Pharm: Adrenergic

Front 1

how can synthesis of Epi, NE or Dopamine be modulated?

Back 1

inhibit syn at RLS (tyrosine hydroxylase)- not clinically important
incr syn by supplying levodopa (parkinsonism)
false substrates enter syn path at decarboxylation step (b/c non-selective) to form false NTs

Front 2

what are the 2 primary degradative pathways of NE? where/how does each work?

Back 2

MAO- neuronal; metab free NE and D in n terminal
COMT- extraneuronal; act in synaptic cleft

Front 3

what do MAO inhibitors do? COMT inhibitors?

Back 3

incr NE, D, and 5HT in n terminals in periphery and CNS
COMT inhibitors not used on their own; used with levodopa in parkinsons

Front 4

where is NE syn?

Back 4

in vesicles in n terminals
syn from dopamine that enters vesicle via transporter (also moves NE from cytoplasm to vesicle)

Front 5

what is the action of reserpine?

Back 5

IRREVERSIBLY INHIBITS transporter on vesicle in n. terminal that moves dopamine in to make NE
result: net loss of NE (also D, 5HT) in n. terminal (degraded by MAO) and decr SNS activity

Front 6

what are some side effects of reserpine?

Back 6

PNS dominance:
decr BP
nasal stuffiness
diarrhea
depression
parkinsonism and galactorrhea due to decr D

Front 7

what is the main method of termination of NE?

Back 7

reuptake into presynaptic terminals
-neuronal uptake moves NE into cytoplasm
-vesicular uptake moves NE into vesicle

Front 8

what are 4 subst that block neuronal uptake of NE?

Back 8

cocaine
tricyclic antidepressants (imipramine)
antidepressants (SNRIs ex: duloxetine)
adrenergic neuron blockers

Front 9

what is the effect of cocaine on NE and SNS responses?

Back 9

responses are potentiated
incr BP and HR
overdose-> MI, CNS bleed

Front 10

what is the effect of cocaine on adrenergic neuron blockers?

Back 10

action of adrenergic neuron blockers is impaired by cocaine b/c cant get to site of action

Front 11

what is the effect of cocaine on indirect sympathomimetic amines?

Back 11

action is IMPAIRED b/c they cant get to site of action?

Front 12

what are some examples of drugs that enhance noradrenergic transmission?

Back 12

amphetamines (incr rel)
cocaine (inhibit reuptake)
phenylephrine (R agonist)

Front 13

what are ex of drugs that block/reduce noradrenergic transmission?

Back 13

reserpine (inhibit vesicular storage)
phentolamine (R antagonist)

Front 14

what is the rank of potencies on aR?

Back 14

Epi > NE > isoproterenol

Front 15

what is the rank of potencies on bR?

Back 15

Isoproterenol>Epi>NE

Front 16

what antagonist works best on aR?

Back 16

phentolamine

Front 17

what antagonist works best on bR?

Back 17

propanolol

Front 18

what are 3 general mxns of actions of agonists?

Back 18

DIRECT- act on R (NE, Epi)
INDIRECT- incr NE rel (amphetamines, tyramine)
REFLEX effects- if alter BP

Front 19

what are the CVS effects of NE?

Back 19

activates a1,a2, b1
incr TPR
direct incr in HR
reflex decr in HR

Front 20

what are the CVS effects of Epi?

Back 20

activates a1, a2, b1, b2
at low doses has b2 affects- vasodilation
at high doses has a1 affects- vasoconstriction
incr in HR (b1)
systolic BP incr but diastolic BP may go down

Front 21

what are the CVS effects of isoproterenol?

Back 21

acts on b1, b2
lg incr in HR (direct and reflex)
overall decr in TPR; early incr in systolic BP due to incr in contractility

Front 22

what are 3 types of mm with b2R?

Back 22

bronchial sm m
vessel sm m
uterine sm m

Front 23

how does the b2R mediate sm m relaxation?

Back 23

incr cAMP via Gs
also incr glycogenolysis

Front 24

which receptors are mediated by an incr in IP3/DAG?

Back 24

a1 (Gq)

Front 25

which receptors act via an incr in cAMP?

Back 25

b1, b2, b3, D1

Front 26

which receptors act via a decr in cAMP?

Back 26

a2

Front 27

a pt that has taken cocaine presents with incr HR and BP. what mxm mediated the incr in HR?

Back 27

incr cAMP via b1R

Front 28

a pt on phenylephrine for nasal congestion presents with in incr in BP. what mxn underlies the incr in BP?

Back 28

incr IP3, DAG via a1

Front 29

what are the effects of a1R activation?

Back 29

vasoconstriction
mydriasis due to contraction of the dilator mm of the pupil

Front 30

what are the effects of a2R activation?

Back 30

inhibits adrenergic and cholinergic n terminal rel
inhibits insulin rel from pancreatic beta cells
some vasoconstriction

Front 31

what are the effects of activation of b1R?

Back 31

incr rate and contractility of heart
incr conduction velocity
stim renin rel from JG cells

Front 32

what are the effect of activation of b2R?

Back 32

bronchial, vascular and uterine sm m relaxation
TREMOR (somatic n terminals)
stim glycogenolysis in liver

Front 33

what is the importance of the b3R?

Back 33

inhibits contraction of detrusor m
involved in lipolysis

Front 34

what are the terms for incr HR, incr contractility and incr conduction velocity?

Back 34

positive chronotropism, inotropism, dromotropism

Front 35

is NE or Epi a potent bronchodilator?

Back 35

Epi
mediated by b2R
also decr mast cell secretion

Front 36

what are the effects of dobutamine?

Back 36

activate b1R
no change in TPR
direct incr in HR, no reflex

Front 37

what R does phenylephrine act on?

Back 37

a1>a2 agonist

Front 38

what R does clonidine act on?

Back 38

a2>a1 agonist

Front 39

what R does isoproterenol act on?

Back 39

b1=b2 agonist

Front 40

what does terbutaline do? what are some ex of other drugs in the same catergory?

Back 40

b2R agonist
also salmeterol (long acting)
albuterol, metaproterenol (short acting)

Front 41

what are 3 important uses of a sympathomimetics?

Back 41

1. reduce regional blood flow: local anesthetics in dentist, prolongs local effect and slows systemic absorption
2. nasal decongestants: if taken systemically may cause incr BP, can only use 4-5d or become habituated; ex: phenylephrine, oxymetazoline
3. dilate pupil

Front 42

why is NE not used in conjunction with local anesthetics?

Back 42

causes too much vasoconstriction because has no b2R effect
may cause sever ischemia and sloughing of tissues

Front 43

what is an ex of an a1-sympathomimetic?

Back 43

phenylephrine:
specific a1R agonist
incr TPR-> incr BP-> reflex bradycardia
can block reflex bradycardia with atropine (muscarinic antagonist)
used clinically for: hypotensive states
mydriatic
nasal decongestion

Front 44

what is an ex of an a2 agonist?

Back 44

clonidine:
decr SNS outflow
used for HTN or opiod withdrawal

Front 45

what is an ex of a b1 agonist?

Back 45

dobutamine:
used for short term management of pump failure (after surgery, MI, acute CHF)
long term efficacy uncertain: enhance renal perfusion despite low CO