Antihypertensives part 1 Flashcards
what is arterial blood pressure directly proportional to
Cardiac output and peripheral vascular resistance
what controls cardiac output and peripheral vascular resistance
Baroreflexes and Renin-Angiotensin-Aldosterone System (RAAS)
What are the types of Hypertension
Primary/essential HTN
Malignant HTN
Resistant HTN
Pulmonary HTN
Pseudo-HTN
White Coat/Office HTN
Isolated Systolic HTN
What is the BP for Stage 2 hypertension
140 or higher OR / 90 or higher
what is the BP for Stage 3 hypertension
Higher than 180 AND / OR / higher than 120
what are the end-stage complications of uncontrolled HTN
Heart Disease
Heart Failure
Stroke
Chronic Kidney Disease
What are the antihypertensive drug categories
Diuretic agents
ACE inhibitors
ARBs
Calcium Channel Blockers
Beta-adrenergic Blockers
Alpha-adrenergic Blockers
What are the categories of Diuretics
Distal Tubule Diuretics (Thiazides)
Loop Diuretics
Potassium Sparing Diuretics
Carbonic Anhydrase inhibitors
Osmotic Diuretics
What are Thiazides/distal tubule diuretics
Hydrochlorothiazide
Chlorthalidone
Metolazone
Indapamide
What is the MOA for Thiazides
Blocks reabsorption of Na+ and Cl- in the early segment of the distal convoluted tubule -> increase water retention -> increase urine
*most commonly used
What is the site of action for thiazides
*Distal tubule, proximal tubule
What is Hydrochlorothiazide
Thiazide diuretic
prototypical drug
ideal starting agent for HTN, chronic edema or idiopathic hypercalciuria
Can also treat CaOx stones and Meniere’s disease
What is the pharmacokinetics of Hydrochlorothiazide
oral - onset 2 hours
absorbed rapidly and eliminated unchanged
What are the AE/SE of hydrochlorothiazide
Increased toxicity of digitalis or lithium
hypokalemia, hyperuricemia, hyperglycemia, hypotension, hyponatremia, hypercalcemia
When is hydrochlorothiazide contraindicated?
in Gout
What drug combinations can cause hypokalemia with hydrochlorothiazide
if given with corticosteroids or ACTH
What is the outcome of combining HCTZ with alcohol, barbituates or narcotics
orthostatic hypotension
What is Chlorthalidone
thiazide - like diuretic
used for HTN, HF, hypercalciuria, diabetes
What are the pharmacokinetics of chlorthalidone
oral or IV (IV is rare)
long half-life, low bioavailability
excreted in urine unchanged
What are the SE/AE of Chlorthalidone
hyponatremia
hypochloremia
hypotension
hypokalemia
What is Metolazone
Thiazide-like diuretic
usually added to a loop diuretic in the tx of edema in HF
10x more potent than HCTZ
*Safe in renal insuff
what are the pharmacokinetics of Metolazone
oral admin
excreted in the urine unchanged
What are the SE/AE of Metolazone
hyponatremia
hypochloremia
hypotension
hypokalemia
What is Indapamide
Thiazide-like diuretic
HTN and Decompensated HF
Not commonly used
What is the pharmacokinetics of Indapamide
oral admin
Hepatic Metabolism, excreted in urine and bile
What are the AE/SE of Indapamide
hyponatremia
hypochloremia
hypotension
hypokalemia
What are the loop diuretics
Furosemide (Lasix)
Bumetanide (Bumex)
Torsemide (Demadex)
What is the MOA for loop diuretics
blocks reabsorption of sodium and chloride in the thick segment of the ascending loop of Henle - prevents passive reabsorption of water
Inhibit chloride reabsorption
What is the site of action for loop diuretics
Loop of Henle
What are the primary side effects of loop diuretics
Hyponatremia
dehydration
hypotension
hypokalemia
hyperglycemia
dose-dependent ototoxicity
-Caution in pts w sulfa allergy
What are the drug interactions with Furosemide (lasix)
Digoxin
K+ sparing diuretics
Lithium
Antihypertensive agents
NSAIDs
What is Furosemide (lasix)
Loop-diuretic - Most common
good when needing to move large volumes of fluid
- HF, decompression cirrhosis, acute pulmonary edema
Hypercalcemia
especially useful in severe renal impairment
*thiazide can be added if needed
What are the pharmacokinetics of Furosemide (Lasix)
Oral admin
Diuresis begins 60 minutes after admin and lasts 8 hours
hepatic metabolism - renal excretion
What inhibits the effects of furosemide
probenecid and indomethacin
what types of drugs have increased toxicity with furosemide
ototoxic and nephrotoxic drugs and lithium
What is Bumetanide
Loop-diuretic - most potent
used for edema caused by heart failure, chronic renal disease and cirrhosis
hypercalcemia
what is the pharmacokinetics of Bumetanide
Oral admin
onset: 30-60 minutes
Duration: 4-6 hours
what can large doses of Bumetanide cause
severe myalgias
What is not an AE/SE of Bumetanide
no Ototoxicity reported
What are the drug interactions with Bumetanide
Digoxin
K+ sparing diuretics
lithium
antihypertensive agents
NSAIDs
What is Torsemide
Loop diuretic
used for Edema caused by HF, chronic renal disease and cirrhosis
HTN
Hypercalcemia
What are the pharmacokinetics of Torsemide
Oral admin
onset: within 60 minutes
Duration: 6-8 hours
What are SE/AE of Torsemide
Headache and dizziness
Hyponatremia
hypochloremia
Dehydration
Hypotension
Hypokalemia
Hypoglycemia
dose-dependent ototoxicity
what are the drug interactions with Torsemide
Digoxin
K+ sparing diuretics
Lithium
Antihypertensive agents
NSAIDs
What are K+ Sparing diuretics
Amiloride (Midamore)
Spironolactone(aldactone)
Trimterene (Dyrenium)
Eplerenone (Inspra)
what is the MOA for K+ sparing diuretics
blocks the action of aldosterone in the distal nephron -> retention of K+ and increase the excretion of Na+
Also blocks androgen receptors-> blocks androgen synthesis
(inhibits potassium secretion and influence sodium excretion- reduced K+ loss in urine)
what is the site of action for K+ sparing diuretics
Distal Tubule
What are the primary side effects of K+ sparing diuretics
Hyperkalemia
Anuria(trimterene-rare)
what is spironolactone
aldosterone antagonist, K+ sparing
used for HTN, edema in HF, ascites, cirrhosis, nephrotic syndrome, hyperaldosteronism, ache
most commonly used with a thiazide/loop diuretic to counteract K+ wasting effects
What is the pharmacokinetics of Spironolactone
Oral admin
Effects are delayed, can take up to 48 hours
What are the AE/SE of spironolactone
hyperkalemia, Endocrine effects (gynecomastia)
What are the interaction with Spironolactone
with drugs that raise K+ levels, increase risk for digitalis toxicity
What are other conditions that can be treated with Spironolactone
anti-androgen effects can treat chronically oily skin, acne, hirsutism
Is spironolactone safe during pregnancy
NO
What is Eplerenone
aldosterone antagonist, K+ sparing
used to treat edema in HF, resistant HTN and hyperaldosteronism
What are the pharmacokinetics for Eplerenone
Oral admin
Metabolized by CYP
What are the AE/SE for Eplerenone
Hyperkalemia
Less risk for gynecomastia than spironolactone
What is Amiloride
non-aldosterone antagonists, K+ sparing
3rd or 4th line to tx HTN/HF
may correct metabolic alkalosis caused by other diuretics
What is the pharmacokinetics of Amiloride
oral admin
more rapid onset than spironolactone
What are the SE/AE of amiloride
Hyperkalemia
Nausea
Vomitting
leg cramps
dizziness
diabetics may develop glucose intolerance
What is Triamterene
non-aldoserone antagonists, K+ sparing
HTN/Edema
produces mild diuresis
can be used alone or in combo (thiazide diuretic to treat HTN)
What are the pharmacokinetics of Triamterene
Oral admin
initial resposne develops within hours
what are the SE/AE of triamterene
May turn urine blue
causes crystalluria and cast formation and decreased renal blood flow - caution with renal disease
Hyperkalemia, N/V, leg cramps, dizziness
what are Carbonic Anhydrase inibitors
Acetazolamide (diamox)
What is the MOA for Acetazolamide
inhibits carbonic anhydrase in the proximal rental tubule -> promoting renal excretion of Na+, K+, bicarboate and water
what is the site of action for Acetazolamide
Proximal tubule
What are the pharamacokinetics of Acetazolamide
oral or IV admin
Eliminated renally
What are the AE/SE of Acetazolamide
metabolic acidosis
renal stones
hyperammonemia in cirrhotic pts
conta in pts with sulfa allergy
What is contraindicated with the use of Acetazolamide
Sulfa allergy
What is Acetazolamide used for
cardiac anhydrase inhibitor
chronic open-angle glaucoma and prophylaxis of altitude sickness
What are osmotic diuretics
Mannitol (resectisol)
What is Mannitol
osmotic diuretic
maintains urine flow following acute toxic ingestion of substrates capable of producing acute renal failure
reduction of intracranial pressure
glaucoma treatment
What is the MOA for Mannitol
increase concentration of filtrates in the kidney and blocks reabsorption of water
what is the site of actio for Mannitol
glomerulus/proximal convoluted tubule
what is the pharmacokinetics of Mannitol
IV admin
Onset: 30-60 minutes
Duration: 6-8 hours
what are the SE/AE of Mannitol
HA
Nausea
Dizziness
Polydipsia
Dehydration
Confusion
Chest pain
Is mannitol safe in pregnancy
YES
What is hypercacemia
when there is too much calcium within the blood
normal serum calcium levels is ~8-10.5mg/dL
What are symptoms of severe hypercalcemia that require treatment
Neuomuscular effects: impaired concerntation, confusion, fatigue and muscle weakness
GI effects: nausea, abd pain, anorexia, constipation
Renal effects: polydipsia and polyuria resulting from nephrogenic diabetes insipidus and nephrolithiasis resulting from hypercalcemia
Cardiovascular effects: HTN, vascular calcification, shorted QT interval
What is the safest and most effective treatment of hypercalcemic crisis
saline rehydration
furosemide (lasix) diuresis
What should NOT be used to treat hypercalcemia
Thriazide Diuretics
they can exacerbate hypercalemia by increasing tubular calcium resoprtion
What is nephrogenic diabetes insipidus
body makes enough vasopressin but your kidneys don’t respond to the hormone as they should.
As a result, too much fluid gets flushed out in your urine. Causes include: some medicines, especially those used to treat bipolar disorder link
how is nephrogenic diabetes insipidus diagnosed
based on uring and blood tests
what are the symptoms of nephrogenic diabetes insipidus
polyuria and plolydipsia (risk of dehyrdration)
What is the treatment of nephrogenic diabetes insipidus
directed towards individuals symptoms
ensure proper fluid intake and reduce urine output
HCTZ (inhibits amount of salt absobed by kidneys and reduces water loss)
What are renin-angiotensin-aldosterone system (RAAS) agents
Common:
ACE inhibitors (ACEi)
Angiotensin receptor blocker (ARBs)
Aldosterone antagonists
Less common:
Renin inhibitor
Endothelin Anatgonist
What are ACE inhibitors
Enalapril
Captopril
Lisinopril
What is suppressed with ACE inhibitors
suppressed synthesis of angiotensin II
suppressed aldosterone, resulting in natriuresis
Decreased peripheral vascular resistance
What are ACE inhibitors the first line treatment of
HTN in pts with high coronary disease risk, diabetes, stroke, heart failure, myocardial infarction or chronic kidney disease
preferred in pts with diabetic nephropathy b/c glucose levels are not affected and drugs are renoprotective
What is the MOA for ACE inhibitors
inhibits ACE -> reduces levels of angiotensin II -> suppresses aldosterone excretion -> decreases peripheral resistance AND increases sodium and water excretion
What is enalapril
RAAS - ACE inhibitor
used for treatment of HTN with pts w/ increased CAD risk, DM, stroke, MI, HF, CKD
preferred in pts with diabetic nephropathy
what are the pharmacokinetics of Enalapril (Prinivil)
oral (prodrug- undergoes hepatic metabolism), IV admin
dose adjust in kidney disease
What are the AE/SE of ACE inhibitors
First dose hypotension, cough, hyperkalemia, renal failure, angioedema, neutropenia
What are the interactions and contraindications for ACE inhibitors
Contra in pregnancy
Interactions w diuretics, antihypertensives, drugs that raise K+ levels, lithium, NSAIDs
What is Captopril (Capoten)
RAAS- ACE inhibitor
Tx of HTN in pts w incr CAD risk, DM, stroke, MI, HF, CKD
-Preferred in pts w diabetic nephropathy
-Not common 1st line agent
What is a unlikely SE/AE of captopril
infrequently causes agranulocytosis or neutropenia
What are the pharmacokinetics of Captopril
oral admin, 2-3 times per day
dose adjust in kidney disease
DOES NOT undergo hepatic conversion to active metabolites
What is Lisinopril
RAAS- ACE inhibitor
used to treat HTN and HF
Preferred in pts w diabetic nephropathy, can cause some lowering of blood sugars
What are the pharmacokinetics of ACE inhibitors
oral admin - once daily
dose adjust in kidney disease
DOES NOT undergo hepatic conversion to active metabolites
What are Angiotensin Receptor Blockers (ARB)
Losartan
Valsartan
Candesartan
Olmesartan
What is the MOA of ARB medications
Blocks angiotensin II receptors in blood vessels, adrenals and other tissues -> dilation of arterioles and veins
What is Losartan (Cozaar)
RAAS - ARB
used to treat:
HTN
stroke prevention
Diabetic nephropathy
reduces serum uric acid levels
What are the pharmacokinetics of Losartan
oral, once daily dosing
extensive first-pass hepatic metabolism (converstion to active metabolite)
Are ARB medications safe in pregnancy
NO
What are the AE/SE of ARB medications
Angioedema and renal failure
Drug interactions: additive effect w antihypertensive drugs
What is Valsartain
1st IRB approved for HF
HTN
What are the pharmacokinetics of Valsartan
oral admin, TWICE daily dosing
What is Candesartain
RAAS- ARB
used to treat HTN and HF
once daily dosing
inactive metabolites
What is Olmesartan
RAAS-ARB
used to treat HTN
once daily dosing
inactive metabolites
significant mean blood pressure reduction
What are Renin Inhibitors
Aliskiren
inhibits renin, acting early in the RAAS
what is the MOA for Aliskiren
binds tightly with renin and thereby inhibits the cleavage of angiotensinogen into angiotensin I
can influence entire RAAS
What are the pharmacokinetics of Alikiren
oral admin - metabolized by CPY3A4
bioavailability low, doing wiht high fat meal makes it lower
half-life 24 hours
what are the AE/SE of Aliskiren
diarrhea, cough, angioedema
Contraindicated in pregnancy
What are Endothelin Antagonists
Ambrisentan
Bosentan
What is the MOA for Ambrisentan
selectively blocks type A endothelin receptors
What is the MOA for Bosentan
Nonselectively blocks endothelin receptors
What are the uses for ambrisentan
treatment of pulmonary arterial hypertension (PAH)
improve exercise ability, delay clinical worsening of PAH
can be used in combo with tadalafil
What are the SE/AE of Ambrisentan
edema, nasal congestion, palpitations, abdominal pain, constipation
