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Flashcards in Adrenergic Drugs Deck (128):
1

Synthesis of NT in Adrenergic nerve terminal

1. tyrpsine is actively transported into nerve endings
2. is converted into DOPA by tyrosine hydroxyls (Rate-limiting step)
3. DOPA is converted to dopamine by DOPA decarboxylase
4. DA is metabolized to NE via Dopamine beta decarboxylase
5. NE is taken up & stored in granules; NE not stored in granules is called the mobile pool--this can be inactivated by MAO

During depolarization, Ca2+ enters the presynaptic terminal via the voltage-dependent Ca channels-->degranulation of storage vesicles-->NE released via exocytosis into synaptic junction

Actions:
1. NE can activate pre junctional receptors = alpha 2 receptors (feedback regulation system-->inhibition of further release)
2. can activate postsynaptic receptors (alpha 1 & beta 1-3 receptors)

2

Termination of NE action

1. mainly by reuptake (via NET= NE transporter)
2. Diffusion away from receptor site with eventual metal by catechol-o-methyl transferase (COMT) in plasma or liver

3

MAO inhibitors

increase the pre junctional levels of NE

4

Displacers

indirect acting sympathomimetics displace the stored NE

5

uptake inhibitors

indirect actinv sympathomimetics inhibit the uptake into nerve cell-->increases post junctional levels/actions of NE

6

alpha 2 receptor

pre-synaptic autoreceptor

coupled to G2-->inhibition of adenyl cyclase-->decrease cAMP

7

D1 receptors

activates adenyl cyclase-->increases cAMP

8

alpha 1 receptors

coupled to Gq-->stimulates PLC-->activates IP3 & DAG pathway

9

beta receptors

coupled to Gs-->activation of adenyl cyclase-->increased cAMP

10

Things that affect PVR

alpha 1: vasoconstriction-->increase TPR-->Increase BP

beta 2: vasodilation-->decrease TPR-->decrease diastolic BP

11

alpha 1 receptor locations & actions

1. most vascular smooth muscle-->vasoconstriction--> Increase TPR & Increase BP
2. Pupillary dilator muscle-->contraction-->dilates pupil
3. Prostate (ductus deferens & seminal vesicles)--> contraction-->ejaculation

12

alpha 2 receptor locations & actions

1. postsynaptic CNS adrenoceptors-->probably multiple
2. presynaptic nerve terminals-->inhibition of NT release--> decrease sympathetic outflow
3. some vascular smooth muscle (nasal mucosa)--> nasal decongestion
4. fat cells--> inhibition of lipolysis

13

beta 1 receptor locations & actions

1. heart--> increase F & rate of contraction
2. juxtaglomerular cells--> increase renin release

14

beta 2 receptor locations & actions

1. bronchial relaxation-->bronchodilation
2. uterine relaxation
3. vascular bed in skeletal muscle

vasodilation-->decrease TPR
4. skeletal muscle-->promotes K uptake
5. human liver-->activates glycogenolysis
6. increase pancreas insulin secretion

15

beta 3 receptor locations & actions

Fat cells-->activates lipolysis

16

D1 receptor locations & actions

dilates renal bv

17

D2 receptor locations & actions

nerve endings--> modulates NT release

18

Indirect agonist types:

1. act via displacement of stored catecholamines from adrenergic nerve ending
ex) amphetamine & tyramine

2. act via inhibition of repute of catecholamines already released
ex)cocaine & TCAs

some drugs may have direct & indirect actions

19

Indirect acting adrenergic agonists

1. tyramine
2. amphetamine
3. ephedrine*
4. metaraminol*
1-4 increase release of NE
5. cocaine (blocks reuptake

20

Nonspecific Adrenergic Agonists

1. NE: a1=a2, B1>>B2
2. Epi: a1=a2=b1=b2
3. Dopamine: D1=D2>B1>>a
4. Ephedrine: a1=a2=b1=b2

21

a1=a2=b1=b2

Epi & Ephedrine

22

alpha 1 agonists

1. phenylephrine
2. methoxamine
3. metaraminol

23

alpha 2 agonists

clonidine

24

non-specific beta agonists

isoproterenol; B1=B2

25

beta 1 agonists

dobutamine

26

beta 2 agonists

1. terbutaline*
2. albuterol*
3. metaproterenol
4. ritodrine*

27

NE

non-specific adrenergic agonist: a1=a2; B1>>B2

28

Fendolopam

D1 agonist

29

Adrenergic effect on BV
a1 -->
B2-->

a1--> increases arterial resistance
b2-->promote sm relaxation-->decrease arterial resistance

skin & splanchnic vessels have predominantly alpha receptors & constrict in the presence of Epi & NE

30

Adrenergic effect on Heart

1. direct effects via B1 receptors-->increased Ca influx into cardiac cells = Pacemaker activity increased (+ chronotropic effect)
2. conduction velocity in AV node increased
3. intrinsic contractility is increased (+ inotropic effect)

31

Beta & alpha receptors in pancreatic islets

b receptors-->increase insulin secretion
alpha2 receptors-->decrease insulin secretion

32

Effect of Insulin

1. Increased glycogen synthesis: insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; 2. lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood.

33

+ inotropic effect

intrinsic contractility increased

34

+ chronotropic effect

pacemaker activity increased

35

Phenylephrine effect on BP

alpha 1-->increase TPR --> Increase BP

also decreases venous capacitance

this leads to a dose-dependent rise in BP

36

Stimulation of B1 receptors in heart

increase CO & BP

37

Affect of stimulation of b2 receptors on BP

decrease peripheral resistance via vasodilation in certain vascular beds

38

Isoproterenol effect on CO & BP

increase CO; decrease peripheral resistance by activating B2 receptors

lowers BP via B2; raises HR via B1

39

Phenylephrine effect on BP & HR

raises BP (via alpha 1 receptors) but not HR bc no effect on beta receptors

40

Epi effect on BP & HR

increases BP & HR

41

antimuscarinics vs alpha 1 effect on eye

alpha 1-->only mydriasis, no cycloplegia
antimuscarinics-->cycloplegia

42

increased alertness, reduced fatigue, anorexia, euphoria, insomnia

effect of non-catecholamines (i.e. amphetamines) on CNS

in very high doses: aggressiveness, marked anxiety, convulsions

catecholamines don't enter CNS

43

effect of stimulating receptors located on radial pupillary dilator muscle of iris

alpha receptors; stimulation-->mydriasis (dilation)

44

phenylephrine use

used as mydriatic for retinoscopy

45

epinephrine use in glaucoma

non-selective agonist used to increase the outflow of aqueous humor via uveocleral veins (obsolete) in treating glaucoma

46

apraclonidine use

alpha 2 selective agonist used to decrease aqueous secretion in the treatment of glaucoma

47

brimonidine use

alpha 2 selective agonist used to decrease aqueous secretion in the treatment of glaucoma

48

timolol

beta antagonist used to treat glaucoma: decrease the production of aqueous humor

(affects beta receptors in ciliary body)

49

beta 2 receptor stimulation in bronchial smooth muscle:
effect & use

bronchodilation; used to treat bronchial asthma

50

Adrenergic affects on Respiratory tract

1. decongestant action of adrenoreceptor stimulants (via alpha receptors)
2. B2-->bronchodilation of bronchial sm

51

Adrenergic affects on GU tract

1. B2 receptors in uterus-->relaxation; used in premature labor
2. alpha1A receptors in bladder base, urethral sphincter & prostate mediate contraction-->promotes urinary continence
3. B2 receptors in bladder wall-->relaxation
4. alpha receptor activation in ductus deferens, seminal vesicles & prostate -->ejaculation

52

Epi

1. very potent vasoconstrictor & cardiac stimulant
2. increase in systolic BP due to positive inotropic (Increase FOC) and chronotropic (Increase HR) effects via B1
3. effect on skeletal m bv

53

low-dose epi which receptors predominate

beta 1, 2

54

high-dose epi which receptors predominate

alpha 1, 2, b1 no beta 2

55

EPI affect on skeletal m bv

activates B2 receptors-->dilation-->decrease TPR-->decrease diastolic BP

contributes to increased blood flow during exercise

56

NE

1. more alpha action than beta
2. relatively little action on b2
3. increase TPR & BP (systolic & diastolic) via alpha 1
4. compensatory baroreflex activation-->overcomes direct positive chronotropic (increase HR) effects of NE
5. positive inotropic (increase FOC or contractility) effects on heart via B1

57

Isoproterenol

1. very potent beta receptor agonist; little effect on alpha
2. + chronotropic & inotropic actions
3. potent vasodilator (bc activates beta receptors almost exclusively)-->increase in CO assoc w fall in diastolic & MAP

58

Dopamine

1. activates D1 receptors in several vascular beds--> vasodilation
2.

59

Dobutamine

relatively B1 selective synthetic catecholamine

60

low doses of dopamine (2-5mcg)

acts primarily on dopaminergic receptors--> increased renal, coronary & cerebral blood flow

61

infusion rate of dopamine above 5mcg

stimulates beta receptors and increases release of NE--> increase in cardiac contractility

62

high doses of dopamine (infusion rate between 10-20mcg)

begins to act on alpha receptors-->vasoconstriction

63

amphetamine

indirect acting CNS stimulant; peripheral actions mediated through release of catecholamines

Sx: stimulant effect on mood

64

methamphetamine

very similar to amphetamine with a higher ration of central to peripheral action

65

dextroampheramine aka

adderall

66

methylphenidate aka

ritalin

67

ephedrine MOA & use

found in various plants i.e. ma huang; mild stimulant in CNS;
MOA= displaces NE from storage vesicles in presynaptic neurons

68

pseudoephedrine

aka sudafed; narrows bv-->decreases swelling & congestion

69

phenylephrine

relatively pure alpha agonist
used as nasal decongestant & mydriatic

70

xylometazoline & oxymetazoline

direct acting alpha agonists

used as topical decongestants bc promote constriction of nasal mucosa

71

Clonidine
1. receptor type
2. use
3. side effects
4. warnings/special uses

1. alpha 2 selective agonist
2. used in HTN, diabetic diarrhea, narcotic addicts & to treat benzodiazepam withdrawals
3. postural hypotension, dry mouth, sedation, rebound hypertension
4. don't stop treatment abruptly bc withdrawal & rebound hypertension

72

methyldopa
1. receptor type
2. use
3. side effects
4. warnings/special uses

1. alpha 2 selective agonis
2. used in HTN, diabetic diarrhea, narcotic addicts & to treat benzodiazepam withdrawals; DOC IN PREGNANCY
3. postural hypotension, dry mouth, sedation, rebound hypertension
4. DOC in pregnancy

73

apraclonidine

clonidine derivative used in glaucoma

74

bromonidine

clonidine derivative used in glaucoma

75

tyramine

normal byproduct of tyrosine metabolism in the body; has similar effect to NE;

found in high concentrations in fermented foods i.e. cheese & smoked/aged fish

when given parenterally-->indirect sympathomimetic action bc of release of stored catecholamines

Clinical: greatly intensified in patients treated with MAOI--> marked increase in BP, so patients on MAOI should be careful eating tyramine-containing foods i.e. smoked/pickled fish & cheese

76

example of physical antagonism

activated charcoal-->adsorbs

77

example of chemical antagonism

antacids

78

bronchospasm, mucous membrane congestion, angioedema & severe hypotension

anaphylaxis
Tx: IM epinephrine .3-.5mg; supplemented by glucocorticoids & antihistamines

79

anaphylaxis is mediated by

Type 1 immune reaction; IgE-mediated reaction

80

Tx of acute hypotension

usually of short duration while giving IV fluids

NE, Phenylephrine when vasoconstriction is desired

81

massive MI can lead to

cardiogenic shock and acute HF;

positive inotropic agents (-->increase FOC) used to avoid this: dopamine or dobutamine

82

drugs used in emergency management of complete heart block & cardiac arrest

isoproterenol & epi

83

drugs used to avoid cariogenic shock & acute HF following massive MI

dopamine or dobutamine

84

modafinil use

new amphetamine substitute used to treat narcolepsy

85

albuterol uses

beta 2 agonist

used to treat bronchial asthma, premature labor & threatened abortion

86

salmeterol use

beta 2 agonist used to treat bronchial asthma

87

phenylephrine use

used for fundus exam

88

clonidine use

moderate to severe hypertension

89

epinephrine use

to prolong duration of local anesthetics (i.e. lidocaine) & reduce systemic toxicity

90

alpha 1 receptor agonist effects on BP & HR

i.e. phenylephrine, methoxamine
increase BP
decrease HR

91

alpha 2 receptor agonist use

ie clonidine, alpha-methyl dopa
decrease BP, used as anti-hypertensives

92

beta 1 & beta 2 agonist use

increase HR, SV, CO

ie isoproterenol, dobutamine (b1>b2)

93

beta 2 agonist use

decrease TPR, bronchodilation
ie salmeterol, albuterol, terbutaline

94

Dobutamine

beta 1 stimulator

95

alpha 1 effect in the prostate

contraction of the ductus deferens & seminal vesicles (resulting in ejaculation)

96

alpha 2 affect on fat cells

inhibition of lipolysis

97

alpha 2 affect on some vascular smooth muscle cells in the nasal mucosa

nasal decongestion

98

beta 2 affect on skeleton muscle

promotes K+ uptake

99

beta 2 affect on the human liver

activates glycogenolysis
(increases pancreas insulin secretion)

100

D1 affect on smooth muscle

dilates renal blood vessels

101

D2 affect on nerve endings

modulates NT release

102

alpha 1 increases PVR by affecting arterial or venous resistance

ARTERIAL (it increases arterial resistance!!!)

103

beta 2 affects PVR by?

promotes smooth muscle relaxation--> decreases arterial resistance

104

beta 1 affects the heart BY

increasing calcium influx into cardiac cells

105

the skin & splanchnic vessels are predominantly _____ receptors and _____ in the presence of NE & E

1. alpha 1 receptors
2. constrict

106

NE acts best on

alpha 1 = alpha 2 = beta 1; VERY LITTLE effect on beta 2!

107

_____ receptors result in increased insulin secretion

beta receptors

108

______ receptors result in decreased insulin secretion

alpha 2

109

phenylephrine's effect on BP

phenylephrine = alpha 1 --> increases TPR--> increase BP

it also DECREASES venous capacitance

this leads to a dose-dependent rise in BP

110

stimulation of beta 1 receptors in the heart-->

increases HR & CO--> increases BP

111

stimulation of beta 2 receptors in the heart-->

decreased peripheral resistance (via vasodilation in certain vascular beds)

112

a nonselective agonist like isoproterenol will--->

1. increase in CO (by activating beta 1 receptors) but also
2. decreases peripheral resistance by activating beta 2 receptors

113

phenylephrine use

mydriatic for retinoscopy

114

epinephrine use

glaucoma bc increases outflow of aqueous humor via uveocleral veins (obsolete)

remember mystics also increase outflow (i.e. pilocarpine, physostigmine, carbechol)

115

alpha 2 selective agonist examples and uses in treating glaucoma

1. apraclonidine & brimonidine
2. decrease aqueous secretion

116

beta antagonists ie timolol use in treating glaucoma

decrease the production of aqueous humor (affects bet ain ciliary)

117

useful in premature labor

beta 2 receptors in uterus mediate relaxation

118

receptors stimulated to promote urinary continence

1. alpha 1a: located in bladder base, urethral sphincter & prostate

2. beta 1 receptors in the bladder wall also mediate relaxation

119

receptor in the bladder wall that mediates relaxation and is use??

1. beta 2
2. used to promote urinary continence

120

stimulation of _____ receptor stimulates renin secretion

beta 1

121

what will happen to systolic & diastolic BP with epinephrine use

1. systolic BP increases: vasoconstriction from alpha 1 stimulation
2. diastolic BP may decrease: beta 2 receptors in skeletal muscles--> dilation of vessels

remember #2 promotes blood flow to muscles during exercise

122

High dose of epinepherine

NO beta 2 just alpha 1= alpha 2 = beta 1 -->high dose Epi = NE

123

low dose epinephrine

beta 1 & beta 2 & alpha 1 & alpha 2; so low dose epinephrine = same beta effects as isoproterenol

124

how does dopamine affect BP

D1 in vascular beds--> vasodilation

125

Does methamphetamine has a higher ratio of central or peripheral actions

central

126

low doses of dopamine (2-5 mug)

act primarily on dopaminergic receptors-->increased renal, coronary and cerebral blood flow

127

doses of dopamine above 5mcg/min

dopamine stimulates beta receptors and increases release of NE--> increase cardiac contractility

128

doses of dopamine between 10-20mcg/min

dopamine acts at alpha receptors-->vasoconstriction