Diuretics and hypertension Flashcards
BP equation
cardiac output x peripheral vascular resistance
primary hypertension makes up
85-90%
risk factors of HTN
family history, sex, diet, smoking, diabetes, hyperlipedemia, age, race
the goal of pharmacotherapy
reduce diastolic blood pressure to reduce incidence of end organ damage
drugs work to
reduce CO and reduce PVR by vasodilation and decrease blood volume
4 targets of therapy
Brain (control autonomic output from CV control center), heart (reduce CO), Kidney (RAAS), vasculature (vasodilators)
Things to consider when making therapy decisions
JNC8, compensatory responses, ADR, cost, factors with compliance, baseline BP
the principle of diuretics
where Na goes, water will follow, ussed for HTN, edema, CHF, hepatic cirrhosis, diabetes insipidus, renal diseases
Three major mechanisms involved in excretion
glomerular filtration (in bowman’s capsule), tubular secretion (active transport), reabsorption (urine back to plasma)
Glomerulus is responsible for
filtering water and ions
Proximal convoluted tubule
50% of filtered water is reabsorbed, glucose and bicarb also, contains pumps for tubular secretion of drugs into urine, diuretic activity of acetazolamide and mannitol
Descending Loop of henli
water can still be reabsorbed, Na and K also move back into plasma, diuretic activity of mannitol, loop diuretics and thiazide diuretics
Ascending loop of henli
K and Na (thicker portion has Na only) reabsorbed, often called diluting loop, diuretic activity is loop diuretics
distal convoluted tubule
Na, H2O and Ca reabsorbed, hormonal involvement, K and urea secreted back into urine, macula densa serve as feedback for detecting amount of Na reabsorption
If a high amount of Na is detected in DCT…
a message is sent to slow filtration
Collecting duct
85% of filtered Na has been reabsorbed, all drugs that act prior to this point can cause K loss and can be significant, diuretic activity: K sparing diuretics and osmotic diuretics
we give drugs to alter gradients and pull water to…
the urine
any time Na is reabsorbed…
the urine will be left with a negative charge, this is compensated for by secreting K in the urine
Carbonic anhydrase inhibitors
CA is an enzyme responsible for facilitating H and Na exchange that results in reabsorption, blocking these causes diuretic effect; least used
where do carbonic anhydrase inhibitors work
in the proximal convoluted tubule
Acetazolamide
CA inhibitors; decrease Na, HCO and H2O reabsorption, IV, PO and opthalmic drops, used for alkalinization, metabolic alkalosis, glaucoma, acute mt disease, renal stones, cheap, old, not used
Methazolamide
CA inhibitor never used for anything
Loop diuretics
block Na, K, Cl transporter blocks reabsorption, which eliminates reabsorption K intracellularly which limits need for K only transporter, reduces amt of Ca and Mg moving in and out of urine
Uses of loop diuretics
most efficacious of diuretics, edamatous conditions (CHF etc) acute pulmonary edema, hypercalcemia, hyperkalemia, acute renal failure
ADR of loop diuretics
hypokalemia, hyperuricemia, hypomagnesemia, dehydration
Considering extremes with diuretics
Thanksgiving, can take more, if ill can take less
Furosemide (Lasix)
Loop diuretic, 20-80mg PO once daily, dosing 1mg IV=2mg PO**, CHF, not recommended for HTN, may need KCl supp, maybe sulfa alergy?, old, cheap
Bumetanide (Bumex)
Loop Diuretic, More potent than lasix (1:40), 1 mg IV= 2 mgPO, CHF but not first line, end stage/advanced, ADR hypokalemia, old and cheap
Torsemide (demadex)
Loop diuretic, IV and PO, most infrequently used, 1:2 to lasix
Ethacryanic acid (Edecrine)
Loop diuretic, IV and PO, prodrug, DOC for sulfa allergy, very little if any use
Thiazide diuretics
block Na/Cl transporter, which drives Na into cell and Ca into blood, increased excretion of Na and H2O and K, and increase reabsorption of Ca, HTN
Thiazide like diuretics
hydrocholrothiazide, chlorthalidone, indapamide, metolazone
ADR of thiazide diuretic
Hypokalemia, hypercalcemia, hyperuricemia, hyperlipidemia, impaiired carbohydrate tolerance, hyponatremia
Hydrochlorothiazide (Hydrodiuril)
HCTZ, thiazide, PO only, DOC for many HTN pt, combo therapy, compromises kidney fx, old and cheap
Metolazone (Zaroxolyn)
thiazide diuretic, potent (1:10 HCTZ), HTN, CHF*(stage 3 and 4) and edema, often KCl supp
Indapamide
Thiazide diuretic, HTN and edema, once daily, rarely used
Chlorthalidone
thiazide diuretic, HTN and edema, once daily, rarely used, combo with atenolol
Potassium sparing diuretics
aldosterone antagonist or Na channel blockers
aldosterone antagonists
spironolactone, eplernone, block receptors, which increase Na passing into collecting duct for urine excretion, no K effect
Na channel blockers
Triamterene, amicride, block epithelial Na channels directly, which reduces Na reabsorption and reduced K excretion, and increase Na passing in to collecting duct
Spironolactone (aldactone)
aldosterone antagonist, PO, adjust for renal, high protein bound, use CHF, edema, ascites, also hypokalemia, HTN, acne, aldosteronism; avoid in renal failure; ADR: hyperkalemia, fatigue, nausea etc; take w/ food
Which is most common aldosterone antagonist
spironolactone (aldactone)
Eplerenone (inspra)
aldosterone antagonist, rare CHF, HTN, ADR: hyperkalemia, hypertriglyceridemia, niche: absent hormonal adrs
Triamterene
Na channel blocker, never used by self, HTN, edema, ADR: hyperkalemia, dehydration, black box for hyperkalemia
Amiloride
Na channel blocker, rare use by self, HTN not CHF, once daily, ADR: hyperkalemia, hyperchloremic metabolic acidosis
osmotic diuretics
Mannitol, via osmotic pressure, excreted but not reabsorbed, neither is H2O, used to reduce ICP, ADR: extracellular volume expansion, dehydration, hypernatremia
Antidiuretic hormoone antagonists
Demeclocycline, antibiotic, reduces H2O reabsorption by inhibiting effects of ADH in collecting tubule, use hyponatremia, SIADH, ADR: diabetes insipidus, renal failure
Most common used Diuretic
loop (furosemide and bumetanide) and Thiazide (hydrochlorothiazide)
All diuretics are associated with
increase Na and H2O excretion, risk dehydration and hyponatremia
It is important to keep in mind levels of
potassium, need it excreted or reabsorbed
when should pt take diuretics
in the morning
