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Flashcards in Adrenergics Deck (152):
1

Direct acting adrenergic agonists:endogenous catecholamines (and D1 agonist) Drugs

Epinephrine
Norepinephrine
Dopamine
Fenoldopam

2

Epinephrine receptors

Alpha and beta2
Low dose: beta effects (vasodilation)
High dose: alpha effects (vasoconstriction)

3

Epinephrine effect

**High dose-> potent vasopressor** : increases BP (systolic > diastolic) -> +ve chronotropic and inotropic effects (beta 1) and vasoconstriction (alpha 1) -> increases CO (and O2 demand from heart)

Bronchodilation (beta 2)
Relaxed GI smooth muscle with contracted sphincters
Relaxed detrusor (beta 2) and contracted sphincter (alpha 1)
Prostatic smooth mm. contraction

Metabolic: hyperglycemia due to increased glycogenolysis and glucagon release (beta 2); net inhibition of insulin secretion (alpha 2 inhibits while beta 2 enhances secretion)
Increased lipolysis through beta 3 activation (increased cAMP and HSL)

**DOC for pts in anaphylactic shock**; cardiac arrest, asthma attacks combined with local anesthetics to increase duration; glaucoma (decreased production of aqueous humor)

4

Epinephrine PK

Rapid onset
Brief duration

Administered through IV in emergencies

Other routes include SC, ET tube, inhalation, topically in the eye

Do not give orally due to inactivation by intestinal enzymes

5

Epinephrine Adverse

CNS disturbances: Restlessness, fear, apprehension, headache, tremor (may be secondary to effects outside of CNS)

ICH due to increased BP

Cardiac arrhythmias-especially in patients on digitalis

Pulmonary edema

6

Epinephrine "other"

Synthesized from tyrosine in the adrenal medulla

Polar molecule: does not enter CNS in therapeutic doses

Metabolized by COMT and MAO -> VMA and metanephrine

Hyperthyroid may enhance CV actions likely due to upregulation of receptors

Cocaine prevents reuptake

Beta blockers cause predominate alpha effects such as increased TPR and BP

7

Norepinephrine receptor

alpha and beta 1 >beta 2

8

Norepinephrine effect

Vasoconstriction (alpha 1) -> increased PVR -> increased SBP/DBP and MAP
Bradycardia due to decreased sympathetic outflow following the baroreceptor response (indirect effect through M2)
Induces hyperglycemia (less potent than epi)
Limited therapy value: *can treat shock*, but dopamine is better due to preservation of renal blood flow

9

Norepinephrine adverse

NE may cause kidney shutdown

10

Norepinephrine Other

Baroreceptor reflex coutneracts local action which can be blocked by pretreatment with *atropine* -> reveals direct effect of tachycardia

11

Dopamine receptor

D, alpha, beta

12

Dopamine effect

Central regulator of movement

CVS: low doses vasodilate (D1 receptors, cAMP) especially at renal, mesenteric and coronary
**DOC for cardiogenic and hypovolemic shock** : increase GFR, renal blood flow and sodium excretion -> preservation of renal function

Inotropic effect at intermediate concentration (beta 1) and increasing release of NE

Increase in systolic BP

High concentration -> alpha 1 mediated vasoconstriction

13

Dopamine PK

Ineffective orally (metabolism by MAO and COMT)

14

Dopamine adverse

Overdose-> sympathomimetic symptoms

Can cause nausea, HTN, arrhythmia but is short lived due to rapid metabolism to HVA

15

Dopamine other

Dopamine does not cross BBB

16

Fenoldopam receptor

D1

17

Fenoldopam effect

Peripheral vasodilation -> used in short term management of inpatient HTN

18

Fenoldopam PK

give continuously via IV, not bolus

19

Direct acting adrenergic beta agonists

Isoproterenol
Dobutamine
Terbutaline
Alburterol
Salmeterol
Formoterol

20

Isoproterenol receptor

Beta 1 and 2

21

Isoproterenol effect

CVS: increase CO through rate and force of contraction (AV block or C arrest)

Major Decrease in TPR through vasodilation (beta 2) because there is no alpha 1 opposing it
Slight increase in SBP, decrease in MAP and DBP, tachycardia

Bronchodilation and GI smooth muscle relaxation mediated by beta 2
Use **stimulate heart in emergency**

22

Isoproterenol PK

most reliable when given parenterally or inhaled

23

Isoproterenol adverse

similar adverse effects compared to epi:
CNS disturbances: Restlessness, fear, apprehension, headache, tremor (may be secondary to effects outside of CNS)

ICH due to increased BP

Cardiac arrhythmias-especially in patients on digitalis

Pulmonary edema

24

Dobutamine receptor

beta 1

25

Dobutamine effect

**Acute management of congestive heart failure**: increases contractility
Increases CO with little change in heart rate -> O2 demands of the myocardium are not significantly affected gives it an advantage over other sympathomimetics

26

Dobutamine PK

can build up tolerance with long term use

27

Dobutamine other

Racemic mixture: -ve alpha one and beat beta one agonist; +ve alpha 1 antagonist and potent beta 1 agonist
Net effect: selective Beta 1

28

Terbutaline receptor

Beta 2

29

Terbutaline effect

Bronchodilator
Emergency treatment of **status asthmaticus**
Reduces uterine contraction in premature labor

30

Terbutaline PK

Resorcinol ring -> not metabolized by COMT giving it a longer duration
Oral, Inhalation or SC

31

Terbutaline other

Selectivity is lost at high concentrations
Used in treatment of asthma without having effects on heart

32

Albuterol other

Selectivity is lost at high concentrations
Used in treatment of asthma without having effects on heart

33

Salmeterol and Formoterol other

Selectivity is lost at high concentrations
Used in treatment of asthma without having effects on heart

34

Albuterol Receptor

Beta 2

35

Salmeterol and Formoterol receptor

Beta 2

36

Albuterol effect

Inhalant bronchodilator; relief of symptoms in asthma

37

Salmeterol and Formoterol effect

Bronchodilator
Long acting-> not used for prompt relief of bronchospasm

38

Salmeterol and Formoterol PK

Slow onset, but prolonged action (12 hrs) after inhalation

39

Direct acting alpha agonist drugs

Phenylephrine
Clonidine
Methyldopa
Brimonidine

40

Phenylephrine receptor

alpha 1

41

Phenylephrine mechanism

Peripheral vasoconstriction

42

Phenylephrine effects

Vasoconstrictor: increase SBP and DBP
Nasal decongestant
Mydriasis
Tx of supraventricular tachycardia

43

Phenylephrine Other

NO direct effect on heart, but does cause reflex bradycardia after parenteral administration

44

Clonidine receptor

Alpha 2

45

Clonidine Mechanism

Partial agonist** : activation of *central alpha 2 receptors* suppresses sympathetic outflow

46

Clonidine effect

Antihypertensive

47

Clonidine PK

Acute rise in BP due to transient vasoconstriction when given IV, but not orally

48

Clonidine adverse

Centrally acting antiadrenergic drugs: sedation, mental lassitude, impaired concentration

49

Methyldopa adverse

Centrally acting antiadrenergic drugs: sedation, mental lassitude, impaired concentration

50

Methyldopa receptor

alpha 2

51

Methyldopa mechanism

Central acting anti HTN

52

Methyldopa effect

Metabolized to alpharmethylnorepinephrine which causes effects similar to clonidine: decrease TPR and BP
*DOC in pregnant patients with HTN*

53

Methyldopa adverse

Can cause +ve Coombs test or hemolytic anemia or hepatitis

54

Brimonidine receptor

alpha 2

55

Brimonidine mechanism

Decrease aqueous humor production along with increased outflow

56

Brimonidine effect

Decrease intraocular pressure in glaucoma

57

Indirect acting Adrenergic agonist drugs

Amphetamine
Methylphenidate
Tyramine

58

Amphetamine mechanism

Displaces catecholamines from storage vesicle
Weak inhibitor of MAO
Blocks catecholamine reuptake

59

Amphetamine Effect

Increase BP through alpha 1 and Beta effects
Central stimulatory action: alertness, decrease fatigue and appetite, insomnia
Tx of depression, narcolepsy, and appetite suppression (in the past)

60

Amphetamine adverse

Fatigue and depression follow stimulation

61

Amphetamine other

releasing agents potentiate actions of endogenous NE by causing release from presynaptic vesicles

62

Methyphenidate other

releasing agents potentiate actions of endogenous NE by causing release from presynaptic vesicles

63

Tyramine other

releasing agents potentiate actions of endogenous NE by causing release from presynaptic vesicles

64

Methyphenidate Mechanism

Structural analog of amphetamine

65

Methyphenidate indication

Tx of ADHD in children

66

Tyramine Indication

Not clinically useful, found in fermented foods (cheese and wine)

67

Tyramine PK

Byproduct of tyrosine metabolism, normally oxidized by MAO

68

Tyramine Adverse

******Serious vasopressor episodes in patients on MAO-I's after release of NE*******

69

Cocaine Receptor

DAT
SERT
NET

70

Cocaine mechanism

Blocks dopamine (major effect), serotonin, and NE transporters -> potentiation and prolonged effects

71

Cocaine effect

Sympathomimetic
Therpeutic use: blockage of voltage gated sodium channels -> local anesthetic

72

Cocaine Adverse

Intense euphoria from blockage of dopamine reuptake in limbic system

73

Cocaine other

Monoamine reuptake inhibitor

74

Atomoxetine receptor

NET

75

Atomoxetine Mechanism

Selective NET inhibitor

76

Atomoxetine Indication

Tx of ADHD

77

Atomoxetine other

Monoamine reuptake inhibitor

78

Ephedrine receptor

alpha and beta

79

Ephedrine effect

Vasoconstriction and cardiac stimulation -> increase BP
Bronchodilation (prophylactic tx of asthma because it is slower onset and less potent than epi or isoproterenol)
Synergistic effect with Anti-AChE in treatment of myasthenia gravis
*Mild CNS stimulation (alertness) and increased athletic performance*

Pressor in spinal anesthetisa, works for MG; asthma

80

Ephedrine PK

NOT a catecholamine -> poor substrate for COMT and MAO -> longer duration of action
Excellent oral absorption, enters CNS

Eliminated unchanged in urine

81

Ephedrine Adverse

Herbal supplements banned in 2004 due to life threatening cardiovascular reactions

82

Ephedrine other

Induces release of NE* and activates adrenergic receptors*
Use declining due to better drugs with fewer side effects

83

Pseudoephedrine mechanism

ephedrine enantiomer

84

Pseudoephedrine receptor

alpha and beta

85

Pseudoephedrine effect

Nasal decongestant with an H1 histamine antagonist

86

Alpha antagonist drugs

Phenoxybenzamine
Phentolamine
Prazosin
Terzosin
Doxazosin
Tamsulosin
Yohimbine

87

alpha 1 blockers

-osins

88

Phenoxybenzamine receptor

non selective alpha

89

Phenoxybenzamine mechanism

alkylation *irreversibly* blocks receptor

slightly alpha one selective
Also blocks H1, M and 5-HT receptors; inhibits NET

90

Phenoxybenzamine effect

CVS: prevents vasoconstriction of peripheral blood vessels -> reflex tachycardia

Presynaptic alpha 2 block -> increase CO

91

Phenoxybenzamine indications

*DOC Pheochromocytoma* blocks effects of excess catecholamines (may require a beta blocker to control tachycardia after alpha blockade is established)

Historically used to lower BP, but was unsuccessful (block presynaptic alpha 2)

92

Phenoxybenzamine adverse

Postural hypotension
Nasal stiffness
Nausea and vomiting
Inhibit ejaculation
Contraindicated in patients with decreased coronary perfusion due to reflex tachycardia

93

Phenoxybenzamine contraindication

Patients with decreased coronary perfusion

94

Phentolamine receptor

nonselective alpha

95

Phentolamine mechanism

*Reversible* alpha blocker

Serotonin blocker
Muscarinic, H1 and H2 agonist

96

Phentolamine indications

Dx and control hypertensive episodes of pheochromocytoma
Prevents dermal necrosis when NE extravasates
**Antihypertensive in stimulant OD, sudden withdrawal of sympatholytics (clonidine), interaction between MAO-Is and tyramine*

97

Phentolamine adverse

Postural hypotension-baroreceptor reflex and alpha 2 blockade on cardiac nerves
Arrhythmia and angina

Contraindicated in patients with decreased coronary perfusion

98

Prazosin receptor

Selective alpha 1
Useful in treatment of HTN

99

Prazosin mechanism

decrease TPR through relaxation of arterial and venous smooth muscle

100

Prazosin effects

**decrease BP without reflex tachycardia (alpha2)**
Decrease LDL/TAG, increase HDL
Improves urinary blood flow

101

Prazosin Indications

Suppress sympathetic outflow from CNS

Tx of HTN, BPH

102

Prazosin Adverse

Not the DOC for primary HTN

First dose effect may cause exaggerated hypotensive response and syncope (adjust first dose 1/4 of normal)

103

Terazosin and Doxazosin receptor

Selective alpha 1
Useful for treatment of HTN

104

Terazosin and Doxazosin mechanism

Structural analog of prazosin -> longer half life -> less frequent dosing
Decrease TPR through relaxation of arterial and venous smooth muscle

105

Terazosin and Doxazosin effect

**decrease BP without reflex tachycardia (alpha2)**
Decrease LDL/TAG, increase HDL
Improves urinary blood flow

106

Tamsulosin effect

Relaxes genitourinary smooth muscle

107

Terazosin and Doxazosin indication

Suppress sympathetic outflow from CNS

Tx of HTN, BPH

108

Tamsulosin indication

Used in treatment of BPH with little effect on BP
(reduced orthostatic HTN)

109

Terazosin and Doxazosin adverse

Not the DOC for primary HTN

First dose effect may cause exaggerated hypotensive response and syncope (adjust first dose 1/4 of normal)

110

Tamsulosin adverse

Not the DOC for primary HTN

First dose effect may cause exaggerated hypotensive response and syncope (adjust first dose 1/4 of normal)

111

Tamsulosin receptor

Selective alpha 1
Treatment of HTN

112

Tamsulosin mechanism

Selective for alpha1A receptor found in genitourinary smooth muscle

113

Yohimbine receptor

alpha 2

114

Yohimbine mechanism

alpha 2 blocker -> indirect adrenergic agonist

115

Yohimbine effect

increase NE release -> increase BP

116

Yohimbine indication

treatment of *erectile dysfunction*, but has been replaced by PDE-5 inhibitors

117

Yohimbine contraindications

Can reverse effects of alpha 2 agonists (clonidine--bad!)

118

Beta antagonist drugs

Propranolol
Nadolol
Timolol
Atenolol
Metoprolol
Esmolol

119

Propranolol receptor

Beta 1 and 2

120

Propranolol mechanism

CVS: decrease HR and contractility
Increase TPR (beta 2)

Metabolic: decrease glycogenolysis and glucagon secretion -> severe hypoglycemia in patients on insulin

121

Propranolol indication/effect

Used in treatment of:
HTN (through decreased CO, no the DOC)
Migraine (blocks vasodilation)
Hyperthyroidism
Chronic angina (decrease O2 requirements)
A-fib, MI (protective)
Performance anxiety/stage fright (DOC)*
Essential tremor

122

Propranolol Adverse

**Bronchoconstriction->contraindicated in patients with COPD or asthma; variant angina**

Impair recovery from hypoglycemia in insulin dependent patients -> syncope. Mask signs (ex. tachycardia seen in such episodes)

CNS: sedation, dizziness, lethargy, fatigue, depression

123

Propranolol other

Does not induce postural hypotension because alpha 1 receptors remain active

Reduce HDL, and increase LDL and TAGs (block activation of HSL) -beta 1 selectively actually improve the lipid profile

Abrupt withdrawal -> HTN

124

Nadolol indication/effect

long term treatment of angina and HTN

125

Timolol indication/effect

HTN, prophylaxis for migraines
Glaucoma (open angle)

126

Atenolol and Metoprolol indication/effect

Management of HTN in patients with impaired pulmonary function or IDDM

127

Atenolol and Metoprolol receptor

B1 cardioselective

128

Timolol receptor

Beta 1 and 2

129

Nadolol receptor

beta 1 and 2

130

Esmolol receptor

beta 1 cardioselective

131

Atenolol and Metoprolol other

less likely to produce bronchospasm

long term management of angina; s/p MI reduces mortality

132

Esmolol indication/effect

Useful in controlling arrhythmia (supraventricular or thyrotoxicosis), perioperative HTN, and MI in acutely ill patients

133

Esmolol other

Safer in critically ill patients
PK: ultra short acting, administer IV

134

Alpha 1 and Beta antagonists

Labetalol
Caverdilol

135

Labetalol receptor

alpha 1 and beta

136

Labetalol mechanism

Decrease in BP:
alpha 1 ->relaxation of arterial smooth muscle
beta 1 ->blocks sympathetic reflex
beta 2 -> sympathomimetic action contributes to vasodilation

137

Labetalol PK

more potent beta antagonist
Oral: chronic HTN
IV: emergencies

138

Labetalol Adverse

Orthostatic hypotension and dizziness (alpha 1)

139

Carvedilol indication/effect

used on patients with CHF and HTN

140

Carvedilol other

antioxidant properties

141

Pindolol receptor

partial beta agonist

142

Pindolol mechanism

Beta blocker with intrinsic sympathomimetic activity helps manage HTN

143

Pindolol indication / effect

causes a smaller reduction in resting HR and BP

Preferred in patients with diminished cardiac reserve or propensity to bradycardia

HTN in pregnant women

144

Alpha methyltyrosine
aka metyrosine
mechanism

Blocks NE and E synthesis through competitive *inhibition of tyrosine hydroxylase*

145

Alpha methytyrosine/ metyrosine indication/effect

used in adjuvant therapy with phenoxybenzamine in treatment of malignant pheochromocytoma (when surgery is not possible)

146

Reserpine (obsolete) mechanism

*Irreversible damage to VMAT* ->decrease NE and dopamine availability -> sympatholytic response

147

Reserpine indication/effect

Unable to concentrate and store NE and dopamine in the vesicle -> continuous breakdown by MAO
Decrease BP and HR

148

Reserpine other

historical treatment of HTN

149

Guanethidine mechanism

Uptake into nerve terminal via NET -> storage in vesicle and displacement of NE -> NE depletion

150

Guanethidine indication/effect

anti-hypertensive that was used in the early 1970s

151

Guanethidine adverse

orthostatic HTN and male sexual dysfunction

152

Guanethidine other

also disrupts the release of NE from the nerve terminal