Lecture 1 - Antihypertensives Flashcards
List some thiazide diuretics
hycrochlorothiazide
chlorthalidone
List some loop diuretics
furosemide
ethacrynic acid
List a potassium sparing diuretic
spironolactone
List some ACEi’s
enalapril
fosinopril
List some ARB’s
losartan
candesartan
List some vascular CCB’s (calcium channel blockers)
nifedipine - long-acting
amlodipine
List some cardiac CCB’s (calcium channel blockers)
verapamil
diltiazem
List some B blockers
propranolol
metoprolol
List some alpha 1 receptor antagonists
prazosin
List some alpha 2 receptor agonists
clonidine
List some vasodilators
hydralazine
minoxidil
nitroprusside
What is the formula for BP?
BP = CO x TPR
What does CO (cardiac output) depend on?
- venous return
- venous tone
- blood volume
- heart rate
- contractility
What does TPR (total peripheral resistance) depend on?
- resistance vessel diameter
- arterial tone
What are chronic increases in BP usually due to?
normally due to increased arterial resistance
-total peripheral resistance (TPR)
90% is ______ hypertension
essential
10% has a _______ cause
definable
What OTC & Rx drugs can cause hypertension?
- estrogens (oral contraceptives)
- NSAIDs
- antidepressants, cyclosporin, amphetamines (stimulants)
- decreased compliance
What conditions can cause hypertension?
- renal artery stenosis (renovascular hypertension)
- coarctation of the aorta
- phaeochromocytoma (catecholamine secreting tumor), primary hyperaldosteronism
What are the three major compensatory responses to a decrease in blood pressure?
1) Decreases RPP (renal profusion pressure)
Increase sodium retention
2) RAAS
Aldosterone
3) SNA (sympathetic nervous activity)
norepinephrine
List some potential causes of a drop in BP?
- hypovolemia (hemorrhage, dehydration)
- postural (orthostatic hypotension)
- heart failure
- antihypertensive
What does an increase in SNA do to raise BP??
increase HR
increase ionotropy (muscle contraction)
increase venous preload
*All 3 increase CO
What does an increase in RAAS do?
increase venous preload -leads to increased CO increase arterial afterload -leads to increased TPR increase sodium retention in the kidney -leads to increased blood volume
Non-pharms for hypertension?
- sodium restriction
- weight loss
- exercise
- reduced alcohol intake
- smoking cessation
- relaxation
List the 1st line pharmacological treatments for hypertension
- ACEi’s, ARB’s
- diuretics
- CCB (calcium channel blocker)
- B blocker (but not in uncomplicated hypertension)
List the other pharmacological treatments for hypertension
- alpha 1 antagonist
- alpha 2 agonist
- vasodilator
____ used to be first line single therapy in uncomplicated hypertension (but this is changing now!)
thiazides
Thiazides:
Dose response for blood pressure lowering is relatively ____
flat
Thiazides:
Increasing dose produces little ______ in effect
improvement
Thiazides:
What complications can increase with dose?
hypokalemia glucose intolerance increased LDL (low density lipoprotein)
Loop diuretics:
Useful in ____ impairment and edematous states
renal
GFR < 50 mL/min
Loop diuretics:
Greater diuretic but weaker ______
antihypertensive
Loop diuretics:
Extreme _____ imbalance possible
electrolyte
Loop diuretics:
____ onset and _____ acting
fast
short
Loop diuretics:
Are they a good choice for long term treatment?
No
Potassium sparing diuretics:
Useful with ____ to decrease potassium loss
thiazides
Potassium sparing diuretics:
Are effective when increased BP due to ??
mineralocorticoid excess
Major problem with thiazides and loop diuretics?
electrolyte problems
- hypokalemia
- hypercalcemia (thiazides)
- hypocalcemia (loop)
Problems with thiazide diuretics?
- decreased insulin release (hyperglycemia)
- increased LDL levels (bad)
- increased incidence of erectile dysfunction
- vascular volume contraction (decrease blood volume)
Problems with loop diuretics?
- deafness (if given with aminoglycoside antibiotic)
- vascular volume contraction (decreased blood volume)
Problems with potassium sparing diuretics?
- hyperkalemia
- estrogenic effects - gynecomastia, impotence
Where do thiazide and loop diuretics work?
they decrease sodium retention in the kidney
What are the 2 renin angiotensin system inhibitors?
ACEi’s
ARB’s
MOA of ACEi’s
- decrease AII levels (angiotensin 2)
- decrease TPR
- decrease aldosterone
- increase in plasma potassium
MOA of ARBs
- blocks AII receptors (angiotensin 2)
- decrease TPR
- decrease aldosterone
- increase in plasma potassium
List some points about renin angiotensin system inhibitors (ACEi’s and ARBs)
- effective even with low renin levels
- metabolically neutral (glucose, lipids not altered)
- first line in hypertension, CHF and or diabetic nephropathy
- little or no reflex increase in cardiac output
- possible problems
- rash, cough (ACEi’s), hyperkalemia, proteinuria, angioedema
What is currently the first line single therapy in uncomplicated hypertension?
renin angiotensin system inhibitors (ACEi’s and ARBs)
ACEi’s and ARBs are _____ in benefits and side effects
similar
When do you recommend renin angiotensin system inhibitors ?
- heart failure
- left ventricle dysfunction
- post myocardial infarction
- diabetes
- systolic dysfunction
- proteinuria (chronic kidney disease)
*suggested these agents may have benefits in addition to their blood pressure lowering
Renin Angiotensin System Inhibitors (ACEi’s and ARBs):
____ reflex tachycardia
little
- baroreceptors reset
- decrease in NE release
Renin Angiotensin System Inhibitors (ACEi’s and ARBs):
Contraindicated in _______
pregnancy
List the medications involved in CHF
ACEi, B-Blocker, diuretic, digitalis:
- low plasma potassium increases digitalis toxicity
- increased aldosterone may decrease Pk
- diuretic may decrease Pk
- ACEi and B-blocker may increase Pk
*Pk = plasma potassium
Where do ACEi work?
- inhibit angiotensin converting enzyme
- decrease RAAS (because ACEi’s are renin angiotensin aldosterone system inhibitors)
- decrease sodium retention
- decrease arterial afterload
- decrease venous preload
Describe calcium channel blockers
Block L-type calcium channels - but really two sub-classes:
- one predominately vascular
- one predominately cardiac
Vascular calcium channel blockers are known as ________
dihydropyridines
Give examples of vascular calcium channel blockers (dihydropyridines)
amlodipine
nifedipine
Give examples of vascular and cardiac (non-dihydropyridines)
verapamil
diltiazem
Dihydropyridines (nifedipine and amlodipine):
Describe them
- greater affinity for vascular calcium channels
- used for angina, Raynauds and hypertension
- reduce TPR without apparent cardiac actions
- diuretics may block nifedipine effects on BP
- used for hypertensive crisis
What are non-dihydropyridines used for?
used in hypertension if also concern about heart rate control in atrial fibrillation or in patients with angina
Describe diltiazem
- used to treat angina and hypertension
- both vascular and cardiac effects
Describe verapamil
- blocks mainly in the heart (limited vascular tissue)
- should not be combined with a beta blocker (both drug classes block AV node)
- contraindicated in heart failure
Why can’t you combine Verapamil with a beta blocker?
it will slow the heart way too much since both drug classes block AV node (both drugs decrease HR)
____ _____ blockers are another first line single therapy in uncomplicated hypertension
calcium channel
When are calcium channel blockers useful?
Where beta blockers are contraindicated
Calcium channel blockers are not contraindicated in ??
obstructive airway diseases
or
diabetes
Why are calcium channel blockers useful in african americans?
Because they are resistant to ACEi
List some more points about calcium channel blocker?
- low incidence of side effects - but expensive
- neutral metabolic profile
Calcium channel blockers:
What are the adverse effects related to?
Vasodilation
Calcium channel blockers:
adverse effects?
headache
flushing
edema
constipation
Calcium channel blockers can be used in the presence of what other coexisting conditions?
- angina pectoris
- Raynaud’s phenomenon
- asthma or COPD
Where do dihydropyridines work?
-decrease arterial afterload
Where do non-dihydropyridines work?
- decrease ionotropy (muscle contraction)
- decrease HR
Propranolol and metoprolol are ??
beta-blockers
MOA for beta blockers
unknown but they work
Are beta-blockers recommended as single therapy?
No
- good as a second drug to block reflex activation of the heart by SNS
- not recommended as single therapy in uncomplicated hypertension
- given for hypertension when concomitant diseases also benefit
- post-MI
- heart failure
Problems with beta blockers?
- NOT metabolically neutral - may increase TGs/decrease HDLs
- avoid sudden withdrawal
- increased incidence of ED
- increased incidence of type 2 diabetes
- doesn’t protect against stroke
When would you avoid beta blockers?
asthma, COPD, peripheral vascular disease, insulin dependent diabetes (use with caution)
When are beta blockers a good choice?
In patients with:
- glaucoma
- supraventricular arrhythmia
- heart failure (ALWAYS)
- MI
- angina
Where do beta blockers work?
- decrease RAAS
- decrease isotropy
- decrease HR
Prazosin is an _______
alpha 1 antagonist
Prazosin:
Not effect as a single agent for chronic _______
hypertension
What does prazosin do?
- vasodilates arteries and veins
- decreases insulin resistance (good)
Where is prazosin useful?
in BPH (benign prostatic hyperplasia)
Prazosin:
Shown to decrease nightmares in _____
PTSD
Problems with prazosin?
- fluid retention with long-term treatment (give with a diuretic)
- first dose effect (initial large drop in BP)
- orthostatic hypotension
Where does an alpha 1 blocker work?
-decreases arterial afterload therefore decreases TPR
Clonidine is an ________
alpha 2 agonist
Describe clonidine
- acts on central vasomotor centers
- decreases sympathetic nerve activity from CNS
- autonomic system remains intact - reflexes intact
- orthostasis rare
- give as two unequal doses (high dose at night to cause sedation)
- limited use due to sedation and dry mouth
- rebound hypertension upon rapid cessation of drug
Where do alpha 2 agonists work?
decrease SNA (sympathetic nerve activity)
- decrease arterial afterload
- decrease venous preload
- increase isotropy
- increase HR
Are vasodilators used alone for chronic blood pressure lowering?
No
What is an example of a vasodilator?
hydralazine
minoxidil
sodium nitroprusside
Describe hydralazine?
- greater arteriolar effect
- give with B-blocker and diuretic
- can be used in pregnancy (safe and works)
Problems with hydralazine?
- may cause lupus like syndrome
- may increase SNA - myocardial stimulation
- headache, flushing nausea, hypotension, tachycardia, angina pectoris
Describe Minoxidil (vasodilator)
- arteriolar dilator
- give with B blocker and diuretic
- for severe hypertension (refractory)
- may cause pericardial effusion
- hirsutism (growth of unwanted male pattern hair in women) - problem?
- *this drug is now marketed for male pattern baldness
- problems similar to hydralazine
Describe sodium nitroprusside
- venous and arteriolar dilator
- rapid onset (1 min)
- rapid offset (5 min)
- blood pressure titratable
- for hypertensive encephalopathy
- potential for cyanide toxicity
- If it used for more than a day or two, cyanide toxicity is a worry
Where do arterial vasodilators work?
decrease arterial afterload
Where do venous vasodilators work?
decrease venous preload
Where do arterial and venous vasodilators work?
- decrease arterial afterload
- decrease venous preload
Target BP for patients below 80 years of age if uncomplicated
140/90 mmHg or less
If patient has other conditions like atherosclerotic cardiovascular disease, diabetes mellitus, chronic kidney disease (proteinuria) it is better if target BP is ??
below 140/90
What do younger patients respond best to?
ACEi, ARB or B blockers
*But B blockers may be inferior to protect from stroke
What do black patients and elderly patients respond best to?
- respond best to thiazide diuretics or long-acting CCB
- however, patients may have other indications (heart failure, post-MI) suggesting need for ACEi or ARB
