Antihypertensives Day I Flashcards
lifetime risk for HTN
90%
HTN is a risk factor for what diseases
heart dz
stroke
heart failure
renal dz
examples of how HTN develops:
sex, stress, genetics, sympathetic stimulation, CO, renal sodium retention, GI - obesity, alcohol, micronutrients, insulin, aldosterone, age
risk factors for HTN
smoking, BMI >30, physical inactivity, dyslipidemia, DM, renal dysfunction, men >55 women >65, family hx of premature CV dz
ages of men vs women for risk factors of HTN
men >55 women >65
BMI of what increases risk of HTN
> /=30
2 types of HTN
essential & secondary
what is essential HTN
natural process causing HTN - 90% of cases
usually a hereditary component
what is secondary HTN
caused by other disease state: chronic kidney dz, renovascular dz, cocaine, tumor, natural supplements
what is systolic BP
number that represents the cardiac contraction
what is diastolic BP
number that represents nadir (lowest point) aka filling of heart
what is cardiac output
amount of blood pumped out by ventricles (represents SBP)
what is TPR
total peripheral resistance
sum of peripheral resistance in peripheral vasculature (represents DBP)
equation for BP
BP = CO x TPR
2 major mechanisms of pathogenesis of HTN
- increase in peripheral resistance
2. increased CO
how is increased peripheral resistance a mechanism of pathogenesis of HTN
functional vascular constriction/structural vascular hypertrophy
-over activity of sympathtetic nervous system (NOR, EPI) & genetic components
how is increased cardiac output a mechanism of pathgenesis for HTN
- increased preload - increased fluid, excess sodium intake, renal sodium retention
- venous constriction - excess RAAs stimulation, sympathetic nervous system overactivity
majority of pts will require how many meds to control HTN
at least two
life style modifications for HTN
stop smoking, weight loss, DASH diet, dietary sodium reduction, increased physical activity, limit alcohol (1/female, 2/male)
what is the most effective life style modification to lower HTN
weight loss - pts wont change everything at once so pick this major one to focus on and give small goals at a time
firstline options for HTN (4)
- thiazides
- CCB’s
- ACE-I
- ARBs
which of the first line choices for HTN is best?
none, all of the four classes are equally efficacious
which of the first line drugs are not the best choice for blacks
ACE-I and ARBs - response is completely different than other races
patients with HTN that also have DM or renal dz first line choices
ACE-I or ARBs –> even in blacks
can ACE-I and ARBs be used together
NO - increases renal failure
if pt has a cardiac hx and HTN what else can you use
beta blocker
3 options for treatment approach to HTN
- 1 drug - max out dose before adding next drug
(used if pt absolutely does not want to be on more than one drug) - 1 drug then add 2nd drug prior to maxing out doses, then 3rd
(used most - bc most pts need 2 drugs to fix HTN, so start asap with 2) - start 2 drugs only if SBP >160 and DBP is >100 - max out doses then 3rd drug
(for exam purposes only - in real life, still would start only one at a time in case of rxn you know which drug is causing it)
3 examples of thiazide diuretics
HCTZ, chlorthalidone, metolzaone
MOA of thiazide diuretics
inhibit sodium reabsorption in the distal tubule
which thiazide diuretic is the most potent
metolzaone - rarely used except for lasix resistance, only one dose needed
where do thiazide diuretics work in the kidney
DCT
typical dose of thiazide diuretics
25mg most efficacious
can start at 12.5 but doesn’t do much
50mg - increases side effects with little increase in efficacy
ADE of thiazide diuretics
orthostatic hypotension (minimal in comparison)
electrolyte abnormalities
photosensitivity
increase in urination
what electrolyte abnormalities come with thiazide diuretics
decrease: K, Na
increase: Ca, uric acid, glucose (minimal)
precautions (not CI’s of thiazide diuretics)
- caution in sulfa allergies (contraindication if anaphylaxis otherwise, monitor)
- ineffective in pts with severe renal dz CrCl
examples of ACE inhibitors
benazepril, captopril, enalapril, fosinopril, lisinopril (main one used)
= the ‘prils
MOA of ACE inhibitors (3)
inhibits ACE to block production of AT II
inhibits breakdown of bradykinin (vasodilator)
dilates the efferent arteriole of kidney - positive effect - good for renal or DM pts
benefits of ACE-I on bradykinin (1)
disadvantages of ACE-I on bradykinin
benefit: lowers BP
disadvantage: inflammatory mediator = increase inflammation = cough
place in therapy for ACE inhibitors
a first line drug for HTN
first line option in CKD
used in CHF
dose of ACE-I
often 1/day sometimes twice/day esp in CHF
what labs to monitor with ACE-I
serum K+ and sCr w/i 4 weeks of initiation or dose increase
-normal to see a benign increase in creatinine - kidney getting used to drug (should only be
what is angioedema
swelling of face lips eyes throat = life threatening = can’t use ACE-I ever again, questionable to use ARBs due to potential for crossreactivity
ACE-I and salt substitutes
cannot take salt substitutes bc will increase K+ even more (salt substitutes use K instead of Na)
ADE of ACE-I
- cough - up to 20% ( a good amount of pts) due to bradykinin incr
- angioedema - rare
- hyperkalemia - esp with CKD or DM
- other: neutropenia, agranulocytosis, proteinuria, glomerulonephritis, acute renal failure
CI’s of ACE-I
- pregnancy
- previous angioedema
- bilateral renal artery stenosis - renal toxicity
DI’s of ACE-I
- K+ supplements
- K+ sparing diuretics
- NSAIDS - can incr BP on its own by constricting prostaglandins in afferent arteriole of kindey - if 1/mo OK, but not if 800mg 3x/day
dosing of ACE-I
most 1/day - can be dose more than 1/day to incr efficacy
except captopril which is 2-3/day
which ACE-I is a prodrug and of what
enalapril is a prodrug of enalaprilat
which ACE-I is only one available in IV form
enalapril
most commonly used ACE-I and dosing
lisonpril - 10-40mg daily
which ACE-I decreases absorption if taken with food
captopril
least used ACE-I and why
captopril - multiple dosing/day and cant take with food
what does ARB stand for
angiotensin II receptor blockers
examples of ARBs
irbesartan, losartan, olmesartan, valsartan
= ‘sartans
which ARB can cause chronic diarrhea
olmesartan
MOA of ARBs
inhibits angiotensin II at its receptor sites
(AT II is made but blocked)
does not inhibit bradykinin
ARBs place in therapy
one of first line drugs in HTN
first line option for CKD
used in CHF
dose of ARBs
once daily
labs to monitor with ARBs
potassium
ADE of ARBs
hypotension, orthostatic hypotension, angioedema, hyperkalemia, dizziness
CIs of ARBs
- pregnancy
- caution in renal artery stenosis (ACE-I’s is absolute CI)
- technically can be used if angioedema present with ACE-I but can be cross reactive so better to just pick something else
DIs of ARBs
K+ supplements
K+ sparing diuretics
NSAIDS
what is the only drug in the renin inhibitor class
aliskiren
MOA of Aliskiren
first oral agent that directly inhibits renin
role in treatment for aliskiren
unclear with HTN bc new drug
downside of aliskiren
increased SEs and decreased efficacy
ADRs of aliskiren
ADRs are similar to ACE-I and similar to ARBs = don’t use together
is aliskiren used as monotherapy or combo therapy
either
CCBs
calcium channel blockers
2 categories of calcium channel blockers
- non dihydropyridines
2. dihydropyridines
examples of nondihydropyridines
verapamil diltiazem (has lots of formulations that cannot be interchangeable)
examples of dihydropyridines
amlodipine (most used)
nifedipine (2nd most)
felodipine
isradipine
role of calcium channels in the body
- when channels are opened: causes calcium influx into smooth muscle (cardiac and peripheral vasculature)
- results in activation of intracellular calcium with ultimately leads to muscle contraction (activates myosin and actin)
MOA of CCBs
inhibits calcium influx into cells to prevent muscle contraction
inhibition at cardiac smooth muscle (decreases ionotropy & chronotropy)
inhibition at vascular smooth muscle - vasodilation
MOA of dihydropyridines
inhibits calcium influx into vascular smooth muscle - not the heart = peripheral vasodilation = pooling in feet and legs = edema
**may be used in CHF bc doesn’t work on the heart
non dihydropyridines MOA
inhibits calcium influx into cardiac smooth muscle
- decrease rate and force of contraction
- can’t be used in CHF
CCB place in therapy
first line option for HTN
other uses of CCBs
- diltiazem and verapamil - supraventricular tachycardia, atrial fibrillation
- verapamil - migraine prophylaxis
ADE of all CCB
hypotension
ADR of non dihydropyridines
- constipation **
- bradycardia
- exacerbation of CHF
- heart block
- gingival hyperplasia
ADEs of dihydropyridines
- peripheral edema - worst with nifedipine - dose effect (incr with dose)
- reflex tachycardia
- flushing
- H/A
DI with verapamil -
metabolized by C P450 3A4 and also inhibits
dihydropyridines are useful for pts with
isolated increased SBP
Clevidipine I (IV only) is CI in
soy or egg allergy
1 in how many adults have HTN
1 in 3 adults
example of loop diuretics
furosemide (lasix)
bumetanide
torsemide
**not first line for HTN, just other types of diuretics
how do thiazide diuretics and loop diuretics help HTN
these do not lower blood pressure
they are good at fluid removal (which indirectly helps lower BP)
MOA of loop diuretics
- inhibits active transport of NA Cl and K in thick ascending lim of loop of Henle causing excretion of these ions
- collecting duct excretes more water in response
place in therapy for loop diuretics
- CHF
- Edema
- HTN - not commonly used for
ADE of loop diuretics
- electrolytes abnormalities
- dehydration (peeing too much)
- ototoxicity (if combined with other ototoxic drug - aminoglycocides = bad)
- increase SCr (if pt is dehydrated, decr dose)
what electrolyte abnormalities do loop diuretics cause
decr: K, Na, Ca, Mg
incr: uric acid (gout pts)
dose of furosemide (lasix)
usually 1/day but can be 2/day
if 2/day: every 6 hours (laSIX) both doses before 4 pm (9a & 3p) so that by bedtime, peeing slows
precautions with loop diuretics
gout pts
sulfa allergic pts
nephrotoxicity
2 types of potassium sparing diuretics
- aldosterone receptor blockers (NOT ARBs)
2. Potassium Sparing Drugs
examples of aldosterone receptor blockers
- spironolactone
2. eplerenone
MOA of aldosterone receptor blockers
competes with aldosterone prevents sodium reabsorption and potassium excretion (dependent on presence of aldosterone)
examples of potassium sparing drugs
triamterene
amiloride
moa of potassium sparing drugs
block sodium reabsorption and potassium excretion, effect independent of aldosterone***
where do K sparing diuretics work
collecting duct
K+ sparing diuretics place in therapy
HTN: in combo with thiazide (not usually monotherapy) not first line Spironolactone - class IV heart failure (also III) - mortality benefit
ADE of K+ spring diuretics
-specifically spironolactone
Hyperkalemia (caution in renal failure pts)
spironolactone - gynecomastia, menstrual irregularites
use of eplerenone
eplerenone - more selective thus less side effects but not used much because most of the research data is with spironolactone
