Fenoterol/Ipratropium bromide (Inhaler)
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 BRAND NAMES
 MECHANISM OF ACTION
Fenoterol is a short-acting Beta2 adrenergic receptor agonist.
Beta2 receptors are the predominant adrenergic receptors in bronchial smooth muscle. The binding of Fenoterol to Beta2 adrenergic receptors in bronchial smooth muscle, activates the intracellular adenylate cyclase, an enzyme which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). The increase of cAMP determines:
- Bronchodilation: Increased intracellular cyclic AMP (cAMP), increases the activation of cAMP-dependent protein kinase A, which inhibits the phosphorylation of myosin and lowers intracellular calcium levels within the muscle. Lower levels of calcium cause relaxation of the smooth muscle and therefore bronchodilatation.
- Inhibition of the release of mast cell mediators.
- Increased mucociliary clearance.
In high doses fenoterol also affects the striated muscles (tremor) and the the β1-receptors (the predominant receptors in the heart) and has an influence on lipid and sugar metabolism (lipolysis, glycogenolysis and hyperglycaemia) and relative hypokalaemia due to increased K+ uptake in the skeletal muscle.
Due to the density of β2-receptors in the myometrium, fenoterol also relaxes the uterine muscles. This effect is particularly pronounced in the pregnant uterus and at considerably higher doses.
Ipratropium bromide is an anticholinergic (parasympatholytic) agent.
it prevents the increases in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) which are caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle. This results in decreased contractility of smooth muscle in the lung.
Following inhalation of this combination, bronchodilatation is induced within a few minutes and the effect persists for 3 – 5 hours for Fenoterol and up to 6 hours for ipratropium bromide.
- Prevention and treatment of bronchospasm in asthma and chronic obstructive pulmonary disease (COPD)
- Acute asthma episodes:
- Adults and children over 6 years: 50 µg fenoterol/20 µg ipratropium bromide (1 dose). This will usually be adequate to relieve bronchospasm in the majority of patients, however, if required, a second dose may be taken, preferably after 5 minutes. . If an attack has not been relieved by 2 administrations, further administrations may be required. In these cases, patients should consult the doctor or the nearest hospital immediately
- Intermittent and long-term treatment:
- Adults: 50 µg fenoterol/20 µg ipratropium bromide (1 dose) up to 4 times a day.
- Children (over 6 years of age): The drug should only be used on medical advice and under the supervision of an adult. 50 µg fenoterol/20 µg ipratropium bromide (1 dose), up to a maximum of 3 actuations per day
- Hypersensitivity to Fenoterol, ipratropium bromide, atropine or any of its derivatives.
- Hypertrophic obstructive cardiomyopathy or tachyarrhythmia.
 WARNINGS AND PRECAUTIONS
- Use with caution in patients with underlying cardiovascular disorders (Monitor heart rate), diabetes, hypertension and hyperthyroidism.
- Immediate hypersensitivity reactions may occur, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm and oropharyngeal edema.
- Use with caution in patients with narrow-angle glaucoma (Worsening of narrow-angle glaucoma may occur).
- Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction
- Potentially serious hypokalemia may result from excessive Beta2 agonist therapy.
- Beta blockers: Beta blockers (medications used to slow down the heart beat), especially nonselective ones may block bronchodilatory effects of beta-agonists and produce severe bronchospasm. Patients with asthma should not normally be treated with beta blockers.
- Nonpotassium-sparing diuretics: As with other beta-agonists, Fenoterol may produce significant hypokalemia in some patients. Co-administration of nonpotassium-sparing diuretics (such as loop diuretics or thiazide diuretics) which cause hypokalemia as a side effect, may worsen hypokalemia. Hypokalemia may result in an increased susceptibility to arrhythmias in patients receiving digoxin. Additionally, hypoxia may aggravate the effects of hypokalemia on cardiac rhythm. Consider monitoring potassium levels
 PREGNANCY AND LACTATION
The potential risk for humans is unknown. this combination should be avoided as a precautionary measure in the first three months and during the later stages of pregnancy, taking in account the potential of Beta2 agonists to inhibit uterine contraction. During the further period of pregnancy the product should be administered only if clearly needed under the direct supervision of a doctor.
 SIDE EFFECTS
Possible side effects include: muscle tremors, nervousness, palpitations, tachycardia and dry mouth can occur, especially at high doses. Occasionally, dizziness, headache and sweating have been reported. In very rare cases local irritation or allergic reactions have been reported.
Treatment with Beta2-agonists can cause severe hypokalemia.
The use of anticholinergics, such as ipratropium bromide, can cause urinary retention in patients with obstruction of the urinary tract.