Earley: Antihypertensive Agents Flashcards
Define the following:
Normal BP Prehypertension HTN Hypertension stage 1 Hypertension stage 2
120/80 120-139/81-90 >140/90 Stage 1: 140-159/90-99 Stage 2: >160/100
What BP should you shoot for in patients less than 60 years old with hypertension?
<140/90
What BP should you shoot for in patients greater than 60 years old with hypertension?
<150/90
What BP should you shoot for in patients with diabetes?
<140/90
This form of HTN makes up 85-90% of cases
essential hypertension
What types of diseases/conditions cause secondary hypertension?
sleep apnea drug-induced chronic kidney disease primary aldosteronism renovascular disease chronic steroid therapy pheochromocytoma coarctation of the aorta thyroid/parathyroid disease
What are some factors contributing to essential hypertension?
obesity stress lack of exercise diet alcohol intake smoking
What is the prevalence of HTN in the US? What population is it most common in?
~30%
highest prevalence in the elderly
What are some complications of HTN?
cardiovascular disease: stroke, atherosclerosis, heart failure
renal damage
retinal damage
**starting at 115/75mmHg, risk doubles each increase of 20/10mmHg
What are some lifestyle modifications that can help treat hypertension?
reduce weight to normal BMI (can shave off 5-10mmHg/10kg loss) DASH eating plan (8-14mmHg) restrict dietary sodium (2-8mmHg) increase physical activity (4-9mmHg) reduce alcohol consumption stop smoking
Explain the DASH diet for HTN patients
fruits and veggies and low fat dairy
reduce sodium
whole grains, poultry, fish, nuts
reduce red meat, sugar, total saturated fat and cholesterol
What is mean arterial pressure?
dependent on CO * PVR
What are the three types of diuretics for HTN treatment?
thiazides *most commonly used
loop diaretics: furosemide, bumetanide **for severe HTN and heart failure
K+ sparing diuretics: spironolactone, amiloride, triamterene **reduce heart failure mortality
How do diuretics work?
increase Na+ and water excretion, thus decrease CO due to decreased blood volume
after 6-8 weeks, CO will return to normal but PVR will decline
typically lower BP by 10-15mmHg in most patients
This is the most commonly used diuretic
Thiazides
Ex: hydrocholorthiazide, chlorothiazide
What are some toxic effects of diuretics?
K+ depletion (except for K+ sparing diuretics) Mg+ depletion impaired glucose tolerance increased serum lipids gout (increased uric acid)
What can minimize K+ depletion while taking a diuretic?
limiting Na+ intake
This is an agent that prevents adrenergic transmission
reserpine
**used infrequently
This is a selective alpha-1 adrenergic receptor blocker
prazosin
terazosin
doxazosin
This is a beta adrenergic blocking agent
propranolol
These anti-HTN agents act directly on the CNS
clonidine
methyldopa
How does reserpine work to decrease blood pressure?
depletes neurotransmitters in the nerve endings of the brain and periphery - depresses sympathetic nervous system centrally and peripherally and decreases HR, contractility and PVR
Adverse effects of reserpine?
depression insomnia nightmares orthostatic hypotension impotence
**used infrequently
How do selective alpha 1 antagonists, like prazosin work?
block alpha 1, decrease vasoconstriction, decrease peripheral vascular resistance and decrease BP
What are some adverse effects of prazosin?
1st dose phenomenon (sudden severe fall in BP)
dizziness
headache
When are alpha 1 selective antagonists used?
used in stage 1 and stage 2 HTN in combo with a diuretic and a beta blocker
How do beta blockers work?
block cardiac B1 receptors to decrease CO
block renal B1 receptors to lower renin and PVR
Non-selective beta blocker
Main effect is to decrease HR
propranolol
What are some adverse effects of propranolol and other non-selective beta blockers?
bradycardia aggravates asthma (blocks airway - prevents smooth muscle relaxation)
When are beta blockers used?
used in stage 1 or 2 HTN alone or in combo with a diuretics and/or a vasodilator
Which drugs interact unfortunately with propranolol?
verapamil
diltiazem
digitalis
List two beta blockers that are cardioselective for beta 1, and are the most widely used beta blockers for HTN
metoprolol
atenolol
Combined nonselective beta and alpha-1 blocker. Beta blocking action is more prominent.
Used i.v. for hypertensive emergencies
labetalol
How does alpha-methyldopa decrease BP?
alpha methyldopa is metabolized to alpha methyl NE, which is an alpha2 agonist, so it suppresses catecholamine release at nerve terminals; this decreases PVR and HR
Adverse effects of alpha-methyldopa and clonidine?
sedation dry mouth drowsiness impotence bradycardia rebound HTN when you withdraw from it
When is clonidine used?
stage 1 and 2 HTN
When is methyldopa used?
for HTN during pregnancy
List three drug classes that work as vasodilators
calcium channel blockers (nifedipine)
direct acting vasodilators (sodium nitroprusside)
K+ channel openers (minoxidil)
How do calcium channel blockers work?
inhibit Ca++ entry through L-type voltage gated Ca++ channels
This Ca++ channel blocker is a phenylalkylamine
verapamil
This Ca++ channel blocker is a benzothiazepine
diltiazem
This Ca++ channel blocker is a dihydropyridine
amlodipine
Selective blockade of vascular Ca2+ channels
Main effect: vasodilation–>lower PVR–>lower BP
amlodipine
Adverse effects of amlodipine:
flushing
ankle edema
reflex tachycardia
When is amlodipine used?
in HTN (esp for African Americans) angina
Mechanism: Blockade of Ca2+ channels in the vasculature, heart muscle and AV node
Main effects: same as amlodipine group
Adverse effects: Similar to amlodipine except that they do not cause reflex tachycardia
verapamil
diltiazem
You should be cautious when prescribing verapamil and diltiazem with what drugs?
when used with beta blockers or digitalis, can cause AV block
**this is not the case for amlodipine
This is a direct acting vasodilator, which increased NO and increases cGMP
Sodium nitroprusside
How does sodium nitroprusside work?
generates NO which is a rapid acting venous and arteriolar vasodilator
Adverse effects of Na-nitroprusside?
reflex tachycardia
severe hypotension
possible cyanide poisoning
When is Na-nitroprusside used?
in hypertensive emergencies
This is a potassium channel opener which causes decreased BP
Minoxidil
How does Minoxidil, a K+ channel opener, decrease BP?
opens K+ channels –> smooth muscle hyperpolarization –> smooth muscle relaxation –> arterial dilation –> decreased PVR –> decreased BP
List some general drug classes that affect the renin-angiotensin-aldosterone system
ACE inhibitors: captopril, lisinopril
Ang II receptor blockers: losartan, valsartan, irbesartan
renin inhibitors
How do ACE inhibitors decrease BP?
decrease circulating levels of Ang II –> decrease PVR –> decrease BP
Adverse effects of ACE inhibitors?
skin rash
dry cough
hyperkalemia **when you activate the RAAS, you increase sodium retention and increase K+ excretion
When are ACE inhibitors used?
stage 1 and 2 HTN
CHF
Drug of choice in HTN patients with diabetes, because it does not have effects on plasma lipid levels
captopril
**and other ACE inhibitors
When should ACE inhibitors not be used?
during pregnancy!!
**also not very affective in African Americans
How do Ang II receptor inhibitors decrease BP?
selective block the Ang II receptor –> decrease PVR –> decrease BP
Adverse effects of Ang II receptor inhibitors?
no cough!! **could be an alternative to ACE inhibitors if not well tolerated
otherwise similar to ACE inhibitors
**also toxic to fetus
This is a renin inhibitor, which inhibits the conversion of angiotensinogen to Ang I; equally as effective as ACE inhibitors and ARBs
Aliskiren
Side effects of Aliskiren, a renin inhibitor?
diarrhea stomach pain heartburn cough rash dizziness fetal toxicity
**don’t use in patients with diabetes or CKD
Describe how you might approach the treatment plan for a patient with HTN
- implement lifestyle interventions
- set blood pressure goal and initiate BP lowering meds based on age, diabetes, and chronic kidney disease
- for people less than 60 yo, aim for a BP <140/90
- if non-black, try thiazide-type diuretics, ACEI or ARB or CCB alone or in combo; if black, try thiazide-type diuretics or CCB
What should you do if your patient is not reaching your goal blood pressure?
reinforce medication and lifestyle adherence add additional medication class not previously prescribed
What are 3 different strategies when starting a medication regimen for patients with HTN?
- start one drug, titrate to max dose, then add second drug
- start one drug, add second drug before achieving max dose on first drug
- begin with both drugs at the same time, as separate pills or a combo
Definition (AHA): BP > 140/90 mmHg (130/80 with diabetes and CKD) for patients prescribed 3 or more antihypertensive medications at optimal doses
or
BP controlled with 4 or more antihypertensive drugs
resistant hypertension
What percentage of HTN patients have resistant HTN?
up to 40% !!!
Adherence to HTN meds is higher for (blank) and/or lower number of doses per day
Adherence may be higher for (blank) and (blank) vs. diuretics and β-blockers.
Adherence to (blank) changes are even worse, ~10-20% for Na+ reduction.
single drug;
RAS and Ca++ channel blockers;
dietary
Review: which blood pressure meds should be used first for black patients?
thiazide type diuretic
Ca++ channel blocker
**ACE inhibitors & ARBs not particularly effective
