HTN Drugs Chapter 11

Question 1

Diuretics

Answer 1

Usage: HTN to lower BP via reduction of blood volume
Include thiazides (eg hydrochlorothiazide) and the loop diuretics (eg furosemide; used in moderate and severe HTN and hypertensive emergencies).
Minimal compensatory responses.

Question 2

What are the possible effects of using sympathoplegics

Answer 2

Reduction of venous tone, HR, contractile force of heart, cardiac output, and total peripheral resistance.

Question 3

Name the overall classes of sympathoplegics

Answer 3

Baroreceptor-Sensitizing Agents
CNS-Active Agents 
Ganglion-Blocking Drugs
Postganglionic Sympathetic Nerve Terminal Blockers
Adrenoreceptor Blockers

Question 4

Baroreceptor-Sensitizing Agents

Answer 4

Veratrum alkaloids

Increase sensitivity of baroreceptor sensory nerves and reduce sympathetic outflow while increasing vagal tone to heart.

Question 5

CNS-Active Agents

Answer 5

Alpha2-selective agonists (clonidine, methyldopa) cause a decrease in sympathetic outflow by activation of α2 receptors in the CNS.

Reduce BP by reducing CO, vascular resistance, or both.

Question 6

Adverse Effects of CNS-Active Agents

Answer 6

Compensatory response in salt retention
Sudden discontinuation of clonidine causes rebound HTN (admin phentolamine)
Methyldopa causes hematologic immunotoxicity, which can lead to hemolytic anemia
Cause sedation

Question 7

Ganglion-Blocking Drugs

Answer 7

Hexamethonium and trimethaphan lower BP

Question 8

Postganglionic Sympathetic Nerve Terminal Blockers

Answer 8

deplete adrenergic nerve terminal of its NE stores (reserpine) or deplete and block release of stores (guanethidine, guanadrel) can lower BP. Compensatory response is salt and water retention

Question 9

MAO Inhibitors

Answer 9

cause formation of false transmitter (octopamine) in sympathetic postganglionic neuron terminals and lower BP. Sympathetic impulses which release mixture of octamine (low efficacy) and NO from vesicles, results in a smaller than normal increase in vascular resistance.

Question 10

What is the interaction between MAO inhibitors and indirect-acting sympathomimetics

Answer 10

Tyramine may cause release of large amounts of NE and result in hypertensive crises because can’t be metabolized by MAO.

Question 11

Adrenoreceptor Blockers

Answer 11

Alpha1-selective (prazosin, doxazosin, terazosin) – reduce vascular resistance and venous return

Beta-blockers – initially reduce CO, but after a few days may decrease vascular resistance from reduced angiotensin levels, as BB reduce renin release.

Question 12

What are the possible mechanisms of vasodilators

Answer 12

Release of NO
Opening of K+ channels (leads to hyperpolarization)
Blockade of calcium channels
Activation of D1 dopamine receptors

Include: hydralazine, minoxidil, calcium-channel blockers, nitroprusside, diazoxide and fenoldopam

Question 13

How are Hydralazine and Minoxidil administered?

Answer 13

Oral admin; more effect on arterioles than veins

Question 14

Hydralazine

Answer 14

acts through release of NO; at doses >200mg/d can cause lupus

Question 15

Minoxidil

Answer 15

prodrug and its metabolite minoxidil sulfate is a K+ channel opener that hydrolyzes and relaxes vascular smooth muscle.

Question 16

What are the compensatory effects and adverse effects of Minoxidil?

Answer 16

Compensatory effects included marked salt and water retention, and severe tachycardia so much be administered with BB and diuretic.
Can cause hirsutism.

Question 17

Name the calcium channel-blocking agents

Answer 17

nifedipine, verapamil, diltiazem

Question 18

What can occur with verapamil and diltiazem?

Answer 18

Verapamil and diltiazem can cause bradycardia and increased PR interval via reduction in contractility, HR, and atrioventricular conduction.

Question 19

How do you administer calcium channel-blocking agents and what are they used for?

Answer 19

Orally active; chronic use in HTN.

Question 20

Nifedipine

Answer 20

prototype dihydropyridine calcium channel blocker, and many other dihydropyridines are available (amlodipine, felodipine, isradipine).

Question 21

Which vasodilators are used in HTN emergencies

Answer 21

Nitroprusside, Diazoxide, and Fenoldopam (parenteral)

Question 22

Nitroprusside

Answer 22

light-sensitive, short-acting agent that must be continuously infused. Release of NO from drug stimulates GC and increase cGMP concentration in smooth muscle

Question 23

Diazoxide

Answer 23

thiazide derivative but lacks diuretic properties. Admin IV bolus or as infusion and duration of several hours. Opens K+ channels and relaxes smooth muscle cells. Also reduces insulin release (treat hypoglycemia)

Question 24

Fenoldopam

Answer 24

dopamine D1 receptor activation causes arteriolar vasodilation. Given by IV infusion and short duration of action for HTN emergencies

Question 25

Angiotensin-Converting Enzyme (ACE) Inhibitors MOA

Answer 25

Captopril
Inhibit ACE, kininase II, and peptidyl dipeptidase, cause a reduction in blood levels of ATII and aldosterone and an increase in endogenous vasodilators of kinin family.

Question 26

Usage of ACE-I

Answer 26

HF, diabetes, HTN

Question 27

Toxicities of ACE-I

Answer 27

cough and renal damage

contraindicated in pregnancy

Question 28

Angiotensin II Receptor Blockers (ARBs)

Answer 28

Losartan

Competitively inhibit ATII at its AT1 receptor site.

Question 29

Which are more effective ACE-I or ARBs?

Answer 29

ARBs are as effective as ACE inhibitors in lowering BP and lower incidence of cough. Both are contraindicated in pregnancy.

Question 30

What is the one renin inhibitor and what are its toxicities?

Answer 30

Aliskiren

Headache and Diarrhea

Question 31

Explain the principle of Stepped Care (Polypharmacy)

Answer 31

progressive addition of drugs to a regimen, starting with one (usually a diuretic) and adding in a stepwise fashion sympathoplegics (a BB), ACE inhibitor, and vasodilators (usually Ca2+ channel blocker). Goal is the control of the compensatory responses while producing additive therapeutic effects.

Question 32

Explain the influence of age and ethnicity on antihypertensive drugs

Answer 32

older patients of most races respond better to diuretics and BB than to ACE-I. AA of all ages respond better to diuretics and Ca2+ channel blockers.

Question 33

What do you give during a hypertensive emergency?

Answer 33

use powerful vasodilators (nitroprusside, fenoldopam, or diazocide) are combined with diuretics (furosemide) and BB to lower BP to 140/90.