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Sympathomimetics Flashcards

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1
Q

List the G-protein/effector/2nd messengers for alpha 1 receptors:

A
  • G-protein: Gq (stimulatory)
  • effector: Phospholipase C
  • 2nd messengers: IP3, DAG, Ca2+
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2
Q

List the G-protein/effector/2nd messengers for alpha 2 receptors:

A
  • G-protein: Gi (inhibitory)
  • effector: adenylate cyclase
  • 2nd messenger: cAMP
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3
Q

List the G-protein/effector/2nd messengers for beta 1 receptors:

A
  • G-protein: Gs (stimulatory)
  • effector: adenylate cyclase
  • 2nd messenger: cAMP
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4
Q

List the G-protein/effector/2nd messengers for beta 2 receptors:

A
  • G-protein: Gs (stimulatory)
  • effector: adenylate cyclase
  • 2nd messenger: cAMP
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5
Q

List the 5 2nd messengers involved in adrenergic G-protein coupled receptors:

A
  • cAMP
  • cGMP
  • IP3
  • Ca2+
  • DAG
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6
Q

Stimulation of alpha 1 receptors results in what effect on Ca2+?

A

increased Phospholipase C –> increased Ca2+

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7
Q

Simulation of alpha 2 receptors results in what?

A

inhibition of adenylate cyclase –> decreased cAMP

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8
Q

Stimulation of beta 1 receptors results in what?

A

stimulation of adenylate cyclase –> increased cAMP

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9
Q

Stimulation of beta 2 receptors results in what?

A

stimulation of adenylate cyclase –> increased cAMP

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10
Q

Beta 2 receptors are primarily found in the (heart/lungs) and have a (higher/lower/equal) affinity for Epi.

A
  • lungs
  • higher
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11
Q

Beta 1 receptors are primary found in the (heart/lungs) and have a (higher/lower/equal) affinity for Epi.

A
  • heart
  • equal
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12
Q

Stimulation of dopamine 1 receptors has what effect?

A
  • stimulation of adenylate cyclase in neurons and vascular smooth muscle
  • increased cAMP
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13
Q

Stimulation of dopamine 2 receptors results in what?

A
  • inhibition of adenylate cyclase
  • open K+ channels
  • decreased Ca2+ influx
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14
Q

Which dopamine receptors are centrally located?

A

dopamine 2

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15
Q

Where are the catecholamines synthesized?

A

Dopamine: CNS neurons
Epinephrine: 2nd order neurons of SNS in the adrenal medulla
Norepi: 2nd order neurons of the SNS, adrenal medulla, CNS neurons

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16
Q

Define “sympathomimetic”

A

a drug that mimics the effect of Epi and Norepi

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17
Q

How are sympathomimetics grouped?

A

by mode of action and spectrum of affected receptors

  • direct mode: directly interacts with and activates receptor
  • indirect mode: 1) displace catecholamines from adrenergic nerve ending OR 2) inhibition of reuptake of catecholamines
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18
Q

List the tissues where apha-1 receptors are located;

A

bladder sphincter
liver
pupil dilator muscle
uterus
vascular smooth muscle

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19
Q

List the tissues where alpha-2 receptors are located:

A

platelets
post-ganglionic sympathetic neurons
vascular smooth muscle

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20
Q

List the tissues where beta-1 receptors are located:

A

heart
pancreas

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21
Q

List the tissues where beta-2 receptors are located:

A

bladder wall
liver
vascular smooth muscle
uterus

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22
Q

List the tissues where beta-3 receptors are located:

A

adipose tissue

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23
Q

List the alpha-1 agonists:

A
  • Epi
  • Norepi
  • Phenylephrine
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24
Q

List the alpha-1 antagonists:

A
  • Phentolamine
  • Phenoxybenzamine
  • Prazosin
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25
List the alpha-2 agonists:
Clonidine Dexmedetomidine
26
List the alpha-2 antagonists:
Yohimbine
27
List the beta-1 agonists:
- Dobutamine - Dopamine - Epi - Norepi
28
List the beta-2 antagonists:
Atenolol Metoprolol
29
List the beta-2 agonists:
Albuterol Terbutaline
30
List the beta-2 antagonists:
Propranolol
31
Receptor selectivity of phenylephrine:
A1 > A2 >>>>>> B
32
Receptor selectivity of clonidine:
A2 > A1 >>>>> B
33
Receptor selectivity of norepi:
A1 = A2 B1 >> B2
34
Receptor selectivity of epinephrine:
A1 = A2 B1 = B2
35
Receptor selectivity of dobutamine:
B1 > B2 >>>>>> A
36
Receptor selectivity of isoproterenol:
B1 = B2 >>>>> A
37
Receptor selectivity of albuterol/terbutaline:
B2 >> B1 >>>>> A
38
Receptor selectivity of dopamine:
D1 = D2 >>>> B >> A
39
What is the parent drug from which sympathomimetic drugs are derived?
Phenylethylamine
40
2 effects sympathomimetics can have on the metabolism:
1) enhance glycogenolysis in the liver 2) metabolic acidosis (high presence)
41
Sympathomimetic effects on blood vessels:
A: increase arterial resistance B: increase smooth muscle relaxation
42
Sympathomimetic effects on blood pressure:
pure A: increase peripheral arterial resistance, decrease venous capacitance (increase BP, decrease HR d/t baroreceptor increase vagal tone) pure B: increase CO, decrease PVR (increased/decreased SBP with decreased DBP) mixed: skeletal muscle bed relaxation (decreased DBP) + alpha constriction of arterial beds
43
Sympathomimetic effects on heart:
B1: increase chronotropy, increase conduction velocity through AV node, increase contractility
44
Sympathomimetic effects on respiratory tract:
B2: bronchodilation
45
Sympathomimetic effects on eye:
A: mydriasis
46
Sympathomimetic effects on GI tract:
A & B: relaxation
47
Sympathomimetic effects on GU tract:
A & B: uterus A: urinary continence (bladder base and urethral sphincter)
48
Describe the order of events of formation of Epinephrine:
Tyrosine Dihydroxyphenylalanine Dopamine Norepi Epi
49
Tyrosine --> DOPA is catalyzed by...
tyrosine hydroxylase
50
DOPA --> Dopamine is catalyzed by...
DOPA decarboxylase
51
Dopamine --> Norepi is catalyzed by...
dopamine-B-hydroxylase
52
Norepi --> Epi is catalyzed by...
phenylethanolamine-N-methyltransferase
53
What is the rate limiting step of catecholamine synthesis?
formation of DOPA from tyrosine by tyrosine hydroxylase
54
The rate limiting step of catecholamine synthesis is regulated by what mechanism?
Norepinephrine negative feedback loop
55
In what 3 ways are catecholamines removed from the site of action?
1) reuptake into the presynaptic nerve (80%) 2) reuptake by extraneuronal tissues (contain the MAO and COMT) 3) diffuse away from synaptic cleft (enters circulation and metabolized in kidney and livery by COMT and MAO)
56
What is COMT short for?
catechol-O-methyltransferase
57
Describe the effects of Epinephrine:
- positive inotropic and chronotropic actions on heart - vasoconstriction - decreased total peripheral resistance (--> DBP) in skeletal muscle beds
58
Dose/onset/duration of Epi:
- dose: 10-100mcg bolus; 0.01-0.2 mcg/kg/min - onset: 30-60 sec - duration: 5-10 min
59
Describe the effects of Norepi:
- vasoconstriction - increased SBP, DBP, coronary blood flor - ? decreased HR - decreased blood flow to major organs
60
Dose/onset/duration of Norepi:
- dose: 0.04-0.4 mcg/kg/min - onset: <1 min - duration: 2-10 min
61
Describe the effects of dopamine:
D1: vasodilation, increased renal/mesenteric/coronary/cerebral BF D2: inhibits Norepi release B1: increase myocardial contractility/SV/CO, inotropic A: vasoconstriction
62
Describe the effects of Isoproterenol:
- pure B1 & B2 agonist - positive chronotropic and inotropic effects - increased rate of cardiac pacemaker discharge - potent vasodilator (decreased SVR & pulm VR) - increase CO, decrease DBP, slight increase SBP - potent relaxation of bronchial smooth muscle
63
Which sympathomimetic is used in inhaler form in the cath lab?
Isoproterenol
64
Describe the effects of Dobutamine:
- selective B1 agonist - increased myocardial rate and force of contraction - facilitates AV conduction
65
"Sympathectomy" is another name for what?
spinal anesthesia
66
Why might a patient get nauseated after receiving a spinal?
increased vagal activity after sympathectomy causes increased peristalsis of the GI tract (treat the BP w/ Ephedrine and the nausea should improve)
67
What is the MOA of Phenylephrine?
- pure A agonist - acts directly on the receptors
68
Describe the effects of Phenylephrine:
- intense peripheral vasoconstriction - increased SBP, DBP - reflex bradycardia - decongestant
69
What is the MOA of Ephedrine?
- both A and B stimulation - mixed direct and indirect actions - prevents breakdown of NE by MAO --> increased release of stored NE
70
Describe the effects of Ephedrine:
- increased CO, BP, HR
71
Why should Ephedrine be used cautiously in patients on MAOIs?
MAOIs sensitize the patient to indirectly acting sympathomimetics --> hypertensive emergency
72
Where does Vasopressin act on the body?
direct action on vascular smooth muscle
73
What are some precautions to using vasopressin?
- reduction in CO, myocardial contractility, and coronary BF
74
Describe albuterol's MOA:
- short-acting B2 agonist - inhaled - used for rapid relief of wheezing, bronchospasm, and airflow obstruction
75
Describe Salmeterol/Formoterol's MOA:
- long-acting B2 agonist - always used in combination therapy
76
What are 2 side effects of inhaled B2 agonists?
- tremors - tachycardia
77
What drug is a quick treatment for hyperkalemia?
inhaled Albuterol
78
Describe the MOA and uses of Terbutaline:
- B2 agonist - tocolytic
79
What is the MOA of selective phosphodiesterase inhibitors?
- decrease hydrolysis of cAMP - augmentation of myocardial performance independent of the SNS
80
Describe the effects of selective phosphodiesterase inhibitors:
- positive inotropic effects - vascular and smooth muscle relaxation
81
What patients would benefit from selective phosphodiesterase inhibitor therapy?
acute cardiac failure needing increased myocardial contractility and vasodilation
82
What drug class does Milrinone belong to? What is this drug used for?
- selective phosphodiesterase inhibitor - has minimal effect on HR and myocardial O2 consumption - beneficial for LV dysfunction after cardiac sx
83
Ionized calcium is a potent (chronotrope/inotrope).
inotrope
84
What does the drug Levosimenden do?
- increases contractility by increasing the sensitivity of the myocardium to Ca2+ - increases CO - decreases SVR and pulm VR

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