Drugs used in HTN Flashcards
How do diuretics work in treating HTN?
Lower BP by reduction of blood volume (and possibly a direct vascular effect).
How do you use a diuretic?
monotherapy or adjunctive with other antihypertensives (like beta blockers)
What type of diuretic is used in mild HTN?
What type of diuretic is used to treat severe HTN and used in hypertensive emergencies?
thiazides (ex. hydrochlorothiazide)
furosemide (loop diuretic)
People with what type of hypertension require diuretics?
patients with edematous conditions like heart failure and renal insufficiency and that have “volume dependent hypertension” with low renin have better responses
Why might a patient have a poor response to a diuretic?
overwhelmind load of dietary sodium or high renin (so impaired capacity to excrete sodium)
What is another name for CNS-Active Agents ?
alpha 2 agonists (ex. clonodine and methyldopa)
How do alpha 2 agonists work?
Agonists of postsynaptic alpha2 adrenoceptors in the RVLM that decrease sympathetic impulses from the RVLM to heart and blood vessels. These lower BP by reducing vascular resistance and decreasing CO. Use with “triple combinations”
What are other uses for clonodine? Why?
analgesic in neuropathic pain approved for ADHD–> because it releases endogenous opiates
What are some adverse effects of alpha 2 agonists?
sedation, drowsiness, fatigue (can cross BBB), rebound HTN (with clonodine)
What is the major compensatory response seen with alpha 2 agonists?
salt retention
What vasodilators release NO?
nitroprusside
Adverse effects of hydralazine.
very toxic (tachycardia, palpitations, salt retention) and can induce lupus (hemolytic anemia)
ROA and MOA of nitroprusside.
short-acting pro-drug agent that must be infused; releases NO and stimulates guanylyl cyclase to increase cGMP concentration in smooth muscle to RELAX arteries and veins. This increases TPR and induces venous pooling (decrease CO)
What vasodilators work by Opening potassium channels→hyperpolarizaiton.
Minoxidil
Diazoxide
MOA of minoxidil.
Prodrug that opens K+ channels to relax arteriolar smooth muscle. Only used in severe hypertension.
Compensatory responses of minoxidil and hydralazine.
Compensatory response is tachycardia and salt retention(increase in renin release) so must take with beta-blocker and diuretic
What is another use of minoxidil?
Can be used as topical agent for baldness (leads to hirsutism)
Which vasodilators work by blocking L-type calcium channels?
NifeDIPINE (prototype dihydropyridine calcium channel blocker) Verapamil, diltiazem
How do dihydopyridines work?
decrease BP by relaxing arteriolar SM and decreasing PVR (VERY FEW baroreceptor-mediated compensatory responses)
What vasodilator works to activate D1 dopamine receptors?
Fenoldopam
What are the 2 main types of angiotensin antagonists?
ACE inhibitors
ARBs
List the ACE inhibitors?
captopril, Lisinopril, Enalapril, Ramipril
What is the MOA of ACE inhibitors?
1) stop the conversion of angiotensin to angiotensin II, reduce blood levels of angiotensin II and aldosterone, and increase “kinin” vasodilators
2) Increase renal blood flow without increase in GFR
What do you use ACE inhibitors for mainly?
best drug to treat CHF because dilated arteries and veins!
What are the contraindications of ACE inhibitors?
pregnancy (2nd and 3rd trimesters)a
renal disease (renal artery stenosis)
high potassium diets
What is the main adverse effects of ACE inhibitors? Why?
cough- when you inhibit ACE, you get increase in chymase (kinins) that can bind to receptors in the through and cause a cough
*angioedema also occurs
What are ACE inhibitors used for?
congestive heart failure, renal protection in diabetes, and high-renin hypertension
List the ARBs?
losartan, valsartan, Irbesartan, Telmisartan, candesartan
What is the MOA of ARBs?
competitively inhibit antiotensin II at its AT1 receptor site. Cause vasodilation and increase sodium and water excretion to decrease TPR, plasma volume, CO and BP
What are the adverse effects of ARBs?
not in pregnancy
lower incidence of cough compared to ACE inhibitors (no effect on bradykinin)
What is the MOA of aliskiren?
inhibit renin’s actions on angiotensinogen
What are the adverse effects of aliskiren?
diarrhea and headache
NO cough, avoided in human pregnancy
List the 5 steps used for controlling HTN.
- Lifestyle measures (diet, salt restriction, reduced weight)
- Diuretics (a thiazide)
- Sympathoplegics (a beta-blocker)
- ACE inhibitor
- Vasodilator (usually calcium channel blocker first)
When is monotherapy used?
useful in patients with mild and moderate HTN and is becoming more popular due to its efficacy, simplicity, and low toxicity
Both blacks and older people have poor responses to what type of antihypertensive?
beta blockers
What do you give in a hypertensive emergency?
a vasodilator, diuretic, and beta blocker to lower BP to range of around 140-160/90-110).
What is labetalol? When is it given?
non-selective beta + alpha 1 antagonist
ONLY in hypertensive emergencies
What is carvedilol? What is its MOA?
non-selective beta + alpha 1 antagonist
1) Antioxidant (scavenges ROS)
2) Protects membrane from lipid peroxidation (prevents LDL oxidation and LDL uptake into coronary blood vessels)
Carvedilol is used in what type of patients?
mild to moderate CHF and HTN patients
What is Nebivolol? What is its MOA?
highly beta1 selective drug
1) NO mediated vasodilation
2) Antioxidant activity
3) Increase SV while maintaining CO
What type of patients do you use Nebivolol on?
best beta blocker to treat metabolic syndrome
What does captopril do that other ACE inhibitors do not?
increase synthesis of renal prostaglandins and delays progression of renal disease in diabetics
What is the most potent vasoconstrictor in the body?
angiotensin II
List the 5 major actions of angiotensin II.
- vasoconstriction
- increase thirst (to increase blood volume)
- stimulate release of ADH from pituitary
- stimulate zona glomerulosa in AC to release aldosterone (increase K+ aborb)
- cardiac and vascular hypertrophy
What is special about the ARB losartan?
prodrug that it metabolized, competitive antagonist of Thromboxane A2 receptor to attenuate platelet aggregation, and INCREASES uric acid excretion
What is the main type of patient you would treat with losartan?
hypertensive patient with gout
What type of HTN do CCB’s like dihydropyridines best treat? What other disease does CCB treat?
low-renin hypertension (such as elderly subjects with systolic hypertension and African Americans) and CAD
What is the MOA of hydralazine?
selective arteriolar smooth muscle relaxer (no effect on veins) that triggers reflex sympathetic stimulation to increase catecholamine and renin secretion to cause Na+ retention.
When and why would you use nitroprusside?
Good for people who just had MI or who have ventricular failure, because you want as little blood putting a load on the heart as possible (dilation of arteries and veins reduces TPR so reduced afterload)
What type of anti-hypertensive has been shown to provide secondary protection in CAD?
beta-blockers
Which beta1 blocker is considered a standard treatment option with ACE inhibitors and diuretics?
bisoprolol
