2.1 Pharm Exam2: Antihypertensives

Front 1

______________ in arterial walls provide feedback control of blood pressure via _______,______,& ______

Back 1

Baroreceptors (carotid & aortic sinus)

via heart, kidneys, & vessels

Front 2

When BP (decreases/rises) the baroreceptors are stimulated, leading to what 2 things?

Back 2

BP increases

decreased cardiac output & vasodilation

(= decreased BP)

Front 3

What 2 things contribute to arterial BP?

Both of these things are controlled by what 2 mechanisms?

Back 3

Arterial blood pressure = Cardiac Output (CO) x Total Peripheral Resistance (TPR)

CO & TPR controlled by;
-- Baroreflexes mediated by autonomic nervous system
-- Renin-angiotensin-aldosterone system

Front 4

(Symp/Para) nervous system maintains rapid immediate blood pressure regulation

How?

Back 4

Sympathetic nervous system

- Baroreceptors in aortic arch and carotid sinus maintain impulses to cardiovascular centers in hindbrain.
- Reflex responses mediate firing of sympathetic and parasympathetic nervous system

Front 5

Drop in BP leads to an (increase/decrease) in sympathetic activity. What does this lead to?

Back 5

increase

1. activation of beta1 in the heart--> inc. CO

2. activation of alpha1 in smooth m.--> inc peripheral resistance

BOTH--> increase in blood pressure

Front 6

A decrease in BP is also reacted to by the Renin-Angiotensin-Aldosterone System (RAAS)

Describe.

Back 6

- Kidney maintains blood volume and provides for long-term blood pressure control

1. dec. renal blood flow-->

2a. dec GFR--> inc renal Na & H2O retention--> incr. blood volume--> inc BP

2b. inc. renin--> inc. angiotensin II (most potent circulating vasoconstrictor)-->↑ in TPR--> inc. BP

3. Angiotensin II ALSO--> inc. aldosterone secretion ---> inc. renal Na+ absorption--> inc. blood volume → ↑ BP

Front 7

____________ causes DIRECT vasoconstriction at the level of the blood vessels

TOO much of this can lead to......

Back 7

Endothelin

fibrosis, hypertrophy, inflammation (via too much vasoconstriction)

Front 8

Hypertension is defined as a sustained

diastolic > ________ accompanied by an elevated systololic > ________

What does hypertension lead to?

Back 8

Diastolic > 90 mmHg

Systolic > 140 mmHg

- Leads to increased arteriolar resistance and reduced capacitance of venules

Front 9

Primary hypertension (w/o any underlying cause aside from family history) occurs in 90-95% of patients. Secondary Hypertension is most commonly due to what underlying factors?

Back 9

- Underlying cause-chronic renal disease
- Na+ & water retention
- Elevated renin levels
- Pheochromocytoma
- Conns Syndrome

Front 10

What are the Antihypertensives
 Therapeutic Goals?

Back 10

- Achieve target b.p: < 140/90
- Diabetic patients or chronic kidney disease:
< 130/90
- Reduction of hypertension associated morbidity and mortality.
- Reducing risk of target-organ damage (cardiovascular & cerebrovascular events, heart failure & renal damage)

Front 11

Q: A pt presents w/ persistant severe hypertension & is prescribed a drug associated w/ tachycardia, significant edema, & hypertrichosis. What is the likely drug?

Back 11

Minoxidil

Front 12

5 
Antihypertensives 
Non-Pharmacological Management

(THESE ARE ALWAYS DONE BEFORE PHARM)

Back 12

- Weight reduction (most hypertension pts obese)
- Alcohol cessation
- Exercise
- Reduction in dietary sodium intake
- Overall dietary review

Front 13

What is the initial DOC for Stage 1 Hypertension (BP of 140/90-159/99 mmHg) w/o any other cardiovascular risk factors?

Back 13

Thiazide diuretic = Hydrochlorothiazide (Esidrix)

Front 14

What is the initial DOC for stage 2 Hypertension (BP > 160/100 mmHg) w/o any other cardiovascular risk factors?

Back 14

Two drug combinations:

Thiazide diuretic + ACE inhibitors

Front 15

What is the initial DOC for Hypertension + other cardiovascular diseases/risk factors?

Back 15

Combination of:

Diuretics

ACE inhibitors

ARBs

beta-blockers

Ca2+ channel blocker

(all indicated)

Front 16

3 types of Diuretic Agents:

Back 16

Thiazides:
- Hydrochlorothiazide (Esidrix)

Loop Diuretics:
- Furosemide (Lasix)

- Ethacrynic acid (Edecrin)

K-Sparing Drugs:
- Spironolactone (Aldactone)

Front 17

(thiazide) Diuretic Agents: MOA

Back 17

Increase urine flow
⇓
Alteration of electrolyte reabsorption or secretion (inhibits NaCl cotransporter in DCT)
⇓
Diuresis
⇓
Increased Na excretion
⇓
Loss of water
⇓
⇓ Extracellular volume

Front 18

___________ Diuretic Agents are most commonly used. When are they not effective?

Back 18

thiazides (Hydrochlorothiazide)

- effective in controlling BP, preventing MI, stroke & CHF, act on DCT, more effective then β-blockers in geriatric patients.

NOT effective in renal dysfunction

Front 19

Thiazide diuretics: Side Effects

Back 19

Hydrochlorothiazide Side effects:
- Hypokalemia
- Hypercalcemia

- Hyponatremia

(can lead to a gouty attack)

Front 20

When are Loop Diuretics better?

Back 20

Much better for edema & CHF

- best at getting rid of water bc more Na+ reabsorption blocked in the loop than in the DCT where thiazides work.

Front 21

Diuretic Agents: Loop Diuretics MOA

Back 21

Loop Diuretics:
Rapid acting (in thick ascending loop of Henle)
Inhibits reabsorption of NaCl (inhibits Na/K/Cl co-transporter)
⇓
⇑ Excretion of NaCl and water
⇓
⇓ Extracellular Volume
⇓
⇓ BP
Indicated in patients with renal compromise

Front 22

Loop diuretics: Side Effects

Back 22

Furosemide/Ethacrynic Acid Side effects:
- Hypokalemia (worse than thiazide diuretics)
- Hypocalcemia

- Hyponatremia
- Metabolic alkalosis

- hypomagnesemia

- ototoxicity (irreversible ringing in ears)

- Sulfa sensitivity

Front 23

Diuretic Agents: K-sparing Drugs MAO

Spironolactone (Aldactone)

Back 23

- Aldosterone antagonist.
- Potasssium-sparing.
- Used as an adjunct with other diuretics to prevent hypokalemia.
- Inhibition of Na+ reabsorption in the collecting ducts
- further reduces blood pressure.

Front 24

Postasium-sparing diuretics: Side Effects

Back 24

Spironolactone Side Effects:
- Gynecomastia (antiandrogen effect)
- Hyperkalemia

*DO NOT give to MALES long-term

Front 25

β-Adrenoceptor Blocking Agents: Indications

Back 25

HYPERTENSION

- More effective in treating younger patients.
- Indicated for co-existing conditions:
-- myocardial infarction
-- angina pectoris
-- chronic heart failure

Front 26

Antihypertensives
 β-Adrenoceptor Blocking Agents: Non-selective Drugs (2)

Back 26

Non-selective (β1 & β2 blockers):
- Propranolol (Inderal)
- Timolol (Betimol)

(*pronanolol crosses BBB, can be used for thyroid disorders)

Front 27

Non-selective β-Adrenoceptor Blocking Agents: Antihypertensive Effects (MOA)

Back 27

- Reduce cardiac output (--> reduce HR)
- Reduce sympathetic outflow (cardiac)
- Reduce renin secretion (kidney)
- Reduce formation of angiotensin (kidney)
- Reduce secretion of aldosterone (kidney)

= reduced HR, contractility, & blood volume--> decr BP

Front 28

Non-selective (β1 & β2) blockers: Contraindications

Back 28

(Use with caution)

diabetes

asthma

COPD

Front 29

Why should you NOT use non-selective Beta blockers in an asthmatic patient

Back 29

beta2 blockers--> bronchoconstriction

Front 30

Why would you be concerned with using non-selective Beta blockers with diabetics?

Back 30

You block all (adrenergic) symptoms of hypoglycemic except sweating (cholinergic). It masks problems.

Front 31

Antihypertensive Agents:

Selective (β1) blockers Drugs (2)

Back 31

Selective (β1) blockers:

- Atenolol (Tenormin)
- Metoprolol (Lopressor)

Front 32

How does (cardiac) beta1 activation increase BP?

Back 32

NE acts on beta1 receptors-->

stimulates Gs-->

incr in cAMP-->

incr in Ca2+-->

incr myosin-actin interaction-->

incr in cardiac contractility-->

incr in stroke volume & CO-->

incr in BP

Front 33

Selective β1-Adrenoceptor Blocking Agents: Effects

Back 33

Selective β1-Adrenoceptor Blocking Agents:
- Selective blockade of β1-adrenergic receptors located chiefly in cardiac muscle
- Reduction of sympathetic outflow and renin activity
- Reduction in rate and force of cardiac contractility.

Front 34

Selective β1-Adrenoceptor Blocking Agents: Indications & Cautions

Back 34

indications: Less likely than non-selective β-blockers to cause bronchoconstriction in pt w asthma/COPD (or w history of bronchospasm)

contraindications: Use with caution in patients with asthma and COPD

Front 35

Antihypertensives 
β-Adrenoceptor Blocking Agents: Side Effects

Back 35

- Abrupt discontinuation of β-blockers may cause reflex tachycardia, increased blood pressure & nervousness. (NEVER STOP ABRUPTLY)

Side effects: hypotension, lipid unfriendly, bradycardia, fatigue, lethargy, decreased libido, sexual dysfunction.

Front 36

Which beta-blocker causes the worst sexual/libido dysfunction?

Back 36

propanolol

Front 37

What are the only beta-blockers that can be used in a pt w/ dyslipidemia?

Back 37

pinidolol & acebutolol

(all others are lipid unfriendly)

Front 38

__________________ antihypertensives work by blocking the conversion of angiotensin I to angiotensin II

(renin--> angiotensin I--> angiotensin II)

Back 38

ACE inhibitors

Front 39

ACE Inhibitor Drugs:

Back 39

- Enalapril (Vasotec) (pro-drug, needs activation)
- Captopril (Capoten)

Front 40


Antihypertensives
 Angiotensin Converting Enzyme 
(ACE) Inhibitors MAO

Back 40

*Inhibit production of angiotensin II from angiotensin I
--->Reduction aldosterone secretion and water and Na+ retention.
& Diminshed inactivation of (incr) bradykinin
--> Vascular smooth muscle vasodilation & reduction of peripheral vascular resistance

= decreased BP

Front 41

ACE inhibitors: Indications

Back 41

HYPERTENSION

Indicated in patients with co existing diabetes (or renal dysfunction), myocardial infarction, heart failure.

(*slows progression of diabetic nephropathy

vasodilates EFFERENT arterioles of kidneys--> improves renal profusion)

Front 42

ACE inhibitors: Contraindications

Back 42

Contraindicated in patients with bilateral renal artery stenosis.
*Pregnancy: Highly fetotoxic (abortion or renal failure)

Front 43

ACE Inhibitors: Side Effects

Back 43

- Dry Cough* (due to incr bradykinin)
- Angioedema (lips, ankles, tongue, due to vasodilation)

Front 44

________________ work by blocking the action of angiotensin II at AT1 receptors. What does this prevent?

Back 44

Angiotensin II AT1 subtype receptor antagonists

prevents;

-vascular hyperplasia & hypertrophy

-vasoconstriction directly & via inc NE release

-salt retention via aldosterone & tubular Na+ reabsorption

Front 45

Antihypertenisve Drugs:

Angiotensin II Receptor Antagonists (ARB)

Back 45

- Losartan (Cozaar)
- Valsartan (Diovan)

Sartans

Front 46

Angiotensin II Receptor Antagonists (ARB): MAO

Back 46

MAO:

Blockade of angiotensin II receptors/ block effects of Angiotensin II-->
- Inhibition of aldosterone secretion
- Vasodilation and reduction in TPR.
= dec BP

Front 47

Angiotensin II Receptor Antagonists (ARB): Indications

Back 47

HYPERTENSION (esp mild)

- intolerance to ACE inhibitors (no effect on bradykinin, doesn't cause cough)
- Heart failure
- Diabetic nephropathy (Reduces this!)

Front 48

Angiotensin II Receptor Antagonists (ARB):
Contraindications

Back 48

- Pregnancy
- Hyperkalemia (in high doses)

Front 49

Angiotensin II Receptor Antagonists (ARB):
Side Effects

Back 49

- Hypotension
- Dizziness
- similar to ACE inhibitor with reduced incidence of cough

Front 50

Antihypertensive Renin Inhibitors

What is the only drug?

How do they work?

Back 50

Aliskiren (Tekturna)

-w/o renin, can't make angiotensin II, work the same as angiotensin II receptor antagonists

-same contraindications

*usually combined w a diuretic agent

Front 51

Antihypertensives
 Calcium Channel Antagonists Drugs

Back 51

-Nifedipine (Adalt) = both cardiac & vascular smooth muscle
-Verapamil (Isoptin) = cardiospecific

Front 52

Calcium Channel Antagonists: MOA

Back 52

Blockade of calcium channels
--> Inhibition of Ca+ influx into vascular (and/or cardiac) smooth muscle cell.
--> Decrease in smooth muscle tone & vascular resistance
--> Reduction in peripheral resistance

= dec. BP

(direct vasodilators w/ neg ionotropic effect)

Front 53

Calcium Channel Antagonists: Indications

Back 53

HYPERTENSION w/

- Angina
- Diabetes
- Peripheral Vascular disease
- Asthma

Front 54

Calcium Channel Antagonists:
Side Effects

Back 54

- Dizziness
- Headache
- Fatigue
- Constipation (biggest problem w/ verapamil)

- GERD

Front 55

Antihypertensives Drugs:

α1-Adrenoceptor Antagonists

Back 55

(-sin)

PRAZOSIN (Minipress)
Terazosin (Hytrin)
Doxazosin (Cardura)

Front 56

α1-Adrenoceptor Antagonists: MOA

Back 56

Inhibition of α1 receptors in resistance vessels of skin, mucosa, intestine & kidney-->
Dilatation of resistance and conductance vessels
= Decrease in BP

Front 57

α1-Adrenoceptor Antagonists: Clinical Use

Back 57

- Moderate hypertension

- BPH (symptomatic relief, relaxes prostate)

* Often administered with a diuretic and β adrenoceptor antagonist

Front 58

α1-Adrenoceptor Antagonists: Side Efects

Back 58

- First dose syncope
- Orthostatic hypotension
- Tachycardia
- Nasal Congestion
- Dizziness

* use caution, may cause dangerous vasodilation

Front 59


Antihypertensives Drugs:

α1 & β Adrenoceptor Antagonists

Back 59

Labetalol (Trandate)
Carvedilol (Coreg)

Front 60


α1 & β Adrenoceptor Antagonists: MOA

Back 60

- Reduces heart rate and contractility (β-blockade)

&
- Vasodilation and reduction of peripheral resistance (α-blockade)

= dec BP

Front 61


α1 & β Adrenoceptor Antagonists: Indications

Back 61

- Mostly used for heart failure
- Indicated in hypertensive emergencies & pheochromocytoma.

Front 62

Antihypertensives Drugs:


Vasodilators

Back 62

HYDRALAZINE (ALAZINE)
SODIUM NITROPRUSSIDE
Minoxidil (Rogaine)
Diazoxide (Proglycem)

Front 63

Vasodilators: MOA

Back 63

Cause smooth muscle relaxation (vasodilation)

--> reduction of total peripheral resistance

--> decr BP

(sodium nitroprusside donates NO--> inc cGMP--> vasodilation)

(hydralazine only causes arteriole relaxation, sodium nitroprussode causes balanced vasodilation)

Front 64

Vasodilators: Clinical Use

Back 64

Resistant HYPERTENSION

Hypertensive crisis

- Sodium nitroprusside is rapidly acting & used in medical emergencies

- Minoxidil is used to treat male pattern baldness

-Hydralazine is used to treat pregnancy induced hypertension

*Hydralazine & minoxidil most often used in combo with a diuretic to avoid water retention and an ACE inhibitor

Front 65

Vasodilators: Side Effects

Back 65

- reflex tachycardia

- edema
- Can lead to toxicity especially in the renally compromised
- Orthostatic Hypotension
- Will have rebound when used alone

Front 66

Sodium nitroprusside has a very short half life and is only effective through IV administration. Why should it not be infused to rapidly or used longer than 2 days?

Back 66

can cause cyanide toxicity

Front 67

which vasodilator may cause hypertrichosis?

Back 67

Minoxidil

(used to treat baldness)

Front 68

Antihypertensives Drugs:
Centrally-Acting Sympathomimetic Agents

Back 68

Clonidine (Catapres)
Methyldopa (Aldomet)

Front 69

Centrally-Acting Sympathomimetic Agents: MOA

Back 69

- Synaptic α 2-receptor agonists
- Inhibition of adrenergic tone
- Reduction of NE release
- Decreased total peripheral resistance
- Reduction in baroreceptor reflexes
- Decreased heart rate
- Reduced renin activity.

= decr HR

Front 70

Clonidine: Clinical Use

Back 70

- used in Heroine withdraw patients

- Seldom used to treat hypertension alone
- Can be used in the renally compromised patient

(acts directly on alpha2 receptors)

*combine w/ diuretic

Front 71

Clonidine: Side Effects

Back 71

- Drowsiness/ Sedation

- Restlessness
- Dry Mouth
- Constipation

*NEVER discontinue abruptly = Rebound hypertension

Front 72

Methyldopa (aldomet) clinical uses

Back 72

* first line tx for hypertension on pregnancy

Front 73

Methyldopa: MOA

Back 73

(pro-drug) Active metabolite: α-methylnorepinephrine

Activates presynaptic inhibitory α adrenoceptors & postsynaptic α 2 receptors in CNS-->
Reduces sympathetic outflow & total peripheral resistance.

Front 74

Methyldopa: Side Effects

Back 74

- edema (use low dose to prevent)

- hepatitis

- hemolytic anemia

Front 75

DOC for hypertensive patients at risk for angina pectoris

Back 75

Beta-blockers + Ca2+ channel blockers

Front 76

DOC for hypertensive diabetic patient

Back 76

ACE inhbitor (enalapril)

or ARB instead

if you add diuretics use caution!

Front 77

DOC for hypertensive patient w/ recurrent stroke

Back 77

ACE inhibitor

Front 78

DOC for hypertensive patient w/ heart failure

Back 78

diuretics + beta blockers + ACE inhibitors + ARB

(ALL)

Front 79

DOC for hypertensive patient w/ previous MI

Back 79

beta blockers (always) + ACE inhibitors

Front 80

DOC for hypertensive patient w/ chronic renal disease

Back 80

ACE inhibitor

or ARB (if pt has stenosis)

Front 81

Hypertensive Emergency

Back 81

Highly elevated BP (> 180/120 mmHg) associated with acute or immediately progressing target organ injury.

Front 82

Hypertensive Urgency:

Back 82

Highly elevated BP (>180/120 mmHg) NOT associated with acute or immediately progressing target organ injury.

Front 83

Treatment of Hypertensive Urgency:

Back 83

- Increase dose of current medication
- Addition of new antihypertensive agent
- Acute administration of short-acting oral agent (captopril, labetalol)
- captopril = ACE inhibitor short acting - 15 min and w/in next 15min a good drop in hypertension. give another does in an hour. now bp should be stabilized.

Front 84

Antihypertensives
Special Considerations: Elderly

Back 84

Elderly:
Go low, go slow!!
Close monitoring for side effects

Front 85

Antihypertensives
Special Considerations: Pregnancy

Back 85

Pregnancy:
ACE Inhibitors and Angiotensin II receptor blockers contraindicated.

Methyl-dopa, hydralazine & calcium channel blockers widely used.

Front 86

Q: A patient w/ a history of calcium oxalate renal stones is starting diuretic therapy. What drug should you use?

Back 86

A: Hydracorothiazide

(will retain calcium & prevent stone formation)

Front 87

Antihypertensives
Special Considerations: African-Americans

Back 87

- Diuretics decrease morbidity and mortality.
- May not respond well to monotherapy with β-blockers or ACE inhibitors. Need combination therapy.

Front 88

Antihypertensives
Special Considerations: Obstructive Airway Disease

Back 88

Avoid β-blockers

(use selective if you must use beta blocker)

Front 89

Antihypertensives
Special Considerations: Diabetes

Back 89

ACE inhibitors or Angiotensin II receptor blockers to control bp and slow renal deterioration.

Front 90

Q: Pt w/ acute hypotension comes in.

Hypovolemia ruled out

Family indicates OD of unknown antihypertensive

Phenylephrine (alpha1-agonist) administered

No change

2nd dose of phenylephrine shows mild success

What antihypertensive did the patient OD on?

Back 90

prazosin (alpha1-blocker)