Antihypertensive medication 2 Flashcards
Calcium channel blockers are the first line treatment for hypertension in?
Elderly
Where are the calcium channels found?
1) Heart
2) Blood vessels
Are calcium blockers safe in renal failure?
Yes (along with clonidine “sympatholytic”, and others)
What is the use of calcium channel blockers?
- They’re useful in hypertension as they dilate peripheral arteries and decrease the TPR by relaxing the vascular smooth muscle
- They can be used alone or combined with other drugs
- Well tolerated in renal failure
What are the classes of calcium channel blockers?
1) Dihydropyridines (DHPs, like Nifedipine)
2) Phenylalkylamines (verapamil)
3) Benzothiazepines (diltiazem)
What are the different drugs under dihydropyridine?
1) Nifedipine
2) Amlodipine
3) Nitrendipine
4) Nisoldipine
5) Nicardipine
6) Isradipine
What is the mechanism of action of the dihydropyridine calcium channel blockers?
They work on the BV more than the heart, causing vasodilation, which will lead to reflex tachycardia as they don’t work much on the heart
What are the drugs under phenylalkylamines?
Verapamil
What is the mechanism of action of phenylalkylamines?
Blocks the calcium channel in the heart mainly and to a small extent in the blood vessels, and thus it has an important effect on tachyarrhythmias, making it an anti-arrhythmic, vasodilating, and cardio-suppressive drug.
What are the drugs under benzothiazepines?
Diltiazem (the only one used clinically)
What is the mechanism of action of benzothiazepines?
same same phenylalkylamines
What are the commonly used calcium channel blockers?
1) Nifedipine
2) Amlodipine
3) Felodipine
4)Verapamil (auses gingival hyperplasia)
5) Diltiazem
6) Clevidipine (formulated for IV only)
What is the site of action of dihydropyridines?
They act mainly on the smooth muscles of the blood vessels, resulting in coronary vasodilation, which is associated with reflex tachycardia (amlodipine reflex tachycardia is milder than nifidepine) and increased CO
When is dihydropyridine used?
Hypertension
What is the site of action of verapamil (phenylalkylamine)?
It affects all calcium channels but mainly those of the heart, causing vasodilation and slowing the AV conduction reducing the force of contraction of the heart
When is phenylalkylamine used?
1) Hypertension
2) Angina
3) In some SVTs
What is the site of action of diltiazem?
With an intermediate property, it results in vasodilation and depresses the AV conduction mildly with mild inotropic effects
When is diltiazem used?
1) Angina
2) In some Arrhythmias
What are the adverse effects of calcium channel blockers?
1) Constipation
- Due to the relaxation of the smooth muscles of the GI
- Most common with verapamil and diltiazem and it can be avoided by avoiding high doses
2) Heart failure
- Verapamil and diltiazem depress the contractility of the heart which could worsen/result in heart failure
- More likely if they are used with cardiac depressants like beta-blockers
- We still combine b-blockers to CCB in cases of angina, IHD, & Severe hypertension but it should be done cautiously
3) Disturbance of the cardiac conduction
- The AV-node suppression can result in AV node block, which could lead to sinus arrest, sino-atrial block, sinus bradycardia, or AV block
4) Exacerbation of ischemic chest pain
- Dihydropyridines like nifedipine can worsen angina as it cause reflex tachycardia
- DHP should be avoided in myocardial infarction ad it can be fatal
5) Vascular headache
- Due to vasodilation of the cerebral blood vessels, most common with DHP
What are the drug-drug interactions of calcium channel blockers?
1) Beta-blockers
- Can be used with nifedipine and DHP
- Should be avoided with verapamil unless the patient has a normal cardiac function other than that it could lead to cardiac failure
2) Digoxin
- Verapamil increases digoxin plasma levels by 30-50% which could lead to AV block
- Digoxin has a narrow therapeutic index and thus this could lead to toxicity
3) Grape-fruit
- It inhibits hepatic microsomal enzyme increasing the bioavailability of nifedipine which could lead to toxicity, and this might cause hypotension
4) Cytochrome P450 Inhibitors
- CCB particularly DHP, are metabolized by oxidation in the liver and they might compete with other drugs for this pathway
What is a direct vasodilator?
They are a group of drugs that relax the smooth muscles lowering the peripheral resistance
- Their use is declining
What are the different classes and drugs of direct vasodilation?
1) Hydralazine (Aprizoline)
2) Minoxidil (loniten)
3) Sodium nitroprusside (nipride, nitropress)
4) Diazoxide (hyperstat)
5) Fenoldopam
What is the mechanism of action of hydralazine?
It reduces blood pressure by relaxing the smooth muscles of the arteries increasing the K+ efflux and decreasing the Ca+2 influx
- It elicits the baroreceptor reflex which means that it has to be coadministered with a diuretic to counteract the sodium and water retention, and a b-blocker to prevent the tachycardia
What is the clinical use of hydralazine?
- Safe in pregnancy (along with carvedilol, labetalol, nifedipine, and methyldopa)
- It is used in chronic hypertension and hypertensive crises which accompanies acute glomerulonephritis/eclampsia
