Antihypertensives Flashcards
How many children in the U.S. have hypertension?
4% of youth, and another 10% have elevated BP (prehypertension)
What is directly proportional to cardiac output and peripheral vascular resistance
Arterial blood pressure
Cardiac output and peripheral vascular resistance are controlled by what?
Baroreflexes and Renin-Angiotensin-Aldosterone System (RAAS)
Define primary or essential hypertension?
Hypertension with no identifiable cause
Define resistant hypertension?
Despite lifestyle modifications, diuretic and 2 other medications, no to little improvement in BP control (need to rule out secondary cause)
What is the goal of treatment in treating pulmonary hypertension?
Aimed at lessening symptoms and improving quality of life due to no cure
What are the end-stage complications of uncontrolled HTN?
Heart Disease
Heart Failure
Stroke
Chronic Kidney Disease
What are the types of diuretics used for hypertension?
Distal tubule diuretics (Thiazides)
K-sparing diuretics
Loop diuretics
Carbonic Anhydrase Inhibitors
Osmotic Diuretics
What is the general MOA of diuretics?
Increase water and sodium excretion to lower blood volume which in turn decrease BP
What is the MOA of Distal Tubule Diuretics (Thiazides)?
Inhibit sodium and chloride reabsorption in the distal tubule, resulting in mild diuresis (increases water and sodium exrection)
What is the site of action of Thiazides?
Proximal Tubule
What are the most commonly used diuretic?
Thiazides
What are the different Thiazides?
Hydrochlothiazide
Chlorthalidone
Metolazone
Indapamide
What is the use of hydrochlorthiazide?
Ideal starting agent for HTN, chronic edema, idiopathic hypercalcinuria
Treat kidney stones in Meniere’s disease, but inneffective in renal impairment
What is a severe side effect in hydrochlorthiazide?
Increases toxicity of digitalis or lithium
What are the contraindications of Hydrochlorothiazide?
Avoid in patients with gout
Can cause hypokalemia, especially if given with corticosteroids or ACTH
What are the side effects of Hydrochlorothiazide?
Hypokalemia
Hyperruricemia
Hyperglycemia
Hypotension
Hyponatremia
Hypercalcemia
When treated with Hydrochlorothiazide what co-administration can cause orthostatic hypotension?
Alcohol, Barbiturates, and Narcotics
What is the PK of Hydrochlorothiazide?
Oral admin, onset in 2 hours. Absorbed rapidly and eliminated primarily unchanged
What is the only Thiazide available in intravenous formulation, although use is very rare?
Chlorthalidone
What are the clinical uses of Chlorthalidone?
HTN, HF, hypercalciuria, diabetes
What is the MOA of Loop Diuretics?
Blocks reabsorption of sodium and chloride in the thick segment of the ascending loop of Henle, prevents passive reabsorption of water
What is the most commonly used loop diuretic?
Furosemide
What are the clinical uses of Furosemide?
Good when needing to move large volumes of fluid: HF, decomp cirrhosis, acute pulmonary edema
Hypercalcemia
Especially useful in severe renal impairment
Thiazide can be added if needed
What medications are loop diuretics?
Furosemide
Bumetanide
Torsemide
What is the MOA of K+ sparing diuretics?
Inhibit potassium secretion and influence sodium excretion (reduces potassium loss in the urine)
What is the site of action of K+ sparing diuretics?
Distal tubule
What are the side effects of K+ sparing diuretics?
Hyperkalemia, anuria (trimterene-rare)
What are the K+ sparing diuretics?
Amiloride
Spironolactone
Triameterne
Eplerenone
What are the clinical uses of Spironlactone as a diuretic?
HTN, edema in HF, ascities, cirrhosis, nephrotic syndrome, hyperaldosteronism, acne
Due to its anti-androgen effect what other conditions is spirnolactone prescribed?
Acne, chronically oily skin, hirsutism
What are the adverse effects of Spironolactone?
Gynecomastia
Increased risk for digitalis toxicity when co-administered
What are the contraindications of Spironolactone?
Pregnancy
What are the clinical uses of Eplernone?
Edema in HF, resistant HTN, hyperaldosteronism
What is the MOA of Amiloride?
Inhibit K+ loss by direct blockade of Na+/K+ exchange in the distal nephron
What are the clinical uses of Amiloride?
3rd-4th line to treat HTN, HF
Can be used to treat ascites as well as polyurea/polydisia due to lithium-induced nephrogenic diabetes insipidus
What is the only Carbonic Anhydrase Inhibitor?
Acetazolamide
What is the MOA of Acetazolamide?
Inhibits carbonic anhydrase in the proximal renal tubule, promoting renal excretion of Na+, K+, bicarbonate, and water
What are the clinical uses of Acetazolamide?
Cardiac anhydrase inhibitor
Chronic open-angle glaucoma
Prophylaxis of altitude sickness
What are the side effects of Acetazolamide?
Metabolic acidosis, renal stones, hyperammonemia in cirrhotic patients
What is the MOA of Osmotic Diuretic?
Promotes diuresis in kidneys by increasing the concentration of flitrates in the kidney and blocking reabsoprtion of water by kidney tubules
What is the site of action of osmotic diuretics (Mannitol)?
Glomerulus/proximal convoluted tubule
What are the clinical uses of Mannitol?
Maintains urine flow following acute toic ingestion of substances capable of producing acute renal failure
Reduction of intracranial pressure
Glaucoma
What are the side effects of Mannitol?
Headache, nausea, dizziness, polydipsia, confusion, chest pain
What are the neuromuscular effects of severe hypercalcemia?
Impaired concentration, confusion, fatigue, and muscle weakness
What are the GI effects of severe hypercalcemia?
Nausea, abdominal pain, anorexia, constipation, and rarely, peptic ulcer disease
What are the renal effects of hypercalcemia?
Polydipsia and polyuria resulting from nephrogenic diabetes insipidus, and nephrolithiasis resulting from hypercalciuria
What are the cardiovascular effects of hypercalcemia?
Hypertension, vascular calcification, shortened QT interval on electrocardiogram. Cardiac arrhythias are rare.
What is the treatment of hypercalcemic crisis?
Saline rehydration
Furosemide diuresis (low dose)
What diuretic class should NOT be used to treat hyercalcemia?
Thiazide diuretics, because they increase tubular calcium resorption
Describe the disease process of Nephrogenic Diabetes Insipidus?
Kidneys have partial or complete resistance to effects of antidiuretic hormone (vasopressin) - results in excretion of large amounts of diluted urine
What are the symptoms of Nephrogenic Diabetes Insipidus?
Polyuria and polydipsia (risk of dehydration)
What drugs can lead to Nephrogenic Diabetes Insipidus?
Lithium, Amphotericin B, Ofloxacin, Orlistat
Should stop medication
What is the treatment of Nephrogenic Diabetes Insipidus?
Hydrochlorothiazide (inhibits amount of salt absorbed by kindeys and reduces water loss) - helps to correct the hypernatremia
Combination with Amiloride (helps maintain potassium level)
What is the MOA of ACE Inhibitors?
Inhibits ACE, red levels of angiotensin II, suppress aldosterone excretion, decrease peripheral resistance and increase sodium and water excretion
Reduces both preload (promote natriuresis) and afterload (decrease vasoconstriction)
What are the ACE Inhibitor drugs?
Enalapril
Captopril
Lisinopril
What are ACE Inhibitors the first line treatment for?
Treatment of HTN with high risk of coronary disease, diabetes, stroke, heart failure, MI, or chronic kidney disease
Preferred in patients with diabetic nephropathy
What are the side effects of ACE Inhibitors?
First dose hypotension, dizziness, proteinuria, rash, tachycardia, hyperkalemia, headache, cough, angioedema
What is the PK of Enalapril?
Oral is prodrug, once ingested converted to enalaprilat
IV form is enalaprilat
What are the severe side effects of Captopril?
Causes agranulocytosis or neutropenia (not commonly given)
Per Francis, what is the best ACE Inhibitor that he would want on a deserted island to treat hypertension?
Lisinopril
If someone has an angioedema reaction to an ACE Inhibitor can they be prescribed another ACE Inhibitor?
No
What are the Angiotensin Receptor Blocker (ARB) agents?
Losartan
Valsartan
Candesartan
Olmesartan
What is the MOA of ARB agents?
Blocks angiotensin II receptors in blood vessels, adrenals, and other tissues, dilation of arterioles and veins
What is the primary clinical use of ARB’s?
HTN and HF
What are the side effects of ARB’s?
Dry cough, hyperkalemia, skin rassh, hypotension, altered taste
What is the only Renin Inhibitor agent?
Aliskiren
what is the MOA of Aliskiren?
Binds tightly with renin and thereby inhibits the cleavage of angiotension into angiotensin I
Can influence the entire RAAS
When is Aliskiren contraindicated?
Pregnancy
Adrenergic blocking drugs have what effects on the heart?
Decrease blood pressure
Decrease heart rate and force of contraction
What are the three sites of action of sympathoplegic drugs?
Blocks at 3 different levels
Peripherally
Centrally
Ganglionically
What are the indications of alpha-blockers in hypertension?
Moderately hypertensive patients, pheochromocytoma, BPH, Raynaud’s disease, clonidine withdrawal
What are the toxicities of alpha-blockers?
Fluid retention, headache, nasal stuffiness, dry mouth
What are the indications of beta-blockers in hypertension?
Angina, hypertension, secondary prophylaxis in MI, arrhythmias
What are the toxicities of beta-blockers?
Rebound hypertension with sudden withdrawal, bronchoconstriction, GI upset, fatigue, nightmares, decreased libido
Alpha adrenergic receptor antagonists inhibit the effects of
Catecholamines (norepinephrine. epinephrine, dopamine)
What is the MOA of Phenoxybenzamine?
Irreversible noncompetitive blocker of peripheral alpha 1 and alpha 2 adrenergic receptors
What are the indications of Phenoxybenzamine?
Used in treatment of sweating and hypertension associated with pheochromoctoma
Only effective reflex tachycardia
What is pheochromocytoma?
A rare, usually benign tumor on top of the adrenal glands (release too much norepi and epi)
What is the primary indication of Phentolamine?
Pheochromocytoma
What are the other indications for Phentolamine?
Dermal necrosis or hypertensive crisis after clonidine withdrawal
What are the two Alpha-1 Selective Blockers?
Prazosin and Doxazosin
What are the four Nonselective Beta Blockers?
Propranolol
Nadolol
Pindolol
Timolol
What are the indications to use Propranolol?
Performance anxiety
Postural tremor
Migraine prevention
Thyrotoxicosis
Portal hypertension
What are the CNS effects of Propranolol?
Depression
Dizziness
Lethargy/fatigue
Weakness
Hallucinations/Vivid dreams
Memory loss
Visual distrurbances
Is Nadolol typically used in practice?
No
What is the only use for Pindolol in the U.S.?
HTN, should be avoided in patients with prior MI or angina due to sympathomimetic effects
What are the Beta-1 Selective Sympathetic Antagonists?
Metoprolol
Atenolol
Nebivolol
What is a very common Beta-1 Selective Antagonist due to its many indications and less bronchial constriction than propranolol?
Metoprolol
Why is Atenolol less effective than Metoprolol?
Less effective in preventing complications of HTN, though it has the same indications
What mixed alpha and beta blocker is considered safe in pregnancy and used to manage hypertension in pre-eclampsia?
Labetalol
When should calcium channel blockers be avoided?
Avoid in acute coronary syndrome, pre-existing conduction disorders, symptomatic hypotension
Are Non-dihydropyridines cardio-selective or vascular selective?
Cardio-selective
Are Dihydropyridines cardio-selective or vascular selective?
Vascular selective
Verapamil mainly affects the
myocardium
When is Verapamil not recommended?
Patients with sick sinus syndrome, AV nodal disease, or heart failure
When is Diltiazem indicated?
Anti-arrhythmic effect, cam also lower BP
According to Francis, what is the best and most common anti-hypertensive?
Amlodapine; has greater effect on smooth muscle in peripheral vasculature and has minimal effect on cardiac conduction
When is Amlodapine not recommended?
Heart Failure
What are the two venous vasodilators?
Isosorbide dinitrate
Nitroglycerin
Of the venous vasodilators, which is the prodrug and converted to nitric oxide in the body?
Nitroglycerin
Nitroglycerin is usually given sublingually but can be administered via what other routes?
IV/fluid
Ointment
Patch
What are the indications for Isosorbide dinitrate?
Prophylaxis of acute angina
Esophageal spasm
HF in black patients with Hydralazine
Hydralazine in combination with nitrates are effective in treating
heart failure
What is the most characteristic side effect associated with Hydralazine?
Lupus-like syndrome (malar like rash)
What arterial vasodilator causes salt and water retention?
Diazoxide
What is the most significant side effect associated with Diazoxide?
Excessive hypotension (some cases can result in stroke and myocardial infarction)
NOT A FRIENDLY DRUG!
What is the MOA of Minoxidil?
Hyperpolarization of cell membranes through opening of potassium channels, which allows for greater blood flow and oxygenation to hair follicles
Due to acting both on venous and arterial vasculature, this drug is most commonly used in hypertensive emergencies due to drastically dropping blood pressure?
Nitroprusside
What are the two centrally acting agents?
Clonidine
Methyldopa
What is the MOA of Clonidine and Methyldopa?
Block sympathetic activity by binding to and activating centrally-located alpha 2 adrenoreceptors reducing sympathetic outflow
When treating hypertension with either Clonidine or Methyldopa what do you need to be cautious of?
Rebound after withdrawal of medication
What are the indications for Clonidine?
Treatment of HTN, menopausal flushing, opioid or ETOH withdrawal, Tourette’s syndrome, 2nd line agent for ADHD
What is the primary indication for Methyldopa?
Hypertension during pregnancy
What condition can Methyldopa treatment lead to?
Autoimmune hemolytic anemia if used for long duration
What are the three initial therapy agents in treating hypertension?
Thiazide diuretics, ACEi, ARB’s
What two anti-hypertension classes can’t be used together due to the high risk of kidney failure?
ACEi and ARB’s
What drug classes should be used in a patient with hypertension and concomitant high angina pectoris risk?
B-blockers
Ca2+ channel blockers
What drug classes should be used in a patient with hypertension and concomitant diabetes?
ACE inhibitors
ARB’s
Diuretics second line
What drug classes should be used in a patient with hypertension and concomitant recurrent stroke?
ACE inhibitors
What drug classes should be used in a patient with hypertension and concomitant heart failure?
All anti-hypertensives
What drug classes should be used in a patient with hypertension and concomitant chronic renal disease?
ACE inhibitors and ARBs
What is the disease process of Nephrogenic Diabetes Insipidus?
Kidneys have partial or complete resistance to effects of antidiuretic hormone (vasopressin), results in large amounts of diluted urine
What are the symptoms of Nephrogenic Diabetes Insipidus?
Polyuria and Polydipsia
What is the treatment for Nephrogenic Diabetes Insipidus and how does it help correct hyponatremia?
Hydrochlorothiazide, it inhibits amount of salt absorbed by kidneys and reduces water loss
