Beta-adrenergic blockers decrease cardiac output by reducing the sympathetic nervous system response. They inhibit the binding of epinephrine and norepinephrine to specific beta-receptors located in various sites throughout the body. Beta-1 receptors are specifically found in the heart and kidneys. Beta-2 receptors can be found in the lungs, muscles, and within the gastrointestinal region. The overall effect of beta-blockers is the reduction in heart rate and contractility. This leads to a decreased vascular resistance and lower blood pressure. Beta-blockers are often indicated in patients with arrhythmias including tachycardia and atrial fibrillation. They are also used in patients with angina, chest pain, and myocardial infarction.
Beta-blockers that specifically target beta-1 receptors are considered cardioselective and are the preferred treatment in hypertension. Cardioselective beta-blockers including atenolol (Tenormin), metoprolol (Lopressor), and esmolol have a better side-effect profile. In contrast, nonselective beta-blockers including propranolol (Inderal), timolol, and nadolol have a greater effect on the bronchial and gastrointestinal receptors. Typical dosing for the common beta-blocker atenolol are 25mg, 50mg, and 100mg which are slowly titrated based on the patient’s initial response. Metoprolol is dosed similarly but with a maximum dosage of 200mg.
Common side effects seen with beta-blockers include hypotension, fatigue, headaches, weakness, dizziness, diarrhea, abdominal cramps, cold hands/feet, bronchoconstriction, and wheezing. Asthmatics and patients with chronic obstructive pulmonary disease are cautioned against taking beta-blockers because of bronchoconstriction. Diabetics are also at risk for hypoglycemia because beta-blockers inhibit the liver’s ability to convert glycogen to glucose. More importantly, beta-blockers will mask the tachycardia symptom seen in hypoglycemic patients.
ACE inhibitors are drugs that indirectly lower blood pressure by working on the renin-angiotensin-aldosterone system and by blocking the breakdown of bradykinin in our bodies. Normally, our kidneys react to a drop in blood pressure by producing renin which converts angiotensinogen to angiotensin I. Subsequently, angiotensin I is converted to angiotensin II by angiotensin-converting enzyme, or ACE for short, and then angiotensin II goes on to cause vasoconstriction. By blocking ACE and preventing vasoconstriction, and by blocking the breakdown of a strong vasodialator named bradykinin, ACE inhibitors are able to cause a decrease in blood pressure. Interestingly, African-American patients have lower levels of plasma renin and as a result ACE inhibitors tend to be less effective in this patient population.
The two most commonly used ACE inhibitors are Enalapril (Vasotec, Epaned) and Lisinopril (Zestril, Prinivil), however, there are several others in this class of drugs that work by the exact same mechanism. Dosing for Enalapril usually begins a 5 mg/day and has a maximum of 40 mg/day whereas Lisinopril dosing starts at 10 mg/day with a maximum dosage of 80 mg/day.
Common side effects of ACE inhibitors are dizziness, headache, diarrhea, hypotension, and a dry cough. ACE inhibitors may also cause changes seen on laboratory results such as: hyperkalemia, elevated BUN and creatinine levels, and hyperuricemia. Very rarely ACE inhibitors may cause an anaphylactic reaction or angioedema which are both emergent conditions. ACE inhibitors are also contraindicated in pregnancy due to risks of birth defects.
Statins are used to lower cholesterol by inhibiting HMG-CoA reductase which prevents 3-hydroxy-3methylglutayl-CoA from converting to melvalonic acid and stops cholesterol synthesis in the liver. Statins also increase in LDL receptors on the cell surface to enhance uptake and catabolism of LDL, thus lowering plasma lipoproteins and cholesterol levels.
Common statins that are used are Lipitor (Atorvastatin) and Crestor (Rosuvastatin). To use lipitor and Crestor for hypercholesterolemia, you want to start patient on 10-20 mg PO qd and increase dose in 2-4 weeks.
Adverse effects of statins to be aware of are increased concentrations of liver enzymes, muscle injury like rhabdomyolysis, and increased risk of diabetes. Other adverse effects are cognitive loss, neuropathy, pancreatic and hepatic dysfunction, and sexual dysfunction.
Calcium Channel Blocker
Calcium channel blockers are divided into two groups: dihydropyridines and non dihydropyridines. CCBs are commonly used for lowering blood pressure, alerting heart rate, preventing cerebral vasospasm and to reduce chest pain caused by angina pectoris. CCBs work by blocking the influx of calcium into vascular smooth muscle and to the myocytes, therefore causing vasodilation, reducing workload of the heart muscle, slowing down the conduction of electrical activity within the heart, and by blocking calcium signal on the adrenal cortex, they directly reduce aldosterone production, which causes lower blood pressure.
Commonly used dihydropyridines are Amlodipine (Norvasc) and Felodipine (Plendil) for hypertension. Dosing for Amlodipine and Felopdipine is 5 mg po qd. Commonly used non-dihydropyridines for angina are Diltiazem (Cardizem) and Verapamil (Calan). Start dose for Diltiazem is 30 mg po qid and Verapamil is 80 mg tid.
Common side effects of CCBs are lightheadedness, low blood pressure, slow heart rate, drowsiness, constipation, swelling of the feet ankles and legs, increased appetite, GERD, bleeding gums, and sexual dysfunction.
Angiotensin II Receptor Blockers (ARBs)
Angiotensin II has several effects on our body’s blood pressure regulation including increases in: sympathetic activity, tubular sodium and chloride retention, water retention, aldosterone secretion, arteriolar vasoconstriction, and vasopressin. All of the previous cause an increase in our blood pressure. By blocking the receptors to which angiotensin II binds ARBs are able to lower the patient’s blood pressure.
The two most commonly used ARBs are Losartan (Cozar) and Valsartan (Diovan), however, there are several others in this class of drugs that work by the exact same mechanism. Dosing for Losartan usually begins a 50 mg/day and has a maximum of 100 mg/day whereas Valsartan dosing starts between 80 and 160 mg/day with a maximum dosage of 320 mg/day.
Similar to ACE inhibitors, common side effects of ARBs are dizziness, headache, diarrhea, and hypotension. However, unlike ACE inhibitors, ARBs are much less likely to cause a dry cough. ARBs may also cause changes seen on laboratory results such as: hyperkalemia, neutropenia, and thrombocytopenia. Very rarely ARBs may cause an anaphylactic reaction or angioedema which are both emergent conditions. ARBs are also contraindicated in pregnancy due to risks of birth defects.
Aldosterone antagonists work to prevent aldosterone from binding to mineralocorticosteroid receptors located in the kidneys. Aldosterone’s primary action is to increase sodium and water reabsorption and potassium excretion leading to higher blood pressure. By antagonizing these mechanisms, a diuretic effect is achieved leading to a decreased water volume and blood pressure.
The commonly used aldosterone antagonists are Eplerenone (Inspra) which is dosed at 25mg, 50mg, and 100mg. Spironolactone (Aldactone) is dosed similarly. For both drugs, maximal response can be expected around 48 hours after the first dose. Spironolactone is considered a non-selective drug that is known to mimic the effects of hormones. On the other hand, eplerenone is selective and has a lower affinity to cause sex-related side effects. Other frequent side effects seen with aldosterone antagonists include hyperkalemia, nausea, abdominal pain, diarrhea, headache, gynecomastia, sexual dysfunction, and metabolic acidosis.