htn prescribing pharm mod 5

THIAZIDE DIURETICS

First line initial HTN therapy with no other indications
 Mechanism- Blocks reabsorption of NACL in the early segment of the
distal convoluted tubule, there is NACL retention in the nephrons
causing increased flow of urine.
 Indications- Edema
 Decrease morbidity and mortality
 Inexpensive
 Monitor- Baseline weight, vitals, and electrolytes
 Caution- History of renal impairment, diabetes, gout, digoxin, lithium,
other HTN medications
 Dosing- Start low adjust doses slow

LOOP DIURETICS

Furosemide (Lasix) or Torsemide (Demadex)-
 Indicated for HTN- or Edema disorders
 Action- Prevent reabsorption of NACL in the ascending limb of the loop of
Henle, inference cause profound diuresis.
 Indication- HTN that can’t be controlled with Thiazide and k+ sparing
 Monitor- Baseline weight, vitals, and electrolytes
 Caution- History of renal impairment, diabetes, gout, digoxin, lithium,
ototoxic drugs, NSAIDS, other HTN medications
 Dosing- Start low adjust doses slow
 Adverse- Hypokalemia, hyponatremia, dehydration, hyperglycemia,
hyperuricemia, cholesterol changes

POTASSIUM-SPARING DIURETICS

Spironolactone, Triamteren, Amiloride
 Indication- Hypertension and edema
 Can be used alone for treatment of HTN, typically adjunct to thiazides and loops
for potassium sparing properties
 Mechanism- blocks aldosterone in the distal nephron, which promotes NA+/k+
secretion causing retention, diuresis is minimal because most NA+ has already been
reabsorbed before reaching the distal nephron
 Monitor- Hyperkalemia
 Drug interactions- (agents that raise k+ levels) ACEI, ARBs, direct renin inhibitors
 Benefits- Patients with severe heart failure can reduce mortality and hospital
admissions
 Spironolactone- Steroid derivative: monitor for gynecomastia, menstrual
irregularities, impotence, hirsutism, and deepening of the voice
Black Box Warning: Triamterene and Amiloride for hyperkalemia, which is potentially fatal if
uncorrected. Potassium levels should be monitored at treatment start, when the dosage is changed, and
during illnesses affecting renal function.

DUAL THERAPY

To meet BP goals,
 2 or more drugs, don’t cross drug classes
 Safe
 Diuretic & ACEI
 Diuretic & Beta-blocker
 ACEI, CCB, and diuretic .
 Not safe
 2 loop diuretics
 2 beta blockers
 For BP that is not controlled, targeting BP at different sites by
different mechanisms of actions can be more effective
 Drugs can offset adverse effects of another’s drug class
 Example- Loop diuretic and potassium sparing diuretic

PATIENTS WITH COMORBIDITIES

Initiation of first line medications can vary by co-morbidity
 Morbidity and mortality maybe reduced by using a different
medication as first line
 Ace Inhibitors- ACEI
 Angiotensin II receptor blockers- ARBs
 Calcium Channel Blockers- CCBs
should also be considered as first line options
 Initiation of first line medications can vary by co-morbidity
 Other medications maybe used in adjunct

ACE INHIBITORS

Mild to moderate essential hypertension
 Drugs- Lisinopril, benazepril, captopril, enalapril
 Mechanism- Blocks actions of angiotensin II
 May take weeks to see full benefits
 Benefits- don’t interfere with cardiovascular reflexes causing severe orthostatic hypotension or
reducing exercise capacity. No hypokalemia, glucose, or uric acid.
 Baseline- BP and renal functions
 Monitor- hyperkalemia, creatinine 2-4 weeks after initiation, annually
 Dose low- first dose vasodilation due to abrupt drop in angiotensin II levels
 Educate client to prevent non-compliance , keep log of pressures
 Side effects- cough, angioedema, neutropenia (rare)
 Contraindications- bilateral renal stenosis or stenosis in the artery leading to single remaining kidney
Black Box Warning: 2nd and 3rd trimester use of ACEI can cause fetal injury. Specific effects: hypotension, hyperkalemia, skull
hypoplasia, pulmonary hypoplasia, anuria, renal failure (reversible/irreversible), and death. Women who become pregnant should
discontinue treatment. Exposed infants should be monitored for oliguria, hypotension, and hyperkalemia.

ANGIOTENSIN II RECEPTOR
BLOCKERS

 Indication- Hypertension
 Heart failure, diabetic nephropathy, and MI/stroke prevention
 Drugs- Losartan, Valsartan, candesartan
 Mechanism- Block production of angiotensin II
 Research- doesn’t show same decrease in morbidity/mortality as ACEI
 Baseline- BP and renal functions
 Monitor- hyperkalemia, creatinine 2-4 weeks after initiation, annually (GFR and
proteinuria for pts with diabetic nephropathy)
 Adverse effects- lower risk of angioedema, cough (do not inhibit kinase II causing
increase in bradykinin levels in the lungs)
 Contraindications- bilateral renal stenosis or stenosis in the artery leading to
single remaining kidney, use in caution with medications that increase K+

CALCIUM CHANNEL BLOCKERS

2 Types- decrease heart rate, affect AV conduction
 Dihydropyridines- Nifedipine- hypertensive emergency
 Mechanism- Act on the arterioles
 Nondihypdropyridines- Verapamil & diltiazem
 Mechanism- Act on the arterioles and the heart / vasodilator

NONDIHYDROPYRIDINES

Verapamil
 Indications- angina pectoris, essential hypertension, and cardiac dysrhythmias
 Oral 20% oral absorption, 30 minutes to affect, peak about 5 hours
 Mechanism- Primary effects is vasodilation, reduced arterial pressure, and
increased coronary perfusion.
 Neutralized effects - Increases heart rate, lowers BP, increases contractile force
 Elimination- in urine
 Side effects- very little constipation, headache, flushing, dizziness, edema of the
ankle and feet (vasodilation), gingival hyperplasia
 Adverse effects- Bradycardia (cardiac failure- 2nd or 3rd degree AV block, sick sinus
syndrome)
 Drug interactions- Drugs that suppress impulse conduction: Digoxin (increases
Digoxin level 60%), Beta-blockers have same effect on heart
 Diet- Avoid Grapefruit juice- can decrease absorption and hepatic metabolism
 Diltiazem
 Similar to Verapamil
 May cause eczema like rash

DIHYDROPYRIDINES

 Absorption
 IR-50% oral absorption, peak about 30 minutes
 SR- peak 20 minutes-6 hours
 Elimination- urine
 Side effects- Minimal constipation, headache, flushing, dizziness,
edema of the ankle and feet (vasodilation), gingival hyperplasia
 Adverse effects- reflex tachycardia, increase cardiac O2 demand can
increase pain with angina (can combine with beta blocker)

ADRENERGIC ANTAGONIST

Alpha- adrenergic antagonist
 Beta-adrenergic antagonist (beta-blockers)- once considered
first line for HTN, new studies show less effective.
 Olol drugs
 Indications- HTN, angina, cardiac dysrhythmias, MI, decrease
perioperative mortality, hyperthyroidism, anxiety, migraine
prophylaxis
 Adverse- bradycardia, decrease cardiac output, AV heart block,
precipitate heart failure, rebound cardiac excitation
 Drug interactions- Calcium Channel Blockers, insulin (decrease
awareness of low blood sugar, so body may not autocorrect)

VASODILATORS

Essential hypertension, hypertensive crisis, angina
pectoris, heart failure
 Risk- Postural hypotension
 Nitroprusside-dilates arteries and veins
 Hydralazine- dilates arterioles
 Adverse- Reflex tachycardia, SLE like syndrome, & increased blood volume
 Minoxidil- dilates arterioles
 Adverse- Reflex tachycardia, hypertrichosis, and sodium/water retention

COMORBIDITY CONSIDERATIONS

Diabetes- ACEI and ARBs slows progression of diabetic
nephropathy, can slow renal damage and reduce albuminuria
 CCB- also indicated, higher incidence of MI than ACEI/ARBs
 Renal disease 2nd to Nephrosclerosis- ACEI and ARBs slow
progression best, all classes show benefit.
 ACEI/ARB- often used in combination with LOOP diuretic
 Avoid potassium sparing

AFRICAN AMERICANS

Health disparities- 50% higher mortality heart disease, 2Xs more likely to
die from stroke and 6Xs more likely from HTN related renal disease
 Stress lifestyle modifications- “salt sensitive”, smoking sensation
 Medication regimen- Review comorbidities versus alternate medications
 African American (AA) with comorbidities should follow the
recommendations of the protocol for the health disparity to slow
progression of disease
 AA Diabetic with proteinuria- ACEI
 If dual therapy needed: Lisinopril & Hydrochlorothiazide or Benazepril and
amlodipine
 African Americans with NO comorbidities
 Diuretics work well- First line medication
 CCBs and alpha/beta blockers work better than ACEI and beta-blockers

SPECIAL CONSIDERATIONS

Pregnant women- labetalol or methyldopa, Magnesium sulfate
to prevent seizures
 Breastfeeding- Beta-blockers (diuretics- safe may suppress
supply)
 Older adults- ACEIs, diuretics, Beta-blockers, monitor hydration.
Avoid central acting alpha agonist an peripheral alpha- 1
antagonist

HYPERTENSIVE EMERGENCY

 BP systolic 180/ diastolic 100
 Evidence of end organ damage
 Papilledema, intracerebral hemorrhage, MI, CHF, etc
 Lower BP rapidly over 1 hour
 Hypertensive Urgency
 Severe but no organ damage
 Lower slowly over 24-48 hours
 Medications
 Sodium Nitropursside
 Fenoldopam
 Labetaol
 Clevidipine

SODIUM NITROPRUSSIDE

First line, IV
 Effects within seconds and baseline within short time of discontinuing
 Mechanism- arterial and venous dilator
 Metabolism-
 5 cyanide groups and active form of nitric oxide
 Cyanide converted to thiocyanate in liver, excreted in urine over days
 Adverse effects-
 Excessive hypotension- precipitous drop (ha, n/v, sweating, palpitations)
 Cyanide poisoning- rare, can co-administer with thiosulfate (used for detox)
 Thiocyanate toxicity-
 If administered over several days
 CNS-disorientation, psychotic behavior, delirium
 Monitor plasma levels, keep below 0.1 mg/ml

FENOLDOPAM

IV
 Effects within 5 minutes , rapid onset- short duration
 Mechanism-
 Activates dopamine-1 receptors on arterioles to cause vasodilation
 Increased renal function
 Metabolism-
 Hepatic and renal, plasma half life 5 minutes
 Cyanide converted to thiocyanate in liver, excreted in urine over days
 Adverse effects-
 Hypotension, ha, flushing, dizziness, and reflex tachycardia
 Tachycardia can cause ischemia in angina patients (beta blocker)
 Increased intraocular pressure (caution with glaucoma)

LABETALOL
CLEVIDIPINE

 Indications
 Safe in angina and MI (alpha)
 Avoid in asthma, AV block, cardiogenic shock, bradycardia, bronchial
spams (beta can aggravate)
 Mechanism- Blocks alpha and beta receptors
 BP reduced by arteriolar dilation (alpha) and
 Prevents reflex tachycardia (beta)
 Clevidipine
 Mechanism- Dihydropyriden Calcium Channel Blocker
 Adverse- ha, n/v
 Rapid onset- short duration (about 1 minute)