Pharm 1 - Anti-Hypertensive Drugs 1 (Nierenberg)

Front 1

Olmesartan

Back 1

An ARB

Front 2

In older pts - systolic vs. diastolic

Back 2

If they have isolated systolic increase, just treating the systolic is often good enough.

Front 3

Sensor of drop in BP

Back 3

Aortic arch and carotid. (stretch receptors)

Front 4

Body reflexes to a drop in BP

Back 4

Vasomotor center in brainstem increases ACh to hit nicotinic and then more NE to cause vaso and venoconstriction alpha1) to increase preload and inc BP.

Also increase in HR at SA node (NE to beta1 receptor)
Increase in contractility at LV with beta1 receptors.

Affects the AV node to increase conduction.

Renin stimulated with NE in JGA to conv angiotensinogen to A1, then A1 to A2 by ACE.
AII then vasoconstricts by hitting angiotensinI receptor, causes release of aldosterone (to tell kidney to retain salt and water to inc preload), and causes vasoconstriction of the efferent arteriole to maintain perfusion in the kidney.

There are also branches of sympathetics stimulated to tell the adrenal to produce Epi and NE.

Front 5

4 big classes of anti-HTN drugs

Back 5

Diuretics
Inhibitors of RAA (renin, angiotensin, aldosterone) system
Vasodilators - these don't interrupt, but produce vasodil on their own.
Sympatholytic agents

Front 6

Are calcium entry blockers diuretics?

Back 6

Yes

Front 7

Hydrochlorothiazide pharmacodynamics

Back 7

Block reuptake of Cl and Na from tubular fluid. Decreases SVR too.
Decreases BP by 10-15 mm Hg

Can also work for edema

Front 8

Hydrochlorothiazide
Pharmacokinetics

Back 8

F=70%.
Excreted unchanged in urine.
Short half-life.
Not avail IV

Front 9

Hydrochlorothiazide
Toxicity

Back 9

Allergy to sulfa antibiotics, causes K , Mg, Na, Cl depletion, metabolic alkalosis, worsens hyperuricemia.

Front 10

Hydrochlorothiazide special consid

Back 10

More SEs in geriatric pts, avoid in pregnancy, ineffective in pts with reduced GFR.

Don't give before bedtime (will pee all night)

Monitor BUN, creatinine, K, Mg, edema.

Front 11

The other popular diuretic

Back 11

chlorthalidone.

Front 12

Lisinopril

Back 12

ACE inh - tx of CHF, good at preserving renal function (diabetics - inhibits constriction of efferent arteriole which angII normally does), preserves LV func after MI, acute management of MI.

By inhibiting ACE, it stops AII from vasoconstricting thigns (periph and renal eff arteriole) and stop stimulation of aldosterone

Front 13

Lisinopril
Pharmacokinetics

Back 13

Excreted in urine unchanged.

Front 14

Lisinopril
Toxicity

Back 14

Orthostatic hypotension.
CAUTION IN PTS WITH RENAL ARTERY STENOSIS (can get really low perfusion pressure and cause renal failure).

Caution in pts with renal problems in general.

Front 15

Lisinopril
Interactions

Back 15

NSAIDs reduce ability to lower BP. Can get hyperkalemia with KCl.

Front 16

Lisinopril
special considerations

Back 16

Discontinue diuretics before using these.
Abnormal cartilage in fetus (contraind in pregnancy)

MONITOR KIDNEY FUNC - ESPECIALLY CREATININE!!!

Front 17

Captopril

Back 17

An ACE that isn't used often anymore because it causes lots of coughing.

Front 18

Losartan

Back 18

ARB (angiotensin 1 receptor blocker)
Also good for CHF (just like ACEinh)

It reduces the production of aldosterone and also reduces vasoconstriction.

Good with diabetics just like ACEinh

Front 19

Losartan
Pharmacokinetics

Back 19

F=30%
Active metabolite is 40x more potent.

Front 20

Losartan
toxicity

Back 20

Dizziness, worsening of renal failure. (but note it is good with diabetics!!!)

Front 21

Losartan
Special consid

Back 21

Not used in pregnancy, avoid in pts with renal artery stenosis.

Monitor kidney func especially creatinine!!!

Front 22

Nitroprusside

Back 22

Best used in emergency situations to reduce dramatic HTN
Don't rx for more than 24 hours, and only available IV

Metabolized to release CN- (cyanide - metab in liver) and NO.

A very potent vaso and venodilator.

Front 23

Pathway of NO

Back 23

NO activates guanylate cyclase and this makes cGMP from GTP. This then interferes with actin-myosin leading to vasodilation. cGMP is then hydrolyzed to GMP by PDE.

Front 24

Nitroprusside
special considerations

Back 24

Accum of CN- and thiocyanate (thio is made from CN- in the liver)

Use with caution in pts with increased intracranial pressure.

Can cause metabolic acidosis.

Front 25

Hydralazine

Back 25

Tx of HTN, CHF and causes vasdilation

Induces endothelium to produce NO which then passes to SM and induces prod of cGMP...

Front 26

Hydralazine
Pharmacokinetics

Back 26

PO, IM or IV
Metab in GI mucosa and liver. Excreted as metabolites in the urine.
F=40%

Front 27

Hydralazine
Special considersation

Back 27

More dangerous in pts with renal disease, prior stroke, angina. May also get drug-induced lupus. Also avoid in pts with coronary artery disease

Never use as monotherapy because edemaa and reflex tachycardia will result.

SAFE IN PREGNANT WOMEN

Front 28

Hydralazine
discovery of mech of action

Back 28

Sloughed off endothelial cells and saw that this no longer worked

Front 29

Verapamil is similar to...

Back 29

nifedipine, amlodipine, diltiazem, nicardipine

These are great for HTN plus angina.

Front 30

Verapamil

Back 30

Calcium entry blocker
Good for antiHTN, angina (especially variant/prinzmetals), antiarrythmic.

Inhib slow channel calcium influx to dilate periph arterioles and also has a negative inotropic effect (explains antiangina)

Front 31

Verapamil
pharmacokinetics

Back 31

F=30%
Cleared by kidney and liver (produces active metabolites)
Available po or iv

Front 32

Verapamil
special consid

Back 32

Additive toxic effects on heart with beta blockers.
Can worsen AV block, CHF and bradycardia.
Concern with clearance in pts with renal or liver disease.
Don't use in pregnant women.

Front 33

Nifedipine may..

Back 33

increase risk of MI (it is a CEB)

Front 34

In black pts, what is more useful?

Back 34

diuretics and CEBs

Front 35

Single drugs can reduce BP by...

Back 35

10-12 mm Hg

Front 36

Pt with diabetes and HTN

Back 36

GIVE ACEinh OR ARB!!!
(lisinpril or losartan)