Flashcards in Adrenergic Drugs Deck (128)
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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
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alpha 1 agonists
1. phenylephrine
2. methoxamine
3. metaraminol
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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
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