

 

50

How do you treat muscarinic poisoning?

Atropine

51

How do you regenerate AChE in response to organophosphate poisoning?

Pralidoxime (2-PAM)

52

How does 2-PAM work?

It phosphorylates AChE, causing organophosphate to leave

 

*If you wait too long organophosphate becomes permenately stuck

53

Name 6 muscarinic receptor antagonists?

Atropine

Tropicamide

Ipratropium

Scopolamine

Benztropine

Trihexyphenidyl

54

What is atropine used for?

Atropine CAUSES the following

Decreases secretion (salivary, sweat)

Mydriasis and cyclopegia

Hyperthermia

Tachycardia

Sedation

Urinary retention and constipation

Behavioral exciation and haullucination

55

What is tropicamide used for?

Dilates the eyes

56

What is ipratropium used for?

Asthma and COPD

57

What is scopolamine used for?

Used in motion sickness

Causes sedation and short term memory block

58

What is benztropine and trihexyphenidyl used for?

Parkinsonism

Acute extrapyramidal symptoms induced by antipsychotics

59

Nicotonic receptors are found on ganglion  and skeletal muscles.

 

What drugs can be used to inhibit ganglion NN receptors?

Hexamethonium

Mecamylamine

60

Why aren't ganglionic blocking agents used today?

Very toxic

61

Even though both PNS and SNS synpase at Nn only the dominant ANS will be inhibited, allowing the other uneffected. In which systems does the SNS and the PNS dominant?

SNS dominates in vascular tone and sweat glands

PNS dominates in everything else

 

Thus, a block of the heart's NN means PNS is inhibited, resulting in tachycardia

Similarly, a block of a vessel's NN means SNS is inhibited, resulting in vasodilation

62

What are the four main adrenergic receptors?

a1, a2, B1, and B2

63

Where are alpha 1 receptors located and what effect does SNS have on them?

Eye - radial muscle (contraction - mydriasis)

Arterioles (contraction - increase in TPR, diasoltic pres)

Veins (contraction - increase in venous return)

Bladder (contraction - urinary retention)

Penis (ejaculation)

Liver (increase glycogenolysis)

Kidney (decrease renin release)

64

Where are alpha 2 receptors located and what effect does SNS have on them?

Nerve terminals - Decrease NE synthesis

Platelets - Aggregation

Pancreas - Decrease insulin secretion

65

Where are beta 1 receptors located and what effect does SNS have on them?

Heart:

  • SA node (increase HR)
  • AV node (increase conduction velocity)
  • A/V muscles (increase contraction)

Kidney: Increase renin release

66

Where are beta 2 receptors located and what effect does SNS have on them?

Blood vessels (vasodilation - decrease TPR, dias press)

Uterus - Relaxation

Bronchioles - Dilation

Skeletal muscle - Increase glycogenolysis

Liver - Increase glycogenolysis

Pancreas - Increase insulin secretion

67

Where are dopamine 1 receptors located and what effect does dopamine have on them?

Kidney - Vasoilation (increase in RBF, GFT, Na secretion)

68

To what receptors does dopamine bind?

D1 at low doses

B1 at medium doses

Alpha1 at high doses

69

Some drugs exert both alpha and beta effect. Explain when one domaints over the other

At lower doses, drugs tend to effect more beta response while at higher doses, drugs tend to cause more alpha response

70

Name two alpha1 agonists and their effects

Alpha1 agonists 

  • Increase TPR
  • Increase BP
  • Potential reflex bradycardia
  • NO change in pulse pressure (sys pres - dia pres)

 

Alpha 1 receptors cause vasoconstriction resulting in increase TPR and thus BP

-Phenlyephrine: Treats nasal decongestant and causes mydriasis

-Methoxamine: Treats paroxysmal atrial tachycardia

71

Name two alpha2 agonists and their effects

Alpha2 agonist binding causes decreased sympathetic output by decreasing NE synthesis

 

Clonidine - Mild to moderate HTN

Methyldopa - Mild to moderate HTN

72

Name 6 Beta agonists and their effect

B1 cause increase HR, SV, CO, and PP

B2 cause decrease TPR and BP

 

Isoproterenol (B1=B2) used for bronchospasm, heart block, and baryarrhythmias

Dobutamine (B1>B2) used for CHF

Salmeterol, alubterol, and terbutaline (B2) for asthma

Ritodrine (B2) for premature labor

 

 

73

NE and E are mixed agaonsits. Which receptors do they bind to and what effect do they have?

NE binds to a1,a2,B1 

A1: Increase TPR, BP

B1: Increase Hr, SV, Co, PP

 

E binds to all adrenergic receptors

Low dose

  • B1: Increase HR, SV, CO, PP
  • B2: Decrese TPR, BP

Medium dose

  • B1: Increase HR, SV, CC, PP
  • B2: Decrease TPR, BP
  • A1: Increase TPR, BP

High dose

  • A1: Increase TPR, BP

  • Potential reflex bradycardia

74

What are NE and E used for?

Cardiac arrest

Adjunct to local anesthetic

Hypotension

 

E is also used for asthma and anaplhyaxis

75

What is tyramine

Found in red wine and cheese

Can cause hypertensive crisis by stimulating the release of NE from its vesicles 

 

*Tyramine is inhibited by MAO-A and therefore its concentration is greatly limited when taken orally

76

What is amphetamine

Used to treat narcolepsy and ADHD

77

What is epherdrine?

Used for cold medication

78

What are three drugs that act as indirect adrengeric receptor agonists? (In other words, they stimulate the release of NE into the synpatic cleft)

 

What two drugs inhibit NE release into the synaptic cleft?

Stimulate release

Tyramine (stimulates NE release)

Amphetamine (stimualtes DA, NE, 5HT release)

Ephedrine

Inhibit release

  • Bretylium
  • Guanethidine

79

Where is MAO A and B found?

MAO A - Liver but also anywhere (metabolizes NE, 5HT, and tyramine)

MAO B - Brain (metabolizes D)

80

What do alpha receptor antagonists do and what are some examples?

They decrease TPR and BP and are thus used to treat HTN, pheocromocytoma (eye tumor due to excess NE release), and BPH

Nonselective blocks

  • Phentoalmine
  • Phenoxybenzamine

A1 blockers

  • Prazosin, doxazosin, terazosin, tamsulosin

A2 blockers

  • Yohimbine (orthostatic hTN and impotence)
  • Mirtazipine (antidepressant)

 

81

What do beta receptor antagonists do and give some examples

B1 antagonists: Decrease HR, SV, CO, renin, aqu humor

B2 antagonist: Vasoconstriction of blood vessels and bronchiols, decrease glycogenolysis

Acebutolol

Atenolol

Metoprolol

Pindolol

Propranolol

Timolol

 

82

What is the difference between open-angle and closed-angle glaucoma?

Open - Decreased reabsorption of aqueous humor from the posterior chamber out between the lens/iris muscle and into the Canal of Schlemm

Closed - Blockage of canal - EMERGENCY

 

*Use beta blockers to decrease aq. secretion and use muscarinic activators to imrpove drainage through canal

-Pilocarpine and echthiophate: Activate M receptors to cause ciliary muscle contraction which increases flow through canal of Schlemm; echthiophate is an organophoshpate (AChE inhibition will increase outflow)

-Timolol: Beta blocker taht will block NE and thus decrease aqueous humor formation

83

What are three examples of zero-ordered drugs?

PEA looks like a zero

 

Phenytoin

Ethanol

Aspirin

84

How would you treat aspirin and amphetamine toxicity?

Aspirin is a weak acid and thus you would need to give sodium bicarbonate to promote acid elimination

 

Amphetamine is a weak base and thus you would nee to give ammonium chloride to promte basic elimination

85

What are the enzymes involved in breaking down ethanol into acetate? What drugs can inhibit this?

Ethanol to acetylaldehyde via alcohol dehydrogenase; inhibited by fomepizole

 

Acetylaldehyde to acete via acetylaldehye dehydrogenase; inhibited by disulfiram

 

*Disulfirm allows for the accumulation of acetylaldehye dehydrogenase which leaves the person with hang-over effects 

86

Besides ethanol, what else can fomepizole metabolize?

Methanol (otherwise would be broken down by alcohol dehydrogenase into formaldehyde which is very toxic and can cause blindness or keto acidosis)