What Class doe the following drugs belong?
Chlorthalidone
Hydrochlorothiazide (HCTZ)
Indapamide
Metolazone
Thiazide (Thiazide-like Diuretics) - weak diuretic
MOA of HCTZ and Chlorthalidone? and action site?
Na+ & Cl- are not reabsorbed = ↑ excretion.
Action site: Distal tubule
First line Thiazide for Uncomplicated HTN?
HCTZ
HCTZ is a better antihypertensive than it is a diuretic
Warnings for HCTZ?
Sulfa allergies [sulfonamide]
Dose in AM so pt does not pee all night . Check BMP after 2-3 wks
Drug interactions: Quinidine [Long QT]
Drug interactions for HCTZ?
Drug interactions: Quinidine [Long QT]
Decreases effects of: anticoags, uric acid agents, sulfonylureas, insulin
↑ effects of: anesthetics, digoxin, lithium, loop diuretics, Vit D
↓ by: NSAIDs, COX2s, BAS
↑ hypokalemia: Amphotericin B, corticosteroids
Indications for Chlorthalidone?
Similar to HCTZ, 10x greater potency at Na/Cl cotransporter!
Better for HTN than HCTZ?
ADRs for Chlorthalidone?
Same as HCTZ but more hypokalemia/electrolyte imbalance issues than HCTZ
1/2 life and elimination of Chlorthialidone?
Longer half life [47 hrs]
Eliminated: renal, bile, urine
What class do the following drugs belong?
Furosemide [Lasix]
Torsemide [Demadex]
Bumetanide [Bumex]
Loop Diuretics
Site of action for Loop Diuretics?
Furosemide, Torsemide, Bumetanide
Action site: Ascending Loop of Henle
1st line for diuretic for Acute pulmonary edema, CHF, Edema, Nephrotic syndrome, Cirrhosis, Chronic kidney dz, HTN, Severe hyperkalemia?
Furosemide [Lasix]
Contraindication for Furosemide [Lasix]?
Sulfa Allergy
Warnings for Furosemide?
Drug interactions: Aminoglycosides, some chemo drugs (ototoxicity)
↑ anticoagulant activity and dig arrhythmias ↑ lithium levels, NSAID, Sulfonylureas (hyperglycemia) ↓ diuretic response Ampho B [nephrotoxicity]
ADRs for Furosemide (Lasix)?
Hypokalemia [Can precipitate arrhythmia], Hyponatremia, Hypomagnesemia, Hypocalcemia
Hyperuricemia, Hyperglycemia
Ototoxicity [Tinnitus, hearing loss, usually reversible], Sulfa allergy? ↑ LDL, TC, Tg. ↓ HDL.
MOA for Furosemide, Torsemide, Bumetanide?
Loop Diuretics
↑ urinary Na+ and Cl- excretion and Ca++ and Mg excretion
Is Bumetanide more or less potent than Furosemide?
Bumetanide is 40x more potent than furosemide
What Class do the following drugs belong?
Triamterene [Dyrenium]
Amiloride [Midamor]
Spironolactone [Aldactone]
Eplerenone [Inspra]
Potassium-Sparing Diuretics
MOA of Potassium-Sparing Diuretics?
Triamterene, Amiloride, Spironolactone, Epelerenone
Rarely used as monotherapy [combined w/ other diuretic to prevent K+ loss]
Na+ channel inhibitors
Loops & thiazides drive Na+ to collecting duct leading to ↑ K+ excretion
Amiloride and triamterene block Na+ channels, ↓ K+ excretion.
Little effect on Na+ excretion, may ↓ uric acid excretion
CI for Potassium-Sparing Diuretics?
Renal Failure
ADRs for Potassium-Sparing Diuretics?
Triamterene, Amiloride, Spironolactone, Epelerenone
Hyperkalemia→ can be lethal!
Triamterene: N/V, leg cramps, dizziness, photosensitivity, hyperglycemia, interstitial nephritis, nephrolithiasis
Amiloride: N/V/D, HA
What Class doe the following drugs belong?
Captopril (Capoten) Enalapril (Vasotec) Lisinopril (Zestril, Prinivil) Benazepril (Lotensin) Fosinopril (Monopril) Trandolapril (Mavik) Ramipril (Altace) Quinapril (Accupril) Perindopril (Aceon)
ACE Inhibitors —- RAAS drugs
How do ACEs work?
ACE enzyme: converts angiotensin I to angiotensin II
Angiotensin II→ Vasoconstrictor, stimulates synthesis/release of aldosterone [leads to Na+/K+ retention→ ↑ B/P, inactivates bradykinin breakdown
ACE converts bradykinin to an inactive peptide → more bradykinin → more NO → vasodilation! + cough :[
How do ACE inhibitors work?
ACE inhibitors→ Vasodilator ↓ B/P b/c it blocks ACE enzyme
Increased: vasodilation (arterial & venous)
Reduces: arterial & venous pressure, ventricular afterload & preload and blood volume [natriuretic, diuretic], morbidity & mortality post MI [improves ventricular function post MI]
↓ sympathetic activity, ↓ cardiac/vascular hypertrophy
What is the 1st line for HTN [not for general black population]
CKD
Reduce major CVD outcomes in pts w/ diabetes
ACE inhibitors (-opril)
What class do the following drugs belong to?
Losartan (Cozaar) Valsartan (Diovan) Candesartan (Atacand) Eprosartan (Teveten) Irbesartan (Avapro) Olmesartan (Benicar) Telmisartan (Micardis)
Angiotensin Receptor Blockers (ARBs)
-sartan
MOA of ARBs? (-sartan)
Blocks: type 1 angiotensin II receptors on blood vessels and the heart and stimulation of vascular smooth muscle contraction
Do not increase bradykinin [No cough, angioedema]
Contraindication for ACE inhibitors and ARBs?
PREGNANCY!
esp. ACE inhibitors (fetal/neonatal mortality!)
ADRs for Angiotension-Converting-Enzyme inhibitors?
Dry cough
hyperkalemia [renal insufficiency, w/ concomitant K+-sparing diuretics]
↓ renal fxn [renal stenosis, pre-existing renal disease]
first dose hypotension
ANGIOEDEMA
ADRs for ARBs?
Hyperkalemia
Rhabdomyolysis
The following drug belongs to what class?
Aliskiren [Tekturna]
Direct Renin Inhibitors
MOA of Aliskiren?
Direct inhibition of renin secretion [renin secretion is rate limiting step in RAAS]
*ACEI/ARBs = incomplete blockade of RAAS
Indication for Direct Renin Inhibitors?
Not first line:
Take ACEI off if you use this in DM & renal insufficiency
ADRs and Warnings for Direct Renin Inhibitors?
Aliskiren
Drug intxn: ↑ [] by cyclosporine, itraconazole
Angioedema, hyperkalemia, renal impairment.
What class do the following drugs belong to?
Spironolactone (Aldactone)
Spironolactone/HCTZ (Aldactazide)
Eplerenone (Inspra)
Aldosterone Antagonists
MOA of Spironolactone?
Aldosterone mineralocorticoid derived from cholesterol
Spironolactone competitive antagonist for androgen receptors (Mineralocorticoid receptor blocker)
- Displaces testosterone from binding sites
- Increases testosterone clearance
- Increases estradiol production
MOA for Eplerenone?
More selective for aldosterone receptors
Indications for Eplerenone?
Post-MI CHF, HTN
Fewer anti-androgen side effects
Indications for Spironolactone?
Edema due to HF, cirrhosis, nephrotic syndrome
HTN [compelling indication post-MI or HF]
primary hyperaldosteronism
severe HF
LV dysfunction [with ACEI/ARB, diuretic, beta blocker]
Off label: hyperandrogenism [Hirsutism, PCOS, congenital adrenal hyperplasia - CAH]
ADRs for Spironolactone?
Hyperkalemia gynecomastia mastodynia erectile dysfunction stevens-johnson GI bleed
ADRs for Eplerenone?
Hyperkalemia (CI in renal impairment)
What class do the following drugs belong to?
Verapamil
Diltiazem
Calcium Channel Blockers
MOA of Calcium Channel Blockers?
Verapamil
Diltiazem
Cardiac effects: Primary action: heart→ reduce Ca++ entry in the heart [Dihydropyridines have minimal effects on Ca++ entry in heart muscle]
Slow pacemaker activity - HR decreases, slows conduction b/n atria & ventricles. Lessens strength of contraction - decreased SV. Class IV antiarrhythmics
Vascular effects: lesser effect on arterioles and more depression of heart [no tachy!]
Indications for Verapamil?
Angina, arrhythmia, HTN
Reduces afterload and myocardial contractility, improves LV diastolic fxn
Contraindications for Verapamil?
Calcium Channel Blocker
Heart failure!
severe LV dysfunction, hypotension/shock, sick sinus syndrome [unless pt has pacer], 2nd or 3rd degree AV block, WPW, Lown-Ganong-Levine syndrome, pre-existing systolic HF, conduction defects or bradycardia, B-blockers
Drug Interactions for Verapamil?
Drug intxn: EtOH, P450 - grapefruit juice, Digoxin, Lithium
P450!
Indications for Diltiazem?
Angina - inc exercise tolerance due to increased O2 demand
Less potent vasodilator and inotrope than verapamil
IV: ↓ BP and PVR and HR
Oral: decreases HR, BP
Contraindications for Diltiazem?
Calcium Channel Blocker
Similar to Verapamil…
Heart failure! -
severe LV dysfunction, hypotension/shock, sick sinus syndrome [unless pt has pacer], 2nd or 3rd degree AV block, WPW, Lown-Ganong-Levine syndrome, pre-existing systolic HF, conduction defects or bradycardia, B-blockers
What out for liver problems with Diltiazem!
It is also a P450 substrate and inhibitor (like Verapamil)
Avoid grapefruit juice with CCB (Diltiazem/Verapamil)
What Class do the following Drugs belong to?
Amlodipine [Norvasc] Nifedipine [Procardia] Clevidipine [Cleviprex] Nimodipine [Nimotop] Felodipine [plendil] Nicardipine [Cardene]
Calcium Channel Blockers: Dihydropyridines
-ipine
All of the Dihydropyrides that we learned about are P450 drugs!
Amlodipine (P450)
Nifedipine (P450)
Clevidipine (P450)
Amlodipine MOA?
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle.
Nifedipine MOA?
The mechanism by which nifedipine reduces arterial blood pressure involves peripheral arterial vasodilatation and, consequently, a reduction in peripheral vascular resistance. … Nifedipine is a peripheral arterial vasodilator which acts directly on vascular smooth muscle.
Clevidipine MOA?
Clevidipine is a dihydropyridine L-type calcium channel blocker. L-type calcium channels mediate the influx of calcium during depolarization in arterial smooth muscle.
Most selective for smooth muscle, primarily used for HTN due to reduction of PVR
Pregnancy Category of Amlodipine and Nifedipine?
Category C
ADRs for Amlodipine and Nifedipine?
Edema, dizziness, flushing, palpitation, fatigue, nausea, abdominal pain
ADRs for Nifedipine, Clevidipine, Amlodipine?
Calcium Channel Blockers: Dihydropyridines
Flushing, HA, hypotension, reflex tachycardia
Edema: Direct arteriolar dilatation without venous dilation
I
ncreased hydrostatic pressure
Fluid shifts to gravity dependent compartments
More common in DHP CCBs due to potency of vasodilation. Worse at end of day. Improves with LE elevation
The following drugs are first line for HTN in pregnancy. What class do they belong to?
Propranolol, Atenolol, Metoprolol, Carvedilol, Labetalol
Beta Blockers
MOA of Beta Blockers?
Beta adrenergic receptor antagonists
Indications for use of Beta Blockers?
-olol
MI
HF
HTN
Contraindications for Beta Blockers?
Contraindicated in hypoperfusion (preshock) or heart failure [Sx: cold extremities, cyanosis, oliguria, decreased mentation
Warnings with Beta Blockers?
Avoid ISA beta blockers, caution w/ asthma, taper doses up and down
Can lead to lifethreatening Bronchoconstriction in COPD patients.
Can delay recovery from hypoglycemia in T1DM and blunt hypoglycemic sx
What Class do the following drugs belong to?
Clonidine
Methyldopa
ALPHA AGONISTS
Centrally acting sympatholytics
What do Alpha Receptors do in the body?
Block sympathetic activity within the brain
Activate a2 receptors: Decrease heart rate and contractility
Reduced sympathetic output to the vasculature: decreases sympathetic vascular tone, vasodilation, reduced systemic vascular resistance [decreases arterial pressure
MOA of Clonidine?
Partial agonist, low efficacy, high affinity. Exact MOA unknown
MOA of Methyldopa?
A2 agonist
Indication for Methyldopa???
HTN in pregnancy!
Indication for Clonidine?
HTN
Decrease diarrhea in pts w/ diabetic neuropathy
Substance withdrawal [↓ cravings & sympathetic nervous activity]
Post menopausal hot flashes [patch]
ADHD
ADRs for Clonidine?
Alpha Agonist
IV and patch: rebound Hypertension!
Dry mouth, sedation, erectile dysfunction, dizziness, constipation, bradycardia, less ADRs with patch
abrupt d/c: nervousness, HA, agitation, tremor, rebound HTN
Drug interactions for Clonidine?
Drug interactions: Digoxin beta blockers CCBs - bradycardia EtOH barbiturates - CNS depression TCAs - hypotensive effect minimized Antipsychotics - orthostasis
ADRs and drug interactions of Methyldopa?
Alpha Agonist
Fatigue, sedation, HA, weakness [transient]
Hemolytic anemia
Liver failure
Edema - treat with diuretic
Drug interactions: lithium