Adrenergic Agonist, Diuretics, ADH Flashcards
What causes the release of adrenergic amines?
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
Axoplasmic uptake
Reuptakes NE in synapse
–> is sensitive to cocaine and tricyclics which inhibit it so more NE is in synapse –> increased BP
Reserpine
inhibits granular pump –> accumulates catecholamines in vesicles
depleter
Guanethidine
induces release from vesicle
slow acting
depletes NE stores
reduces responses to sympathetic stimulation
Degradation of adrenergic amines
COMT (catechole-O-methyl transferase)
- important in liver for inactivating circulating catecholes
MAO (monoamine oxidase)
- types a (intestine and brain), b (organs)
MAO inhibitors
- Pargyline (seligeline)
- potentiates the action of catecholamines
- avoid foods with tyramine –> hypertensive crisis
Beta 1 receptor
Isoproterenol > epi = norepi
- adrenergic cardiac effects, renin release
- located in heart, JG apparatus, and adipose tissue
- acts to increase cAMP via Gs(alpha)
Alpha 1 receptor
epi >= norepi»_space;iso
- mediates smooth muscle contraction (vessels)
- activates PLC –> increase [Ca2+] via IP3
Beta 2 receptor
iso > epi»_space;» norepi (NE not a substrate for beta 2)
- relaxation of smooth muscle (vessels)
- acts to increase cAMP via Gs(alpha)
Alpha 2 receptor
epi >= norepi»_space; iso
- inhibition of neural NE release
- prejunctional nerve terminal, platelets, guy, medulla
- acts to decrease cAMP or activate Na/H antiporter
Dopaminergic receptor
dopamine is substrate
- dilation of renal and mesenteric vasculature
Dobutamine
selective beta 1 agonist (only one!!!!)
- positive inotrope
- used in CHF and acute MI with HF
- administered IV
Phenylephrine
alpha 1 agonist
- used to reverse hypotension and paroxysmal atrial tachycardia
- increases BP
Terazosin
- azosin suffix
- alpha blocker!
Metaproterenol, Albuterol, Terbutaline, Ritodrine, Salmeterol
Selective beta 2 agonists!
- used for bronchodilation (asthma) and to delay labor
- SE = tachycardia and palpitations
- decrease BP`
Clonidine, alpha-methyldopa, Guanabenz
Alpha 2 agonists
- antihypertensives, also ADHD
Epinephrine
alpha 1, beta 1, and beta 2 receptor activity
- vasoconstricts (alpha 1), vasodilates (beta 2)
- directly increases HR and contractility (beta 1)
Norepinephrine
alpha 1 and beta 1 activity
- vasoconstricts (alpha 1), increased HR and contractility (beta 1)
Isoproterenol
- synthetic catecholamine stimulating beta receptors
- vasodilates (beta 2), tachycardia (beta 1)
Dopamine
- positive inotrope (beta 1)
- vasoconstrictor (alpha 1) at higher doses
Amphetamine
releases NE from nerves –> increases BP
- reverses direction of axoplasmic pump
Ephedrine
Pseudoephedrine
release NE from nerves by reversing axoplasmic uptake pump –> increases BP
uses - bronchospasm or nasal congestion
Loop Diuretics
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
Thiazide Diuretics
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
What part of MAP equation do diuretics affect?
The stroke volume portion of CO –> which results in affecting the venous return curve
Potassium sparing diuretics
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
ADH
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
Demecocycline
antibiotic with ADH antagonist activity
Where are Na+ sensors?
macula densa
Osmotic Diuretics
mannitol
- not reabsorbed in nephron –> exerts osmotic effect to retain water in nephron tubule –> more urine
reduces body water
reduces intracranial or intraocular pressure
Carbonic Anhydrase Inhibitors
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
Organic Anion Transporter Inhibitors
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
