Cardio VI Flashcards
What are the three prototypical Thiazide diuretics?
Chlorthalidone
Hydrochlorothiazide
Metolazone
Indapamide
What is the MOA of thiazide diuretics like chlorthalidone?
block the Na/Cl cotransporter in the distal collecting ducts
What is the effect of thiazide diuretics on Ca?
Increase reabsorption (therefore decreasing excretion)
What is the effect of thiazide diuretics on the vasculature? How?
Vasodilation
Increased Ca leads to increase NO synthesis
What are the drugs that cause Ca loss? Ca reuptake?
Loss = loop diuretics Uptake = thiazide diuretics
Thiazide diuretics are indicated with edema caused by what?
CHF
Hepatic cirrhosis
Renal disease
When are thiazide diuretics contraindicated for edema?
if GFR is less than 30-40 ml/min
Why are thiazide diuretics used to treat HTN?
Inexpensive, well tolerated
Why are thiazide diuretics used in treating renal stones?
Increase Ca uptake= decrease in urine
Why are thiazide diuretics used to treat nephrogenic DI?
reduce urine volume and increase Na reabsorption
Do thiazide diuretics cause hypokalemia?
Yes
What is the cause of nephrogenic DI?
Loss of aquaporins
What are the major adverse effects of thiazide diuretics?
Hypokalemia
Metabolic acidosis
How do thiazide diuretics cause hyperglycemia?
Impairment of pancreatic insulin secretion
What is the relationship between thiazide diuretics and hyperlipidemia?
increases total serum cholesterol
How do thiazide diuretics cause hyponatremia?
increased Na excretion
What drug class share cross-reactivity with thiazide diuretics?
sulfa drugs
What are the two prototypical inhibitors of renal epithelial Na channels?
Amiloride
Triamterene
What is the MOA of amiloride?
Inhibit renal epithelial Na channels in the late distal tubule and collecting duct by competing with Na for the channel
What group of diuretic drugs have to be used in combination with another diuretic class?
epithelial Na channel inhibitors
True or false: Na channel inhibiting diuretics have only a weak diuretic effect on their own
True
How is it that Na channel inhibitors are K sparing diuretics?
If you inhibit the Na channel, K will not flow out of the cell
What is the main use of Na channel inhibitors?
used in combination with loop diuretics to prevent hypokalemia
What is the MOA of chlorthalidone?
Thiazide diuretic
What is the MOA of hydrochlorothiazide?
thiazide diuretic
What is the MOA of metolazone?
Thiazide diuretic
What is the MOA of indapamide?
Thiazide diuretic
What is the MOA of triamterene?
Renal epithelial Na channel inhibitor
Which type of diuretic is K sparing?
Inhibitors of renal epithelial Na channels (amiloride/triamterene)
Aldosterone blockers
What is the MOA of spironolactone?
Aldosterone receptor antagonist
What is the MOA of eplerenone?
Aldosterone receptor antagonist
What is the effect of activation of the aldosterone receptor on renal epithelial cells?
Increase Na/K pump on basolateral side, and increased channels on the lumenal side.
Causes increased K excretion, decreased Na excretion
What part of the renal tubule are aldosterone receptors found?
distal tubule and collecting duct
What happens when you block aldosterone?
Decreased K loss
Increased Na loss
Increased water loss
Which type of diuretic does not require access to the tubular lumen to induce diuresis?
Aldosterone receptor antagonists
Are spironolactone and Eplerenone competitive or noncompetitive aldosterone receptor antagonists?
Competitive
How do aldosterone receptor blockers like spironolactone prevent LV remodeling and cardiac fibrosis?
Inhibit matrix metalloproteases
Inhibit protein kinase C
How do aldosterone receptor blockers like spironolactone prevent sudden cardiac death? (3)
- improve HR variability
- Reduce QT dispersion
- Prevent severe hypokalemia
What are the hemodynamic effects of aldosterone inhibitors?
BP reduction
Moderate diuresis and natriuresis
What are the vascular effects of aldosterone inhibitors?
Decrease vascular NAD(P)H oxidase activity
What are the clinical uses of aldosterone inhibitors?
Edema and HTN
heart failure
What is the diuretic of choice when treating hepatic cirrhosis?
Aldosterone inhibitors
What is the most severe adverse effect of aldosterone inhibitors?
Hyperkalemia
What is the diuretic treatment of choice for primary hyperaldosteronism?
Aldosterone antagonists
What are the two main mechanisms by which diuretics lower BP?
Decrease TPR and Na/water
What is the upper limits of normal BP?
120/80
What is the range of high-normal BP?
120-140 /80-90
What is the range of BP for stage 1 HTN? What medication should you consider using? How often should you recheck?
140-160 / 90-100
Thiazide
3 months
What is the range of BP for stage 2 HTN? What medication should you consider using?
> 160 / >100
Thiazide and ACEI
2-4 weeks
What is the range of BO to diagnose isolated systolic HTN?
> 140 /
What are HTN crises?
High blood pressure and/or organ damage
What is a HTN urgency?
NO associated end organ damage
Have hours/days to treat
What is a HTN emergency?
Markedly elevated BO WITH end organ damage
have minutes/hours to treat
What are the four end organs in HTN emergencies?
Kidney
Brain
Heart
Retina
What is resistant HTN?
BP that is uncontrolled despite the use of three or more anti-HTN drugs (one of which is a diuretic)
What is pseudo-resistant HTN?
Uncontrolled HTN d/t white coat effect or poor adherence to HTN meds
Who is more at risk for HTN, females or males? Why?
Females–loss of estrogen
Which ethnicity is at higher risk of HTN?
African-americans
What is primary HTN?
Idiopathic rise in BP
What are the causes of secondary HTN?
Renal disease
Primary aldosteronism
What are some of the uncommon causes of secondary HTN?
Pheochromocytoma
Cushing syndrome
Hyperparathyroidism
Coarctation of the aorta
What should be you intent when treating HTN?
Treat with the intent of reducing CV events
What is the BP goal of treating pts
140/90
What is the BP goal of treating pts > 60 yo?
150/90
What medication should you consider adding if treating a stage 1 HTN pt for more than 3 months without a significant drop in BP?
Add ACEI
What is the diet for HTN?
DASH diet
How much EtOH is helpful with HTN?
2 drinks / day
True or false: once initiated, HTN is a lifelong disease
True
Why is it that there is no baroreceptor reflex in HTN?
Chronic HTN resets the reflex
Mean arterial pressure = ?
CO * TPR
CO = ?
HR * SV
What is the drug that is indicated for HTN secondary to another disease?
ACEI
What are the drugs that should be used to treat HTN with coronary artery disease?
Beta blocker
ACEI
What is the first line regimen for left ventricular dysfunction?
ACEI
Diuretic
Beta blockers
What is the first line regimen for HTN with previous ischemic stroke?
ACEI Thiazide diuretic (?)
What are the drugs that should be added on to HTN w/ DM?
thiazide
Beta blocker
CCB
What are the drugs that should be added on to HTN w/ coronary artery disease?
Aldosterone antagonist
CCB
thiazide
What are the drugs that should be added on to HTN w/ left ventricular dysfunction?
Aldosterone antagonist
Hydralazine
What enzyme is released by the kidneys to cleave angiotensinogen to angiotensin I?
Renin
What is the effect of angiotensin II?
Vasoconstriction and aldosterone release
Release vasopressin
What is the effect of aldosterone?
Increase Na reuptake
Increase K output
What is the enzyme that cleaves angiotensin I to angiotensin II?
ACE
What is the effect of increased Na at the tubular macula densa?
Vasoconstriction
Which are the three MOA of treating HTN via the angiotensin pathway?
Inhibit renin
Inhibit ACE
Inhibit angiotensin receptor
