133 Hypertension Flashcards
Prevalence of hypertension
1 in 4 adult americans
smoking is a worse factor of CVD than hyptertension
Classifications of hypertension
Consensus treatment of blood pressure guidelines
factors that affect BP
- volume
- cardiac output
- peripheral vascular resistance
Volume receptors (high, low)
High Pressure: Carotid sinus, aortic arch, left ventricle, and the juxtaglomerular apparatus
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Low Pressure: Cardiac atria, right ventricle, and pulmonary vessles
Effectors: RAA, Sympathetic nerves, ANP, ADH, Pressure natriuresis
Effect: Urine Na+ excretion
•Regulation of sodium, predominantly by the kidney, controls the volume of the extra-cellular compartments (intravascular)
Diuretics: Distal Convoluted Tubule
- •Class often called Thiazides because hydrochlorothiazide is the most well known and recognized
- -Hydrochlorothiazide (HCTZ), Chlorthalidone, Metolazone
- •Inhibit the Na – Cl symporter in the distal convoluted tubule.
- •Side effects: Impotence, fluid and electrolyte imbalances, impaired glucose tolerance, and increased cholesterol
- Hypokalemia, hyponatremia, hypercalcemia
- Shown to decrease cardiovascular morbidity and mortality (low doses that do not cause hypokalemia). A first line treatment option for hypertension.
Thiazides example SOAP
Diuretics: Loop
- •Agents: Furosemide (Lasix), Torsemide (Demadex), Bumetanide (Bumex)
- •Inhibit the Na+-K+-2Cl- symporter in the thick ascending limb of the loop of Henle.
- •Side effects: Fluid and electrolyte imbalances, volume depletion, ototoxicity, hyperuricemia, hyperglycemia, increased LDL and triglycerides
- -Hypokalemia, hypocalcemia, and hypomagnesemia
- Used for volume overload (rapid diuresis). Used for HTN particularly in chronic kidney disease. Can also be used with normal saline to treat hypercalcemia. Used for Heart Failure fast.
Loop Diuretics SOAP
Diuretics: K+ Sparing
- Agents: Triamterene, Amiloride, Spironolactone, Eplerenone
- Mechanism: Triamterene and Amiloride inhibit renal epithelial Na+ channels in the late distal tubule and collecting duct. Spironolactone and Eplerenone antagonize the mineralocorticoid receptor on epithelial calls in the late distal tubule and cortical collecting duct.
- Happens at Principal Cell in collecting tubule (main job is to absorb Na+)
Side effects:
- Amiloride and Triamterene: Hyperkalemia, nausea, vomiting
- Spironolactone: Hyperkalemia, gynecomastia
- Adjunctive treatments with diuretics to avoid hypokalemia. Use caution if at risk for hyperkalemia.
Potassium Sparing Diuretics SOAP
Spironolactone
Amiloride
General effect of diuretics on body (leading mechanism) + Summary info
- Lower blood pressure by decreasing intravascular volume (and cardiac output). With chronic use, they promote vasodilation.
- Main side effects are electrolyte abnormalities and volume depletion.
- Drug interactions center on exacerbation of electrolyte abnormalities or volume depletion.
- Distal convoluted tubule diuretics (thiazides) have been shown to lower blood pressure and decrease cardiovascular morbidity and mortality. They are first line agents for many patients.
- •If the proximal tubule absorbs > 60 of sodium, why are proximal tubule diuretics not good for hypertension ?
- •Which is better for hypertension, a loop diuretic or a thiazide diuretic ?
- •Will a diuretic make a person urinate more ?
•If the proximal tubule absorbs > 60 of sodium, why are proximal tubule diuretics not good for hypertension ?
-When kidney senses lots of sodium loss at PCT the other parts (DCT and OMCD) rev up so net loss Low
•Which is better for hypertension, a loop diuretic or a thiazide diuretic ?
-Loop diuretic acute aggressive volume loss, thiazide better for uncomplicated patient for controlling chronic HTN
•Will a diuretic make a person urinate more ?
-First couple days you lose 5% volume, but after then you shouldn’t be peeing any more
Renin Angiotensin System overview and players
Aldosterone:
- •Aldosterone is produced by the Zona Glomerulosa of the Adrenal Cortex
- •It acts in the distal nephron to cause Na+ absorption, and K+ and H+ excretion
Drugs Affecting the Renin-Angiotensin System
•Angiotensin Converting Enzyme Inhibitors:
- Captopril, enalapril, lisinopril, quinapril, ramipril, benazepril, fosinopril …
-Mech: Block the conversion of angiotensin I to the active angiotensin II by inhibiting angiotensin converting enzyme.
•Angiotensin II Receptor Blockers:
-Losartan, candesartan, irbesartan, valsartan …
Mech: -Block the Angiotensin II receptor. There are two angiotensin II receptors (referred to as AT1 and AT2), and the ARBs in current use block the type 1 receptor (AT1). The type 1 receptor is found in myocardial tissue, brain, kidney, smooth muscle cells, and adrenal glomerulosa cells.
Angiotensin converting enzyme inhibitors (ACE-I):
Angiotensin converting enzyme inhibitors (ACE-I):
-Block the conversion of angiotensin I to the active angiotensin II by inhibiting angiotensin converting enzyme.
Captopril, enalapril, lisinopril, quinapril, ramipril, benazepril, fosinopril
Renin Angiotensin System:
Effect of ARB
- Block the Angiotensin II receptor. There are two angiotensin II receptors (referred to as AT1 and AT2), and the ARBs in current use block the type 1 receptor (AT1). The type 1 receptor is found in myocardial tissue, brain, kidney, smooth muscle cells, and adrenal glomerulosa cells.
- Losartan, candesartan, irbesartan, valsartan …
Side effects of ACE-Is and ARBs
- •ACE-I: Cough, hyperkalemia, renal failure, fetal toxicity, angioedema
- •ARBs: Hyperkalemia, renal failure, fetal toxicity. Rare angioedema, no cough.
- •Why is there no cough, much less angioedema with ARBs?
- -Less Bradykinin
increased risk of birth defects with ACEs and ARBs
ACE-I/ARB SOAP
- •Hypertensive patients, particularly:
- -Patients with heart failure
- -Patients with diabetes/proteinuria
- -Patients with CAD/post MI
- •Excellent adjunctive agents (particularly diuretics)
- •ARBs have an excellent side effect profile, many are now generic
•Thinking of electrolytes, why do ACE-I (or ARBs) work well with thiazide type diuretics?
Similarly, what would you have to watch for when using ACE-I (or ARB) with potassium sparing diuretics?
•Thinking of electrolytes, why do ACE-I (or ARBs) work well with thiazide type diuretics?
-Thiazide cause more sodium delivery to distal part of kidney which is exchanged for potassium so you get hypokalemia, but ACE-I cause this exchange to happen less so you get hyperkalemia, so using both gives happy medium
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•Similarly, what would you have to watch for when using ACE-I (or ARB) with potassium sparing diuretics?
-Potassium sparing will cause you to hold on to K, and ACE-I also reduce the exchange and casue hyperK so watch for this!
Centrally Acting Agents Hypertension
- Agents: Methyldopa, clonidine, guanabenz, guanfacine
- Mechanism:
- Methyldopa replaces norepinepherine in the secretory vesicles of adrenergic neurons. Although it is a potent vasoconstrictor, it acts centrally on the brain to inhibit central adrenergic outflow.
- Clonidine (guanbenz, guanfacine) stimulates the centrally located α2-receptor
SIDE EFFECTS:
•Methyldopa: Sedation, dry mouth, decreased energy, depression, liver toxicity
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•Clonidine, Guanabenz, Guanfacine: Sedation/somnolence, dry mouth, depression, bradycardia. Can get withdrawal symptoms (headache, HTN, tremors, sweating) if high dose is stopped suddenly.
SUMMARY:
•The centrally acting agents work by central inhibition of adrenergic outflow.
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•Side effects are primarily CNS related, and prevent them from being first line agents
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•Useful adjunctive agents with minimal interactions with other drug
Methyldopa
-Methyldopa replaces norepinepherine in the secretory vesicles of adrenergic neurons. Although it is a potent vasoconstrictor, it acts centrally on the brain to inhibit central adrenergic outflow.
Side effect: •Methyldopa: Sedation, dry mouth, decreased energy, depression, liver toxicity
Population: •Well established agent, particularly in pregnancy. Side effects make it an alternative option.
