HTN Flashcards
Verapamil
aralkylamine CCB
contains basic tertiary amine required for activity and salt formation
marketed as racemate. S - enantiomer is more potent
MOA: acts on slow Ca channel (L channel) which slow AV conduction and sinus rate and increases PR interval
Effects: afterload (artery), contractilitly, BF. It reduces ventricular resistance and BP.
Has negative chronotropic and inotropic effects
Use: angina, atrial flutter, atrial fibrillation, PSVT, and essential HTN (oral med)
Metabolism: CYP 3A4 —> active metabolite (OND)
It is an inhibitor of CYP 3A4 and p-glycoprotein
preg category C
ADR: HA, dizzy, edema, constipation
DDI: drugs that can also inhibit 3A4, p-gp, Ca channels, and shorten QT interval
Diltiazem
Benzothiazepine CCB
cis entantiomer is active (has 4 stereoisomers)
higher affinity for vascular Ca channels than for myocardial or nodal channels
dilates peripheral arteries and arterioles
use: angina, artrial fibrillation, atrial flutter, PSVT, migraine, pulmonary HTN, and HTN
Following IV admin, there is a reflex response to inc HR and CO
Undergoes CYP 3A4 —> inactive metabolites (OOD, OND)
undergoes hydrolysis —> 50% active
it is an inhibitor of CYP 3A4 and p-gp
ADR: edema, HA, less gingival hyperplasia
Nifedipine
DHP CCB
does not have a basic N
1,4 ring is essential for activity
unsubstituted non basic N on ring is also important
has been most highly associated with gingival hyperplasia.
As a result of their selectivity for vascular versus myocardial or node calcium channels, the DHPs are indicated primarily for the hypertension and/or angina.
Amlodipine
DHP CCB
has basic nitrogran off of alkyl chain
has long half life due to Cl- substituent. Felodipine also has long half life due to two Cl- substituents
retards the first pass effect
has decreased reflex
Clevidpine
DHP CCB
IV only as lipid mixture in soy oil (allergies are a concern)
Use: quickly need to control HTN
It is easily hydrolyzed
half life = 15 minutes
Nicardipine
DHP CCB
some selectivity for coronary arteries which may decrease side effects such as dizziness while still providing antianginal effects.
Felodipine
DHP CCB
longer half life
more selective for vascular tissue vs cardiac tissue than most of the others(Nisoldipine is most selective). Reflex still occurs
Isradipine
DHP CCB
produces vasodilation like the others but also has some effect on the SA node which blunts the reflex response. Little action on the mycocardium so little negative inotropic effects are seen and there is little effect on the AV node so it may be used in patients where AV block is a problem or more easily combined with a Beta blocker.
Nisoldipine
DHP CCB
1000X more selective for vascular tissue
short t 1/2
can decrease reflex
Nimodipine
DHP CCB
lipid soluble compound (cross BBB)
Use: cerebrel vasospasm
Hydralazine
vasodilator
Use: pre-eclampsia (it is preg category C), CHF, pulmonary HTN, HTN
half life = 3 - 5 hr
MOA: involve opening of K+ channels in vascular smooth muscle resulting in hyperpolarization and decreased Ca+2 entry leading to decreased contraction.
acts as nitric oxide donor
causes a potent reduction in perfusion pressure that activates a reflex response leading to increased sympathetic outflow. For this reason it may exacerbate angina or precipitate an MI.
inhibition of dopa decarboxylase may occur leading to decreased neurotransmitter biosynthesis and peripheral numbness
results in retention of Na+ and water which is commonly seen with the vasodilators and results from sympathetic stimulation and decreased renal perfusion pressure resulting in increased proximal reabsorption of Na+ and water.
metabolism: acetylation (fast and slow)
ADR: risk of falls, Dizziness, drowsiness, headache, constipation, loss of appetite, fatigue, and nasal congestion
Allergy: rash, itching, swelling, dizziness, and trouble breathing
DDI: isoniazid, procainamide, quinidine, phenytoin and penicillamine —> inc risk of SLE (more likely to be seen with slow acetylators and more associated with parent drug)
Minoxidil
Vasodilator
Acts as prodrug
MOA: opens K+ channels, decreasing the positive potential in vascular tissue and hyperpolarizing the cell. BF increased to skin, muscle, GI, heart (mainly arteries).
There is reflex response including increased renin release
Use: HTN, effectiveness increase when used with beta blocker
Well absorbed
metabolized by liver to glucuronide (inactive, major) and sulphate conjugates (active, minor)
half life = 3 -4 hours, duration = 24 hours (persists in vasculature)
ADR: reflex sympathetic response (inc CO, Na/H2O retention), ST segment depression, T wave inversion (seen 2 weeks after initial therapy), hypertrichosis (hair growth thru effects on K+ channel)
Sodium nitroprusside
acts on both arterials and venules
IV
Use: HTN emergency, lower BP during anesthesia, dec CO in CHF (acute decompensation heart failure), dec myocardial O2 demand after acute MI, dec preload/afterload
onset: 30 seconds
Duration: 3 minutes
toxicity develops after one hour of use
look at breakdown of compound on page 61
ADR: vasodil leading to hypotension, cyanosis if high dose or fast infusion,
May want to add thiosulfate to therapy to prevent cyanide toxicity
diazoxide
use: HTN emergencies
similar structure to thiazide, but does not cause diuresis
MOA: activates K+ channel resulting in hyperpolarization of arterial smooth muscle
solely acts on arterioles and reflex activation occurs. Na/H2O retention occurs. Stimulates renin release. Hyperglycemia is seen due to agents ability to inhibit insulin secretion (opening of K+ channel)
admin: IV
half life: 20 - 60 hours
ethacrynic acid
Loop diuretic
preg cat B
metab: conjugation with SH
Duration: 4- 8 hour
urinary excretion
DDI: aminoglycosides (inc ototoxicity, nephrotoxicity), agents that affect K+ levels
Furosemide
loop
preg cat C
Metab: gluc
duration: 6 -8 hr
urinary excretion
DDI: aminoglycosides (inc ototoxicity, nephrotoxicity), agents that affect K+ levels
Bumetanide
loop
preg cat C
metab: gluc
duration: 4 -6 hr
urinary excretion
DDI: aminoglycosides (inc ototoxicity, nephrotoxicity), agents that affect K+ levels
torsemide
loop
preg cat B
metab: benzylic oxidation to acid
duration: 6- 8 hr
urinary excretion
DDI: aminoglycosides (inc ototoxicity, nephrotoxicity), agents that affect K+ levels
hydrochlorothiazide
thiazide
category B pregnancy
medium PPB
95% renal elimination
dose: once a day
onset after dosing: 24 hr
more useful in pt with low renin, high sodium, HTN, blacks, elderly, obese
spironolactone
potassium sparing site IV diuretic
Use: hyperaldosteronism, edema, HTN, CHF, hirusitism + androgenic alopecia + dermatitis in women, post MI treatment, male pattern bladness
DOES NOT INVOLVE CYP
parent drug is active and also forms several active metabolites such as canrenone
duration: 2 -3 days
high PPB, bioavailability
preg cat C
ADR: drowsiness, headache and rash (Stevens-Johnson possible), nausea, diarrhea and gastritis, hyperkalemia, gynecomastia, impotence, menstrual disorders
DDI: K+ sparing diuretics, K+ supplements
Eplerenone
site IV, K+ sparing diuretic
Use: post MI, HTN, left ventricular failure (due to aldosterone or heart remodeling)
more specific inhibitor of mineralcorticoid receptor
devoid of androgenic effects
metab: CYP 3A4
ADR: hyperkalemia, dizzy, GI
preg cat B
amiloride
site IV diuretic
preg cat B
duration: 24 hrs
NOT metabolized
utilize OCT
basic guanidine
pka 8.7
has the ability to block Lithium entry through the channel and has been used in treating Li induced diabetes insipidus
Triamterene
site IV diuretic
preg cat C
duration: 7 - 9 hr
metab: hydroxy - triamterene
excreted in urine
can delocalize charge
less basic than amiloride
pka 6.2
Captopril
ACEI
ionizes easily
high oral bioavail (75%)
food dec its effect
fast onset (0.5 hr)
short duration (2-6 hr)
low PPB
has sulfhydrl group
no hepatic activation
renal elimination
linsinopril
ACEI
has acid
low oral bioavail
food has no effect
onset 2 -4hr
duration >36 hr
no sulfhydryl group
no hepatic activation
renal elim
Benazepril
ACEI
S2’ functionality
food has no effect
onset 1 hr
duration 24 hr
high PPB
no sulfhydryl group
hepatic acitvation
eliminated in bile and renal
Fosinopril
ACEI
food has no effect
onset 1 hr
duration 24 hr
high PPB
no sulfhydryl group
hepatic activation
balanced elimination
moexipril
ACEI
low oral bioavail
food dec its effect
onset 1 hr
duration 24 hr
no sulfhydryl
hepatic activation
mostly elim in feces
Trandolapril
ACEI
food slows its effect
no sulfhydryl group
hepatic activation
mostly elim in feces
Angiotensin II
losartan
ARB
CYP 3A4 metabolized to acid with increased activity
high PPB
non competitive for Ang I receptor
food dec its effect
Valsartan
ARB
tetrazole is acidic in nature
high PPB
food dec its effect
mostly fecal elim
non competitive inhibitor of Ang I receptor
azilsartan
ARB
no tetrazole
does contain acid
competitve inhibitor for Ang I receptor
high PPB
urine and feces
food has no effect
Aliskiren
renin inhibitor
oral drug
prevents conversion of angiotensinogen to Ang I
transition state inhibitor
ACEI or ARB use may inc renin release
no impact of bradykinin
24 hr plasma half life
potent
CYP 3A4 metabolism
