Exam 2: Hypertensive Drugs Flashcards
Blood pressure is directly proportional to what two things?
CO and vascular resistance
What is the most common cause of failure of HTN drug therapy?
Non-compliance
In regards fo HTN, what do thiazide diuretics do?
Used in mild-moderate HTN to lower BP by 10-15.
-Increase sodium and H20 excretion will ultimately lower BP
What are the common side effects of diuretics?
- Reduced glucose tolerance
- Increased plasma lipid concentration
- impotence
- Gout
- Hypokalemia
How do Sympatholytic drugs work?
-Decrease BP by reducing sympathetic vasomotor tone
Why are sympatholytics commmonly combined with diuretics?
Sympatholytics activate baroreflexes and generally cause Na and H2O retention
What two drugs are the centrally acting sympatholytics?
Clonidine and methyldopa
What is the MOA of clonidine and Methyldopa?
Stimulate medullary Alpha2 adrenergic receptors, leading to decreased peripheral sympathetic nerve activity
***remember alpha2 is inhibitory!
What are the adverse effects of centrally acting sympatholytics?
- sedation
- xerostomia
- ED
- Methyldopa may also produce hemolytic anemia with positive Coombs test, hepatotoxicity, and increased prolactin secretion (gynecomastia)
What are the contraindications for centrally acting sympatholytics?
- Not recommended for Monotherapy because of CNS effects
- sudden withdrawal of clonidine can lead to Hypertensive crisis
- TCAs and yohimbine inhibit clonidine therapeutic action
What kind of drug is Prazosin?
A1 adrenergic antagonist
What are the indications for Prazosin?
- Reduces NE vasoconstriction
- decreased peripheral vascular resistance (Decrease BP)
- Beneficial for BPH and does not affect plasma lipids
What are the adverse effects of Prazosin?
- Postural hypotension (first dose phenomenon)
- Na and water retention
- reflex tachycardia
How do B-Blockers work to decrease BP?
Blocks B receptors in the heart to reduce CO, kidneys to reduce renin secretion, and CNS to reduce sympathetic vasomotor tone
Why are b blockers commonly combined with other drugs?
To counteract reflex tachycardia and increase renin secretion
B-blockers are preferred for patients with what conditions?
Angina, post MI, migraines, and HF
Who are B-blockers least preferential in?
Patients with high physical activity, African heritage, asthma, DM, hypercholesterolemia, and peripheral vascular disease
How do Nebivolol decrease ED?
Nebivolol increases NO, which increases Vasodilation, which decreases ED
What are the contraindications to B blockers?
- DM
- End stage HF
- Bradycardia
- Heart block
- Asthma
What two drugs are combined A1 and B blockers? What is their general indication?
Labetalol and Carvedilol
-Used for vasodilation without reflex tachycardia
What are the indications for labetalol?
- Decrease BP in hypertensive emergencies
- Pregnancy (stronger than Methyldopa)
What are the indications for Carvedilol?
Hypertension and HF, especially post MI
What are the adverse effects of Carvedilol and Labetalol?
- Orthostatic hypotension
- Bronchoconstriction
- Labetalol is hepatotoxicity, emergency use only
What drug dilates both veins and arteries?
Sodium nitroprusside
What two vasodilators are used for chronic oral treatment?
Hydralazine and CCBs
Hypotension caused By a vasodilator can be accompanied by what other symptoms?
- Reflex tachycardia and increased myocardial contraction
- increased renin secretion
- fluid retention
- Headaches
- palpitations
What are the indications for Hydralazine?
- Dilates arterioles but not veins
- used in chronic therapy of severe HTN
- Used in severe HTN or HTN emergencies in pregnancy
What are the adverse effects of hydralazine?
- HA, nausea, anorexia, angina, ischemic arrhythmias
- SLE in slow acetylators
What are the two vasodilators that specifically act through NO?
Hydralazine and sodium nitroprusside
What are the indications for sodium nitroprusside?
- Rapidly lowers blood pressure and the effect disappears in minutes after discontinuation
- Used for emergency HTN situations
What are the adverse effects of Sodium nitroprusside?
- Cyanide accumulation
- Metabolic acidosis, arrhythmias, excessive hypotension (deficiency in cyanide metabolism)
What the is MOA of Fenoldopam?
-Specific agonist D1 receptors and postsynaptic receptor stimulation relaxes arteriolar smooth muscle
What is the indications of Fenolopam?
Emergency hypertensive situations
What are the specific pharmacokinetics of Sodium nitroprusside?
Metabolized rapidly in the liver to thiocyanate
What are the adverse effects of Fenoldopam?
-Reflex tachycardia, Headache, and flushing
What kind of drugs are Nifedipine and amlodipine?
Dihydropyridines
What is the MOA of CCBs?
- Orally active, bind to L type channels in the myocardium to decrease contractility and conduction.
- Vasodilation
What kind of muscle muscle do CCBs relax?
-Relaxes all muscle that depend on Calcium for normal resting tone and contraction
What are the major cardiac effects of CCBs?
- Decrease contractility (inotropic)
- Decrease impulse generation in the SA node (Chronotropic)
- Decrease AV node conduction (Dromotropic)
Which CCBs has most of its effects in the cardiac muscle?
Which in vascular muscle?
Which has equal effects?
Cardiac muscle: Verapamil
Vascular smooth muscle: Nifedipine
Equal: Diltiazem
Which CCB is the most likely to produce reflex tachycardia?
Nifedipine
**highest vasodilation, marked hypotension, and reflex tachycardia
What are the adverse effects of CCBs?
- Dihydropyridines cause most vascular side effects like reflex tachycardia
- Gingival hyperplasia
- constipation
What are the contraindications of Verpamil and diltiazem?
- SA or AV node abnormalities, B blockers
- HF
How do ACE inhibitors prevent hypertension?
- Reduce direct vasoconstriction by ATII
- Reduce the release of aldosterone
Do ACE inhibitors cause reflex sympathetic activation?
NO, because there are AT receptors presynaptically and baroreceptors, so these drugs reset the set point on baroreceptors
ACE inhibitors are the DOC for HTN with what conditions?
DM, CKD, and HFrEF
Why are ACE inhibitors commonly given with diuretics?
- Enhance the antihypertensive efficacy of diuretic drugs
- Balance the adverse effects of diuretics
What is the DOC for CKD even without HTN?
ACE inhibitors, they decrease proteinuria and stabilize renal function
-Particularly indicated in diabetic nephropathy
What are the adverse effects of ACE inhibitors?
- Orthostatic Hypotension and dizziness
- Dry hacking cough
- Angioedema and anaphylaxis
- Acute renal failure in patients with bilateral renal artery stenosis
What are the contraindications to ACE inhibitors?
- Pregnancy
- Potassium sparing diuretics
- Combination with NSAIDS will cause vasodilation (bradykinin leads to PG synthesis)
What kind of drugs are Losartan and Valsartan?
ARBs
What are the main differences between ACE inhibitors and ARBs?
-ACE inhibitors have decreased AT2 receptors activity and little CV effects as well as increased bradykinin levels
