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Neorologia > Adrenergic > Flashcards

Adrenergic Flashcards

1
Q

NE synthesis rate limiting step

A

Tyrosine to DOPA via Tyrosine Hydroxylase

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2
Q

VMAT

A

Vesicular Monoamine Transporter:

Transports dopamine into vesicle

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3
Q

Which receptor type is primarily associated with autoreceptor feedback

A

Alpha2 adnrenergic

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4
Q

Autoregulation process

A

Alpha2 coupled to Gi gprotein, decreases cGMP, decreases calcium, decreased vesicular release

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5
Q

L-DOPA to Dopamine

A

Dopa decarboxylase

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6
Q

Dopamine to Noradtrenaline

A

Dopamine beta hydroxylase (DBH)

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7
Q

Noradrenaline to Adrenaline

A

Phenylethanolamine-N-methyltransferase (PNMT)

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8
Q

NE to Epi

A
  1. Some NE diffuses out of vesicle,
  2. is methylated by PHMT to Epi
  3. Epi diffuses back into vessicle
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9
Q

Why can’t pt on MAOI have smoked meat, wine, and fermented cheese?

A

Contains tyramine; A MAO-A inhibitor

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10
Q

Which MAO is more selective and what for?

A

MAO-B ; Dopamine

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11
Q

Reserpine (Serpasil)

MAO and Use

A

Blocks VMAT-2
Previously; CNS-dystonias
previously; anti-hypertensive

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12
Q

Carbidopa (Lodosyn)
MOA
Use
Distribution

A
  • Inhibits Dopa Decarboxylase
  • Adjunctive PD treatment
  • Prevents peripheral conversion of L-Dopa to dopamine
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13
Q

Alpha1
Type
Location
Response

A

Gq
Vascular Smooth Muscle
Glandular Smooth Muscle
Contraction

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14
Q

Alpha2
Type
Location
Response

A

Gi

  • Presynaptic Nerve Terminals
  • Decrease NE release
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15
Q

Beta1
Type
Location
Response

A
  • Gs
  • Cardiac Muscle
  • Increase HR and FOC
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16
Q

Beta 2
Type
Location
Response

A

-Gs
-Vascular Smooth Muscle - Relaxation
Bronchiole Smooth Muscle - Relaxation
Skeletal Muscle - Glycogenolysis
Liver -Glycogenolysis and Gluconeogenesis

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17
Q

Beta 3
Type
Location
Response

A

Gs
Adipose - lipolysis
Bladder SM - Relaxation

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18
Q

Atomoxetine (Strattera)

MOA

A

Selective NERI;

Indirect Agonism

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19
Q

Methylphenidate (Ritalin)

MAO

A

NET, DAT inhibitor;
Indirect Agonism;
Stimulant

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20
Q

COMT

A

Catecol-o-methyltranferase

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21
Q

MAO-A inhibitors consideration,

On-target ADR

A

MAO-A found in gut, dietary restriction may be necessary

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22
Q

Mechanisms to increase presynaptic release of NE and DA

A
  1. Alter VMAT function (direction)
  2. Displace NE from vessicles
  3. Reverse ditrection of NET/DAT
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23
Q

Pseudoephedrine MOA

A

Indirect Agonist + Direct Agonist

a) Displaces vesicles, increases NE/DA presynaptic release in CNS and PNS
b) Direct agonism on both A and B adrenergic receptors

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24
Q

Ephedrine t1/2 compared to NE

A

10X longer, not a substrate for MAO or COMT

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25
Q 
Ephedrine Actions
A1
B1
B2
B2/3
A

A1 - Vasoconstriction, increased TPR, decreased pulmonary secretions
+B1 - Increased FOC
+B2 - Bronchiole SM relaxation
+B2/3 - Thermogenesis

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26
Q

Phentermine (Fastin; Qsymia phentermine/topiramate)

MOA

A

Increase presynaptic release of NE and DA

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27
Q

Phenteramine ADR

A

Increased BP, Tachycardia, heart palpitations, HA, insomnia. Any surprises here?

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28
Q

Amphetamine (Dexedrine, Adderol)

MOA

A

Increases presynaptic release of NE and DA by Reversing direction of DAT
-Also weak inhibitor of MAO

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29
Q

Amphetamine therapeutic use

A

ADHD, Narcolepsy, short term appetite suppression

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30
Q

Methamphetamine (Desoxyn)
MOA
Meth significance
FDA approved indication

A

MOA similar to amphetamine,

  • Methyl group extends half life
  • Narcolepsy
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31
Q

Modafinil (Provigil)

MOA

A

Similar to amphetamines, more selective for DA (+) Neurons in Wakefullness areas of hypothalamus

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32
Q

Modafinil approved uses

A
  • Shift-work disorder

- Off label: excessive fatigue, anti depressant, adhd, bipolar, militarty

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33
Q

Modafinil ADRs

A

Rash

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34
Q

Modafinil selling point over methamphetamine

A

Equivalent wakefulness, no hyperactivity

35
Q

Phenylephrine

MOA

A

Selective Alpha-1 Agonist

36
Q

Phenylephrine Use and PK

A

Not as potent as NE
Longer t1/2
Nasal decongestant

37
Q

Phenylephrine 10% opthalmic solution

A

Mydriatic

38
Q

Extended use of phenylephrine

A

rhinitis medicomentosa, “afrin addiction”

39
Q

Other Alpha-1 agonist uses

A
  • Orthostatic Hypotention
  • Surgical bleeding control
  • Allergic reaction: decrease secretion of mediators (histamine)
  • STRESS INCONTINENCE
40
Q

Clonidine (Catapres)

MOA

A

Selective Alpha-2 agonist

Reduces sympathetic outflow @CNS (Locus Ceruleus) and locally

41
Q

Clonidine most common use

A

HTN secondary to increased SNS outflow

42
Q

Alpha-2 agonist common use

A

HTN secondary to increased SNS outflow

Indirect skeletal muscle relaxant (CNS level)

43
Q

Alpha - 2 (Clonidine) agonist ADRs

A
  • Anticholinergic - like
  • sedation,
  • hypotension
44
Q

Selective Alpha -1 ANTagonist Drugs

A

Doxazosin (Cardura)
Terazosin
Tamsulosin (Flomax)

45
Q

Doxazosin Selectivity

A

1000x higher for Alpha - 1 verses Alpha - 2

Non-selective among blocking A1a, A1b, A1c

46
Q

Alpha blockers and HTN

A

Decrease TPR by blockade of A1b and A1c on VSM

47
Q

Tamsulosin (Flowmax)

A

Selective for A1a receptors

-Located in the trigone muscle –> relaxation of internal urinary sphincter

48
Q

Rx for Pt with HTN and BPH

A

Use non-selective Alpha blocker such as Doxazosin or Terazosin

49
Q

Rx for pt w/ Orthostatic Hypotension and BPH

A

Use Tamsulosin (Flowmax) to avoid dangerously low hypotension

50
Q

What happened with 5alpha reductase inhibitors and BPH

A

Turned off effects of testosterone, caused ED. ED still an issue after therapy d/c

51
Q

Alpha1 blocker ADRs

A
  • Orthostatic hypotension
  • Nocturia
  • Runny nose
52
Q

A1a and eye surgery

A

Intra-operative floppy iris syndrome

Tamsulosin only –>A1a

53
Q

Selective Alpha -2 antagonists

Eg, Yohimbine

A

Increase sympathetic outflow through a central mechanism

54
Q

Selective Beta -2 Agonists
Use
Overuse

A

SYMPTOMATIC treatment of asthma and COPD

Over use - status asthmaticus
–>pharmacodynamic tolerance by down regulation of Beta2

55
Q

Eg, Beta2 Agonists:

A

Albuterol (Proventil, Ventolin)

56
Q

Metaproterenol (Alupent) Concerns

A

Has some Beta1 affinity –> Cardio ADRs –> Avoid in pt at risk for MI

57
Q

Why not use Long Acting Beta Agonists alone?

A

Only treats symptoms. Doesn’t address underlying cause of inflammation

58
Q

LABA use

A

12 h half life,
Good for pt w/ problems at night or when exercising

NOT for acute attacks

59
Q

Mirabegron (Myrbetriq)

MOA

A

Selective Beta-3 Agonist

60
Q

Mirabegron effect

A

Relaxes Detrusor muscle;

61
Q

Mirabegron Metabolism

A

CYP3A4 and CYP2D6

62
Q

Mirabegron ADRs

A

Increased HR and BP

63
Q

Mirabegron is 2-3x more expensive than Muscarinic antagonists. Why use Mirabegron?

A

Preferred for use in pt with comorbid dementia or on cusp of dementia
Muscarinic antagonist inhibit congative function

64
Q

Pt with stage fright. How to choose a Beta blocker

A

Choose one that does not cross the BBB.

65
Q

Beta antagonist therapeutic uses

A
  • Hypertension
  • Angina
  • Cardiac Arrhythmias
  • Ischemic Heart diseases
  • Hyperthyroidism
  • Prophylaxis for migraine
  • Acute panic attack
66
Q

Beta antagonist Cardio Actions

A

Reduced HG, FOC, BP

Slowed Conduction at AV

67
Q

Beta Antagonist ADRs

A
  • Bradycardia
  • Increased bronchoconstriction
  • Cold extremities
  • Hypoglycemia
  • Weight Gain
  • Fatigue, insomnia, depression, nightmares, fever
68
Q

Beta Blocker Rebound Hypersensitivity

A
  • HTN
  • Angina
  • MI
  • Fatal Arrhythmias
69
Q

ISA beta blockers and rebound hypersensitivity

A

Less common. Partial agonist does not cause upregulation in receptor density

70
Q

Carvediol (Coreg)

A

A competative antagonist of alpha1 and beta2 receptors

ISA and partial agonist to Beta1

  • Vasodiation
  • Contraindicated in asthmatitics
71
Q

Selective Beta1 ANTagonist

Eg

A

Metoprolol (Lopressor)

72
Q

Metoprolol Fun Facts

A

No ISA
Extensive first pass metabolism
BEST CHOICE FOR ASTHMATICS

But watch out for rebound hypersensitivity

73
Q

Onobotulinum Toxin Type A (Botox)

A

Cleaves SNAP-25

Indirect nicotinic and muscarinic receptor antagonist

74
Q

Rimabotulinum Toxin Type B (Myobloc)

A

Cleaves VAMP/Synaptobrevin (vesicular associated protein)

Indirectly cause relaxation of skeletal and smooth muscle

Treatments repeated every 2-3 months

75
Q

Muscarinic Agonists:

Common uses

A

+Non-obstructive gastrointestinal disorders with immobility
+Non-obstructive urinary bladder disorders with immobility
+Xerostomia
+Miosis: iris constriction

76
Q

Atropine and Mycetism

A

In Mushroom poinsoning use Non-selective, competitive mAChr antagonist (Atropine)

77
Q

mACh Agonist contraindications

A 
\+PUD
\+Asthma
\+Recovering from MI
\+BPH
\+PD
78
Q

mACh ANTagonists:

Common Uses

A

GI antispasmotic - relaxes GI and decreases secretions
+IBS
+PUD
+Overactive Bladder/Nocturnal enuresis
+Sinus Bradycardia (IV atropine following MI
+Opthamoology - Mydriasis

79
Q

Additional mAChR Antagonist uses

A

+Adjunctive therapy in PD
+Asthma: Decreased secretions and slight bronchodilation. Ajunct to Beta2 agonists
+Surgery: decrease secretions

80
Q

Bethanachol (Urecholine)

MOA

A

M3 mACh agonist with poor GI absorption –> Slows GI motility and Decreased secretions

81
Q

Bethanachol uses:

A

GI/Bladder emptying disorder in Spinal chord injury patients

*Doesn’t cross BBB FYI

82
Q

Propranolol MOA

A

Non-selective beta-blocker

Competitive Antagonist (No ISA)

83
Q

Propranolol use

A

Anti-hypertensive, anti-arrythmic

Neorologia (12 decks)

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