module 6c Flashcards
Antihypertensive Drugs
BLOOD PRESSURE Blood pressure = CO × SVR CO = cardiac output SVR = systemic vascular resistance Hypertension = high blood pressure
BP
Four stages, based on BP measurements Normal Prehypertension Stage 1 hypertension Stage 2 hypertension
JNC-7: Significant Changes
Joint National Committee
High diastolic BP (DBP) is no longer considered to be more dangerous than high systolic BP (SBP) Studies have shown that elevated SBP is strongly associated with heart failure, stroke, and renal failure
JNC-7: Significant Changes
Joint National Committee
For those older than age 50, SBP is a more
important risk factor for cardiovascular
disease (CVD) than DBP
“Prehypertensive” BPs are no longer
considered “high normal” and require lifestyle
modifications to prevent CVD
JNC-7: Significant Changes
Joint National Committee
Thiazide-type diuretics should be the initial
drug therapy for most patients with
hypertension (alone or with other drug
classes)
The previous labels of “mild,” “moderate,”
and “severe” have been dropped
Cultural Considerations
B-blockers and ACE inhibitors have been
found to be more effective in white patients
than African American patients
CCBs and diuretics have been shown to be
more effective in African-American patients
than in white patients
Classification of BP
Hypertension can also be defined by its cause
Unknown cause
Known as essential, idiopathic, or primary hypertension, 90% of the cases
Known cause
Secondary hypertension,10% of the cases
Antihypertensive Drugs:
Categories
Adrenergic drugs Angiotensin converting enzyme (ACE) inhibitors Angiotensin II receptor blockers (ARBs) Calcium channel blockers (CCBs) Diuretics Vasodilators
Adrenergic Drugs:
Subcategories
Centrally acting A2-receptor agonists
Peripherally acting A1-receptor blockers
Adrenergic Drugs:
Subcategories
Peripherally acting B-receptor blockers (B-blockers)—both cardioselective (B receptors) and nonselective (both B and B2 receptors) Peripherally acting dual A1- and B-receptor blockers
Adrenergic Drugs:
Mechanism of Action
Centrally acting A2-receptor agonists
Stimulate A2-adrenergic receptors in the brain
Decrease sympathetic outflow from the CNS
Decrease norepinephrine production
Stimulate alpha2-adrenergic receptors, thus
reducing renin activity in the kidneys
Result: decreased blood pressure
Adrenergic Drugs:
Centrally Acting
A2-Receptor Agonists
clonidine (Catapres)
methyldopa (Aldomet)
Can be used for hypertension in pregnancy
Adrenergic Drugs:
Mechanism of Action
Peripheral A1-blockers/antagonists Block the A1-adrenergic receptors doxazosin Cardura) prazosin (Minipress) terazosin (Hytrin) Result: decreased blood pressure
Adrenergic Drugs:
Mechanism of Action
Beta-blockers
Reduce BP by reducing heart rate through
beta1-blockade
Cause reduced secretion of renin
Long-term use causes reduced peripheral vascular resistance
Propranolol, atenolol
Newest: nebivolol (Bystolic)—beta1-selective
Result: decreased blood pressure
Adrenergic Drugs:
Mechanism of Action
Dual-action A1- and B-receptor blockers Block A1-adrenergic receptors • Reduction of heart rate 1-receptor blockade) • Vasodilation (1-receptor blockade) carvedilol (Coreg) and labetalol Result in decreased blood pressure
Adrenergic Drugs: Indications
Centrally acting A2-receptor agonists
Treatment of hypertension, either alone or
with other drugs
Usually used after other drugs have failed
because of adverse effects
Adrenergic Drugs: Indications
Centrally acting A2-receptor agonists
Also may be used for treatment of severe
dysmenorrhea, menopausal flushing, glaucoma
Clonidine is useful in the management of
withdrawal symptoms in opioid- or nicotinedependent
persons
Adrenergic Drugs: Indications
Peripherally acting A1-receptor antagonists Treatment of hypertension Some used to relieve symptoms of BPH • tamsulosin (Flomax) Management of severe HF when used with cardiac glycosides and diuretics
Adrenergic Drugs:
Adverse Effects
High incidence of orthostatic hypotension
Most common: Dry mouth, Drowsiness, sedation,Constipation
Other:HA, Sleep disturbances, Nausea,
Rash, Cardiac disturbances (palpitations)
Adrenergic Drugs
B-blockers Act in the periphery Reduce heart rate due to B1-blockade Examples: nebivolol (bystolic), propranolol (Inderal), atenolol (Tenormin)
Adrenergic Drugs
Dual A1- and B-receptor blockers
Act in the periphery at heart and blood vessels
Reduce heart rate (B1-receptor blockade)
Cause vasodilation (A1-receptor blockade)
Examples: labetalol (Normodyne), carvedilol (Coreg)
Angiotensin Converting
Enzyme (ACE) Inhibitors
(end in pril)
Large group of safe and effective drugs Often used as first-line drugs for HF and hypertension May be combined with a thiazide diuretic or calcium channel blocker
ACE Inhibitors:
Mechanism of Action
Renin-Angiotensin-Aldosterone System
Inhibit angiotensin-converting enzyme, which is responsible for converting angiotensin I to
angiotensin II
Angiotensin II is a potent vasoconstrictor and
causes aldosterone secretion from the
adrenals
ACE Inhibitors:
Mechanism of Action
Aldosterone stimulates water and sodium
resorption
Result: increased blood volume, increased
preload and increased BP
ACE Inhibitors:
Mechanism of Action
Block angiotensin-converting enzyme, thus
preventing the formation of angiotensin II
Prevent the breakdown of the vasodilating
substance, bradykinin
Result in decreased systemic vascular
resistance (afterload), vasodilation, and
therefore decreased blood pressure
ACE Inhibitors:
Indications
Hypertension
HF (either alone or in combination with
diuretics or other drugs)
To slow progression of left ventricular
hypertrophy after an MI (cardioprotective)
Renal protective effects in patients with
diabetes
ACE Inhibitors: Indications
Drugs of choice in hypertensive patients with
HF
Drugs of choice for diabetic patients
ACE Inhibitors
captopril (Capoten)
enalapril (Vasotec)
moexipril
perindopril
trandolapril
benazepril, fosinopril, lisinopril (Prinivil and
Zestril), quinapril (Accupril) and ramipril
Newer drugs, long half-lives, once-a-day dosing
ACE Inhibitors
Captopril and lisinopril are NOT prodrugs
Prodrugs are inactive in their administered form and must be metabolized by the liver to an active form in order to be effective
Captopril and lisinopril can be used if a patient has liver dysfunction, unlike other ACE inhibitors that are prodrugs
ACE Inhibitors: Adverse Effects
Fatigue Dizziness Headache Mood changes Impaired taste Possible hyperkalemia Dry, nonproductive cough, which reverses when therapy is stopped Angioedema: rare but potentially fatal NOTE: First-dose hypotensive effect may occur!
Angiotensin II Receptor Blockers
end in artan
ARBs
Newer class
Well tolerated
Do not cause a dry cough
Angiotensin II Receptor Blockers:
Mechanism of Action
Allow angiotensin I to be converted to angiotensin II, but block angiotensin II receptors Block vasoconstriction and release of aldosterone
Angiotensin II Receptor Blockers
losartan (Cozaar, Hyzaar) candesartan eprosartan valsartan (Diovan) irbesartan olmesartan telmisartan
Angiotensin II Receptor
Blockers: Indications
Hypertension
Adjunct drugs for the treatment of HF
May be used alone or with other drugs such as diuretics
Used primarily in patients who cannot tolerate
ACE inhibitors
Angiotensin II Receptor Blockers:
Adverse Effects
Upper respiratory infections
Headache
May cause occasional dizziness, inability to sleep, diarrhea, dyspnea, heartburn, nasal congestion, back pain, fatigue
Hyperkalemia less likely to occur compared
to ACE inhibitors
Calcium Channel Blockers:
Mechanism of Action
Cause smooth muscle relaxation by blocking calcium channels preventing muscle contraction Results in Decreased peripheral smooth muscle tone Decreased systemic vascular resistance Decreased blood pressure
Calcium Channel Blockers
most in in pine or ine
Benzothiazepines diltiazem (Cardizem, Dilacor) Phenylalkamines verapamil (Calan, Isoptin) Dihydropyridines amlodipine (Norvasc), bepridil (Vascor), nicardipine (Cardene) nifedipine (Procardia), nimodipine (Nimotop)
Calcium Channel Blockers:
Indications
Angina Hypertension Dysrhythmias Migraine headaches Raynaud’s disease
Calcium Channel Blockers:
Adverse Effects
Cardiovascular Hypotension, palpitations, tachycardia Gastrointestinal Constipation, nausea Other Rash, flushing, peripheral edema, dermatitis
Diuretics
Decrease plasma and extracellular fluid volumes Results Decreased preload Decreased cardiac output Decreased total peripheral resistance Overall effect Decreased workload of the heart, and decreased blood pressure
Thiazide Diuretics
Thiazide diuretics are the most commonly
used diuretics for hypertension
Listed as first-line antihypertensives in the
JNC-7 guidelines
Vasodilators:
Mechanism of Action
Directly relax arteriolar and/or venous smooth muscle Results in: Decreased systemic vascular response Decreased afterload Peripheral vasodilation
Antihypertensive Drugs
Vasodilators
diazoxide (Hyperstat)
hydralazine Apresoline)
minoxidil (Loniten)
sodium nitroprusside (Nipride, Nitropress)
Vasodilators:
Indications
Treatment of hypertension
May be used in combination with other drugs
Oral diazoxide may be used as an
antihypoglycemic
Sodium nitroprusside and intravenous
diazoxide are reserved for the management
of hypertensive emergencies
Vasodilators: Adverse Effects
Hydralazine
Dizziness, headache, anxiety, tachycardia, nausea and vomiting, diarrhea, anemia, dyspnea, edema, nasal congestion
Sodium nitroprusside
Bradycardia, hypotension, possible cyanide
toxicity (rare)
Vasodilators: Adverse Effects
Diazoxide
Dizziness, headache, anxiety, orthostatic
hypotension dysrhythmias sodium and water, retention, nausea, vomiting, hyperglycemia in diabetic patients
