B.7 Flashcards
Ca2+ channel blockers and other vasodilators
- DHP CCBs: Amlodipine, Felodipine, Nifedipine, Nimodipine
- Non-DHP CCBs: Verapamil
- Other vasodilators: Dihydralazine, Bozentan, Sildenafil
Nifedipine
MOA: DHP Ca2+ channel blocker;
Kinetics: nutrients affect abs. rate, ↑plasma protein binding, Hepatic metabolism (CYP3A4), eliminated via kidney, can be excreten in breast milk (not recommended),
Administration- mostly p.o, i.v, spray for oral mucosa, T1/2-2h;
SEs: Mood disturbances, muscle spasms, myocardial ischemia (→angina, risk for AMI in case of fast release preparations), Edema, headache, dizziness, visual disturbances, palpitations;
Contra-IND: cardiogenic shock, unstable angina (→acute anginic attack), AMI, co-adm. with CYP3A4 inducers (e.g. Rifampin);
Drug-interactions: additive effect with antihypertensive and vasodilators, false-positive result in case of Barium X-ray examination, increase Digoxin cc, Severe hypotension with fentanyl, increases the abs. of metformin;
IND: retard preparations (→chronic stable angina, HTN), Fast release tablets (→Hypertensive crisis, prevention of angina attack), i.v (→vasospastic angina, hypertensive crisis), preeclampsia, achalasia (difficulty swallowing), pulmonary HTN, preterm labor, raynaud syndrome
Felodipine
MOA: DHP Ca2+ channel blocker;
Kinetics: nutrients affect abs. rate, ↑plasma protein binding, Hepatic metabolism (CYP3A4), eliminated via kidney, adm. p.o, extensive first pass (BA 15-20%);
SEs: Edema, headache, dizziness, visual disturbances, palpitations;
Contra-IND: pregnancy, decompensated HF, AMI, unstable angina (reflex tachycardia→Myocardial ischemia), heart valve and heart outflow obstruction; Drug-interactions: additive effect with antihypertensive and vasodilators, increases cc of Tacrolimus;
IND: stable angina, HTN
Amlodipine
MOA: DHP Ca2+ channel blocker;
Kinetics: nutrients affect abs. rate, ↑plasma protein binding, Hepatic metabolism (CYP3A4), eliminated via kidney, adm. p.o;
SEs: Sleepiness, Dyspnea, Abdominal pain, Edema (rare!), headache, dizziness, visual disturbances, palpitations (mostly in women);
Drug-interactions: Hyperkalemia with dantrolene, additive effect with antihypertensive (sildenafil) and vasodilators;
Contra-IND: severe hypotension, cardiogenic shock, aortic stenosis, hemodynamically unstable HF following AMI;
IND: stable & vasospastic angina, HTN
Nimodipine
MOA: DHP Ca2+ channel blocker;
Kinetics: nutrients affect abs. rate, ↑plasma protein binding, Hepatic metabolism (CYP3A4), eliminated via kidney, adm. p.o/i.v, T1/2-1-9h, lipophilic (penetrates via BBB);
SEs: Thrombocytopenia, myocardial ischemia (→angina, risk for AMI in case of fast release preparations), infusion preparation contains ethanol (→alcoholics), Edema, headache, dizziness, visual disturbances, palpitations;
Drug-interactions: additive effect with antihypertensive and vasodilators, co-adm. with CYP3A4 inducers/inhibitors;
IND: prevention and treatment of cerebral vasospasm-induced ischemic nerve damage following subarachnoidal hemorrhage
Verapamil
MOA: Class IV antiarrhythmic, Non-DHP, Cardioselective L-type Ca2+ channel blocker;
Kinetics: adm. p.o/i.v, ↑plasma protein binding (→ NOT dialysable, cc ↑ in liver diseases), extensive 1st pass, hepatic metabolism (CYP3A4, 1A2), renal excretion of metabolites, excreted in breast milk (lactation MUST be suspended);
SEs: Constipation, liver damage, edema, bradycardia, AV-block, Asystolia, Cardia decompensation, hyperprolactinemia, galactorrhea, impotency, in case of i.v adm (→respiratory failure in patients with Duchenne Muscular Dystrophy);
Contra-IND: Severe LV dysfunction (EF<30%→Exception if caused by SVT), Hypotension, shock, sick sinus syndrome, AV-block, A.flutter/A.fib associated with collateral bypass pathway (WPW syndrome), co-adm. with β-blockers, wide QRS VT;
Drug-interactions: ↑bleeding time with aspirin, inhibits the elimination of ethanol (→↑intoxication), ↑Digoxin cc.;
IND: HTN, SVT (2nd line), stable/unstable/vasospastic angina, secondary prevention following MI, bipolar depression, cluster headache
Dihydralazine
MOA: Unknown (may open K+ channels + may inhibit IP3-induced Ca2+-release), relaxes SMC of arteries; Kinetics: p.o/P.E adm., food increases rate of abs, can cross the placenta, ↑protein binding (not dialysable), metabolized in intestinal mucosa and liver (acetylation); IND: Hypertensive crisis (especially in eclampsia→ in combination with methyldopa), as adjuvant in advanced HF;
SEs: fluid retention, reflex tachycardia (→may provoke ischemia!), allergy, immunological reactions (lupus)
Bozentan
MOA: Competitive ET1-R inhibitor →pulmonary vasodilation;
SEs: Hepatotoxicity, anemia, palpitation, edema, Hypotension;
Contra-IND: Pregnancy, lactation;
Drug-interactions: CYP2C9/19 and CYP3A4 inducers (→decreases the efficacy of oral contraceptives), Increased risk of hepatotoxicity in combination with Glyburide;
IND: Group 1 pulmonary HTN
Sildenafil
MOA: PDE5 inhibitor (prevents conversion of cGMP to GMP, thus the vasodilatory effect of cGMP in SMC persist);
Kinetics: adm. p.o (on empty stomach! food reduces rate & extent of abs.), Hepatic metabolism (CYP3A4), excreted with feces;
SEs: Headache, dizziness, color vision disturbances (slight PDE6 inhibition), insomnia, Hypotension (especially in combination with other vasodilators), QT↑, epistaxis, dyspepsia, diarrhea, muscle pain;
IND: Pulmonary HTN, erectile dysfunction (VIAGRA!); Contra-IND: history of Stroke/MI, co-adm. with organic nitrates/sGC stimulators, severe cardiovascular disease, severe liver damage, hypotension, hereditary retinal degeneration (retinitis pigmentosa), unilateral vision loss (in non-arteritic ischemic optic neuropathy)
Group 1 pulmonary HTN
etiology: Idiopathic, Congenital, Drug-induced (e.g. sympatomimetics)
Dihydropyridines
hort acting: Nifedipine, Nimodipine, Clevidipine
Moderate acting: Felodipine, Nitrendipine, Nicardipine, Nisoldipine, Isradipine
Long acting: Amlodipine, Lercanidipine, Lacidipine, Manidipine
non-Dihydropyridines
Phenylalkylamines: Verapamil, Gallopamil, Fendiline
Benzotiazepines: Diltiazetam
Pulmonary HTN
Pulmonary arterial pressure >20mmHg (normal 10-14mmHg)
-Group 1
-Group 2
-Group 3
-Group 4
-Group 5
Pulmonary HTN Group 2
*chronic left-sided HF
*Cardiac valve disease
Pulmonary HTN Group 3
chronic pulmonary disease (COPD, restrictive pulmonary disease)
