Pharm S2B3 - Cv - Anti-Hypertensives

Front 1

What are 85-90% of Hypertension cases due to?

Back 1

Unknown = Essential HTN

Front 2

How is Hypertension usually manifested initially?

Back 2

usually a SILENT DISEASE that is asymptomatic as most hypertensives usually feel well & progressive cardiovascular damage develops very gradually

Generally remains asymptomatic for 15-20 years until vital organs (Heart, brain, kidneys) become damaged

Front 3

What is the 1st step in the treatment of Hypertension?

Back 3

Life-stype modifications
1. exercise
2. weight reduction
3. moderatation of dietary salt, fats, & alcohol
4. avoid or reduce smoking
5. before, or together with, drug therapy

Front 4

What is the most common cause of treatment failure in treating HTN?

Back 4

Non-compliance

Front 5

List the 3 main goals of Anti-HTN drug treatment

Back 5

1. lower BP & keep it normal
2. reduce CV risks
3. produce minimal side-effects without decreasing quality of life

Front 6

-

Back 6

-

Front 7

Aside from mechanism of action, how do most Anti-HTN drugs differ?

Back 7

Adverse or side effects

Front 8

At what diastolic pressure is there inadequate Coronary perfusion & increased CV morbidity & mortality?

Back 8

lower than 90 mm Hg

Front 9

How do drugs lower BP?
1. Reduce blood volume = ?
2. Interrupt Sympathetic tone = ?
3. Vasodilation = ?

Back 9

1. Diuretics

2. Sympatholytics

3. Direct Vasodilators; CCA's; ACE inhibitors & AT-II Antagonists

Front 10

What are the 2 mechanisms in which Diuretics lower BP?

Back 10

1. initially deplete body Na+ stores -> reduce blood volume

2. Later activate K+ channels -> reduce vascular resistance

Front 11

Diuretic that is recommended for Mild to Moderate HTN & when used:
-alone will lower BP in 40-60% of patients, and
-in drug combinations will enhance efficacy of other Anti-HTN drugs

Back 11

Thiazide
-Chlorthalidone
-Indapamide
-Metolazone
-Quinethazone

Front 12

Which doses of Diuretics are higher, those used for Anti-HTN purposes or those used for Diuresis?

Back 12

Diuresis = 100-200 mg

Anti-HTN = 6-12 mg

Front 13

Which diuretic is primarily used for HTN?

Back 13

Thiazide
-Chlothalidone
-Indapamide
-Metolazone
-Quinethazone

Front 14

Which diuretic is primarily used for CHF?

Back 14

Loop
-Furosemide
-Torsemide
-Bumetanide
-Ethacrynic acid

Front 15

What 2 general types of Sympatholytic Drugs are used to lower BP?

Back 15

1. Central agonists = stimulate medullary receptors

2. Peripheral Antagonists = block receptors at nerve endings

Front 16

Why are Sympatholytics generally not recommended for monotherapy?

Back 16

produce Side-effects of:
1. Postural Hypotension
2. Sodium retention

Front 17

List the 4 Centrally Acting Sympatholytics

Back 17

1. Clonidine
2. Methyldopa
3. Guanabenz
4. Guanfacine

Front 18

This is a prodrug Centrally Acting Sympatholytic

Back 18

Methyldopa = converted to alpha-methylnorepinephrine

Front 19

What is the mechanism of action of the Centrally Acting Sympatholytics?

Back 19

Act as AGONISTS that stimulate Medullary Alpha-2 adrenergic receptors to reduce peripheral Sympathetic tone & lower BP by:
1. decreasing Vasoconstrictor tone = Vasodilation
2. Decrease Renal Renin Secretion

Front 20

How are the Centrally Acting Sympatholytics usually administered?

Which one can be used as a Transdermal or Skin Patch?

Back 20

Orally

Clonidine

Front 21

What are the side effects of the Centrally Acting Sympatholytics?

Back 21

CNS effects = Sedation, Nausea, dizziness, nightmaires, depression, Postural Hypotension

Dry mouth

Front 22

Sudden withdrawal of this Centrally Acting Sympatholytic may cause of Hypertensive Crisis

Back 22

Clonidine

Front 23

Centrally acting Sympatholytic that may produce Hemolytic Anemia with a Positive Coombs test

Back 23

Methyldopa

Front 24

What are the possible side effects of Methyldopa use?

Back 24

1. Hemolytic anemia with + Coombs test
2. Hepatotoxicity
3. Gynecomastia
4. Lactation

Front 25

What 3 drugs act by binding to Secretory Vesicles that normally store & release NE in peripheral endings?

Back 25

1. Guanadrel

2. Guanethidine

3. Reserpine

*reduce sympathetic activity by preventing NE release to reduce sympathetic activity, cause vasodilation, & lower BP

Front 26

Sudden release of endogenous NE when _______ is given IV may elevate BP

Back 26

Guanethidine

Front 27

What are the common ADR's of Guanethidine?

Back 27

1. Postural Hypotension
2. Fluid retention
3. Diarrhea
4. Retrograde ejactulation

Front 28

What are the common ADR's of Reserpine?

Back 28

1. Sedation
2. Psychic depression
3. Nasal stuffiness
4. Dry mouth
5. GI disturbances

Front 29

List the Non-selective Beta Antagonists

Back 29

1. Propranolol
2. Cartelol
3. Nadolol
4. Sotalol
5. Timolol

Front 30

List the Cardioselective Beta-1 blockers

Back 30

BEAM
1. Betaxolol & Bisoprolol
2. Esmolol
3. Acebutolol
4. Atenolol
5. Metoprolol

Front 31

List the 3 Intrinsic Sympathomimetic Activity Beta blockers that manufacturers claim produce less Cardiac Depression & are preferred for Hypertensive pts with CHF

Back 31

PAP
1. Penbutolol
2. Acebutolol
3. Pindolol

Front 32

List the 3 ways in which Beta blockers lower BP

Back 32

by blocking Beta receptors in:
1. Heart to reduce CO = Beta-1
2. Kidneys to reduce Renin secretion = Beta-1
3. CNS to reduce sympathetic vasomotor tone

Front 33

In what group of people are the Beta blockers most efficacious in?

Back 33

Caucasians & younger people

Front 34

In what patients are Beta blockers recommended for monotherapy?

Back 34

Young White Males

Front 35

What are Beta blockers combined with other Anti-HTN drugs to counteract? (2)

Back 35

1. Reflex Tachycardia caused by Vasodilators

2. Increased Renin secretion caused by Thiazide & Loops Diuretics

Front 36

What may Beta blockade worsen the symptoms of?

Back 36

1. Pts with reduced Myocardial reserve = Beta-1 blockade
2. Asthma = Beta-2 blockade
3. Peripheral Vascular Insufficiency
4. Diabetes = Beta-2 blockade of Insulin release

Front 37

When may Beta blockers increase exercise tolerance?

When may they decrease exercise tolerance?

Back 37

In patients being treated for Angina

In patients with CHF -> reduces CO -> earlier onset of fatigue

Front 38

How may Beta blockers predispose to Atherogenesis?

Back 38

1. increasing plasma Triglycerides

2. decreasing HDL-cholesterol

Front 39

What does Beta blockade delay the recovery of>

Back 39

Normoglycemia b/c it inhibits hyperglycemic responses mediated by Epinephrine on pancreatic Beta-2 receptors to release Insulin

Front 40

What are minor side effects of Beta blockers?

Back 40

GI = NVD, constipation

CNS = insomnia, lassitude, nightmares, depression

Skeletal muscle tremors

Front 41

List the common ending for the Alpha-1 antagonists

Back 41

-AZOSIN

1. Prazosin
2. Terazosin
3. Doxazosin

Front 42

How do the "-ZOSIN's" reduce blood pressure?

Back 42

Alpha-1 blockade reduces NE-induced vasoconstriction to dilate both arteries & veins

Front 43

What are the common ADR's of the -AZOSIN's?

Back 43

1. Postural Hypotension (usually with 1st dose)
2. Dizziness, headache, drowsiness, palpitations, heachache, easy fatigability

Front 44

What 2 drugs have combined Alpha & Beta blockade?

Back 44

1. Labetalol

2. Carvedilol

*lower BP by non-selective blockade of both Alpha- & Beta receptors

Front 45

What is the Beta:Alpha block ration after ORAL LABETALOL is given?

Back 45

Beta:Alpha = 3:1

Front 46

What are the ADR's of Labetalol & Carvedilol?

Back 46

1. Orthostatic Hypotension
2. Bronchospasm
3. Hepatotoxicity

Front 47

What are Labetalol & Carvedilol used mainly for the treatment of?

Back 47

1. Hypertensive emergencies

2. Pheochromocytoma = tumor of the Adrenal Medulla that secretes Epi & NE

Front 48

Vasodilators given orally for Chronic Anti-HTN treatment

Back 48

Hydralazine or Minoxidil

Front 49

Vasodilators given IV for Hypertensive emergencies (5)

Back 49

1. Sodium Nitroprusside
2. Diazoxide
3. Fenoldopam
4. Enalaprilat
5. Nicardipine

*FENDS

Front 50

These 3 vasodilators dilate ARTERIES selectively without affecting venous smooth muscles

Back 50

1. Hydralazine

2. Minoxidil

3. Diazoxide

Front 51

Dilates arteries by acting as a Dopamine D1-agonist

Back 51

Fenoldopam

Front 52

Non-selective or balanced vasodilator that dilates both arteries & veins

Back 52

Sodium Nitroprusside

Front 53

Are Vasodilators used for Monotherapy? Why?

Back 53

No

Anti-hypertensive effects tend to diminish with time b/c of Reflex Tachycardia & increased Renin secretion

Front 54

When are Vasodilator drugs most effective?

Back 54

When combined with other drugs to prevent undesirable side-effects

Front 55

What are Hydralazine & Minoxidil combined with?

Back 55

1. Diuretics = to avoid fluid retention

2. Beta blockers = to diminish Renin secretion & Reflex Tachycardia
-Renin secretion blockage = Beta-1 blockage
-Reflex Tachycardia blockage = Beta-1 blockage

Front 56

Hypotension produced by any Vasodilator drug will be accompanied by these things

Back 56

1. Reflex Tachycardia, increased Myocardial contractions

2. Increased Renin secretion

3. Fluid retention, headaches, flushing, palpitations, or dizziness

Front 57

What 2 drugs may induce Anginal attacks & Myocardial Ischemia through reflex increases in Cardiac Output in Elderly patients with coronary artery disease?

Back 57

Hydralazine

Minoxidil

Front 58

Vasodilator that may cause a Lupus-like syndrome consisting of fever, skin rashes, arthralgia, & myalgia

Back 58

Hydralazine

Front 59

Vasodilator that causes Hyperthrichosis (excess hair growth); topical ointment "Rogaine"

Back 59

Minoxidil

Front 60

List the drugs contained within the Calcium Channel Blockers class

Back 60

1. Verapamil
2. Diltiazem
3. Dihydropyridines = "-DIPINES"
-Nifedipine

Front 61

What is the mechanism of action of the CCA's in lowering BP?

Back 61

1. reduce IC Ca++
2. relax Arteriolar smooth muscles
3. vasodilation & lower BP

Front 62

Drugs that are equally effective for monotherapy in mild to moderate HTN especially in the Elderly & African-Americans

Back 62

Calcium Channel Blockers

Thiazides

Front 63

CCA that is the strongest Vasodilator and most likely to produce Reflex Tachycardia

Back 63

Nifedipine

*also has smallest inhibition of AV conduction

Front 64

Why do Verapamil & Diltiazem not cause Reflex Tachycardia?

Back 64

b/c they depress SA & AV node conduction directly

Front 65

When are Verapamil & Diltiazem contraindicated?

Back 65

in patients with SA or AV node abnormalities

CHF

*may cause Bradycardia in the presence of SA node dysfunction

Front 66

MC side effect of Verapamil

Back 66

Constipation

Front 67

-

Back 67

-

Front 68

CCA's that are most likely to cause headache, flushing, dizziness, & peripheral edema

Back 68

Dihydropyridines = '-DIPINE's' = Nifedipine

Greatest effect is Vasodilation

Front 69

What is the common ending for ACE inhibitors?

Back 69

-PRIL

Front 70

Only active ACE inhibitor, all others are prodrugs that have to be converted to the corresponding di-acid

Back 70

Captopril

Front 71

How do ACE inhibitors lower BP?

Back 71

Inhibit ACE = inhibit conversion of Antiogentin I -> Angiotensin II

-Inhibit AT-II vasoconstriction
-also inhibit ACE destruction of Bradykinin

Front 72

What are the side effects of the ACE inhibitors?

Back 72

CAPTOPRIL + Hyperkalemia
1. Cough (due to Bradykinin)
2. Angioedema & Anaphylaxis(due to Bradykinin)
3. Proteinuria
4. Taste changes
5. hypOtension
6. Pregnancy proglems (fetal renal damage)
7. Rash
8. Increased renin
9. Lower angiotensin-II

Front 73

List the advantages of ACE Inhibitors

Back 73

1. lower BP without compromising blood supply to the heart, brain, or kidneys

2. side-effects are mild, fewer, & without lipid changes

3. do not cause reflex tachycardia b/c of concurrent baroreceptor resetting or vagal activation

4. are effective orally for monotherapy & will lower BP in 50% of pts with mild to moderate HTN

Front 74

What groups of people are ACE inhibitors most effective in?

Back 74

Young & Middle-aged Caucasians

*less effective in Elderly AA's

Front 75

What 3 things are ACE inhibitors the 1st choice of treatment for HTN in pts?

Back 75

1. Diabetes

2. Chronic Renal disease

3. Left Ventricle Hypertrophy

Front 76

What is the common ending for Angiotensin Receptor Antagonists?

Back 76

-SARTAN

Front 77

Which receptor do the -SARTAN's bind to? Where is this receptor located?

Back 77

AT1 receptor in vascular smooth muscle

Front 78

What are the 2 important differences between Angiotensin receptor antagonists & ACE inhibitors?

Back 78

1. -SARTAN's are more specific than ACE inhibitors b/c AT-II antagonists do not affect Bradykinin metabolism = no coughing or Angioedema

2. -SARTAN's have more complete inhibition of Angiotensin action b/c enzymes other than ACE can generate Angiotensin-II

Front 79

What are some adverse effects of the -SARTAN's?

Back 79

Hyperkalemia

Fetal Renal toxicity

Front 80

What Anti-hypertensive drugs can be used as monotherapy?

Back 80

1. Diuretics
2. Beta blockers
3. ACE inhibitors
4. CCA's

Front 81

With what anti-HTN drugs do Elderly males often complain of Impotence?

Back 81

Thiazides or Sympatholytics