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Renal II Exam 2 > 8-14 DSA - Pharmacology of Antihypertensives > Flashcards

8-14 DSA - Pharmacology of Antihypertensives Flashcards

1
Q

In primary HTN, what are the general classes employed as initial monotherapy?

A

ACE Inhibitors/ARBs
Calcium channel blockers (long-acting)
Thiazide diuretics
Beta-blockers are NOT typically used in the absence of a specific indication

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2
Q

Why do the recommendations for black people differ for treating essential HTN?

A

Exhibit roughly equal efficacy, but some patients will respond to one drug and not to another

  • black patients respond better to thiazide diuretics and CCBs, and respond poorly to ACE inhibitors and beta-blockers
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3
Q

What classes of medications are recommended in kidney disease and HTN?

A

ACE inhibitors and ARBs are recommended in mild-to-moderate chronic kidney disease with or without diabetes because these agents are renoprotective

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4
Q

What is predictive of reduction in CV risk in patients with primary HTN?

A

Generally, the magnitude of BP reduction, not choice of drug, predicts reduction of cardiovascular risk

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5
Q

What are the advantages of monotherapy in treating HTN?

A

Although monotherapy of hypertension is advantageous due to an increase in patient compliance, a decrease in cost, and less adverse effects

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6
Q

What are the advantages in polypharmacy in treating HTN?

A

, polypharmacy is often required to treat many patients with hypertension

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7
Q

What is the rationale behind polypharmacy?

A

The rationale behind polypharmacy is that each of the drugs acts on one of a set of interacting, mutually compensatory regulatory mechanisms for maintaining blood pressure

Additional rationale is minimal toxicity: Two or three drugs at half standard doses might have greater efficacy and less toxicity than one drug at standard or twice standard dose

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8
Q

What are some examples of polypharmacy combinations to treat HTN?

A

ACEIs and calcium channel blockers (trandolapril/verapamil)
ACEIs and diuretics (benazepril/hydrochlorothiazide)
ARBs and diuretics (valsartan/hydrochlorothiazide)
β-blockers and diuretics (propranolol/hydrochlorothiazide)
Centrally acting agent and diuretic (reserpine/chlorothiazide)
Diuretic and diuretic (spironolactone/hydrochlorothiazide, see below)
Triple drug regimens are also common and typically include a thiazide diuretic, a dihydropyridine CCB, and either an ACE inhibitor, an angiotensin receptor blocker, or a renin inhibitor

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9
Q

What is a common choice if a patient no longer responds to the usual dose of loop diuretic?

A

loop and thiazide diuretic

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10
Q

Loop agents and thiazides in combination will often produce diuresis when either agent acting alone is minimally effective. What are the reasons for this?

A

Salt and water reabsorption in either the thick ascending loop (blocked by loop diuretics) or DCT (blocked by thiazides) can increase when the other is blocked; inhibition of both can produce more than an additive diuretic response

Thiazides often produce mild natriuresis (sodium excretion) in the PCT that is usually masked by increased absorption in the thick ascending loop; this combination can therefore block Na+ reabsorption from all three segments (PCT, ascending loop, and DCT)

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11
Q

For systolic heart failure, what combinations of drugs produce major improvement independent of BP?

A

ACE inhibitor or ARB

beta blocker

diuretic

aldosterone antagonist

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12
Q

For post-MI infarction, which drugs produce major improvement in outcome independent of BP?

A

ACE inhibitor

beta blocker

ARB

aldosterone antagonist

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13
Q

For proteinuric kidney disease, which drugs produce major improvement in outcome independent of BP?

A

ACE inhibitor or ARB

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14
Q

For angina pectoris, which drugs produce major improvement in outcome independent of BP?

A

Beta blocker

Ca++ channel blocker

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15
Q

For atrial fib rate control, which drugs produce major improvement in outcome independent of BP?

A

Beta blocker

non-dihydropyridine Ca++ channel blocker

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16
Q

For atrial flutter rate control, which drugs produce major improvement in outcome independent of BP?

A

beta blocker

non-dihydropyridine Ca++ channel blocker

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17
Q

For BPH, which drugs are likely to have a favorable effect on symptoms in comorbid conditions?

A

alpha blocker

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18
Q

For essential tremor, which drugs are likely to have a favorable effect on symptoms in comorbid conditions?

A

Beta blocker (noncardioselective)

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19
Q

For hyperthyroidism, which drugs are likely to have a favorable effect on symptoms in comorbid conditions?

A

beta blocker

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20
Q

For migraines, which drugs are likely to have a favorable effect on symptoms in comorbid conditions?

A

beta blocker

Ca++ channel blocker

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21
Q

For osteoporosis, which drugs are likely to have a favorable effect on symptoms in comorbid conditions?

A

thiazide diuretic

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22
Q

For Raynaud’s Syndrome, which drugs are likely to have a favorable effect on symptoms in comorbid conditions?

A

Dihydropyridine Ca++ channel blocker

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23
Q

What is an important contraindication for an ACE inhibitor?

A

Angioedema

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24
Q

What is an important contraindication for beta blockers?

A

bronchospastic disease

25
Q

What is an important contraindication for reserpine?

A

depression

26
Q

What is an important contraindication for methyldopa?

A

liver disease

27
Q

What is an important contraindication for pregnancy?

A

ACE inhibitor

ARB

renin inhibitor

28
Q

What is an important contraindication for second or third degree heart block?

A

beta blocker

non-dihydropyridine Ca++ channel blocker

29
Q

Which drugs may have an adverse effect on the comorbid condition of gout?

A

diuretic

30
Q

Which drugs may have an adverse effect on the comorbid condition of depression?

A

beta blocker

central alpha-2 agonist

31
Q

Which drugs may have an adverse effect on the comorbid condition of hyperkalemia?

A

aldosterone antagonist

ACE inhibitor

ARB

renin inhbitor

32
Q

Which drugs may have an adverse effect on the comorbid condition of hyponatremia?

A

thiazide diuretic

33
Q

Which drugs may have an adverse effect on the comorbid condition of renovascular disease?

A

ACE inhbitor

ARB

renin inhbitor

34
Q

Is loop diuretic combination recommended for routine outpatient use? Why?

A

Combination can cause profuse diuresis and therefore, routine outpatient use is not recommended (K+ wasting is extremely common)

35
Q

What is a popular choice for combination with loop agents?

A

thiazide

36
Q

What is a common side effect of loop agents and thiazide diurectic combination therapy? How is it managed?

A

Hypokalemia is a common side effect of loop agents and thiazide diuretics, which can initially be managed with dietary NaCl restriction (decreases Na+ delivery to the K+-secreting CCT, thus reducing K+ secretion; has also been shown to potentiate the effects of diuretics in essential HTN) or KCl supplementation

37
Q

What is another way to avoid hypokalemia with combination diuretic therapy?

A

adding K+ sparing diuretics - lowers K+ secretion

38
Q

What patients should not receive K+ sparing diuretics and loop agents or thiazides?

A

people with renal insufficiency

those recieveing ang II antagonists

39
Q

What are some combinations to avoid in treatment of HTN?

A

ACE inhibitors, ARBs, and renin inhibitors (only one at a time)
Beta-blockers and non-dihydropyridine CCBs
Potassium-sparing diuretics and ACE inhibitors/ARBs/renin inhibitors

40
Q

What is HTN urgency?

A

Severe hypertension (> 180/120 mmHg) without acute end-organ damage

41
Q

What is HTN emergency?

A

Severe hypertension (> 180/120 mmHg) with acute end-organ damage

42
Q

What is the general strategy for handling HTN urgency/emergency?

A

Choice of agent and blood pressure goal will vary on a case-by-case basis

In general, controlled and gradual BP reduction (10-20% in the first hour and by a further 5-15% over the next 23 hr) may prevent excessive hypotension that could lead to MI, stroke, or loss of vision

There are some exceptions to the rule regarding gradual BP reduction

43
Q

What 2 drugs work well for HTN emer/urgencies

A

Vasodilators

Adrenergic antagonists

44
Q

What vasodilators are helpful for HTN emer/rgencies?

A
  • *Sodium nitroprusside:** considered the most effective parenteral drug for hypertensive emergencies; potential for cyanide toxicity limits prolonged use
  • *Nitroglycerin**: less antihypertensive efficacy than other agents for HTN emergencies; useful adjunct in patients with cardiac ischemia or after coronary bypass surgery
  • *Nicardipine**: DHP-CCB with longer onset of action and longer elimination half-life, but good safety profile
  • *Clevidipine**: ultra short-acting DHP-CCB is approved only for hypertensive emergencies
  • *Enalaprilat**: rarely used due to slow onset and long duration of action; hypotensive response is unpredictable and dependent on plasma volume and plasma renin activity
  • *Fenoldopam**: maintains or increases renal perfusion by dilating renal arteries; possibly a good choice for patients with renal dysfunction; avoid in glaucoma
  • *Hydralazine**: use of parenteral form limited by prolonged and unpredictable hypotensive effect; considered safe in pregnant patients (see below)
45
Q

What are some good adrenergic antagonists for an HTN emergency?

A
  • *Phentolamine:** nonselective α-blocker used to treat patients with hypertension due to elevated catecholamines (cocaine intoxication, pheochromocytoma)
  • *Esmolol**: rapid but short-acting β1-blocker used to treat aortic dissection or postoperative hypertension
  • *Labetolo**l: combined α- and β-blocker that may be safe in patients with active coronary disease
46
Q

What are some considerations for pharmacotherapy for treating HTN in pregnancy?

A

Consider risks and benefits for both mother and fetus
Maternal benefit is well-established for treatment of severe hypertension (systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 110) in reduction of stroke risk

Timing of delivery: if cesarean delivery is imminent, pharmacotherapy may not be necessary

Maternal or fetal benefits have not been shown for treatment of mild to moderate hypertension
All anti-hypertensives cross the placenta; some may inhibit fetal growth

47
Q

What are some drug options for treatment of acute HTN in pregnancy?

A
  • *Labetalol (IV)**: effective, rapid onset of action, good safety profile
  • *Hydralazine (IV)**: has been used extensively in the setting of preeclampsia
  • *Calcium Channel Blockers**: sustained release nifedipine or immediate release nicardipine; nicardipine can also be given IV; data is more limited for use in pregnancy compared to labetalol and hydralazine
  • *Nitroglycerin (IV)** is a good option for HTN associated with pulmonary edema
48
Q

What are some choices for long-term management of HTN in pregangnt women?

A
  • *Methyldopa**: long-term safety for the fetus has been demonstrated; mild antihypertensive of limited efficacy; sedative effect is bothersome to already fatigued patients; clonidine is another centrally acting sympatholytic that is considered safe in pregnant women
  • *Labetalol**: more rapid onset of action than methyldopa; alternatives in this category include pindolol and long-acting metoprolol; safety is controversial
  • *Nifedipine (extended release)**; other CCBs , including non-DHPs, have been used in pregnant patients, but only small numbers of patients are reported in the literature
  • *Hydralazine**: Due to reflex tachycardia, monotherapy with oral hydralazine is not recommended; hydralazine may be combined with methyldopa or labetalol if needed as add-on therapy
  • *Thiazide diuretics**: use is controversial due to potential fluid loss; some guidelines suggest they are safe to continue in patients who began taking them prior to pregnancy; generally only introduced during pregnancy if pulmonary edema has developed
49
Q

What are some agents contraindicated during pregnancy?

A

ACE inhibitors, ARBs, direct renin inhibitors: these drugs are associated with significant fetal renal and cardiac abnormalities

Nitroprusside: possible fetal cyanide poisoning if used for more than a few hours; last resort for urgent control of severe refractory HTN

50
Q

What is a common pathological process that diuretics are used for? What is this process ‘sensed’ by the body as?

A

A common use for diuretics is for the reduction of peripheral or pulmonary edema that has accumulated as a result of cardiac, renal, or vascular diseases that reduce blood delivery to the kidney

Physiologically, this reduction is sensed as a lack of effective arterial blood volume and leads to salt and water retention, followed by edema formation

51
Q

What edematous states are treated with diuretics?

A

heart failure

kidney disease

hepatic cirrhosis

52
Q

How does edema occur as a result of heart failure?

A

Heart failure reduces cardiac output, which results in a decrease in blood pressure and blood flow to the kidney
Decreases in BP and blood flow is sensed as hypovolemia and leads to renal retention of salt and water
Pulmonary or interstitial edema occur when the plasma volume increases and the kidney continues to retain salt and water, which then leaks from the vasculature

53
Q

How does edema occur as a result of kidney disease?

A

Most kidney diseases cause retention of salt and water

When loss of renal function is severe, there is insufficient glomerular filtration to sustain a natriuretic response and diuretic agents are of little benefit

Patients with mild cases of renal disease can be effectively treated with diuretics when they retain sodium

Diuretics are beneficial in glomerular diseases, such as systemic lupus erythematosus or diabetes mellitus, that exhibit renal retention of salt and water

Loop and thiazide diuretics are beneficial in individuals that develop hyperkalemia associated with early stage renal failure

54
Q

How does hepatic cirrhosis cause edema? Do you give these patients diuretics?

A

Diuretics are useful when edema and ascites (accumulation of fluid in the abdominal cavity) become severe due to liver disease

Aggressive use of diuretics can be disastrous in patients with liver disease (more so than heart failure)

55
Q

What are some nonedematous states that are treated with diuretics?

A

HTN

Nephrolithiasis

Hypercalcemia

Diabetes insipidus

56
Q

How is HTN treated with diuretics?

A

Hypertension

Thiazides are often used because of their diuretic and mild vasodilator activities

Loop diuretics are often reserved for patients with mild renal insufficiency or heart failure

Diuretics are often used in combination with vasodilators (hydralazine, minoxidil) because vasodilators cause significant salt and water retention

57
Q

How is nephrolithiasis treated with diuretics?

A

2/3 of kidney stones contain calcium phosphate or calcium oxalate

Thiazide diuretics enhance Ca2+ reabsorption in the DCT and reduce urinary Ca2+ concentration, making them appropriate agents in the treatment of kidney stones

58
Q

How is hypercalcemia treated with diuretics?

A

Loop diuretics reduce Ca2+ reabsorption and promote Ca2+ diuresis, but can also cause marked volume contraction when used alone (counterproductive)

Saline can be administered simultaneously with loop diuretics to maintain effective Ca2+ diuresis

59
Q

How is diabetes insipidus treated with diuretics?

A

Can be due to either deficient production of ADH (neurogenic or central diabetes insipidus) or inadequate responsiveness to ADH (nephrogenic diabetes insipidus)

Supplementary ADH or one of its analogs is only effective in central diabetes insipidus
Thiazide diuretics can reduce polyuria and polydipsia in both types of diabetes insipidus

Renal II Exam 2 (8 decks)

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