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Pharmacology > Anti-Hypertensives > Flashcards

Anti-Hypertensives Flashcards

1
Q

What factors stimulate increased secretion of Renin?

A
  1. Decreased macula densa intracellular NaCl (from NKCC2)
  2. Decreased afferent renal blood pressure (sensed by JG cells) -> inhibits prostaglandins
  3. Activation of beta-1 adrenergic receptors
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2
Q

Why do NSAIDs interfere with the RAA system?

A

Signalling for release of renin is done via prostaglandins

-> inhibition of synthesis will inhibit the pathway

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3
Q

What inhibits renin release?

A

When angiotensin 2 feeds back on an AT1 receptor (receptor for AT2)

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4
Q

What does ACE do and where is it located?

A

Cleaves Angiotensin 1 to Angiotensin 2, also catalyzes the degradation of bradykinin

Located on vascular endothelium of most organs, but especially lung and kidney

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5
Q

What are the three main effects of angiotensin 2?

A
  1. Increased arterial pressure
  2. Na / fluid retention
  3. Vascular and cardiac remodeling
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6
Q

How does angiotensin 2 affect blood pressure in the kidneys and peripherally in general?

A

Directly causes arteriolar and vasoconstriction, and constricts the efferent arteriole of the kidney, generally increasing or having mixed effects on the GFR

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7
Q

What is the effect of AT2 on the kidney?

A

Directly stimulates Na/H exchanger in proximal tubule, and also enhances aldosterone secretion

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8
Q

What is the effect of AT2 on cardiac / vascular remodelling?

A

Stimulates the migration, proliferation, and hypertrophy of vascular smooth muscle cells, as well as hypertrophy of cardiac myocytes. Promotes myocardial fibrosis through aldosterone.

Also increases preload (volume expansion) and afterload (greater peripheral resistance)

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9
Q

Give two important ACE inhibitors

A

Enalapril

Lisinopril

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10
Q

Why are ACE inhibitors important in chronic heart failure? What effect does this have on cardiac output and stroke volume?

A

Reduce preload and afterload, thus slowing the progress of ventricular dilation

This actually increases cardiac output and stroke volume in CHF

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11
Q

What affect does an ACE inhibitor have on GFR?

A

Tends to decrease GFR due to lack of constriction of efferent arteriole, which helps with proteinuria

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12
Q

What diabetic condition are ACE inhibitors good at treating?

A

Diabetic nephropathy

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13
Q

Give two important side effects of ACE inhibitors?

A
  1. Persistant dry cough
  2. Hyperkalemia (due to decreased aldosterone secretion) -> especially a problem in renal failure or if patient is on another K+ sparing diuretic
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14
Q

Why should NSAIDs not be used with ACE inhibitors?

A

Can precipitate renal injury due to decreased RBF, and cause hyperkalemia

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15
Q

When are ACE inhibitors contraindicated?

A

Pregnant patients -> teratogenic

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16
Q

What is the name of the renin inhibitor?

A

Aliskiren

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17
Q

What are the untoward effects of Aliskeren? Contraindication?

A

Mainly GI disturances and cough

Contraindicated in pregnancy

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18
Q

Give two angiotensin receptor (AT1) blockers: ARBs?

A
  1. Losartan

2. Valsartan

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19
Q

When are ARBs given? Contraindication?

A

In patients who develop ACE-inhibitor-mediated cough, since ARBs do not cause this

Contraindication is still pregnancy

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20
Q

What is the half life of an ACE inhibitor?

A

About 12 hours -> good for pairing with HCTZ or other K+ wasting diuretic

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21
Q

What is the neprilysin inhibitor and how does this work? Who is it used in?

A

Sacubitril

Inhibits neprilysin, which is responsible for cleavage of natriuretic peptides which have good effects.

Used in combination with valsartan for treatment of heart failure

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22
Q

Why are ACE inhibitors and ARBs good in acute myocardial infarction?

A

They reduce cardiac work

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23
Q

What are the four general effects of beta blockers that make them useful for management of cardiac conditions?

A
  1. Decreased cardiac excitability
  2. Antihypertensive effect
  3. Reduced inotropy
  4. Reduced cardiac remodelling (which is normally induced by longterm exposure to NE)
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24
Q

How do beta blockers reduce oxygen consumption by the heart?

A

They reduce the heart rate, allowing for increased filling time and stroke volume

Furthermore, they reduce the inotropy of the heart, resulting in less forceful contractions

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25
Q

How do beta blockers protect against arrhythmias?

A

Slowing of conduction velocity and increasing refractory period in atrial muscle and the AV node

-> this reduces the risk of supraventricular tachyarrhythmias escaping into the ventricles (i.e. atrial tachycardia)

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26
Q

How do beta-blockers work as an anti-hypertensive?

A

Blocking of beta-1 receptors in the JGA will greatly downregulate renin release

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27
Q

When are beta-blockers used as a monotherapy for hypertension?

A

In more complicated hypertension, where there is a co-morbidity responding to beta blockade: i.e. hyperthyroidism, migraine, angina, congestive heart failure, or MI

28
Q

Why are all beta-blockers contraindicated in asthma?

A

Because beta-blockers all tend to undergo extensive CYP450 first pass metabolism, even cardioselective beta-blockers (i.e. A-BEAM) have the potential to antagonize beta-2 receptors depending on the patient’s degree of metabolism

Beta1 blockers are selective but not specific

29
Q

Why might atenolol be used rather than metoprolol?

A

It does not undergo first pass metabolism

Both are beta-1 selective

30
Q

What beta-blockers are not recommended in MI?

A

Acebutolol and pindolol -> beta-blockers with intrinsic b1 sympathetic agonist activity (do not want to stimulate the heart)

31
Q

What is a unique side effect of labetalol?

A

Because of it’s alpha1-blocking activity, it can cause orthostatic hypertension

It is used to manage hypertension in pregnant patients

32
Q

How is carvedilol metabolized, and why is it great for heart failure?

A

Via CYP2D6

Great for heart failure due to inhibition of oxygen radical mediated lipid peroxidation and vascular smooth muscle mitogenesis

33
Q

What is sotalol and its primary indication?

A

A non-selective beta-blocker (like propanolol), but also is a potassium-channel blocker in the heart, delaying repolarization.

-> effective anti-arrhythmic drug by slowing repolarization

34
Q

When is esmolol given?

A

It is a short-acting beta 1 blocker (half-life 10 minutes) given IV in emergency situations to control arrhythmias, acute hypertension, and myocardial ischemia

35
Q

What are the two primary side effects of concern for beta blockers?

A
  1. CNS effects
  2. Hypoglycemia / dyslipidemia (blocking of beta-2/beta-3 effects)
    - > a diabetic patient could only tell they have hypoglycemia via sweating on palms (muscarinic), all other signs would be absent
36
Q

What is the I-funny channel blocker and how does it work?

A

Ivabradine

Blocks the channel in pacemaker cells, especially the SA node which is activated by hyperpolarization, and leads the pacemaker cells to spontaneously depolarize and allow calcium inside

If channel is a nonspecific channel (lets Na+ and K+ flow)

37
Q

When is ivabradine indicated?

A

Patients who are at max dose of beta-blockers and still have a heart rate >70

38
Q

What are the common side effects and contraindications of ivabradine?

A

Atrial fibrillation and visual disturbances.

Visual disturbances are due to enrichment of If channels in the retina.

Contraindication is: pregnancy (teratogenic)

39
Q

What is the mechanism of action of methyldopa?

A

Alpha-2 agonist, like clonidine.

It is a dopamine derivative which is made into methylnorepinephrine

Reduces sympathetic tone throughout the body

40
Q

What is methyldopa indicated for, and what is its common side effect (other than CNS effects)?

A

Indicated for hypertension, especially treatment of hypertension during pregnancy (like labetalol)

Hemolytic anemia (lupus according to sketchy??)

41
Q

What are alpha-1-antagonists typically combined with for treatment of hypertension?

A

Diuretics or beta blockers

-> not good as monotherapy

42
Q

What is the primary calcium channel in the heart?

A

The L type calcium channel, also called slow channel

43
Q

What are the two categories of calcium channel blockers?

A
  1. Dihydropyridines

2. Non-dihydropyridines

44
Q

What is the mechanism of action of dihydropyridines?

A

They bind the L type Calcium channel in its open state, slowing calcium entry when it’s open, but not delaying its closure.

Dihydropyridines are vasoselective (rather than cardioselective), and prevent vascular smooth muscle contraction

45
Q

How do dihydropyridines affect preload?

A

They have no effect on it -> do not cause vasorelaxation. Will also not be associated with orthostatic hypertension

46
Q

What are the dihydropyridines of significance?

A
  1. Nefedipine

2. Amlodipine

47
Q

Why is amlodipine typically given over nefedipine?

A

Nefedipine has a short half-life, and thus often induces a rapid hypotension and reflex tachycardia, causing MI
-> must be given in timed-release form

Amlodipine has a much longer half-life and does not cause this baroreceptive reflex

48
Q

What does amlodipine reduce mortality in?

A

Patients with left ventricular dysfunction / heart failure

-> reduction in afterload

49
Q

What are the common side effects of dihydropyridines?

A

Flushing and peripheral edema (pitting edema of the ankles)

50
Q

What are the non-dihydropyridine calcium channel blockers?

A
  1. Verapamil

2. Diltiazem

51
Q

What is the mechanism of action of the non-dihydropyridine VGCC blockers?

A

They bind to the L type Calcium channel, but are cardioselective and will bind to both the open and inactivated form.

They reduce inward calcium current and delay channel closing, reducing the chronotropy and inotropy of the heart.

There is only minor blockage of L-type calcium channel on arteries

52
Q

What are non-dihydropyridines used to treat and why?

A

Angina -> reduce cardiac work by reduction of inotropism

Supraventricular tachycardias -> delayed AV node conduction

Antiarrhythmia in general

53
Q

What is the important contraindications of nonDHPs?

A

Heart failure -> reduction in cardiac contractility and cardiac block.

Verapamil can also cause hypotension due to alpha-1 blocking effects

AV block -> reduction in conduction

Also, should not be used with beta-blockers due to increased suppression of conduction

54
Q

What is an important drug interaction with verapamil?

A

Decreases digoxin’s renal clearance -> need to lower digoxin’s dose or will be toxic

55
Q

Why are beta-blockers always given with direct arterial vasodilators?

A

Otherwise, will cause reflex tachycardia and increase in renin secretion (beta1-antagonism will counter this)

56
Q

What are the direct vasodilators?

A
  1. Hydralazine
  2. Minoxidil
  3. Sodium Nitroprusside
57
Q

What is the mechanism of hydralizine and why is it not commonly given anymore? When is it given?

A

Mechanism unknown, relaxes arteriolar smooth muscle to reduce preload.

Not commonly given due to lupus-like syndrome.

Now given to patients who cannot handle standard therapy for heart failure (ACE + beta blocker + loop diuretic) in combination with a nitrate to reduce both preload and afterload

58
Q

What is the mechanism of action of minoxidil? How does this relate to its contraindication?

A

Activates ATP-modulated potassium channel in smooth muscle, causing hyperpolarization and arteriolar relaxation

Contraindicated in patients with LV hypertrophy and diastolic dysfunction, as increased preload may lead to heart failure + pulmonary hypertension

59
Q

What is minoxidil used for and given in combination with?

A

Used for complicated hypertension which is poorly responsive to other agents

Given in combination with a loop diuretic (less pulmonary congestion) and beta blocker (less increased cardiac output from preload)

60
Q

What is the primary side effect of minoxidil and how has this been used?

A 
Causes hypertrichosis (excess hair), bad in females, but good in bald males
-> marketed as "Rogaine"
61
Q

What is the mechanism of action of sodium nitroprusside? What does it do to heart rate?

A

Generates nitric oxide, causing both venous and arterial relaxation, and a subsequent decrease in preload and afterload

Actually causes increase in heart rate

62
Q

How does sodium nitroprusside affect cardiac output in normal vs LV dysfunction individuals?

A

Normal: Reduces cardiac output (decreased preload)

LV dysfunction: Increases cardiac output (decreased afterload, preload affects are not as important since heart is already working suboptimally)

63
Q

What is nitroprusside used for?

A

Treatment of hypertensive emergencies such as acute aortic dissection (along with beta-blocker to reduce heart rate) or cardiogenic shock due to massive MI or rupture of papillary muscle

-> situations when both decreased preload and afterload are needed

Also, controlled hypotension in patients under surgical anesthesia

64
Q

What is the relative half life of nitroprusside?

A

Very short, on the order of 2 minutes, given IV

65
Q

What is the main untoward effect of nitroprusside?

A

It is metabolized to cyanide and then nitric oxide. Long-term high doses will lead to cyanide accumulation -> lactic acidosis

Liver normally detoxifies cyanide to thiocyanate

Pharmacology (54 decks)

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