Amlodipine; Uses, Dosage, Side Effects, Interactions, Pregnancy

Amlodipine is a long-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, amlodipine prevents calcium-dependent myocyte contraction and vasoconstriction.

Mechanism of Action of Amlodipine

Amlodipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of amlodipine result in an overall decrease in blood pressure. Amlodipine is a long-acting CCB that may be used to treat mild? to moderate? essential hypertension? and exertion-related angina? (chronic? stable angina?). Another possible mechanism is that amlodipine inhibits vascular smooth muscle carbonic anhydrase I activity causing cellular pH increases which may be involved in regulating intracelluar calcium influx through calcium channels.

The mechanisms by which amlodipine relieves angina are

• Stable angina: amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, thereby lowering myocardial oxygen demand, at any given level of exercise.
• Variant angina: amlodipine blocks spasm? of the coronary arteries? and restores blood flow in coronary arteries and arterioles in response to calcium, potassium, epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro.

Amlodipine has additionally been found to act as an antagonist of the mineralocorticoid receptor, or as an antimineralocorticoid.

Indications of Amlodipine

• Angina pectoris
• Stable & unstable angina
• High blood pressure
• Raynaud’s syndrome?
• Migraine prevention
• Coronary artery disease?
• Heart failure
• Chronic stable angina pectoris
• High blood pressure (Hypertension)
• Ejection fraction >40% Coronary artery disease without Heart failure
• Coronary artery disease in people with either stable angina
• Strokes
• Treatment of uncomplicated hypertension,
• Treatment of essential hypertension in adults.
• Reduction of cardiovascular morbidity in adults with
• Manifest atherothrombotic cardiovascular disease (history of coronary heart disease?, stroke, or peripheral arterial disease)
• Cardiovascular Risk Reduction
• Prevention of Cardiovascular Disease

Contra Indications of Amlodipine

Dosage? of Amlodipine

Strength :  2.5, 5 mg and 10 mg Tablets

Initial dose: 2.5 mg orally once a day
Maintenance dose: 2.5 to 10 mg orally once a day
Maximum dose: 10 mg/day

Hypertension

• Initial dose: 5 mg orally once a day
• Maintenance dose: 5 to 10 mg orally once a day
• Maximum dose: 10 mg/day

Angina Pectoris?

• Maintenance dose: 5 to 10 mg orally once a day
• Maximum dose: 10 mg/day

Coronary Artery? Disease

• Maintenance dose: 5 to 10 mg orally once a day
• Maximum dose: 10 mg/day

Pediatric Dose for Hypertension

• Maintenance dose: 2.5 to 5 mg orally once a da
• Maximum dose: 5 mg/day

Side Effects of Amlodipine

The most common

• Dry cough
• Depression
• Dizziness and light-headedness due to low blood pressure
• Fatigue, especially in the early stages
• Mouth dryness in the early stages
• The most commonrn (a burning feeling in the chest, behind the breastbone or gullet)
• Abdominal or stomach pain
• Constipation
• High blood pressure
• Nausea ,vomiting,
• painful or swollen gums
• numbness or heavy feeling in the jaw
• dull, aching pain in the hip, groin, or thigh
• stomach pain,
• headache,
• reversible hair loss or thinning, and
• fever.

Common

• chills or fever
• headache, severe and throbbing
• joint or back pain
• muscle aching or cramping
• muscle pains or stiffness
• chest pressure or squeezing pain in chest
• excessive sweating
• sudden drowsiness or need to sleep
• coughing up blood
• liver problems–nausea, upper stomach pain, itching, tired feeling, loss of appetite, dark urine, clay-colored stools, jaundice? (yellowing of the skin or eyes)
• decreased amount of urine

Rare

• Anxiety
• change in vision
• chest pain or tightness
• confusion
• cough
• Agitation
• arm, back, or jaw pain
• blurred vision
• chest pain or discomfort
• convulsions
• extra heartbeats
• hallucinations
• headache
• irritability
• lightheadedness
• cold and clammy skin
• fast and shallow breathing
• swelling of your feet, legs, or hands purple spot on your skin caused by internal bleeding
• fast or abnormal heart rate or palpitations
• loss of appetite
• lower back, side, or stomach pain
• mental depression
• muscle pain or cramps
• Swelling of your feet or ankles
• Shortness of breath
• Nausea, fever, dark urine, loss of appetite
• Depression

Drug Interactions of Amlodipine

Amlodipine may interact with following drugs, supplyments, & may change the efficacy of drugs

• aminophylline
• asthma medications (e.g., theophylline)
• diabetes medications (e.g., glyburide)
• calcium channel blocker medicines (e.g., diltiazem, nifedipine, verapamil)
• diltiazem
• medications for abnormal heart rhythms (e.g., disopyramide)
• nitroglycerin
• nonsteroidal anti-inflammatory medications (NSAIDs; e.g., indomethacin, naproxen)
• oral diabetes medications (e.g., metformin, pioglitazone)
• pentoxyifylline
• monoamine oxidase (MAO) inhibitors (e.g., phenelzine, selegiline, )
• other beta-blockers (e.g., propranolol, metoprolol)
• oxtriphylline
• verapamil

• alpha blockers (e.g., alfuzosin, doxazosin, tamsulosin)
• angiotensin converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
• angiotensin receptor blockers Angiotensin II receptor blockers (ARBs); Defination, Types, Mechanism of actions, Indications/Uses, Contra Indications, Side Effects, Drug Interactions,(ARBs; e.g., candasartan, irbesartan, losartan)
• antacids
• “azole” antifungal medications (e.g., fluconazole, itraconazole, ketoconazole)
• barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
• benzodiazepines (e.g., clonazepam, diazepam, lorazepam)
• beta-blockers (e.g., atenolol, metoprolol, propranolol)
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• carbamazepine
• cimetidine
• clopidogrel
• cyclosporine
• dasatinib
• dexamethasone
• diuretics (water pills; e.g., furosemide, hydrochlorothiazide, triamterene)
• duloxetine
• fusidic acid
• haloperidol
• imatinib
• imipramine
• macrolide antibiotics (e.g., clarithromycin, erythromycin)
• metronidazole
• monoamine oxidase inhibitors (MAOIs; e.g., phenelzine, rasagiline, selegiline, )
• pentoxifylline
• phenytoin
• phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• quetiapine
• rituximab
• sertraline
• simvastatin
• tetracycline
• theophylline
• tocilizumab
• warfarin

Amlodipine tablets may lower your blood pressure even more if you are already taking other medicines to treat your high blood pressure.

Pregnancy & Lactation of Amlodipine

Pregnancy

This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Breast-feeding

It is not known if amlodipine passes into breast milk. If you are a breast-feeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children

The safety and effectiveness of amlodipine have not been established for children under 6 years of age.

Combination therapy

Amlodipine can be given as a combination therapy with a variety of medications

• Amlodipine/atorvastatin, where amlodipine is given for hypertension or CAD? and atorvastatin prevents cardiovascular events, or if the person also has high cholesterol?.
• Amlodipine/aliskiren or amlodipine/aliskiren/hydrochlorothiazide if amlodipine alone cannot reduce blood pressure. Aliskiren is a renin inhibitor, which works to reduce primary hypertension (that with no known cause) by binding to renin and preventing it from initiating the renin-angiotensin system (RAAS) pathway to increase blood pressure. Hydrochlorothiazide is a diuretic and decreases overall blood volume.
• Amlodipine/benazepril if either drug has failed individually, or amlodipine alone caused edema?. Benazepril is an ACE inhibitor and blocks the conversion of angiotensin I to angiotensin II in the RAAS pathway.
• Amlodipine/olmesartan or amlodipine/olmesartan/hydrochlorothiazide if amlodipine is insufficient in reducing blood pressure. Olmesartan is an angiotensin II receptor antagonist and blocks part of the RAAS pathway.
• Amlodipine/perindopril if using amlodipine alone caused edema. Perindopril is a long-lasting ACE inhibitor.
• Amlodipine/telmisartan, where telmisartan is an Angiotensin II receptor antagonist.
• Amlodipine/valsartan or amlodipine/valsartan/hydrochlorothiazide, where valsartan is an angiotensin II receptor antagonist.

References