CHAPTER 6: ADRENERGIC AGONISTS- INTRO

Question 1

Adrenergic neurons release?

Answer 1

norepinephrine (NE) as the primary neurotransmitter

Question 2

where are adrenergic neurons localized and what receptors do they act on

Answer 2

-in the CNS and SNS, link ganglia and effector organs
-act on pre or post-synaptic adrenergic receptors

Question 3

neurotransmission of adrenergic neurons (steps)

Answer 3

1. tyrosine and Na+ go into the cell, Tyr is hydrolyzed into Dopamine
2. DOPA enters a vesicle, decarboxylate to make NE
   -MAO can metabolize DOPA not in vesicle and degrade it
3. AP is reached, Ca2+ goes into the cell, and NE is released.
4. NE either binds to presynaptic receptor (neg feedback), or binds to post synaptic receptor and induces intracellular response.
5. NE reuptake occurs, rapidly taken into neuron.
6. OR- NE is metabolized by COMT (methylates) and MAO (oxidase).

Question 4

Reserpine blocks…

Answer 4

the transporter that binds to storage vesicles of catecholamines and stores dopamine into vesicles

Question 5

Guanethidine blocks..

Answer 5

release of NE

Question 6

MAO- mono amino oxidase

Answer 6

oxidase that metabolizes the NE not in the vesicle (DOPA) and degrades it into inactive metabolites and excrete in urine

Question 7

COMT- catechol-o-methyl transferase

Answer 7

takes NE, methylates it, (moves methyl group to noradrenaline, and removes it as an inactive metabolites excreted in urine

Question 8

MAO in reuptake

Answer 8

NE can go back in after released into post synaptic space

can use cocaine, SNRI’s (serotonin), and imipramine to inhibit reuptake

Question 9

Adrenoceptors- alpha and beta
-affinities

Answer 9

Alpha- high affinity for epinephrine, middle is NE, lowest is isoproterenol
EPI-NE-ISO

Beta- high affinity for isoproterenol, middle is Epi, lowest is NE
ISO EPI-NE

Question 10

Adrenergic receptor- a (alpha) subtypes

Answer 10

a1- on POSTsynaptic membrane of effector organs ( a1A, a1B, a1C, a1D)
- high phenylephrine affinity

a2- on PREsynaptic nerve ending, control NE release (a2A, a2B, a2C)
- clonidine affinity (less effect on a1)

Question 11

a1 receptors- location and function

Answer 11

SNS EFFECTS:
-blood vessels- vasoconstrict
-inc peripheral resistance
-inc BP

-iris- mydriasis
-bladder- close sphincter/urine retention

Gq receptor

Question 12

a2 receptors- location and function

Answer 12

-presynaptic nerve memb
-beta cells in pancreas

SNS EFFECTS/ACTIVATION:
-inhibit ACh release
-inhibit insulin release (pancrease beta cells)
-inhibition NE release (presyn receptors activated)

Gi receptor

Question 13

Adrenergic Receptors- beta subtypes

Answer 13

b1, b2, b3:
b1 approx equal NE and EPI affinities
b2 higher EPI affinity than NE

Gs receptorrs

Question 14

b1 receptors- location and function

Answer 14

LOCALIZED IN HEART and KIDNEY
-tachycardia
-inc myocardial contractility (musc strength)
-inc renin release (kidney)
fat tissue- inc lipolysis (breakdown fat for energy in periph tissue)

Question 15

b2 receptors- location and function

Answer 15

-vasodilate (smooth muscle in vessels)
-bronchodilate
-uterine muscle- relax detrusor
periphery- inc muscle and liver glycogen breakdown, inc glucagon release
-inc glucose in BLOOD

Question 16

which two receptors have opposite responses when stimulated?

Answer 16

a1 and b2

Question 17

vasoconstriction and vasodilation- EPI
alpha and beta?

Answer 17

EPI interacts w both a and b receptors
LOW DOSE: B effects (dilate)
HIGH DOSE: a effects (constrict)

Question 18

ABCD- constriction and dilation trick

Answer 18

alpha-constriction
beta-dilation

Question 19

receptor desensitization is?

Answer 19

-prolong exposure to catecholamines reduce response of adrenoreceptors

Question 20

receptor desensitization mechanism

Answer 20

1- sequester/internalize receptors, cant interact with ligand
2-down regulation, receptors disappear (destroy or dec synth)
3- inability to couple G protein bc receptor was phosphorylated on cytoplasmic side

Question 21

direct-acting adrenergic agonists list:

Answer 21

epinephrine (EPI), norepinephrine (NE), isoproterenol, dopamine, phenylephrine, midodrine, clonidine, oxymetazoline
SABAs: albuterol, metaproterenol, terbutaline (SHORT ACT BETA AGON)
LABAs: salmeterol, formoterol, indacaterol (LONG ACT BETA AGON)

Question 22

indirect acting ago

Answer 22

amphetamine, cocaine, tyramine