Pharmacology: Block 4: Anti-Hypertensive Agents

Front 1

What is a normal cardiac output?

Back 1

5 L/min

Front 2

JNC VII classification of normal BP?

Back 2

<120 and <80

(average of two or more seated BP readings in each of two or more visits)

Front 3

JNC VII classification of pre-hypertension?

Back 3

120-139 or 80-89

(average of two or more seated BP readings in each of two or more visits)

Front 4

JNC VII classification of stage 1 HTN?

Back 4

140-159 or 90-99

(average of two or more seated BP readings in each of two or more visits)

Front 5

JNC VII classification of stage 2 HTN?

Back 5

≥160 or ≥100

(average of two or more seated BP readings in each of two or more visits)

Front 6

Mneumonic for secondary HTN?

Back 6

ABCDE.

A = Apnea (sleep apnea), aldosterone excess.
B = Bruits (suggesting renal artery stenosis)
C = Catecholamine excess
D = Drugs: cyclosporine, licorice (glycyrrhizic acid inhibits conversion of cortisol to cortisone.)
E = Erythropoetin excess

Front 7

Why did FDR die? What was his BP when he died?

Back 7

Because of a stroke secondary to HTN. When he died his BP was 300/170.

Front 8

Treating HTN reduces
Stroke:
MI:
HF:
by how much?

Back 8

Stroke: 35-40%
MI: 20-25%
HF: 50%

Front 9

Treating stage 1 HTN: a decade of __ mmHg reduction prevents 1 death for every __ treated.

Back 9

Treating stage 1 HTN: a decade of 12 mmHg reduction prevents 1 death for every 11 treated.

Front 10

HTN worldwide?

Back 10

1 billion people

Front 11

What percentage of those with HTN are not at their goal BP? If they were treated, how many lives could be saved?

Back 11

550 million. Treatment over 10 years could save 50 million lives.

Front 12

Loop diuretics: first line of therapy for what two conditions?

Back 12

CHF and CRF
Not first line for stage 1 or stage 2 HTN

Front 13

Loop diuretics: dosing.

Back 13

Frequent: 2x day

Front 14

Loop diuretics: bio-availability. Exception to this is?

Back 14

80-100%. Exception: furosemide (10-100%)

Front 15

Loop diuretics: elimination?

Back 15

Hepatic (except lasix (renal))

Front 16

Loop diuretics: Interactions

Back 16

less effective with CRF (organic acids), NSAIDs, probenicid (for gout). There is tubular secretion competition.

Front 17

What did physicians notice in WWII when penicillin was running short?

Back 17

They noticed that a large amount of penicillin was excreted in the urine of soliders. They were able to strain the urine to recover it.

Front 18

Loop diuretics: common adverse effects?

Back 18

- Hypokalemia (via K secretion in principal cell)
- Metabolic alkalosis (H secretion from alpha-intercalated cell)

Front 19

Loop diuretics: severe adverse effects?

Back 19

Ototoxicity - tinnitus, hearing loss, vertigo

Front 20

Never give ________ ___ with aminoglycosides!

Back 20

Never give ETHACRYNIC ACID with aminoglycosides!

Front 21

Loop diuretics: less common adverse effects?

Back 21

Hypo Mg, Ca
Metabolic changes: Hyperglycemia, increased LDL, decreased HDL

Front 22

Thiazide diuretics: M of A?

Back 22

Inhibit the Na/Cl symporter in the DCT.

Front 23

Thiazide diuretics: ineffective when pt has a ___ ___. Exceptions to this?

Back 23

Thiazide diuretics: ineffective when pt has a LOW GFR. Exceptions: metalazone & indapamide. (Not used so often)

Front 24

Thiazide diuretics: dosing

Back 24

Once daily (25 mg)

Front 25

Thiazide diuretics: HCTZ half-life?

Back 25

Rapid onset 2 hours (peak 6 hours).

Front 26

Thiazide diuretics: Chlorthalidone: unique property?

Back 26

Long acting.

Front 27

Thiazide diuretics: interactions

Back 27

Less effective with CRF (organic acids), NSAIDs, probenicid. Tubular secretion competition

Front 28

Thiazide diuretics: first line therapy for what?

Back 28

For the uncomplicated pt with HTN.

Front 29

Loop diuretic: name three

Back 29

1. Furosemide
2. Bumetanide
3. Torsemide

Front 30

Thiazide diuretics: name two

Back 30

1. Hydochlorothiazide
2. Chlorthalidone

Front 31

Thiazide diuretics: Common adverse effects?

Back 31

Hypokalemia (b/c of K secretion in the principal cell)
Metabolic alkalosis (H sec in the alpha intercalated cell)
Hypercalcemia (Rx nephrolithiasis, osteoporosis). NOTE, this is not seen with Furosemide.

Front 32

Thiazide diuretics: two life threatening adverse effects?

Back 32

Severe hyponatremia - seen at high doses, idiosyncratic in women.

Prolonged QT, can lead to torsades with quinidine.

Front 33

Thiazide diuretics: less common adverse effects?

Back 33

Hypo Mg
Metabolic changes: hyperglycemia, increased LDL, increased TG.

Front 34

Potassium sparing diuretics: M of A

Back 34

- Competitive antagonist of aldosterone (spironolactone, eplerenone)

- Inhibit epithelial Na channels in principal cells (amiloride, triamterene)

Front 35

Potassium sparing diuretics: level of diuresis

Back 35

Moderate diuresis only.

Front 36

Potassium sparing diuretics: lipid solubility

Back 36

High

Front 37

Potassium sparing diuretics: half-life

Back 37

long (20 hrs)

Front 38

c/c Spironolactone and Eplerenone: gynecomastia

Back 38

Eplerenone is more specific (has less afinity for the androgen and glucocorticoid receptors) thus causes less gynecomastia.

Front 39

Potassium sparing diuretics: access to site of action is independent of ___.

Back 39

Potassium sparing diuretics: access to site of action is independent of GFR.

Front 40

Potassium sparing diuretics: common AE

Back 40

- Hyperkalemia (so limits use in CHF and chronic renal disease)

- Gynecomastia (Spironolactone > Eplerenone

Front 41

Potassium sparing diuretics: life threatening AE

Back 41

Acute renal failure with combination of NSAID + triamterene

Front 42

Can't give a potassium sparing diuretic if the patient has what?

Back 42

High potassium!

Front 43

A patient with no significant PMH has uncomplicated pre-HTN. The next best step is:

a) Suggest a change in lifestyle
b) Thiazide diuretic
c) Lisinopril
d) Verapamil

Back 43

a) suggest a change in lifestyle

Front 44

A patient with HF is being treated with furosemide. Lab tests show that her K is always low. Administering an agent with what action is the next best step?

a) Blocks the Na/K/Cl cotransporter

b) Blocks the Na/Cl symporter

c) Activates the epithelial Na channel of the principal cell

d) Blocks the action of the mineralocorticoid receptor

Back 44

Ans = d

a) Blocks the Na/K/Cl cotransporter - this is what furosemide does

b) Blocks the Na/Cl symporter - what thiazide does - will worsen hypoK

c) Activates the epithelial Na channel of the principal cell - will worsen hypoK

d) Blocks the action of the mineralocorticoid receptor

Front 45

What is angiotensin escape? When does it usually occur?

Back 45

When non-ACE enzymes (chymase, disinhibition of renin) convert Angiotensinogen and angiotensin I to Angiotensin II

Front 46

ACEi: clinical outcomes

Back 46

- Vascular remodeling: inc relaxation, dec fibrosis (inc compliance)

- SNS: dec activation

- Adrenal cortex: dec aldosterone from z.g. --> dec Na retention.

Front 47

ACEi: common AE

Back 47

- Major AE is cough. This is from inc bradykinin, inc substance P in lungs.

- Cough occurs within 1-24 weeks, resolves 4 days after stopping.

- Hyperkalemia: don't give with pts with renal disease, K sparing diuretics

Front 48

ACEi: pharmacology

Back 48

Most are prodrugs: ethyl esters of parent acid converted in liver and intestinal tract.

Front 49

ACEi: route

Back 49

PO (only elanaprilat is IV)

Front 50

ACEi: elimination

Back 50

Mostly renal

Front 51

ACEi: escalating the doseage does what?

Back 51

Prolongs the duration, NOT the peak activity. Peak action for remodeling effects takes weeks.

Front 52

ACEi: drug interactions

Back 52

ASA doses > 236 mg/day can offset ACEi effects.

Front 53

Two ACEi that are not prodrugs

Back 53

Captopril
Lisinopril

Front 54

ACEi: life-threatening AE

Back 54

- Angioedema within 2-4 weeks
- Birth defects

Front 55

ACEi: less common AE

Back 55

Anemia (dose dependent suppression of erythropoetin)

Worsen psoriasis (increase kinins in skin)

Maculopapular rash (e.g. captopril)

Front 56

ACEi: never give to what type of patients?

Back 56

Pregnant patients!

Front 57

Angiotensin II receptor blockers: M of A

Back 57

Competitively inhibit AT1 receptor

Have unapposed AT2 (vasodilatory) effects. Also, by blocking AT1 receptors, this pushes Ang II onto AT2 (vasodilatory) receptors.

Front 58

Angiotensin II receptor blockers: Pharmacology

Back 58

Low bioavailability <50%
Effects longer than predicted
High protein binding

Front 59

ARBs: common AE

Back 59

Hyperkalemia with renal disease and K sparing diuretics

Front 60

ARBs: life-threatening AE

Back 60

- Birth defects (2nd and 3rd trimesters).

- Angioedema (less than with ACEi). Swelling of the face and soft tissue of the throat.

Front 61

ARBs: less comon AE

Back 61

Cough (4 times less likely than ACEi) - doesn't affect bradykinin.

Front 62

The mechanism by which ACEi cause functional renal insufficiency (especially with renal disease) is:

Back 62

Increased flow in the efferent arteriole.

Front 63

CCBs: M of A

Back 63

- Blocks the L-type Ca channels --> decrease transmembrane Ca current by reducing the frequency of opening.

- Relax arteriolar smooth muscle (little effect on venous beds - so NO CHANGE in preload)

Front 64

CCBs: have the most effect on patients with what type of HTN?

Back 64

Pts with severe HTN.

Front 65

Does amlodipine affect HR?

Back 65

No!

Front 66

Effects of vascular selective CCBs

Back 66

Amlodipine

Greatest effects on BP, minimal effect on HR.

Front 67

Effects of cardioselective CCBs

Back 67

Verapamil, Diltiazem

Weaker BP effect, inhibit SA & AV node, blunt reflex tachycardia

Front 68

Amlodipine: can cause reflex what?

Back 68

Tachycardia.

Front 69

CCBs: common AE

Back 69

- Vasodilator effects (flushing, palpitations, edema. esp with dihydropyridines)

- Constipation (Verapamil)

- Gingival hyperplasia (Nifedipine (38%) > diltiazem (21%) > verapamil (19%) > control)

Front 70

Verapamil: AE

Back 70

constipation

Front 71

Nifedipine: AE

Back 71

Gingival hyperplasia

Front 72

CCBs: life-threatening AE

Back 72

- Cardiac conduction defects (verapamil), avoid use with beta blockers

- Avoid short acting dihydropyridines (can cause precipitous drops in BP, worse cardiac outcomes)

Front 73

CCBs: indications for use

Back 73

1 of 2 drugs for stage 2 HTN

Front 74

Verapamil + beta blocker = ?

Back 74

BAD

Front 75

A patient is taking verapamil for the management of HTN and is at max dose. HR is low normal and the pt is otherwise asymptomatic. Addition of which agent is the next best choice:

a) HZTC
b) Diltiazem
c) Atenolol
d) Ispoproterenol

Back 75

A patient is taking verapamil for the management of HTN and is at max dose. HR is low normal and the pt is otherwise asymptomatic. Addition of which agent is the next best choice:

a) HZTC - correct
b) Diltiazem - would slow HR
c) Atenolol - would slow HR
d) Ispoproterenol - would slow HR

Front 76

Shortly after initiation of anti-HTN therapy with a CCB, a pt complains of leg edema, flushing, and palpatations. What agent is most likely responsible?

a) Verapamil
b) Amlodipine
c) Furosemide
d) Diltiazem

Back 76

Shortly after initiation of anti-HTN therapy with a CCB, a pt complains of leg edema, flushing, and palpatations. What agent is most likely responsible?

a) Verapamil - affects heart, not blood vessels

b) Amlodipine - ankle edema and swelling

c) Furosemide
d) Diltiazem

Front 77

Beta-blockers: affect on cardiac output?

Back 77

Makes it drop 15-20%

Front 78

Beta-blockers: drug interactions

Back 78

May cause unopposed alpha-1 induced vasoconstriction and hypertension with:

Ephedrine
Pseudoephedrine
Epinephrine
Phenylpropanolamine
Cocaine

Front 79

Name two beta-blockers with alpha-blocking capabilities

Back 79

1. Labetalol (3:1)
2. Carvedilol (10:1)

Front 80

Esmolol: general

Back 80

Short half-life
Metabolized by plasma and hepatic esterases
IV administration
Renal elimination

Front 81

The non-selective beta-blockers are useful for treating what?

Back 81

Migrane, essential tremor.

Front 82

Beta-blockers: common AE

Back 82

- Metabolic effects: Glucose up, TG up, HDL down!

- Can cause blunting of the hypoglycemic response (non-selective > selective)

- CNS: depression (esp metoprolol), nightmares, hallucinations (lipid soluble > water soluble)

Front 83

Beta-blockers: life-threatening AE

Back 83

- Heart block if given with verapamil, diltiazem, Sick Sinus Syndrome (without a pacemaker)

- Bronchospasm with COPD/asthma

Front 84

Beta-blockers: antidote

Back 84

Glucagon

Front 85

Effect of an alpha-1 blockade?

Back 85

Hypotension

Front 86

Alpha-1 blockers: AE

Back 86

Orthostatic hypotension (90 min after first dose)

ALLHAT study of thiazide vs. doxazosin = increased HF, stroke!

Front 87

Alpha-1 blockers: Recommendations for use

Back 87

Not recommended

Front 88

You recently started a 67 y.o. diabetic male on metoprolol for a prior myocardial infarction and history of poorly controlled HTN. He also takes aspirin and lisinopril (for a long time).

The pt presented to the ED with lightheadedness and suddenly became obtunded. His pulse is 36 bpm and BP is 80 mmHg/palpation. In addition to IV fluids, what is the next best course of action:

1. Isoproterenol
2. HCTZ
3. Glucagon
4. Glycogen
5. Amlodipine

Back 88

Glucagon for beta-blocker overdose

Front 89

A 43 y.o. female presents to your office with poorly controlled HTN. She dislikes taking medications, but reported taking an antihypertensive that controlled her BP as well as her migraines. Which drug was it?

1. HCTZ
2. Metoprolol
3. Atenolol
4. Propranolol
5. Isoproterenol

Back 89

4. Propranolol - nonselective agents are good at treating migranes.

Front 90

HTN in pregnancy: treatment?

Back 90

Methyldopa (inhibits alpha-1).

Don't give ACEi!
Avoid beta-blockers! (growth retardation)

Front 91

Stage 1 HTN: treatment?

Back 91

Thiazide

Front 92

Stage 2 HTN: treatment?

Back 92

Thiazide + ACEi or ARB (if HTN + renal disease), or BB (MI + HTN), or CCB (if contraindications to the above)