3.2 Pharmacology for Hypertension
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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)
What are some examples of Diuretics?
What will decrease Aldosterone production?
AT1 Receptor antagonists (ARBs)
What is the effects of aldosterone?
Acts on the kidney tubule to ↑ Na+ and H20 reabsorption and to secrete K+
What drugs block Aldosterone receptor on the kidney?
- K+- Sparing Agents:
- Spironolactone (more commonly used)
What is the effects of ARBs (AT1 Receptor Blockers)?
- Cellular Hypertrophy
- ↓ Aldosterone production
What is the common suffix of ACEI's?
What is the common suffix of ARBs?
What is the MOA for ARBs (Angiotensin Receptor Blockers)?
Block the effects of Angiotensin II
What is the MOA for ACEIs?
- Inhibits Angiotensin I from becoming Angiotensin II
- Inhibits Bradykinin from becoming inactive peptides
What are the 2 beta blockers that have alpha 1 blocking ability?
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)
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
What are the cardiac and vascular effects for Calcium Channel Blockers (CCB)?
- ↓ Contractility (- inotropy)
- ↓ Heart Rate (-chronotropy)
- ↓ Conduction Velocity (-dromotropy)
- Smooth muscle relaxation
What is the MOA for Calcium Channel Blockers?
Blocks Calcium Channels
What is the common adverse effects for Thiazide Diuretics and Chlorthalidones?
- Pre-Renal Azotemia
- ↓ Glucose Tolerance
What are the cardiorenal effects of ACE inhibitors (ACEI)?
- Decrease blood volume
- Depress sympathetic activity
- Inhibit cardiac and vascular hypertrophy
What is the common adverse effects for ACEIs/ ARB/ DRI?
- ↓ Renal function
- Cough (mainly w/ ACE-I)
- Angioedema (highest incidence w/ ACE-I)
- Birth defects - teratogenicity
What is the common adverse effects for Beta-Blockers?
Decreases blood pressure
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
What is Labetalol and adverse effects and indications for Hypertensive Emergencies?
- Beta Blocker
- Adverse Effects: Vomiting, heart block, burning in throat
- First Line Defense
What is Nicardipine and adverse effects and indications for Hypertensive Emergencies?
- Adverse Effects: Flushing, Tachycardia, H/a, nausea
- First Line
What is Hydralazine and adverse effects and indications for Hypertensive Emergencies?
- Adverse Effects: Tachycardia, flushing, h/a, aggravation of angna
- HTN Emergency in pregnancy (eclampsia)
What is Nitroprusside and adverse effects and indications for Hypertensive Emergencies?
- Adverse Effects: Nausea, muscle twitches, thiocynate and cyanide toxicity
- Not preferred for most hypertensive emergencies
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
What is the Primary Anti-Hypertensives?
- Thiazide Diuretic
- ACE-1/ ARB
- Calcium Channel Blocker (CCB)
What is the Renin-Angtiotensin-Aldosterone System for?
To increase blood pressure
What are the 2 mechanisms that Angiotensin II can do to impact blood volume and blood pressure?
- Has kidneys make Aldosterone (↑ Na+ and H20 absorption by kidney but have K+ excretion)
What is the main Angiotensin receptor?
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
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
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
What are the 4 alternative anti-hypertensives?
- α-1 Blockers
- α-2 Agonists
- Direct Vasodilators
- Neuronal Inhibitors
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
What does stimulation of α-2 receptors do?
- Block release of NE at the sympathetic terminal
What is the name stem for α-1 blockers?
What are α-2 agonists?
- Clonidine (Catapres)
- Methyldopa (Aldomet)
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
For Benign Prostatic Hypertrophy (BPH), what would be a therapeutic drug to use?
What happens if you stimulate α-2 receptors?
- SNS autoreceptors ↓ NE release
- CNS vasomotor center receptors ↓ PVR
- Dorsal horn spinal cord receptors causes analgesia
What is the antihypertensive MOA?
- CNS vasomotor center receptors ↓ sympathetic tone (PVR) and cause vasodilatation
- Ex. Methyldopa; Clonidine
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
What are the 4 drugs used for Hypertensive Emergencies?
What should you not use for Acute HTN?
Sublingual Nifedipine - comes in a gel infused capsule
What drug should you stay away from if you have Bronchospastic disease (asthma)?
What drug should you stay away from if you have 2nd or 3rd degree heart block?
Beta blocker, CCB (non-DHP)
What drug should you stay away from if you have Gout?
What drug should you stay away from if you have Renal Insufficiency?
Potassium-sparing agent, aldo blocker
What drug should you stay away from if you have Kyperkalemia?
ACEI, ARB, DRI, aldo blocker
What drug should you stay away from if you have Pregnancy?
ACEI, ARB, DRI
What is the name stem for beta blockers?
-olol, -alol, -ilol
What is the name stem for vasodilating (DHP) Calcium Channel Blockers?
What is the name stem for thiazide diuretics?
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