11 05 2014 Anti-hypertensive drugs

Question 1

what are the 4 classes of drugs used to treat hypertension

Answer 1

• Diuretics
• Sympatholytics
• Vasodilators
• Drugs that interfere with renin-angiotensin system

Question 2

what are factors that increase cardiac output

Answer 2

1. Excess sodium intake – could be due to an altered renal sodium retention
   - this increases fluid – increases preload – increases CO
2. Renin - RAAS – Increase sodium retention
3. SNS increases HR and contractility

CO = HR X BP

Question 3

What are the targets of Antihypertensive drugs

Answer 3

1. sodium/ Plasma volume
2. RAAS
3. SNS
4. Vascular Smooth muscle

Question 4

Thiazide diuretics
(mechanism)

Answer 4

target Na+ -Cl- exchanger (NCC) symporter – inhibit reabsorption of Na+ in distal tuble

Affects Na+/K+ pump and now K+ is excreted
= hypokalemic statuses

Hydrochlorothiazide
Chlorthalidone

Question 5

Loop Diuretic

Answer 5

Target Na+ K+ 2Cl- symporter in thick ascending limb of nephron

Block reabsorption of Na+

Very potent but very short lived

Ex. Flurosemide

• reserved for CHF or resistant edema

Question 6

Adverse effects of Thiazide/ Loop Diuretic Therapy

Answer 6

1. Volume depletion (hypotension and decrease GFR)
2. Hypokalemia ( increase in distal Na+/K+ exchanger)
3. Hyponatremia
4. Metabolic Alkalosis
5. Increase in uric acid — Gout
6. Hyperglycemia
7. K- sparing agents : hyperkalemia
8. Gynecomastia/ sexual dysfunction ( spironolactone –potassium sparing diuretic)

Question 7

Hydrochlorthiazide

Answer 7

most common drug used – thiazide

Good for volume-overloaded/ salt depedent/ low renin HTN

Question 8

Direct Vasodilators

Answer 8

• calcium channel blockers
• Hydralazine and minoxidil

Adverse effects: fluid retention, tachycardia
-reflex increase in SNS so pair with beta-blocker

Question 9

Calcium channel blockers

1. target
2. any AE?
3. names of drugs
4. interesting fact about two drugs?

Answer 9

Target voltage-sensitive L-Type canals
- affect Ca2+ in smooth muscle, AV and SA node
= relaxation

Metabolically neutral : no effects on glucose

No renal, CNS or pulmonary AE.

AE: edema, flushing, lightheadedness, CONSTIPATION at all doses.

• Bradycardia
• Skin rash is common

Diltiazem
Verapamil
Nifedipine ( Amlodipine)
Nicardipine

• Diltiazem and verapamil inhibit hepatic P450 enzymes

Question 10

Hydralazine

Answer 10

Oral and IV
Short acting

Directly relaxes vascular smooth muscle of pre capillary resistance vessels

Potential for lupus syndrome w/ pericarditis

Question 11

Minoxidil

Answer 11

Very potent oral agent
AEs include hypertrichosis, pericardial effusions, massive fluid retention

Directly relaxes vascular smooth muscle of pre capillary resistance vessels

Question 12

Nitroprusside

Answer 12

Release NO = dilates arterioles and venues (decrease preload and after load)

Cyanide toxicity

Useful in severe or refractory HTN – pulmonary edema emergency

Question 13

Alpha receptor Antagonist

Answer 13

Inhibit vasoconstriction of NE

Decrease total peripheral resistance (TPR) but with LESS tachycardia

Adverse effects: postural hypotension, headache, edema

Question 14

Phentolamine

Answer 14

(IV)
Nonselective alpha receptor antagonists

Adverse Effects: postural hypotension, headache, edema

Question 15

Phenoxybenzamine

Answer 15

Oral
Nonselective alpha receptor antagonist

Adverse Effects: postural hypotension, headache, edema

Question 16

Prazosin, terazosin, doxazosin

Answer 16

Alpha 1 selective antagonists
oral

Also used for symptoms of prostatic hypertrophy.

Blockade of peripheral arterioles and venues

Toxicity: Dizziness, headaches,lassitude

Question 17

CNS- acting Sympathetic inhibitor

Answer 17

Alpha 2 receptor antagonists in the medullary brainstem

Act in CNS to decrease outflow

Clonidine
Alpha methyldopa

Question 18

Clonidine

Answer 18

Oral and transdermal (patch)
Onset 30-60 min – useful for HTN urgencies

AE: sedation, dry mouth, rebound BP (increase)

Sudden withdrawal can result in sudden hypertensive crisis

Question 19

Alpha methyldopa

Answer 19

Oral and IV

AE: sedation ,hepatitis, and coombs pos hemolytic anemia

*** PREGNANCY ASSOCIATED HTN

Question 20

Effects of a beta blocker

- target organs and their effects on them

Answer 20

1. heart
   - slowing of heart range and negative inotropic effect
   = reduction in CO
2. Kidney
   - Inhibition of Renin release (mostly B1)
3. brain
   - possible central action

Question 21

Nonselective Beta Blockers

Answer 21

B1 and B2 receptor antagonists
- propranolol

AE: bronchospasms, worsening of diabetes, hyperlipidemia, prolonged hypoglycemia

May also have fatigue, depression, erectile dysfunction

Question 22

Beta 1 selective agents

Answer 22

Atenolol, metoprolol, bisoprolol
-may enhance Co, contractility and sA node firing.

B1 mediates renin release!!

Inexpensive and have fewer AE

Question 23

Labetalol, carvedilol

Answer 23

• vasodilitary beta blockersnon-selective B/alpha

primarily beta 3:5

Question 24

Nebivolol

Answer 24

B1 selective agent

Release of NO

Question 25

Pindolol, acebutolol

Answer 25

ISA - intrinsic sympathomimetic activity ( beta agonis and antagonist effect) Prevents dangerous bradycardia at night (due to other beta blockers)

Question 26

Adverse Side Effects of Beta Blockers

Answer 26

1. heart - Contradicted during acute heart failure - Intensification of AV block - Arterial insufficiency - bradycardia 2. CNS - depression - confusion - fatigue 3. Pulmonary - Dyspnea - Bronchospasm

Question 27

Indications for use of Beta blocker in HTN

Answer 27

younger patients (greater adrenergic activity or elevation of plasma renin) May have less stroke prevention in the elderly

Question 28

Indications for use of Beta Blocker in Cardiac Disorders

Answer 28

- tachycardia - Chronic LV dysfunction - CAD - coronary artery disease - Hypertrophic subaortic stenosis

Question 29

Indications of beta blocker in non-cardiac disorders

Answer 29

Vascular (migraine) headache prevention Essential tremor and performance anxiety

Question 30

Diltiazem Hydrochloride

Answer 30

Calcium Channel Antagoinst - used in atrial fibrillation - decreases HR - decreases Myocardial contractility - decreases nodal conduction - increases peripheral vasodilation

Question 31

Verapamil Hydrochloride

Answer 31

Calcium channel antagonists - decreases HR - decreases Myocardial contractility (better than other) - decreases nodal conduction (better than others) - increases peripheral vasodilation

Question 32

Nifedipine/ Amlodipine

Answer 32

Calcium channel antagonists - increase/ no change to HR - decreases/no change to Myocardial contractility - no effect on nodal conduction - increases peripheral vasodilation (way better than Diltiazem and verapamil)

Question 33

Nicardipine hydrochloride

Answer 33

Calcium channel antagonists - increase/ no change to HR - no change to Myocardial contractility - no effect on nodal conduction - increases peripheral vasodilation (way better than Diltiazem and verapamil)

Question 34

Renin- Physiological Regulation

Answer 34

1. decrease in renal perfusion = renin release from JG cells 2. Increase SNS via B1 receptors = increase in renin 3. Angiotensin II production and negative feedback = decrease in renin 4. Increase distal tubular Na content = increase in renin release

Question 35

Differences among ACE inhibitor, ARB and Direct Renin inhibitor:

Answer 35

ACE Inhibitor: - decrease AII and Aldosterone - Increase plasma renin level - increase plasma renin activity (PRA) - increase vasodilitary peptides ( bradykinin) ARB: - decrease aldoserone level - Increase plasma Renin level, PRA, and AII levels DRI - decrease PRA - decrease in AI, AII, Aldosterone - Increase Plasma renin LEVEL

Question 36

Potentinal adverse Effects of ACEi, ARB, DRI

Answer 36

1. hyperkalemia (aldosterone inhibition) 2. Hypotension 3. Worsen renal insufficiency ( disproportionate glomerular efferent arterial vasodilation) 4. Fetal injury - ALL INHIBITORS OF RRA ARE CONTRAINDICATED IN PREGNANCY 5. ACE-I Cough

Question 37

What drugs will worsen the following situations of HTN: 1. Pregnancy 2. Depression 3. sexual dysfunction 4. Asthma 5. Gout 6. Constipation

Answer 37

1. ALL RRA agents 2. beta blockers, central inhibitors 3. beta blockers, central inhibitors, spironolactone (potassium sparing diuretic) 4. Asthma: Beta blocker (non selective) 5. Gout - Diuretic 6. Verapamil

Question 38

Captopril, Enanalapril

Answer 38

ACE inhibitors Inhibit peptdyl dipeptdase – affects RAAS and Kallikrein-­‐kinin system Toxicity: ARF in pts wi/bilateral renal artery stenosis; dry cough; angioedema:

Question 39

Losartan, Valsartan

Answer 39

AT1 inhibitors; no effect on bradykinin Similar effects to ACE-­‐I; less cough and angioedema