Anti Hypertensive Drugs Flashcards
Primary Risk Factors for HTN
Family history African ethnicity Male gender Post-menopausal women >20 lbs excess body weight
Associated Risk Factors for HTN
Diabetes
Excess Alcohol
Oral contraceptives
Inactivity
What are pre hypertensive BPs?
120-139/80-89
What are stage 1 hypertensive BPs?
140-159/90-99
What are stage 2 hypertensive BPs?
160/100 and up
In patients less than 60 years old, what is the lowest blood pressure when you would prescribe anti-hypertensive meds?
What would you recommend before then to lower their BP?
When they get above 140/90, you need to prescribe meds.
Before that, use lifestyle modifications to treat HTN
In patients older than 60, at what BP do you start prescribing meds for HTN?
150/90
What are the 4 classes of first-line DOC anti-hypertensives?
Diuretics
Ca2+ channel blockers
ACE Inhibitors
Angiotensin receptor blockers
Thiazide Diuretics
MOA
Block the Na+/Cl- channels in the distal convoluted tubule, increasing Na+ loss and urinary volume.
K+ wasting
Cause some vasodilation via prostaglandin release
Cause increased aldosterone production and insertion of ENaC channels into luminal membrane of principal cells, driving K+ out of the lumen
Thiazide Diuretics
Adverse Effects
Hyponatremia Hyperglycemia Hypokalemia Increased LDL/HDL Metabolic alkalosis
Thiazide Diuretics
What drugs would be OK to coadminister with thiazides to prevent K+ wasting?
Prevent aldosterone from reabsorbing more Na+ in collecting ducts, thus prevent K+ wasting
- Beta Blockers
- ACE inhibitors
- Angiotensin receptor antagonists
Thiazide Diuretics
What drugs should you not coadminister thiazides with?
NSAIDs
May block the vasodilatory effects of the prostaglandins released by the thiazides
Thiazide Diuretics
Contraindications
Hypokalemia
Pregnancy
Thiazide Diuretics
What is their interaction with beta blockers?
May cause hyperglycemia together, though beta blockers may be coadministered to help prevent hypokalemia
List the thiazide diuretics
Hydrochlorothiazide
Chlorthalidone
Loop Diuretics
MOA
Block the Na+/K+/Cl- channel in the thick ascending limb of the loop of Henle
K+ wasting
Venous dilation via Prostaglandin release
Also cause excretion of Mg2+ and Ca2+
Loop Diuretics
List them
Furosemide
Ethacrynic acid (last resort)
Bumetanide
Torsemide
Loop Diuretics
Side Effects
Hypokalemia Metabolic alkalosis Dehydration Hyponatremia Hypomagnesemia Impaired diabetes control Increased LDL/HDL Ototoxicity
Loop Diuretics
Drugs Interactions
Aminoglycosides - exacerbates ototoxicity
NSAIDs- block vasodilatory effects of prostaglandins
List the K+ Sparing Diuretics
Spironolactone
Eplerenone
Amiloride
Triamterene
Spironolactone
MOA
Blocks the aldosterone receptor, thus preventing insertion of ENaC channels into the luminal membrane of the principal cells.
Increase Na+ excretion and spare K+
Spironolactone
Adverse Effects
Hyperkalemia
Anti-androgenic effects - gynecomastia, amenorrhea, impotence
Eplerenone
MOA
Blocks the aldosterone receptor, thus preventing insertion of ENaC channels into the luminal membrane of the principal cells.
Increase Na+ excretion and spare K+
Does NOT have the anti-androgenic effects of spironolactone
Spironolactone and Eplerenone
Drug Interactions
NSAIDs
ACE inhibitors and Angiotensin Receptor Blockers - can exacerbate hyperkalemia by inhibiting aldosterone’s production
Amiloride and Triamterene
MOA
Block the ENaC channel in the principal cells
Amiloride and Triamterene
Drug Interactions
NSAIDs
ACE Inhibitors and Angiotensin Receptor Blockers - may exacerbate hyperkalemia
Would you ever use a K+ sparing diuretic as a monotherapy?
No. Not very strong on their own, but they are good in combination with loop or thiazide diuretics (the K+ wasting drugs)
Ca2+ Channel Blockers
Dihydropyridines are selective for? What is the dihydropyridine drug and its MOA?
Selective for vascular smooth muscle.
Nefedipine is used only in HTN by blocking vascular Ca2+ channels
Ca2+ Channel Blockers
What are the non-dihydropyridine drugs? What are they selective for?
Verapamil and Diltiazem
They act on both vascular and cardiac smooth muscle (though verapamil has a much more potent effect on cardiac smooth muscle)
Nefedipine
Adverse Effects
Acute tachycardia
Peripheral edema
Diltiazem
Adverse Effects
Bradycardia
Verapamil
Adverse Effects
Constipation
Bradycardia
Verapamil and Diltiazem are contraindicated in…?
Patients with conduction disturbances (heart block, etc)
Clonidine
MOA
Alpha-2 receptor agonist
Activates a G-alpha-i cascade, inhibiting adenylyl cyclase to decrease sympathetic outflow from the CNS
Clonidine
Adverse Effects
Sudden withdrawal may lead to a hypertensive crisis
Sedation
Dry mouth
Dermatitis
Why might guanfacine be used in place of clonidine?
Guanfacine has a longer half life, so it is less likely to cause rebound HTN when a patient misses a dose
Methyldopa
MOA
Alpha-2 receptor agonist
Also competes with LDOPA for dopamine decarboxylase, inhibiting dopamine production
Methyldopa
Indications
Used for hypertensive control in pregnant women
Methyldopa
Adverse Effects
Sedation
Hyperprolactinemia
Anemia
Reserpine
MOA
Blocks VMAT vesicular transporter, preventing storage of NE in vesicles. MAO will digest NT in the cytosol.
Reserpine
Indications
Hypertensive patients who are resistant to other drugs
Reserpine
Adverse Effects
Depression
Nasal Congestion
Reserpine
Drug Interactions
Do not give reserpine with a MAO inhibitor, which could reverse reserpine’s effects and cause a hypertensive crisis
Phenoxybenzamine
MOA
Non selective alpha adrenergic antagonist
Phenoxybenzamine
Indications
Pheochromocytoma
Phenoxybenzamine
Adverse Effects
Tachycardia (due to NE binding beta receptors instead of alpha)
Prazosin
MOA
Selective alpha-1-antagonist
Prazosin
Indications
Primary HTN
Benign Prostatic Hyperplasia
Prazosin
Adverse Effects
Orthostatic Hypotension
Dizziness
Beta Blockers
General MOA
Lower contractility of the heart
Lower HR
Prevent renin release, thus decreasing angiotensin II production
What is the prototypical beta blocker?
Propranalol
Nadolol
Nonselective Beta blocker
Longer half life
Pindolol
Partial agonist of Beta receptors
Nonselective
Causes less bradycardia than other beta blockers
Metoprolol
B1-selective beta blocker
Lipophilic
Atenolol
B1-selective
Hydrophilic
Labetolol
Beta blocker with some alpha-blocking activity
Lipophilic
Carvedilol
Nonselective beta blocker that also has alpha-receptor antagonist activity
Vasodilation
Lipophilic
What are the lipophilic beta blockers?
Metoprolol
Labetolol
Carvedilol
Beta Blockers
Side Effects of all BBs
Bradycardia Increased triglycerides Decreased HDLs Hyperglycemia Impaired exercise tolerance
Beta Blockers
Side effects of Nonselective BBs
Bronchiole constriction (increased airway resistance)
Beta Blockers
Side Effects of Lipophilic BBs
Insomnia
Chronic fatigue
Depression
Contraindications for Beta Blockers
Sinus bradycardia
Cardiogenic shock
Heart block
Asthma
Beta Blockers
Drug Interactions
Calcium Channel Blockers - causes reduced contractility and conduction
Vasodilators
General MOA
Vasodilation of small vessels, primarily the arterioles
Hydralazine
MOA and Indications
Vasodilator used in drug resistant HTN and emergencies
Hydralazine
Side Effects
Tachycardia
Angina aggravation
Fluid Retention
NSAIDs can reduce effectiveness
Minoxidil
MOA and Indications
Vasodilator used for drug resistant HTN
Minoxidil
Adverse Effects
Hypertrichosis
Tachycardia
Angina Aggravation
Fluid retention
Nitroprusside
MOA and Indications
Vasodilator used in emergencies
Nitroprusside
Adverse Effects
Cyanide poisoning (gets converted to a cyanide-like metabolite in the liver)
ACE Inhibitors
General MOA
Block production of angiotensin II Prevent vasoconstriction Prevent aldosterone activation Prevent bradykinin degradation Prevent some NE release, growth, and inflammation
List the ACE Inhibitors
Captopril
Enalapril
Lisinopril
Why is Lisinopril the most commonly used ACE inhibitor today?
Captopril had a very short half life.
Enalapril had a longer half life but needed to be metabolically converted, making half life and drug effects more unpredictable
Lisinopril has a rapid onset of action and a more predictable half life
ACE Inhibitors
Adverse Effects
Hyperkalemia
Dry cough
Angioedema (rare)
ACE Inhibitors
Contraindications
Should not be given with K+ sparing drugs
Pregnancy
Bilateral renal stenosis
How do ACE inhibitors help patients who have HF or LV dysfunction?
Prolongs survival by preventing cardiac remodeling
Angiotensin II Receptor Blockers
Which one do we use most?
Losartan
- selective AT1 receptor antagonist
Angiotensin II Receptor Blockers
Adverse Effects
Hyperkalemia
Angiotensin II Receptor Blockers
Contraindications
Pregnancy
Should not be used with K+ sparing drugs
How should you best treat HTN in African Americans?
Monotherapy with diuretics or Calcium channel blockers
What anti-hypertensive meds should you avoid in pregnancy?
ACE inhibitors
Angiotensin receptor blockers
Beta Blockers
What anti-hypertensive meds should you use in pregnancy?
Methyldopa
