Hypertension - Pharmacology Flashcards Preview

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Flashcards in Hypertension - Pharmacology Deck (64):
1

Increasing blood pressure is associated with a progressive increase in the risk of _____ and _______ _____

Stroke; cardiovascular disease

2

As blood pressure rises, does HTN risk rise linearly or exponentially?

exponentially

3

Hypertension is most common in _____ _____

older women

4

Of those with uncontrolled hypertension, what percentage are aware and treated? Aware and untreated? Unaware?

What percentage of hypertensive individuals have controlled HTN?

Aware/treated: 44.8%

Aware/Untreated: 15.8%

Unaware: 39.4%

Controlled: 46.5%

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5

What are the JNC 8 recommendations for target SBP and DBP in individuals...

≥60 years

<60 years

> 18 years with chronic kidney disease

> 18 years with diabetes

≥60 years: less than 150/90

<60 years: less than 140/90

> 18 years with chronic kidney disease: less than 140/90

> 18 years with diabetes: less than 140/90

6

Classifications of ANtihypertensive Drugs

Vasodilators

Agents affecting adrenergic function

Agents affecting RAS

Diuretics

7

What are the direct arterial vasodilators?

 

  1. Hydralazine
  2. Minoxidil
  3. Diazoxide
  4. Nitroprusside
  5. Fenoldopam

8

How do direct arterial vasodilators cause antihypertensive effect?

Cause smooth muscle relaxation of vessels

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9

How can vasodilators lead to increased heart rate? How is this counteracted?

  • Potent reductions in perfusion pressure activate baroreceptor reflexes
  • Baroreceptor activation leads to compensatory increase in sympathetic outflow - reflex release of renin
  • Counteract with concurrent ß-blocker

 

10

What blood pressure is used to determine a hypertensive crisis?

What is the best way to treat this (duration)?

 

BP> 180/120

Gradual injection of vasodilators (nitroprusside) to allow organs to adjust to change in blood pressure

11

What is the difference between hypertensive urgency and a hypertensive emergency?

Hypertensive urgency - elevated BP with no acute or progressing organ injury

Hypertensive emergency - Acute or progressing target-organ damage

12

What pathway to nitric oxide drugs activate?

Guanylate cyclase pathway leading to increase in cGMP and protein kinase G → vasodilation

13

Why don't you use nitroprusside for long periods?

Can cause damage to kidneys with cyanide toxicity

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14

What are some adverse effects of direct arterial vasodilators?

How are these adverse effects reduced?

  • Adverse effects
    • Sodium/water retention
    • Tachycardia and angina
    • Hydralazine can cause lupus like syndrome
    • Minoxidil can cause hair growth (not used with women)
  • Use with diuretic (thiazide) and ß-blocker to reduce fluid retention and reflex tachycardia

15

Why do calcium channel blockers cause less reflex tachycardia than vasodilators?

Smaller HR increase due to the calcium channels that exist on the heart (CCBs don't only affect vascular system)

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16

What are the calcium channel blockers?

  • Nifedipine
  • Diltiazem
  • Verapamil
  • Amlodipine

17

Calcium Channel blockers - what are the differences between dihydropyridines and non-dihydropyridines?

  • Dihydropyridines
    • Baroreceptor mediated reflex tachycardia due to potent vasodilating effects
    • Do not alter conduction through AV node
  • Non-dihydropyridines decrease HR and slow AV node conduction

18

What are the two non-dihydropyridines? 

Verapamil and diltiazem

19

What are some CCB side effects?

  • Flushing
  • Headaches
  • Negative inotropic effect(V>D>N)
  • Constipation (V>D or N)
  • Decreased AV conduction (V = D)
  • Edema (N>V or D)
  • Refractoriness (N)

* N = nifedipine, V = verapamil, D = Diltiazem

20

Which SNS receptors are responsible for the following...

  • Increased contractility
  • Increased HR
  • Vasoconstriction
  • Vasodilation
  • Bronchodilation
  • Increased renin

 

Increased contractility: beta-1
Increased HR: beta-1
Vasoconstriction: alpha-1
Vasodilation: beta-2
Bronchodilation: beta-2
Increased renin: alpha-1, beta-1

21

What are the α1/α2 blockers and what do they do?

Phenoxybenzamine and Phentolamine

Inhibit smooth muscle catecholamine uptake in peripheral vasculature: Vasodilation and BP lowering

22

What are the α1 blockers and how are they different than α1/α2 blockers?

Prazosin, Terazosin, and Doxazosin

  • Smaller increase in heart rate
  • Arterial vasodilation
  • No stimulation in Renin release
  • Does not block α2 thus NE can inhibit its own release

23

What is the first dose effect of α1 blockers? How do you minimize this effect?

  • Orthostatic hypotension
  • Transient dizziness, faintness, palpitations, syncope (w/in 1-3 hours of 1st dose)
  • Reflex tachycardia
  • First dose at bedtime to minimize effect

24

What are α1/ß1/ß2 blockers and how are they different than α1 blockers in terms of adverse effects?

Carvedilol and Labetalol - less orthostatic hypotension and headaches (mild)

25

What are the ß-blockers?

Propanalol (ß1 and ß2)

Metropolol (ß1)

Atenolol (ß1)

Labetalol (ß1/ß2/α1)

26

What are the locations and functions of ß1 receptors? ß2 receptors?

  • ß1 receptors
    • found in the heart and the kidney
    • stimulation increases heart rate, contractility and renin release
  • ß2 receptors
    • Found in the lungs, liver, pancrease, arterioloar smooth muscle
    • Stimulation causes bronchodilation and vasodilation and mediates insulin secreation and glycogenolysis

27

ß-blockers work better in _____ ______ and in _____ _____ when combined with a diuretic

young adults; older adults

28

Low renin levels in a patient make them ____ (more/less) responsive to beta blockers

less

29

Which ß blockers have greater affinity for ß1 receptors than ß2 receptors and how does this relate to their dose?

Metropolol and atenolol - cardioselective ß-blockers

These drugs inhibit ß1 receptors at low to moderate doses

At higher doses they block ß2 blockers

30

In what types of patients are metroprolol and atenolol safer to use?

Safer in patients with bronchospastic disease, peripheral arterial disease, and diabetes

Generally preferred ß-blockers for hypertension

31

What are some potential adverse effects of ß-blockers?

  • Glucose intolerance
  • Bradycardia
  • Bronchospasm
  • Incresed TGs and HDL
  • CNS - depression, fatigue, and sleep disturbance
  • Reduced CO
  • Impotence
  • Exercise intolerance

32

What are the central α2 agonists and what do they do?

Clonidine, Guanabenze and α-methyldopa

Stimulate α-2 adrenergic receptors in the brain which reduces sympatetic outflow from the brains vasomotor center and increase vagal tone

33

What are the central α2 agonist's adverse effects?

  • Sodium/water retention
  • Abrupt discontinuation may cause rebound hypertension
  • Depression
  • Orthostatic hypotension
  • Dizziness

34

What are specific side effects associated with clonidine and methyldopa?

Clonidine - anticholinergic side effects

Methyldopa - can cause hepatitis hemolytic anemia

35

What are the neuronal and ganglionic blockers?

Guanethidine

Guanadrel

Reserpine

Trimethaphan (ganglionic)

36

What are some adverse effects for Reserpine and Guanethidine and how do you avoid these side effects?

  • Sedation (reserpine)
  • Depression (reserpine)
  • Decreased CO
  • Na+/H2O retention
  • Increased gastric acid secretion (reserpine)
  • Diarrhea
  • Bradycardia
  • Orthostatic Hypotension (Guanethidine)

* Use with diurtic (thiazide) to avoid fluid retention

37

What are the diuretics?

Hydrochlorothiazide

Furosemide

Amiloride

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38

What are the causes and consequences of initial diuretic use?

What happens with chronic use?

  • Initial (BP drop)
    • Reduced plasma and stroke volume decreases CO
    • Causes compensatory increase increase in peripheral vascular resistance
  • Chronic use
    • Extracellular and plasma volume return to near pretreatment levels
    • Peripheral vascular becomes lower than pretreatment values (chronic antihypertensive effect)

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39

What are some potential adverse effects of diuretics?

Electrolyte disturbances

Hyperglycemia

Hypotension, orthostasis

Lipid abnormalities

Photosensitivity

Ototoxicity

Hyperuricemia, gout flare

40

What are aldosterone antagonists and what do they do?

Spironolactone and Eplerenone

  • Inhibit the renal (sodiuma and water retention) and extra-renal (fibrosis/inflammation) actions of aldosterone

41

What are the Renin Angiotensin System Inhibitors?

  • Aliskiren (Renin inhibitor)
  • Losartan (AT1 blocker)
  • Captopril
  • Enalapril
  • Lisinopril

42

What do ACE inhibitors do? (Captopril, Lisinopril, Enalapril)

Block angiotensin I to angiotensin II conversion

Block bradykinin degeneration

Stimulate synthesis of other vasodilating substances such as prostaglandin E2 and prostacyclin

Prevent or regress left ventricular hypertrophy

43

What do you monitor when giving ACE inhibitors?

What are some adverse effects of ACE inhibitors?

Monitor serum K+ and SCr within 4 weeks of initiation or dose increase

  • Adverse effects
    • Cough (increased bradykinin)
    • Angioedema
    • Hyperkalemia: particularly in patients with CKD or DM
    • Neutropenia, agranulocytosis, proteinuria, glomerulonephritis, acute renal failure

44

What are adverse effects of Angiotensin II receptor blockers?

Orthostatic hyptension

Renal insufficiency

Hyperkalemia

45

What are the different roles of the AT2 and AT1 receptors

  • AT2
    • Vasodilation
    • Antiproliferation
    • Apoptosis
  • AT1
    • Vasoconstriction
    • Vascular proliferation
    • Aldosterone secretion
    • Cardiac myocyte proliferation
    • Increased Sympathetic tone

46

Angiotensin receptor blockers have higher affinity for which receptor (AT1 or AT2)?

AT1

47

What are the functions and adverse effects of Aliskiren (Renin inhibitor)?

  • Inhibits angiotensinogen to angiotensin I conversion
  • Antihypertensive
  • Does not block bradykinin breakdown
  • Adverse effects
    • Orthostatic hypotension
    • Hyperkalemia

48

What are some precautions to using ACE inhibitors or ARBs

Can cause acute kidney failure in patients with severe bilateral renal artery stenosis or stenosis in artery to solitary kidney

Should not be used with pregnancy

49

What are some potential drug interactions with ACE inhibitors and ARBs

  • Medications that promote hyperkalemia
  • Medications that have activity which is sensitive to changes in serum K+
  • Medications that cause additive antihypertensive effects
  • NSAIDs

50

______ and ____ together have an additive effect

Diuretics; ARBs

51

Which drug is only 35% effective in Blacks and 67% effective in non-blacks - how do you overcome this disparity?

Enalapril - give with hydrochlorothiazide

52

What are the Lifestyle modifications associated with JNC7 regulation hypertension treatment?

  • Reduce weight to normal BMI
  • DASH eating plan
  • Dietary sodium reduction
  • Increase physical activity
  • Reduce alcohol consumption

53

What are some differences between the JNC7 and JNC8 guidelines?

  • JNC8
    • Systematic review
    • Randomized, controlled trials only (vs. range of study designs in JNC7)
    • Graded recommendations
    • No specific lifestyle recommendations
    • Racial, CKD, and diabetic subgroups addressed

54

Grading in JNC8

A:

B:

C:

E:

A: Strong recommendation - high certainty net benefit is substantial

B: Moderate recommendation - moderate certainty net benefit is moderate to substantial

C: Weak recommendation - at least moderate certainty of small net benefit

E: Expert opinion - insufficient or unclear/conflicting evidence

55

In JNC7 the BP goal is ______ regardless of age

In JNC8 the BP goal is _______ in patients 60 and older

<140/90

<150/90 (Grade A)

56

JNC8 recommendations and grades for...

General populations:

Black population:

DM:

CKD:

  • General populations: Thiazide, CCB, ACEi, ARB (Grade B)
  • Black population: CCB or Thiazide (Grade B)
    • Grade C if Black and DM
  • DM: Thiazide, CCB, ACEi, ARB (Grade B)
  • CKD: ACEi or ARB (Grade B)

57

JNC8 treatment strategies (Grade E)...

If goal BP not met after 1 month treatment:

If goal BP not met with 2 medications:

 

  • If goal BP not met after 1 month treatment:
    • increase dose of inital drug or add a second drug (Thiazide, CCB, ACEi, or ARB)
  • If goal BP not met with 2 medications:
    • Add and titrate a third medication
    • DO NOT USE ACE and ARB together

58

When adminstering Diuretics what should be monitored?

ß-blockers?

ACEi and ARBs?

CCBs?

  • Diuretics: BP, BUN/serum Creatinine, electrolytes, uric acid
  • ß-blockers: BP and HR
  • ACEi and ARBs: BP, BUN/serum creatinine, potasisum
  • CCBs: BP and HR

59

What drugs are better in African Americans and why?

Diuretics and CCB > ACEi, ARBs and ß-blockers (these cause 2-4 fold risk for angioedema)

60

What drugs are not used for LVH

Hydralazine and minoxidil

61

What drugs are better tolerated in the elderly?

Thiazide or CCB

62

What drugs are used in pregnant patients?

What drugs are avoided?

Use: Methyldopa, beta-blockers, vasodilators

Avoid: ACEi and ARBs

63

In combination therapy, at least one of the agents should be a ______ _______

thiazide diuretic

64

What is resistant hypertension

Failure to achieve BP goal on full doses of 3 drug regimen including a diuretic