Antihypertensives

Question 1

What types of drugs can be used to treat HTN?

Answer 1

Diuretics
Alpha-2 stimulants
Vasodilators
--hydralazine
--minoxidil
ACE inhibitors
Angiotensin receptor blockers

Question 2

What are the limits to HTN therapy?

What factors affect HTN?

Answer 2

Limits: kidney and blood flow

Factors: age, genetics, race

Question 3

What diuretics are used to tx HTN?

Answer 3

Hydochlorothiazide

Chlorthalidone

Question 4

Why do diuretics work for treating HTN?

Answer 4

with increased BP, Na accumulates in vascular smooth mm and then exchanges for Ca which increases the tone
–causes blood vessel constriction which gives high BP

Diuretics increase Na loss

Question 5

Use of diuretics in pts with HTN

Answer 5

Lower BP when used alone

Prevent “false tolerance” (inc BP which occurs with other antiHTNive drugs)
–prevent sodium accumulation

Good for elderly and African Americas

Question 6

What are things to be careful of with diuretics?

Answer 6

• High blood lipids
• Increased glucose b/c blocks insulin release
• K+ depletion b/c high Na in collecting duct
• DONT USE WITH ASPIRIN
  
  • –part of diuretic effect is production of prostaglandins
  • –aspirin blocks this

Question 7

Alpha-2 adrenergic receptors are found where? Do what?

Answer 7

Found mainly on nerve ends

Inhibit release of neurotransmitter

Decrease sympathetic outflow from brainstem by acting on alpha2a receptors

• -dec NE release
• -baroreceptors still fxn

Question 8

What drugs are alpha-2 stimulants?

Answer 8

Alpha methyl DOPA

Clonidine

Question 9

What side effects can be seen with alpha-2 stimulant use?

Answer 9

Decreased mental acuity
Nightmares
CNS depression

Dry mouth

Rebound inc BP on abrupt cessation

Question 10

Hydralazine

• what does it do?
• what can they cause (in terms of side effect)?
• how can we minimize this?

Answer 10

Releases NO to increase cyclic GMP and dilate ARTERIES

can cause reflex tachycardia
–combine with B-blockers to minimize

Question 11

Why is the difference between slow and fast acetylators important for hydralazine use?

Answer 11

People that are slow acetylators tend to the patients that develop lupus like syndrome with drug use

• -this is not lupus
• -it will stop with cessation of the drug

Question 12

Contrast alpha blockers and hydralazine

Answer 12

Alpha blockers work on arteries and veins
Hydralazine works on arteries only

Less postural hypotension occurs with hydralazine

Question 13

Minoxidil

• -what does it do? how?
• -what can it cause? how do we prevent this?
• -what are other side effects?

Answer 13

Dilates arteries (skin, sk mm, heart, GI tract)
--opens ATP-sensitive K+ channels --> causes hyper polarization

Can cause severe reflex tachycardia
-have to use with B-blocker to prevent

Sodium retention due to increased renin
-have to use with diuretics to prevent

Can cause hair growth - Hirsutism

Question 14

What drug is Rogaine?

Answer 14

Minoxidil

This does not work via hormonal influence, but via direct stimulation of the hair follicle

Question 15

What drugs are ACE inhibitors?

Answer 15

Captopril (8 hr duration)
Enalapril (24 hr duration)

Look for “PRIL”

Question 16

How do ACE inhibitors work?

Answer 16

Block formation of angiotensin II
–end product inhibition by analogues of 2aa fragment

Less angio II means less vasoconstriction
Less aldosterone means Na loss
Block bradykinin metabolism
–vasodilation

Question 17

Advantage of ACE inhibitor therapy

Answer 17

Increased kidney blood flow

• -release of PGE2
• -syngergistic with diuretics

Good in elderly

Like Beta blockers, prevent 2nd heart attack

No reflex tachycardia

No CNS depression

Abrupt withdrawal is not a problem

Question 18

Precautions for use of ACE inhibitors

Answer 18

Chronic non-productive cough
--bradykinin?
Bad in pregnancy
--oligohydramnios (dec amniotic fluid)
--fetal BP dec; renal failure in 2nd, 3rd trimester
Prodrugs don't work in patients with bad livers
--have to be converted there
Loss of taste with captopril
Severe allergic rxn to first dose

Question 19

Angiontensin II receptor blockers (ARBs)

• how do they work?
• examples?

Answer 19

Competitive block of angiotensin II-1 (AT1) receptor
(little block of AT2)

Losartan
Valsartan
“SARTAN”

Question 20

Advantages and disadvantes of ARBs

Answer 20

Advantages

• less cough
• less angioedema

Disadvantages

• oligohydramnios
• less effective in African Americans
• slow acting
  
  • –full effect in ~3 weeks

Question 21

What agents can be used in hypertensive emergencies?

Whats considered to be a hypertensive emergency?

Answer 21

Unstable angina, internal blooding, hypertensive encephalopathy

Nitroprusside
Fenoldopam
Diazoxide

Question 22

Nitroprusside

Answer 22

NO generator

Can cause nausea, disorientation, mm cramps

Also releases cyanide (but not a lot is produced and its converted quickly)

Question 23

Fenoldopam

Answer 23

D1 agonist like dopamine

Question 24

Diazoxide

Answer 24

Like minoxidil but weaker

Duration 12 hrs

Question 25

What is pre-eclampsia?

What is the effective treatment

Answer 25

HTN in pregnancy
(also called “toxemia of pregnancy”)

MgSO4 treats it
–offsets Mg++ loss which occurs in pregnancy