Tenormin

Cardiovascular System , Drugs / September 19, 2016

Class: Cardiovascular System
Dosage Form: Tablets
Description: Cardioselective beta-1-receptor antagonist
Stock: Available
Manufacturer: AstraZeneca

Composition:

1. Tablets:
Atenolol…………..25, 50 or 100 mg
2. Vials (10 ml):
Atenolol………………………….5 mg

Properties:

Pharmacodynamics
Atenolol is a selective beta-1-blocker (i.e acts preferentially on beta-adrenergic receptors in the heart). Selectivity of the drug decreases with increasnig dose.
Atenolol is without intrinsic sympathomimetic and membrane stabilising activities and as with other beta-blockers, has negative inotropic effects (and is therefore contraindicated in uncontrolled heart failure).
As with other beta-blockers, the mode of action of atenolol in the treatment of hyperetnsion is unclea.
It is probably the action of atenolol in reducing cardiac rate and contractility which makes it effective in eliminating or reducing the symptoms of patients with angina.
It is unlikely that any additional ancillary properties possessed by S-atenolol, in comparison with the racemic mixture, will give rise to different therapeutic effects.
Tenormin is effective and well-tolerated in most ethnic populations although the response may be less in black patients.
Tenormin is effective for at least 24 hours after a single oral dose. The drug facilitates compliance by its acceptability to patients and simplicity of dosing. The narrow dsoe range and early patient response ensure that the effect of the drug in individual patients is quickly demonstrated.
Tenormin may, with care, be used successfuly in the treatment of patients with respiratory disease, who cannot tolerate non-selective beta-blockers.
Early intervention with Tenormin in acute myocardial infarction reduces infarct size and decreases morbidity and moratlity. Fewer patients with a threatened infarction progress to frank infarction; the incidence of ventricular arrhythmias is decreased and marked pain relief may result in reduced need of opiate analgesics. Early morality is decreased. Tenormin is an additional treatment to standard coronary care.

Pharmacokinetics
Following intravenous administration, the blood levels of atenolol decay tri-exponentially with an elimination half-life of about 6 hours. Throughout the intravenous dose range of 5-10 mg the blood level profile obeys linear pharmacokinetics and beta-adrenoreceptor blockade is still measurable 24 hours after a 10 mg intravenous dose.
Absorption of atenolol following oral dosing is consistent but incomplete (approx. 40-50%) with peak plasma concentrations occurring 2-4 hours after dosing.
The atenolol blood levels are consistent and subject to little variability. There is no significant hepatic metabolism of atenolol and more than 90% of that absorbed reaches teh systemic circulation unaltered. The plasma half-life is about 6 hours but this may rise in severe renal impairment since the kidney is the majour route of elimination.
Atenolol penetrates tissues poorly due to its low lipid solubility and its concentrations in brain tissue is low. Plasma protein binding is low (approx. 3%).

Indications:

Tenormin is indicated in:

  • Hypertension
  • Angina pectoris
  • Cardiac arrhythmias
  • Myocardial infarction (Early and late intervention)

Contraindicatons:

Tenormin, as with other beta-blockers, should not be used in patients with any of the following:

  • Known hypersenstivity to the active substanc, or to any of the product ingredients
  • Bradycardia (<45 bpm)
  • Cardiogenic shock
  • Hypotension
  • Metabolic acidosis
  • Severe peripheral arterial circulatory disturbances
  • Secord or thid degree heart block
  • Sick sinus syndrome
  • Untreated phaeochromocytoma
  • Uncontrolled heart failure

Drug Interactions:

The following interactions have been reported:

  • Calcium channel blockers (e.g. Verapamil, Dilitiazem):
    • Combined use of beta-blockers and calcium channel blockers with negative inotropic effects can lead to an exaggeration of these effects particularly in patients with impaired ventricular function and/or sino-atrial or atrio-ventricular conduction abnormalities.
    • This may result in severe hypotenson, bradycardia and cardiac failure. Neither the beta-blocker nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.
  • Dihydropyridines (e.g. Nifedipine):
    • Combined therapy may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency
  • Digitalis glycosides (e.g. Digoxin):
    • In association with beta-blockers, may increase atrioventricular conduction time
  • Clonidine:
    • Beta-blockers may exacerbate the reobound hypertension, which can follow the withdrawal of clonidine
    • If the two drugs co-administered, the beta-blocker should be withdrawn several days before discontinuing clonidine
    • If replacing clonidine by beta-blocker, the introduction of beta-blockers should be delayed for several days after clonidine administration has stopped
  • Class I Antiarrhythmics (e.g. Disopyramide, Amiodarone):
    • May have a potentiating effect on atrial-conduction time and induce negative inotropic effects
  • Sympathomimetics (e.g. adrenaline):
    • May counteract the effect of beta-blockers
  • Insulin and Oral Antidiabetics:
    • Intensification of blood sugar lowering effects of these drugs
    • Symptoms of hypoglycemia, particularly tachycardia, may be masked
  • Prostaglandin Synthetase Inhibiting Drugs (e.g. Ibuprofen, Indomethacin):
    • May decrease hypotensive effects of beta-blockers
  • Anesthetics:
    • Attenuation of the reflex tachycardia and increase risk of hypotension
    • Anesthetics causing myocardial depression are best avoided

Side Effects:

Tenormin is well tolerated. In clinical studies, the undesired events reported are usually attributable to the pharmacological actions of atenolol.
The following undesired effects are listed according to frequency and body system affected below:
1. Cardiac Disorders:

  • Common: Bradycardia
  • Rare:
    • Heart failure
    • Precipitation of heart block

2. Vascular Disorders:

  • Common: Cold extremeties
  • Rare:
    • Postural hypotension which may be associated with syncope
    • Intermittent claudication may be increased if already present
    • Raynaud’s phenomenon in susceptible patients

3. Nervous System Disorders:

  • Rare: Dizziness, headache, paresthesia

4. Psychiatric Disorders:

  • Uncommon: Sleep disturbances of the type noted with other beta-blockers
  • Rare:
    • Mood changes
    • Nightmares
    • Confusion
    • Psychoses and hallucinations

5. Gastrointestinal Disorders:

  • Common: Gastrointestinal disturbances
  • Rare: Dry mouth

6. Investigations:

  • Uncommon: Elevations of transaminase levels
  • Very rare: An increase in ANA (antinuclear antibodies) has been observed, however, the clinical relevance of this is not clear

7. Hepatobiliary Disorders:

  • Rare: Hepatic toxicity including intrahepatic cholestasis

8. Blood and Lymphatic System Disorders:

  • Rare:
    • Alopecia
    • Psoriasiform skin reactions
    • Exacerbations of psoriasis
    • Skin rashes
  • Not known:
    • Hypersensitivity reactions, incluing angioedema and urticaria

9. Eye Disorders:

  • Rare:
    • Dry eyes
    • Visual disturbances

10. Respiratory, Thoracic and Mediastinal Disorders:

  • Rare:
    • Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints

11. General Disorders and Administration Site Conditions:

  • Common: Fatigue

Discontinuance of the drug should be considered if, according to clinical judgement, the well-being of the patient is adversely affected by any of the above reactions.

Dosage and Administration:

1. Hypertension:

  • 1 tablet daily
  • Most patients respond to 100 mg daily given orally as a single dose
  • Some patients, however, will respond to 50 mg given as a single daily dose
  • The effect will be fully established after one to two weeks
  • A further reduction in blood pressure may be achieved by combining Tenormin with other antihypertensive agents, for example, with a diuretics

2. Angina:

  • Most patients will respond to 100 mg given orally once or 50 mg given twice daily
  • It is unlikely that additional benefit will be gained by increasing the dose

3. Cardiac Arrhythmias:

  • A suitable initial dose is 2.5 mg (5 ml) injected intravenously over a 2.5 minute period (i.e. 1 mg/minute)
  • This may be repeated at 5 minute intervals until a response is observed, up to a maximum dosage of 10 mg
  • If Tenormin is given by infusion, 0.15 mg/kg bodyweight may be administered over a 20 minute period
  • If required, the injection or infusion may be repeated every 12 hours
  • Having controlled the arrhythmias with inrravenous Tenormin, a suitable oral maintenance dosage is 50-100 mg daily, given as a single dose

4. Myocardial Infarction:
a) Early intervention after acute myocardial infarction:

  • For patients suitable for treatment with intravenous beta-blockade and presenting within 12 hours of the onset of chest pain, Tenormin 5-10 mg should be given by slow intarvenous injection (1 mg/minute) followed by Tenormin 50 mg orally about 15 minutes later, provided no untoward effects have occurred from the intravenous dose
  • This should be followed by a further 50 mg orally, 12 hours after the intravenous dose and then 12 hours later by 100 mg orally, once dailly
  • If braycardia and/or hypotension requiring treatment, or any other untoward effects occurr, Tenormin should be discontinued

b) Late intervention after acute myocardial infarction:

  • For patients presenting some days after suffering an acute MI, an oral dose of Tenormin 100 mg daily is recommended for long-term prophylaxis of myocardial infarction

5. Elderly:
Dosage requirements may be reduced, especially in patients with impaired renal function.

6. Children:
There is no pediatric experience with Tenormin and for this reason it is not recommended for use in children.

7. Renal Failure:
Since Tenormin is excreted via the kidneys, the dosage should be reduced in cases of severe impairment of renal function. No siginificant accumulation of Tenormin occurs in patients who have a creatinine clearance greater than 35 ml/min/1.73 m2 (normal range is 100-150 ml/min/1.73 m2).
For patients with a creatinine clearance of 15-35 ml/min/1.73 m2 (equivalent to serum creatinine of 300-600 µmol/L) the oral dose should be 50 mg daily and the intravenous dose should be 10 mg once every two days.
For patients with a creatinine clearance of <15 ml/min/1.73 m2 (equivalent to serum creatinine of >600 µmol/L) the oral dose should be 25 mg daily or 50 mg on alternate days and the intravenous dose should be 10 mg once every four days.
Patients on hemodialysis should be given 50 mg orally after each dialysis; this should be done under hospital supervision as marked falls in blood pressure can occur.

Overdosage:

Signs and Symptoms
The symptoms of overdosage may include bradycardia, hypotension, acute cardiac insufficiency and bronchospasm.
General treatment should include: close supervision, treatment in an intensive care ward, the use of gastric lavage, activated charcoal and a laxative to prevent absorption of any drug still present in the gastrointestinal tract, the use of plasma or plasma substitutes to treate hypotension and shock. The use of hemodialysis or hemoperfusion may be considered.

Treatment
Excessive bradycardia can be countered with atropine 1-2 mg intravenously and/or a cardiac pacemaker. If necessary, this may be followed by a bolus dose of glucagon 10 mg intravenously. If required, this may be repeated or followed by an intravenous infusion of glucagon 1-10 mg/hour depending on response. If no response to glucagon occurs or if glucagon is unavailable, a beta-adrenoreceptor stimulant such as dobutamine 2.5 to 10 mcg/kg/minute by intravenous infusion may be given. Dobutamine, because of its positive inotropic efffect could also be used to treat hypotension and acute cardiac insufficiency. It is liekyl that these doses would be inadequate to reverse the cardiac effects of beta-blocker blockade if a large overdose has been taken. The dose of dobutamien should therefore be increased if necessary to achieve the required response according to the clinical condition of the patient.
Bronchospasm can usually be reversed by bronchodilators.

Pregnancy and Lactation:

Pregnancy
Tenormin
crosses the placental barrier and appears in cord blood. No studies have been performed on the use of Tenormin in the 1st trimester and the possibility of fetal injury cannot be excluded. Tenormin bas been used under close supervision for the treatment of hypertension in the 3rd trimester. Administration of Tenormin to pregnant women in the management of mild to moderate hypertension has been associated with intra-uterine growth retardation.
Use of Tenormin in women who are, or may become, pregnant requires that the anticipated benefit be weighed against the possible risks, paritcularly in the first and second trimesters, since beta-blockers, in general, have been associated with a decrease in placental perfusion which may result in intra-uterine deaths, immature and premature deliveries.

Lactation
There is significant accumulation of Tenormin in breast milk.
Neonates born to mothers who are receiving Tenormin at parturition or breast-feeding may be at risk of hypoglycemia and bradycardia.

Warnings:

Tenormin as with other beta-blockers:

  • Should not be withdrawn abruptly. The dosage should be withdrawn gradually over a period of 7-14 days, to facilitate a reduction in beta-blocker dosage. Patients should be followed during withdrawal, especially those with ischemic heart disease
  • When a patient is scheduled for surgery, and a decision is made to discontinue beta-blocker tehrapy, this should be done at least 24 hours prior to the procedure. The risk benefit assessment of stopping beta-blockade should be made for each patient. If treatment is continued, an anesthetic with little negative inotropic activity should be selected to minimise the risk of myocardial depression. The patient may be protected against vagal reactions by intravenous administration of atropine.
  • Although contraindicated in uncontrolled heart failure, may be used in patients whose signs of heart failure have been controlled. Caution must be exercised in patients whose cardiac reserve is poor.
  • May increase the number and duration of angina attacks in patients with Prinzmetal’s angina due to unopposed alpha-receptor mediated coronary artery vasoconstriction. Temornin is a beta-1-selective beta-blocker; consequently, its use may be considered although utmost caution must be exercised
  • Although contraindiated in severe peripheral arterial circulatory disturbances, may also aggravate less severe peripheral arterial circulatory disturbances
  • Due to its negative effect on conduction time, caution must be exercised if it is given to patients with first degree heart block
  • May mask the symptoms of hypoglycemia, in particular, tachycardia
  • May mask the signs of thyrotoxicosis
  • Will reduce heart rate, as a result of its pharmacologic action. In the rare instances when a treated patient develops smyptoms which may be attributable to a slow heart rate and the pulse rate drops to less than 50-55 bpm at rest, the dose should be reduced
  • May cause a more severe reaction to a variety of of allergens, when given to patients with a history of anaphylactic reaction to such allergens. Such patients may be unresponsive to the usual doses of adrenaline used to treat the allergic reactions.
  • May cause a hypersensitivity reaction including angioedema and urticaria
  • Should be used with caution in the elderly, staring with a lesser dose
  • Since Tenormin is excreted via the kidneys, dosage should be reduced in patients with a creatinine clearance of below 35 ml/min/1.7 m2
  • Although cardioselective beta-1-blockers may have less an effect on lung function than non-selective beta-blockers, they should still be avoided in patients with reversible obstructive airway disease, unless there are compelling clinical reasons for their use. Where such reasons exist, Tenormin may be used with caution. Occasionally, some increase in airway resistance may occur in asthmatic patients, however, and this may usually be reversed by commonly used dosage of bronchodilators such as salbutamol or isoprenaline.
  • As with other beta-blockers, in patients with a phaeochromocytoma, an alpha-blocker should be given concomitantly

Packaging:

Box of one strip of 14 tablets.
Vial of 10 ml.

Storage:

Store at room temperature, protected from light and moisture.

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