1. Jara – Medrano (“Jarano”)

2. * Indications: acute bronchospasm, severe bronchospasm, acute severe asthma * Pharmacokinetics: * Route: Inhaled, oral * Absorption: Readily absorbed from the GI tract. * Metabolism: Hepatic and in the gut wall. Inhaled has direct effect * Excretion: Via the urine as metabolites and unchanged drug. Some excretion in the feces * Pharmacodynamics: Bronchodilation, increased ciliary action, decreased histamine response (including swelling) Direct-acting sympathomimetic with β-adrenergic activity and selective action on β 2 receptors, producing bronchodilating effects

4. * Indications: Hypertension, Angina pectoris, Cardiac arrhythmia * Pharmacokinetics: * Absorption: Oral (100%), peak plasma conc. After 1.5-2 hours * Distribution: Widely distributed, crosses placenta, enters breastmilk (protein binding 12%) * Metabolism: Hepatic. Undergoes significant first pass metabolism * Excretion: Via the urine, elimination half life: 3-4 hours * Pharmacodynamics: lowers blood pressure, reduces the oxygen requirements of the heart at any given level of effort, decreasing heart rate, cardiac contractility and cardiac output ß-adrenergic receptor-blocking agent with preferential effect on the b1-adrenoreceptors, chiefly located in cardiac muscle

5. IndicationHypertension, Angina pectoris, Cardiac arrhythmia, Adjunct in hyperthyroidism, Prophylaxis of migrane, Stable symptomatic heart failure, Emergency treatment of cardiac arrhythmias, Prophylaxis or control of arrhythmias on induction of anaesthesia, Adjunct in the early management of acute myocardial infarction Pharmacokineti cs Absorption Distribution Metabolism Excretion Duration Completely and readily absorbed orally. Peak plasma concentrations after 1.5-2 hours. Widely distributed, crosses placenta and enters breastmilk. Protein-binding: 12% Hepatic: By oxidative deamination, O-dealkylation followed by oxidation and aliphatic hydroxilation. Undergoes significant first-pass metabolism. Via urine. Elimination half-life: 3- 4 hours (fast hydroxylators), 7 hours (poor hydroxylators). 10-12 hours

6. Pharmacodynami cs ß-adrenergic receptor-blocking agent preferential effect on the b1-adrenoreceptors, chiefly located in cardiac muscle lowers blood pressure if given chronically among the factors that may be involved are: -competitive ability to antagonize catecholamine-induced tachycardia at the b-receptor sites in the heart, thus decreasing heart rate, cardiac contractility and cardiac output inhibition of renin release by the kidneys; -inhibition of the vasomotor centres By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris Metoprolol

7. * Salbutamol: beta-2 selective agonist * Metoprolol: beta-1 receptor antagonist and some antagonistic action on beta-2 receptors * Adrenergic bronchodilators can stimulate cardiovascular beta-1 and beta-2 receptors, occasionally producing adverse effects such as tachycardia, palpitation, peripheral vasodilation, and blood pressure changes. * Direct stimulation of cardiac tissues is mediated by beta-1 receptors and thus less likely to occur with beta-2-selective agents such as salbutamol.

8. * However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. * Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism or underlying cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, or hypertension.

9. * In asthmatic patients, Metoprolol reduces FEV1 and FVC significantly less than a nonselective beta blocker, propranolol, at equivalent beta1-receptor blocking doses.

10. Asthmatic patient with transient hypertensive episode Patient with Congestive Heart Failure having bronchospasm (symptomatic wheezes) Chronic stable angina pectoris with asthma Acute Coronary Syndrome with reactive airway disease

11. Salbutamol should be used with caution in patients with cardiovascular disease. If used, dosing should be individualized and the therapeutic response monitored to limit side effects. Asthma is a compelling contraindication to the use of beta-blockers as anti-hypertensives. Metoprolol may worsen the symptoms of heart failure and reduce the effects of salbutamol. An alternative drug that can be used is Nebivolol. It is a third-generation beta-1 selective blocker that is approved for treatment of hypertension. Nebivolol shows similar efficacy in treating hypertension, and with better tolerability.

12. Contraindications for beta-blockers include acute exacerbations and severe forms of COPD as well as moderate to severe asthma and the regular use of 2 - sympathomimetics. Beta-blocker therapy given with low initial doses on an individual basis careful consideration of the benefit to risk ratio, preferably using cardioselective substances with proven mortality benefits for myocardial infarction and chronic heart failure.

13. * Olenchock, et al. Current use of beta blockers in patients with reactive airway disease who are hospitalized with acute coronary syndromes. Am J Cardiol. 2009 Feb 1;103(3):295- 300. * Hanania, et al. The safety and effects of the beta-blocker, nadolol, in mild asthma: an open-label pilot study. Pulm Pharmacol Ther. 2008;21(1):134-41. * Glaab, et al. Use of Beta Blockers in cardiovascular diseases and bronchial asthma/COPD. Der Internist. Feb 2004 1;45: 221-227

14. * Bauer, K., Kaik, G. and B. Kaik. Osmotic release oral drug delivery system of metoprolol in hypertensive asthmatic patients. Pharmacodynamic effects on beta 2- adrenergic receptors. Hypertension 1994;24;339-346 * Chang, C. L., Mills, G. D., McLachlan, J. D., Karalus, N. C. and R. J. Hancox. Cardio-selective and non-selective beta-blockers in chronic obstructive pulmonary disease: effects on bronchodilator response and exercise. Internal Medicine Journal 40 (2010) 193–200