Adrenergic Agonist, Diuretics, ADH

Question 1

What causes the release of adrenergic amines?

Answer 1

stimulation from nicotinic receptors on post-synaptic surface of post-ganglionic nerve –> depolarization (Na influx) and Ca influx –> release NE and ATP
NE can inhibit its own release

Question 2

Axoplasmic uptake

Answer 2

Reuptakes NE in synapse

–> is sensitive to cocaine and tricyclics which inhibit it so more NE is in synapse –> increased BP

Question 3

Reserpine

Answer 3

inhibits granular pump –> accumulates catecholamines in vesicles
depleter

Question 4

Guanethidine

Answer 4

induces release from vesicle
slow acting
depletes NE stores
reduces responses to sympathetic stimulation

Question 5

Degradation of adrenergic amines

Answer 5

COMT (catechole-O-methyl transferase)
- important in liver for inactivating circulating catecholes
MAO (monoamine oxidase)
- types a (intestine and brain), b (organs)

Question 6

MAO inhibitors

Answer 6

• Pargyline (seligeline)
• potentiates the action of catecholamines
• avoid foods with tyramine –> hypertensive crisis

Question 7

Beta 1 receptor

Answer 7

Isoproterenol > epi = norepi

• adrenergic cardiac effects, renin release
• located in heart, JG apparatus, and adipose tissue
• acts to increase cAMP via Gs(alpha)

Question 8

Alpha 1 receptor

Answer 8

epi >= norepi&raquo_space;iso

• mediates smooth muscle contraction (vessels)
• activates PLC –> increase [Ca2+] via IP3

Question 9

Beta 2 receptor

Answer 9

iso > epi&raquo_space;» norepi (NE not a substrate for beta 2)

• relaxation of smooth muscle (vessels)
• acts to increase cAMP via Gs(alpha)

Question 10

Alpha 2 receptor

Answer 10

epi >= norepi&raquo_space; iso

• inhibition of neural NE release
• prejunctional nerve terminal, platelets, guy, medulla
• acts to decrease cAMP or activate Na/H antiporter

Question 11

Dopaminergic receptor

Answer 11

dopamine is substrate

- dilation of renal and mesenteric vasculature

Question 12

Dobutamine

Answer 12

selective beta 1 agonist (only one!!!!)

• positive inotrope
• used in CHF and acute MI with HF
• administered IV

Question 13

Phenylephrine

Answer 13

alpha 1 agonist

• used to reverse hypotension and paroxysmal atrial tachycardia
• increases BP

Question 14

Terazosin

Answer 14

• azosin suffix

- alpha blocker!

Question 15

Metaproterenol, Albuterol, Terbutaline, Ritodrine, Salmeterol

Answer 15

Selective beta 2 agonists!

• used for bronchodilation (asthma) and to delay labor
• SE = tachycardia and palpitations
• decrease BP`

Question 16

Clonidine, alpha-methyldopa, Guanabenz

Answer 16

Alpha 2 agonists

- antihypertensives, also ADHD

Question 17

Epinephrine

Answer 17

alpha 1, beta 1, and beta 2 receptor activity

• vasoconstricts (alpha 1), vasodilates (beta 2)
• directly increases HR and contractility (beta 1)

Question 18

Norepinephrine

Answer 18

alpha 1 and beta 1 activity

- vasoconstricts (alpha 1), increased HR and contractility (beta 1)

Question 19

Isoproterenol

Answer 19

• synthetic catecholamine stimulating beta receptors

- vasodilates (beta 2), tachycardia (beta 1)

Question 20

Dopamine

Answer 20

• positive inotrope (beta 1)

- vasoconstrictor (alpha 1) at higher doses

Question 21

Amphetamine

Answer 21

releases NE from nerves –> increases BP

- reverses direction of axoplasmic pump

Question 22

Ephedrine

Pseudoephedrine

Answer 22

release NE from nerves by reversing axoplasmic uptake pump –> increases BP
uses - bronchospasm or nasal congestion

Question 23

Loop Diuretics

Answer 23

Furosemide and Bumetanide
- inhibit Na, K, 2 Cl pumps in thick ascending limb of loop of henle (25% of Na reabsorption)
- more Na, K, 2Cl stays in tubule, more water follows –> greater excretion
Uses: edema conditions!!!
SE: affects fluid in ear

Question 24

Thiazide Diuretics

Answer 24

Chlorathalidone, Hydrochlorothiazide, Metalazone
- block NaCl transporter in distal convoluted tubule (8% reabsorption)
- increases excretion of Na, Cl, K, and H20
Uses: HTN!
SE: Hyperglycemia (hyperpolarization of beta cells suppressing insulin release), hyperuricemia, hypokalemia

Question 25

What part of MAP equation do diuretics affect?

Answer 25

The stroke volume portion of CO –> which results in affecting the venous return curve

Question 26

Potassium sparing diuretics

Answer 26

Spironolactone, eplerenone –> inhibit aldosterone receptors
Amiloride, triamterene –> inhibit Na exchange for K and H in collecting duct
Uses: hyperaldosteronism or prevent K wasting
SE: hyperkalemia, gynecomastia

Question 27

ADH

Answer 27

Vasopressin (natural), desmopressin (synthetic)
Uses: diabetes insipidus, bed wetting
- stimulation of GPCR in collecting duct to recruit AQP channels –> water moves by osmosis –> less urine

Question 28

Demecocycline

Answer 28

antibiotic with ADH antagonist activity

Question 29

Where are Na+ sensors?

Answer 29

macula densa

Question 30

Osmotic Diuretics

Answer 30

mannitol
- not reabsorbed in nephron –> exerts osmotic effect to retain water in nephron tubule –> more urine
reduces body water
reduces intracranial or intraocular pressure

Question 31

Carbonic Anhydrase Inhibitors

Answer 31

Acetazolamide

• not useful as diuretics because C.A. is everywhere so screwing with it has massive total affects!
• treat glaucoma, produce urine alkalinization, produce metabolic acidosis, treat Acute Mountain sickness

Question 32

Organic Anion Transporter Inhibitors

Answer 32

Allopurinol - blocks formation of uric acid by inhibiting xanthine oxidase
Probenicid, Sulfinpyrazone
- inhibit renal organc acid transporters to facilitate excretion of uric acid
*Thiazides increase uric acid in plasma because they enhance urate reabsorption