Antihypertensive drugs Flashcards
Formula for BP?
CO x PVR
CO=SV x HR
SV= myocardial contractility and venous return
Venous return= blood volume, venous capacitance tone
Short term regulate BP?
baroreceptor reflex
Long term regulate of BP?
Kidney, Renin-Angiotensin-Aldosterone System
RAAS?
Renin increases ANG II, cause vasoconstriction which raises BP
ANG II also increases aldosterone, salt and water retention, raise BP
Diuretic acute antihypertensive?
increase sodium and water excretion by the kidney, decrease blood volume, decrease CO
Diuretic chronic antihypertensive?
prolonged diuretic use over time CO returns to normal, decrease Na in smooth m cells, decrease PVR
takes about 6-8 weeks
How do diuretics enhance the effects of other drugs?
some drugs cause Na retention, this causes release
Most potent diuretic?
Loop
Most useful diuretic to treat hypertension?
thaizide, first line therapy
Decrease CV events and mortality
When use loop diuretics for hypertension?
reduced renal function
severe hypertension when drugs that retain Na are being used
disadvantage to treat hypertension with loop?
short half life, dont work as well as equally potent dose of a thiazide
Effect of thiazide and loop on serum K levels?
decrease
K sparing use for hypertension?
to counteract the K loss from loop and thiazides
Spironolactone- use with other agent
Eplerenon- use alone or with other agent
Compelling indication for use
Drugs and new onset diabetes?
Diuretics and beta blockers have increased risk
calcium channel blockers neutral or protective
ACE inhibitors and angiotensin receptor antagonists lower risk for new onset diabetes
Use Esmolol to treat chronic hypertension?
no because its an IV drug
Propranolol antihypertensive? (heart)
nonselective beta blocker, decrease heart rate, decrease contractility, decrease cardiac output
Some beta blockers have intrinsic sympathomimetic activity?
they are partial agonists to beta receptor, activating the receptor but not to full potential as beta agonist
Propranolol on kidney?
decrease renin, decrease ang II, decrease aldosterone
Propranolol on CNS?
decrease sympathetic discharge
Not use a beta blocker?
2nd and 3rd degree AV block, asthma, increased RR interval
Adverse effects of beta blockers?
decrease response to exercise bradycardia AV conduction abnormalities beta 2 on smooth muscle in lungs nightmares, lassitude, mental depression, insomnia (CNS effects) (lipid soluble) sexual dysfuntion, increase triglycerides and decrease HDL glucose intolerance unopposed vasoconstriction
long term therapy beta blockers?
up regulate of receptors, rebound hypertension
Verapamil is?
calcium channel blocker, works on smooth m and cardiac muscle
non-dihydropyridines
Nifedipine is?
calcium channel blocker, works only on vascular smooth muscle
dihydropyridine
CCB effect on vasculature?
Block voltage dependent Ca2+ channels on vascular smooth muscle cells in arteries which is important for contraction (relax smooth m, decreases peripheral resistance), not affect venous beds much
If PVR decreases what happens to the heart? BP?
reflex tachy
BP goes down
Will there be reflex tachy with verapamil?
no, decrease cardiac output, decrease HR, decrease conduction, decrease force of contraction, no change in PVR
First line therapy for hypertension with a compelling indication?
Calcium channel blockers
Adverse effects of Verapamil and diliazem?
sinus bradycadria, AV block, exacerbation of heart failure or pulmonary edema
Dihydropyridines adverse effects?
Will lower PVR but will cause reflex tachy
What will cause nidedipine induced peripheral edema?
increase in hydrostatic pressure in the precapillary sphincter
useful agent to combat the nidedipine induced peripheral edema?
ACE inhibitor
Angiotensin II effects?
Adrenal- aldosterone release- Na and H2O (increase volume, increase BP)
Arterioles/venules- vasoconstriction (increase PVR ,increase BP)
facilitate sympathetic activity (increase BP)
Ang II on blood pressure?
rise BP
Ang II effects?
hypertrophy/hyperplaisa of vascular smooth muscle cell, mesagnial cells, cardiac myocytes, cardiac fibroblasts
mycocyte apoptosis, inflammatory mediator, helps regulate GFR
block effects of Ang II?
ACE inhibitor will block angiotensin converting enzyme, Ang I to Ang II conversion (decrease amount of Ang II made)
-will also block inactivation of bradykinin
angiotensin receptor blocker blocks the receptor (decrease effect of Ang II)
renin inhibitor blocks angiotensinogen to ang I
Antihypertensive actions of ACE inhibitors?
decrease ang II, increase bradykinin
dilate arterioles
decrease PVR
Decrease Ang II does what?
decrease aldosterone, decrease sympathetic activity
Why does ACE inhibitor not cause large drop in aldosterone levels?
other things sim aldosterone release
ACEI MOA?
decrease PVR
small effect HR, CO and blood volume
ACEI clinical use?
first line for hypertension with compelling indication
Acute MI/ ACEI?
administer within 24 hrs post MI to decrease mortality
If BP is low, give ACEI?
no
ACEI and diabetic nephropathy?
benificial by decreasing bp and benificial without hypertension too
primary cause of kidney failure?
diabetes
Ang II mainly changes what arteriole in the kidney?
the efferent arteriole, cause dilation
cause intraglomerular hydrostatic pressure to decrease
less damage, decrease proteinuria
Adverse effect ACEI?
Functional renal insufficiency
Predisposing conditions for functional renal insufficiency?
microvascular renal disease renal artery stenosis and a solitary kidney bilateral renal artery stenosis dehydration heart failure nonsteroidal antiinflammatory drug use
How to maintain GFR with renal artery stenosis?
Ang II, constrict efferent arteriole, increase glomerular hydrostatic pressure, maintain GFR
Large decrease in GFR does what to serum creatinine?
go way up, esp in bilateral renal artery stenosis
Diabetes mellitus and kidney disease?
give right amount ACEI, renoprotective
give too much, bad for kidneys
ACEI adverse?
hypotension (initiation of therapy if volume depleted)
Hyperkalemia- renal insufficiency, combo with K sparing diuretics or K supplements
Hematologic effects
Angioedema (bradykinin, substance P)
Cough (bradykinin, substance P)
Contraindications ACEI?
prior history angioedema
Absolute contraindications ACEI?
bilateral renal artery stenosis
renal artery stenosis in sole kidney
teratogenic in 2nd/3rd trimester
ARB?
only blocks the ang II receptor
Aliskiren?
Renin inhibitor, only inhibit bradykinin
ACEI vs ARB/Aliskiren?
ACEI been around longer, prevent destruction of bradykinin
ARBS/Aliskiren- don’t affect bradykinin
Ang II receptor antagonist MOA?
AT1 receptor anagonists blocks effects of Ang II
alternative to patients who cannot tolerate ACE inhibitors
adverse effects ARB?
renal insufficiency, hypotension, hyperkalemia, bilateral renal artery stenosis (contraindicated)
angioedema, low incidence of cough
Aliskiren?
inhibit renin
similar to ACEI/ ARB (theurpeutic and side effects)
no effect on bradykinin
monotherapy or in combo with other agents
Contraindication of use a beta blocker?
2nd/3rd degree AV block
Active asthma
RP interval > 0.24
other Adverse effects of CCB?
Constipation (Flushing, headache, dizziness, peripheral edema)
Clinical use of Angiotensin II receptor antagonist (ARB)?
alternative agent in patient that can not tolerate ACE inhibitors
Clinical use of Aliskiren?
Hypertension ( mono or combines)
