Amlodipine and Hydrochlorothiazide (Research Paper Sample)

Review of Hypertension Medications: Amlodipine and Hydrochlorothiazide
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Review of Hypertension medications: Amlodipine and Hydrochlorothiazide
Blood pressure is the force exerted by blood on the circulatory system. The blood pressure levels are a function of the Cardiac Output multiplied by the Systemic Vascular Resistance (Morelli, 2014). The body physiologically maintains the blood pressure within normal ranges. However, a dysfunction is one of the blood pressure regulation mechanisms can lead to hypertension. Hypertension is the persistent elevation of the blood pressure with a systolic pressure above 140mmHg and a diastolic pressure above 90 mmHg (Morelli, 2014). It is a challenge to obtain the target blood pressure in hypertensive patients without the use of medication. Various drugs are used to control blood pressure in hypertensive patients. These drugs have different efficacy, mode of action, pharmacokinetics and pharmacodynamics properties. This paper is a review of Amlodipine and Hydrochlorothiazide drugs used by hypertensive patients.
Amlodipine
Amlodipine is an antihypertensive and chest pain (angina) drug. It is a selective calcium channel blocker. Calcium channels are in the walls of the blood vessels. They allow the selective permeability of calcium ions which stimulates contractility of the cells to narrow the lumen of the blood vessels (Chung et. al., 2006). Amlodipine acts by binding to vascular smooth muscle carbonic anhydrase that plays a part in Calcium ion transport. This prevents Calcium ion influx into the cells of the arterial vascular walls thus inhibiting contractility of the blood vessels (Dailymed, 2015). As a result, it reduces the peripheral vascular resistance to improve blood flow. As a result, the blood pressure which is the product of the Cardiac Output and the Peripheral Vascular Resistance decreases. In addition to widening the blood vessels, Calcium channel blockers also prevent the entry of Calcium ions into the myocardial cells to slow the heart rate that further reduces the blood pressure, relieve chest pain (angina) and treat irregular heart rate.
Pharmacokinetics
Absorption and bioavailability
Amlodipine undergoes gradual absorption when orally administered. The drug has linear dose-related characteristics. At steady dosing, the drug has small fluctuations in plasma concentrations. Absorption after oral administration is detectable after an hour but reaches peak concentration after 8 hours are (Chung et. al., 2006). Slow absorption is the drug's feature rather than an impact of its formulation. However, the drug is almost completely absorbed in the gastrointestinal tract more so in the small intestines. Absorption is not affected by food thus the patient can be advised to take the medication before or after meals. Following oral administration, Amlodipine has a bioavailability of 60 to 65% (Chung et. al., 2006). Plasma concentrations rise gradually to reach their peak levels after 6 to 8 hours of administration. Intravenous administration of Amlodipine has a 100% bioavailability.
Distribution
The drug has a high degree of plasma protein binding. 98% of the drug binds to plasma proteins mainly albumin for distribution to the various parts of the body. The volume of distribution is comparatively high at 21 liters/Kg (Pubchem, 2015). A large proportion of the overall drug load remains in the tissues rather than the plasma. Following intravenous administration, the drug diffuses from the plasma to the tissues almost completely within 2 hours (Chung et. al., 2006). There is no existing evidence of pharmacokinetic drug interactions that increase or decrease the distribution of Amlodipine. Steady-state plasma concentrations get achieved after seven days of continuous dosing. However, conditions that reduce the plasma protein levels, for example, protein energy malnutrition reduce the distribution of Amlodipine.
Metabolism and elimination
Metabolism of Amlodipine is primarily in the liver. Metabolism is of Amlodipine is by cytochrome P450 3A4 isoenzyme to inactive metabolites (Pubchem, 2015). The drug has a terminal half-life of 30 to 50 hours before being broken down in the liver. The long half-life and the steady state profile of Amlodipine make it a suitable for single daily dosing. The drug’s overall pharmacokinetic properties contribute to its gradual onset of action and consistency over single dosing. The main route of elimination of Amlodipine is through the kidneys. About 90% of Hepatic metabolism converts Amlodipine to inactive metabolites. 10% of the initial drug and 60% of the metabolites are end up in the urine (Dailymed, 2015). Renal impairment has little impact on the elimination of Amlodipine.
Drug Indications
Amlodipine is used to treat various cardiovascular conditions. It is indicated for patients with high blood pressure to normalize it by relaxing the blood vessels thus reducing the peripheral vascular resistance and promoting blood flow. It is also indicated for patients with chronic stable angina as a method of reducing the pain and ensuring normal heart rate (Chung et. al., 2006). Angina is caused by occlusion of the coronary arteries that supply the heart with blood. Amlodipine relaxes the coronary artery promoting blood flow through the coronary arteries to the heart. This relieves the pain. Additionally, the drug decreases the heart rate thus reduce the work done by the heart and the subsequent oxygen requirements to provide relief from chest pain brought by such increased demands on the heart. Amlodipine is also used as a prophylaxis to prevent the recurrence of angina especially before physical exercise or strenuous activities. The drug treats hypertension or angina either as monotherapy or as a combination therapy. Health professionals recommend off label uses of Amlodipine to treat cluster headaches, continuous migraines, Raynaud’s disease and Congestive heart failure.
Adverse Effects
The common adverse effects of using Amlodipine include peripheral edema experienced by 5% of users (Morelli, 2014). Edema comes as a result of excess relaxation of blood vessels to cause pooling of blood in the extremities. As a result, water and ions move from the intracellular fluid to the extracellular fluid causing edema. The other common side effect of Amlodipine is dizziness experienced by 2% of users. Dizziness results from reduced blood flow to the brain. Palpitations are also common among Amlodipine users due to the subsequent interference of ions necessary for impulse generation and conduction in the heart. Less common side effects are nausea, fatigue, abdominal pains, headaches, and flushing. Rare side effects include impotence, insomnia, hepatitis, and blood abnormalities (Morelli, 2014). Encourage the patient to report serious side effects such as rapid and irregular heart rate, fainting and severe chest pain to the physician for additional testing and further management as they arise from Amlodipine toxicity.
Drug Contraindications and Limitations
Advanced age, severe hepatic and renal impairment influence the pharmacokinetic properties of Amlodipine leading to higher plasma concentrations and a longer half-life (Pubmed, 2015). As a result, continuous dosing in such individuals can lead to toxicity. Therefore, it is imperative to adjust the doses in such patients to prevent the drug from reaching toxic levels. Allergic patients and those who have previously experienced serious side effects should not use Amlodipine (Dailymed, 2015). Patients with a history of heart diseases such as aortic stenosis and cardiogenic shock should not use Amlodipine. Patients with normal or low blood pressure should not use Amlodipine as well. Finally, Amlodipine should be avoided by pregnant and breastfeeding mothers and only used if the potential benefits exceed the risks affecting the baby.
Monitoring
Patients on Amlodipine should have their blood pressure monitored closely to determine if the drug is meeting its purpose. Blood pressure monitoring also rules out asymptomatic hypotension that could result from Amlodipine use for timely intervention (Morelli, 2014). The heart rate and preferably an Electrocardiogram (ECG) should be obtained after every six months for patients under long term Amlodipine therapy (Dailymed, 2015). The ECG reveals incidences of abnormal heart rhythms such as palpitations that could be caused by the drug. The plasma concentration of the drug should also be closely monitored more so in patients with hepatic and renal failure owing to their reduced ability to metabolize and eliminate it from the body that predisposes the patient to Amlodipine toxicity. Lipid level monitoring and sodium intake are additional concerns for patients taking Amlodipine.
Hydrochlorothiazide (HCTZ)
HCTZ is another drug used in the management of hypertension. HTCZ is a thiazide diuretic that controls hypertension by eliminating sodium and water. It prevents fluid retention in the body by acting on the kidney nephron to reduce the reabsorption of sodium and water (Morelli, 2014). During ultrafiltration, water and low molecular weight substances are filtered in the Bowman’s capsule. Reabsorption these substances occurs in the nephron. Water, Potassium, Sodium, Chlorine, and glucose are reabsorbed into the blood. HCTZ prevents the reabsorption of Sodium to higher osmotic pressure in the distal convoluted tubule that draws water into the glomerular filtrate (Miyashita et al., 2010). As a result, the excess sodium and water is excreted from the body in urine, therefore, increasing the frequency of urination (diuresis). Diuresis decreases the blood volume going back to the heart. This decreases the Cardiac Output to lower the blood pressure which is a product of the Cardiac Output and Peripheral Vascular ...