7 - Hypertension Flashcards
Diagnosis of HTN
Two or more Diastolics >40
Systolic >90
Pulse pressure >65
Stage 2 HTN
S >160
D>100
Essential HTN
90% of cases, no identifiable cause
Increased PVR
Normal CO
Diuresis
an increase in urine volume
Natriuresis
Increase in Renal sodium
Clinical uses for diuretics
HTN, edema, CHF
Kidney disease, cirrhosis
Hypercalcemia
Diabetes insipidus
Acetazolamide SOA
PCT
(NaHCO3)
Mannitol (or other osmotic agents) SOA
PCT – H20
Furosamide SOA
Thick ascending limb
Thiazides SOA
DCT (early)
(NaCl)
Aldosterone SOA
Collecting tubule
(NaCl)
ADH antagonists SOA
Collecting tubule
(H20)
Adenosine SOA
Affererent arteriole, PCT, Thick ascending limb, Collecting duct
Acetazolamide class, MOA
Carbonic anhydrase inhibitor
Inhibit the formation of CO2 and H20 (from H2CO3) out in the lumen
→ CO2 and H2O are excreted
Prevent the reformation of H2CO3 in the PCT cell
Hemodynamic effect of long-term administration of diuretics
HR and CO are unchanged
Plasma volume = decreased/unchanged
TPR = decreased
Renin = increased
Mechanism for long term vasodilation with long term diuretics
unknown
Diuretics that act in the loop of henle
Furosamide
Bumetanide
Ethacrynic acid
Loop diuretics MOA
Inhibit the Na-K-2Cl symporter in the lumenal membrane
Loop diuretics - Effect on K+ dynamics
No accumulation of K
No K+ outflux back into lumen
NO Mg+ and Ca++ entry
How and where do Mg++ and Ca++ enter the cell in response to K outflux?
From the lumen of the Thick Asc. Limb via the paracellular route
Net ionic effects of loop diuretics
Increases excretion of all:
Na/ Cl / K / Mg / Ca
Increased ____ from loop diuretics is due to PG formation
RBF
Duration of action of loop diuretics depends on ____
Renal function
Toxicities of loop diuretics
Dehydration
Hypokalemic Met. Acidosis
Ototoxicity
Hyperuricemia
Hypomagnesemia
CI’s for loop diuresis
Sulfa allergy
____ are more effective antihypertensives than loops in patients with _________
Thiazides
Normal renal function
Thiazide MOA
Interfere with the NCC (Na-Cl Cotransporter) in the DCT
–> net excretion of Na (with water following)
Thiazides reduce the formation of
calcium stones in idiopathic hypercalcuria
Net ionic effects of thiazides
increase excretion of Cl, Na, K, and HCO3 (high doses only)
Reduce the excretion (Ca+)
Thiazide diuretics
Chlorthiazide
HCTZ
Trichlormethiazide
Methylclothiazide
Polythiazide
Cyclothiazide
Thiazide-like diuretics
Chlorthalidone
Indapamide
Metolazone
Thiazides may open…
Ca++ activated K+ channels
(leading to vasodilation)
Why decrease in peripheral resistance with thiazides?
Negative Na balance
What effect does K have on vascular state
K outflow hyperpolarizes the vascular smooth muscle –> increases vasodilation
In patients with renal insufficiency, thiazides…
lose the anti-hypertensive effect
Thiazide diuretics may cause these conditions
- Hypokalemia, Hyponatremia, Hypochloremic Alkalosis
- Hyperuricemia, Hyperlipidemia, Hypercalcemia
- Erectile dysfunction
CI’s for thiazides
sulfa allergies
Diuretics that act on the collecting tubule
Potassium-sparing
Amiloride
Trimterene
Eplerenone
Spironolactone
Amiloride MOA
Inhibit apical Na channels in collecting tubule
**Reduced Na entry also reduces K+ excretion
Clinical use for amiloride
Adjunct Tx with Thiazide or Loop for CHF or HTN
has some efficacy in reducing BP
Also used in Cirrhosis and edema due to secondary hyperaldosteronism
Amiloride toxicities
Hyperkalemia
Hyperchloremic met. acidosis
CI’s for amiloride
K+ supplementation
ACE inhibitors
Triamterene MOA
Inhibit apical Na+ channels in collecting tubule
also reduces K excretion (d/t reduced sodium entry)
Clinical use for triamterene
Edema associated with CHF, Cirrhosis, nephrotic symdrome, or hyperaldosteronism
Triamterene does not have efficacy in…
lowering BP when used as monotherapy
use in combo!
Toxicities for triamterene
Hyperkalemia, Hyperchloremic metabolic acidosis
CI’s for triamterene
Kidney stones
K supplementation
ACE inhibitors
Both triamterene and Amiloride are secreted in the
PCT
____ increases urinary excretion of Mg++ but ____ does not.
Triamterene does
Amiloride doesn’t
Other class of drugs that act on the collecting ttubule
Aldosterone antagonists
Counteract thiazide postassium loss with
amiloride or triamterene
Drug that controls the number of Na channels in the membrane
antagonist
Aldosterone works in the
nucleus to alter gene transcription
AIP
aldosterone induced proteins
upregulated with increased aldosterone
Function of AIP’s
controls proteins that traffic Na channels in and out of the membrane
Influences the amount of channels in membrane
Aldosterone antagonists downstream effects
Block aldosterone from binding receptor and inducing AIPs and downregulate Na channels for reabsorption from the lumen
LESS REABS. OF SODIUM FROM LUMEN
Aldosterone antagonists
aldosterone
spironolactone
Spironolactone MOA
- blocks acions of aldosterone
- blocks 5a reductase
(5a-reductase creates active metabolites of aldosterone)
Clinical use of spironolactone
HTN or CHF with other diuretics
Aldosterone and RAAS play a role in pathogenesis of
CHF
Tox’s with spironolactone
Hyperkalemia
HyperCL met acidosis
Gynecomastia, impotence, BPH
CI’s for spironolactone
K supplements, ACE inhibitors (promote K retention)
Chronic renal insufficiency
More selective mineralocorticoid receptor antagonist
Eplerenone
Eplerenone MOA
selective antag of MCR in kidney heart BV and brain
Eplerenone uses
HTN alone or combo
Eplerenone therapeutic effect should be observed within
4 weeks
Tox’s for eplerenone
hyperkalemia
Hypertriglyceridemia
CI’s for eplerenone
K supps, K sparing diuretics, ACE inhibitors
Chronic renal insufficiency
Diabetes associated with microalbuminemia
CYP450 3A4 inhibitors (ketoconazole)
