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What is the MOA for Thiazide Diuretics and Chlorthalidone?
- Inhibit transporters that remove Na+ from renal tubular lumen
- Water follows Na+
- Na+ and water content in renal tubular lumen increases resulting in increased urine volume (diuresis)
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What are some examples of Diuretics?
- Hydrochlorothiazide
- Chlorthalidone
- Indapamide
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What will decrease Aldosterone production?
AT1 Receptor antagonists (ARBs)
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What is the effects of aldosterone?
Acts on the kidney tubule to ↑ Na+ and H20 reabsorption and to secrete K+
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What drugs block Aldosterone receptor on the kidney?
- K+- Sparing Agents:
- Spironolactone (more commonly used)
- Eplerenone
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What is the effects of ARBs (AT1 Receptor Blockers)?
- Vasoconstriction
- Cellular Hypertrophy
- ↓ Aldosterone production
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What is the common suffix of ACEI's?
-pril
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What is the common suffix of ARBs?
-sartan
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What is the MOA for ARBs (Angiotensin Receptor Blockers)?
Block the effects of Angiotensin II
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What is the MOA for ACEIs?
- Inhibits Angiotensin I from becoming Angiotensin II
- Inhibits Bradykinin from becoming inactive peptides
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What are the 2 beta blockers that have alpha 1 blocking ability?
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What is the most commonly used Beta-Blockers?
- Atenolol (B1 selective; 2nd gen)
- Metoprolol (B1 selective; 2nd gen)
- Labetalol (Non selevtive; 3rd gen; has alpha 1 blocking activity)
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What is the MOA for Beta-Blockers?
- Beta-1 Selectivity (primary therapeutic target)
- ↓ Renin production
- ↓ Cardiac Output
- Alpha-1 receptor blocking activity (added hypotensive effect): labetalol and carvedilol
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What are the cardiac and vascular effects for Calcium Channel Blockers (CCB)?
- ↓ Contractility (- inotropy)
- ↓ Heart Rate (-chronotropy)
- ↓ Conduction Velocity (-dromotropy)
- Smooth muscle relaxation
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What is the MOA for Calcium Channel Blockers?
Blocks Calcium Channels
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What is the common adverse effects for Thiazide Diuretics and Chlorthalidones?
- Hypomagnesemia
- Hyponatremia
- Hypotension
- Pre-Renal Azotemia
- Hyperuricemia
- Hypercalcemia
- Hypokalemia
- Hypercholesterolemia
- ↓ Glucose Tolerance
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What are the cardiorenal effects of ACE inhibitors (ACEI)?
- Vasodilation
- Decrease blood volume
- Depress sympathetic activity
- Inhibit cardiac and vascular hypertrophy
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What is the common adverse effects for ACEIs/ ARB/ DRI?
- Hypotension
- ↓ Renal function
- Hyperkalemia
- Cough (mainly w/ ACE-I)
- Angioedema (highest incidence w/ ACE-I)
- Birth defects - teratogenicity
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What is the common adverse effects for Beta-Blockers?
Decreases blood pressure
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What is the approach for the initiation of drug therapy for hypertension?
- Thiazide-type diuretic/ ARB/ ACEI/ CCB = Non blacks over 60 (<150/<90) and under 60 (<140/<90), All ages diabetes with no chronic kidney disease
- Thiazide-type diuretic or CCB = Blacks over 60 (<150/<90) and under 60 (<140/<90), All ages diabetes with no chronic kidney disease
- ACEI/ ARB = all ages with chronic kidney disease with/ without diabetes
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What is Labetalol and adverse effects and indications for Hypertensive Emergencies?
- Beta Blocker
- Adverse Effects: Vomiting, heart block, burning in throat
- First Line Defense
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What is Nicardipine and adverse effects and indications for Hypertensive Emergencies?
- Vasodilator
- Adverse Effects: Flushing, Tachycardia, H/a, nausea
- First Line
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What is Hydralazine and adverse effects and indications for Hypertensive Emergencies?
- Vasodilator
- Adverse Effects: Tachycardia, flushing, h/a, aggravation of angna
- HTN Emergency in pregnancy (eclampsia)
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What is Nitroprusside and adverse effects and indications for Hypertensive Emergencies?
- Vasodilator
- Adverse Effects: Nausea, muscle twitches, thiocynate and cyanide toxicity
- Not preferred for most hypertensive emergencies
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What has been dropped as a primary agent to treat HTN in JNC 8 and why?
- Beta Blockers
- Study showed B-Blockers resulted in a higher rate of primary composite outcome of CV death, MI, or stroke
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What is the Primary Anti-Hypertensives?
- Thiazide Diuretic
- ACE-1/ ARB
- Calcium Channel Blocker (CCB)
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What is the Renin-Angtiotensin-Aldosterone System for?
To increase blood pressure
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What are the 2 mechanisms that Angiotensin II can do to impact blood volume and blood pressure?
- Vasoconstriction
- Has kidneys make Aldosterone (↑ Na+ and H20 absorption by kidney but have K+ excretion)
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What is the main Angiotensin receptor?
AT1 Receptor
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What are the adverse drug reactions for taking ACE-I to increase bradykinin levels?
What should you do?
- Angioedema and Cough
- Switch to ARB if cough
- ARB can also cause Angioedema but switch to ARB with caution if compelling reason for ACE-I/ARB
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With a black pt with no chronic kidney disease, what should you give for High Blood Pressure?
- Thiazide-type diuretic or Calcium Channel Blockers, alone or in combo
- ACE/ ARB not preferred
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What should you give to a patient with chronic kidney disease (w/o diabetes) and has high blood pressure?
ACEI or ARB, alone or in combo
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What are the 4 alternative anti-hypertensives?
- α-1 Blockers
- α-2 Agonists
- Direct Vasodilators
- Neuronal Inhibitors
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Where is α-1, α-2, β-1, β-2 located in terms of neurons?
- α-1 = Postsynaptic Neuron
- α-2 = Presynaptic Neuron (autoreceptor)
- β-1 = Postsynaptic Neuron
- β-2 = Postsynaptic Neuron
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What does stimulation of α-2 receptors do?
- Block release of NE at the sympathetic terminal
- Anti-Hypertensives
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What is the name stem for α-1 blockers?
-osin
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What are α-2 agonists?
- Clonidine (Catapres)
- Methyldopa (Aldomet)
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What is the role of α-1 receptors and what happens if you block them?
- Role: Stimulation = vasoconstriction = increases BP
- α-1 Blockers: Vasodilation = decreases BP
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For Benign Prostatic Hypertrophy (BPH), what would be a therapeutic drug to use?
α-1 Blockers
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What happens if you stimulate α-2 receptors?
- SNS autoreceptors ↓ NE release
- CNS vasomotor center receptors ↓ PVR
- Dorsal horn spinal cord receptors causes analgesia
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What is the antihypertensive MOA?
- CNS vasomotor center receptors ↓ sympathetic tone (PVR) and cause vasodilatation
- Ex. Methyldopa; Clonidine
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What is the difference between Hypertensive urgencies and emergencies?
- Urgency - high BP with no acute target organ damage but should receive immediate combo oral antihypertensive therapy. Should be carefully evaluated and monitored for hypertension-induced heart and kidney damage and for identifiable causes of hypertension.
- Emergency - high BP and acute target-organ damage that requires hospitalization and parenteral drug therapy
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What are the 4 drugs used for Hypertensive Emergencies?
- Labetalol
- Nicardipine
- Nitroprusside
- Hydralazine
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What should you not use for Acute HTN?
Sublingual Nifedipine - comes in a gel infused capsule
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What drug should you stay away from if you have Bronchospastic disease (asthma)?
Beta blocker
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What drug should you stay away from if you have 2nd or 3rd degree heart block?
Beta blocker, CCB (non-DHP)
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What drug should you stay away from if you have Gout?
Diuretic
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What drug should you stay away from if you have Renal Insufficiency?
Potassium-sparing agent, aldo blocker
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What drug should you stay away from if you have Kyperkalemia?
ACEI, ARB, DRI, aldo blocker
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What drug should you stay away from if you have Pregnancy?
ACEI, ARB, DRI
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What is the name stem for beta blockers?
-olol, -alol, -ilol
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What is the name stem for vasodilating (DHP) Calcium Channel Blockers?
-dipine
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What is the name stem for thiazide diuretics?
-thiazide
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