Antihypertensive Agents Flashcards
what percent of people have hypertension? by age 80 what percent will have it?
30%; 80%
complications of HTN longterm?
Damages kidney
heart and brain manifested as kidney failure
heart failure
coronary artery disease and stroke
Mean arterial pressure=
CO x PVR
CO=
SVxHR
what system coordinates BP?
autonomic nervous system
pt with HTN have a ____ set point for BP
higher
MOA of diuretics?
Deplete sodium and decrease blood volume
MOA of sympathoplegics?
Decrease peripheral resistance
Decrease CO by
Inhibiting cardiac function
Increasing venous pooling in capillaries
MOA of vasodilators?
Decrease pressure by relaxing/dilating vascular smooth muscle
MOA of angiotensin action blocker?
Decrease peripheral resistance and blood volume
groups of diuretics?
- potassium sparing diuretics
- loop diuretics
- thiazide diuretics
why do we use potassium sparing diuretics?
Use with other diuretics (thiazides &/or loops) to prevent hypokalemia
why do we use loop diuretics?
volume overload
MOA of thiazide diuretics?
- By depleting body stores of sodium (Na), water follows NA, decreasing blood volume.
- Less volume, less cardiac output, eventually less PVR and lower BP
- Initially they decrease blood volume which decrease CO
- After weeks/months they also decrease PVR accounting for their long term effects for BP regulation
- Decrease sodium content of arteriolar smooth muscle which leads to a decrease in muscle contraction in response to norepinephrine and Angiotensin II
what do thiazide diuretics work well for?
BP
prototype thiazide diuretic?
HCTZ hydrochlorothiazide
most common ADR of HCTZ?
- low potassium; can be lethal (contributes to arrhythmias and/or muscle pain)
other ADR of HCTZ?
- low magnesium
- high BS
- increased lipids
- increased uric acid associated with gouty arthritis
- low potassium
how much does HCTZ lower BP?
10-15 mm Hg
What is the dose of HCTZ?
12.5mg capsules
25mg or 50 mg tablets
most are 12.5-25 mg is what most people are on
50 mg dose = more ADRs
what populations respond best to HCTZ?
African-Americans, older patients, obese patients, smokers
goal of sympathoplegics?
inhibiting function of sympathetic nervous system
MOA of centrally acting drugs?
- Reduce sympathetic outflow from the centers in the brainstem that control blood pressure.
- Less SNS outflow, lower BP
- These drugs work on the alpha adrenoreceptors in the brain not in the periphery.
MOA of methyldopa?
Work to decrease BP by decreasing PVR
ADRs of methyldopa?
- Related to the fact that it works in the brain
- Common side effects: sedation, decreased concentration, impotence
- Less common: nightmares, depression, vertigo, lactation
- Rare, but significant: Hemolytic anemia (Type II hypersensitivity)
what centrally acting drug do we use in pregnant woman who need to decrease BP? when else is this drug used?
methyldopa, decreases PVR
otherwise as 2nd or 3rd line due to S/E
how does clonidine work?
Lowers CO by decreasing HR and (PVR) by relaxing capillary venues
what are the ADRs of clonidine?
ADRs (Works in the brain):
- Common ADRs: Dry mouth, sedation, impotence, causes or worsens depression
- Severe ADR: Rebound HTN. If stop clonidine suddenly can get increased SNS outflow from the brain causing sudden, severe increase in BP (higher than when started the med). It lasts for a brief period but has been associated with hypertensive hemorrhage in brain.
- All patients should be educated: DON’T STOP SUDDENLY. The drug must be tapered (decreased slowly over several days)
what should you educate your pt about clonidine?
not to stop suddenly
drug interactions with clonidine?
- Clonidine is less effective in those on tricyclic antidepressants.
- Try not to give with other drugs that make sleepy as sleepiness adds up
when do you use clonidine?
3rd-4th line agent
what is the issue with clonidine?
compliance
have to use for BP have to dose 2x/d
or can use patch for non compliance (applied every 7th day)
MOA of beta blockers?
Decrease BP and CO
- Blocks beta receptors in kidneys
- Blocks peripheral adrenergic receptors mostly in heart, so get less SNS effect (decreasing HR and contractility)
- Beta blockade decreases renin (less angiotensin II and aldosterone, less volume)
absorbtion of beta blockers?
Well absorbed orally as a group, first pass occurs with most in group so oral dose is much higher than IV dose.
distribution of beta blockers?
Large volumes, go everywhere some get into CNS ( those that get into CNS increase chance of CNS side effects)
why selective and non-selective important
ADRs of beta blockers?
- In the heart causes bradycardia, cardiac conduction problems (arrhythmias), decreased pumping action making CHF worse
- In lung can make asthma worse (non-selectives in particular)
- In blood vessels prevents dilation effect that beta 2 gives. This is a problem only if already have a blockage in the blood vessels (peripheral vascular disease)
Other ADRs:
- CNS: depression, sedation, sleep disturbances, rarely psychotic reactions
- In diabetics beta blockers mask symptoms of hypoglycemia
- Withdrawal: Occurs b/c of upregulation of beta receptors (Symptoms: Nervousness, tachycardia, increased BP)
- Don’t stop suddenly, taper
Nonselective beta blockers?
Propranolol (Inderal) - prototype
Nadolol (Corgard)
Carteolol (Cartrol) - not used
Selective beta blockers?
Metoprolol (Lopressor) Atenolol (Tenormin) Betaxolol (Kerlone) Esmolol (Brevibloc) Bisoprolol (Zebeta) Nebivolol (Bystolic)
partial agonist beta blockers?
Pindolol (Visken)
Acebutolol (Sectral)
Penbutolol (Levatol)
beta and alpha antagonists?
Labetalol (Normodyne)
Carvedilol (Coreg)
two types of metoprolol salts?
Lopressor – immediate release 2x/d
Toprol – extended release 1x/d
what is the beta and alpha antagonist that has 2 salt forms?
carvedilol
selective vs. nonselective beta blockers?
- Get greatest effect on BP through beta 1 effect. So just want to block beta 1 receptors (selective)
- Nonselective beta blockers block beta 1 & 2 equally (ex. Propranolol)
- Selective beta blockers block beta 1 more than beta 2 at lower doses. Once dose gets high enough loose selectivity
classic selective B1B? when do we use them?
Metoprolol & Atenolol
- Beta 1 selective beta blockers are better if have DM, asthma or peripheral vascular disease
- These diseases made worse by beta 2 blockade
- If patient has a contraindication & NEEDS a beta blocker better to go with selective
newest B1B? MOA?
nebivolol
- vasodilates** extra compared to others
- So lowers BP and decreases PVR leading to fewer side effects with this beta blocker
what is special about esmolol? what it is used for?
- IV beta blocker, given as a continuous infusion (hospital drug)
- Beta 1 selective & rapidly metabolized
- Used for intra and post op HTN and HTN emergencies especially when tachycardic
- B/c rapidly metabolized when turn on get a quick effect, if decrease BP too much turn it off and it is gone quickly
What are BB good for?
- add on for mild to moderate HTN
- HTN + another problem that BB will help (angina, CAD, Hx MI, CHF, migraines, anxiety)
MOA of alpha receptor blockers?
- Block alpha 1 receptors in arterioles and venules (dilation of vessels).
- Work better in upright position than supine and so when change position can get orthostasis (orthostatic hypotension)
- Sodium and water are retained, usually need a diuretic when use these (one of the reasons not used alone)
ADRs of alpha receptor blockers?
- Orthostatic hypotension
- Profound first dose effect, wears off over time. Give first dose at bedtime and make it small
- More if volume depleted (on a diuretic)
- Dizziness, palpitations, HA, edema and fatigue
Available alpha receptor blockers for HTN?
Prazosin (Minipress)
Doxazosin (Cardura)
Terazosin (Hytrin)
pt that will benefit from alpha blockers?
- Men with prostate enlargement (BPH). Alpha blockers treat BPH too.
- Work better when use with other anti-HTN drugs than when used alone, so it must be a second or third line drug
- Often put on a diuretic first then add a alpha blocker. Diuretics prevent the edema caused by the alpha blockers
