Beta-adrenergic blockers include-

Atenolol, Acebutol, Betaxolol, Bisoprolol,Cartelol,Esmolol, Labetatol,Metoprolol, Nadolol,Penbutolol, Pinodol, Propranolol, Solatol, Timolol,

Refer - Atenolol 

    
Interacting drugs -summary
 

+ Betablockers

Aluminium salts /Barbiturates/Calcium salts /   Choestyramine/Cloestipol/  NSAIDs/

Penicillin- Ampicillin/ Rifamipin/Salicylates/ Sulfinpyrazone

 bioavailability and plasma levels of certain beta blockers may be decreased by these agents, possibly resulting in a decreased   pharmacologic effect.
         
Calcium blockers 

pharmacologic effects of beta-blockers as well as   nifedipine and                               verapramil may be potentiated,. Diltiazem , felodipine and nicardipine
may increase the effect of the beta-blockers. Monitor cardiac function
and decrease the beta-blocker dose if necessary.

Contraceptives Oral  

bioavailability and plasma levels of certain betablockers may be                                   increased

Ethanol + Propranolol

Additive CNS inhibition , increased propranolol levels and increased clearance
 have occured
                     
Flecianide + Betablockers+ Flecainide

bioavailability of either agent may be increased, possibly increasing the  pharmacologic effects

Haloperidol  +   Betablocker/Betablockers + Haloperidol

pharmacologic effects (hypotensive episodes ) of both drugs may be
 increased

H2 antagonists + Metoprolol/Propranolol

 pharmacolkinetic parameters of betablocker metabolized by cytochrome
 P-450 may be altered by cimetidine, pharmacodynamic effects may be
 increased .Ranitidine may increase the bioavailability of metoptolol.
 
Hydralazine +  Metoprolol/propranolol / Betaprolol + hydrazine

serum levels and pharmacolgic efects of betablockers and hydrazine may
be enhanced

Loop diuretics + Propranolol

 propranolol plasma levels and cardiovascular effects may be enhanced.
Atenolol was not affected
 

MAO inhibitors + Metoprolol/Nadolol

bradycardia may develop during concurrent use             

Phenothiazine +  Propranol/ Betablockers + Phenothiazine

propranolol bioavailability and plasma levels and phenothiazine plasma
levels may be increased, possibly resulting in increased effects

Propafenone  +  Betablockers- Metoprolol/propranol

plasma levels of beta blockers metabolized by the liver may be increased

Quinidine  

 plasma betablocker levels may be increased  possibly resulting in increased effects
 

Quinolones + Ciproflocxacin  

bioavailability of betablockers metabolised by cytochrome P-450 may be increased
 

Thioamines  +  betablockers- Metoprolol/ Propranol

 pharmacokinetics of betablockers may be altered, increased pharmacologic effects
                      
Betablockers +

Acetaminophen     

 acetoaminophen clearance may be increased

Anticoagulants 

Propranol may increase the anticoagulant effect of warfarin 

  
Benzodiapines 

effects of benzodiapines may be increased by lipophylic beta blockers.     
  Atenolol does not interact

Clonidine   

 life-threatening and fatal increases in blood pressure have occured after
discontinuation of clonoidine in patients receiving a beta blocker or
 simultaneous withdrawal
 

Disopyramide 

disopyramide clearance may be decreased, adverse effects  may occur (sinus

Epinephrine 

 hypertensive episode followed by bradycardia may occur
 

Ergot alkaloids  

peripheral ischemia manifested by cold extremities, possible                                              peripheral gangrene

Nondepolraizing muscle relaxants 

betablockers may potentiate,counteract or have no effect on the actions of the nonpolarizing muscle relaxants

Prazosin     

 concurrent administration may increase the postural hypotension                                produced by  prazosin

Sulfonylureas

hypoglycemic effects of sulfonylureas may be attentuated

Theophylline 

reduced elimination of theophylline may occur. of one or  both agents.
                                             

Beta -Adrenergic blockers

Most adverse reactions are mild and transcient and rarely require withdrawal of therapy

Hypersensitivity-                                                                                                 Pharnyngitis, photosentivity reacion , erythematous rash, fever combined with aching and sore throat.larhngospam, respiaratory distress,angioedema, anaphylaxis

Cardiovascular-                                                                                               bradycardia, torsades de pointes and other serious new ventricullar arrhythmias, cardiovascular disorder, AICD discharge,

shortness of breath, peripheral vascular insufficiency (cold extremities, paresthesia of hands),arterial insufficiency usually of Raynauds type claudication, heart failure, CHF, sinoartrial block,cerbral vascular accident,

Endocrine-

Hyperglycemia, hypoglycemia, unstable diabetes.

GI-

Gastric/epigastric pain, flatulence, gastritis, constipation, nausea, diarrhea, colon problem,  dry mouth.  vomiting, heartburn, appetite disorder, anorexia, bloating, abdominal discomfort/and  renal and mesentric arterial thrombosis, ischemic colitis, 

GU-

Sexual dysfunction, impotence or decreased libido, dysuria, nocturia, pollakuria, urinary retention  or frequency, urinary tract infection, cystitis, renal colic, GU dosorder, renal failure.  

Hematologic-

Agranulocytrosis, nonthrombocytopenic or thrombocytopenic purpura, bleeding,
 thrombocytopenia, eosinophilia, leukopenia, pulmonary emboli, hyperlipdemia.

Dermatologic-

Rash, pruritus, skin irritation, increased pigmentation, sweating/hyperhodrosis,
 alopecia (includingreversible) dry skin, psoriasis (often reversible), acne, eczema, flushing,  exfoliative dermatitis, peripheral skin necrosis, psoriasiform rash, or exacerbation of psoriasis,  purpura, erythermatous rash.

Ophthamic-

Eye irritation/ discomfort, visual disturbances, dry/burning eyes, blurred vision,
conjunctivitis, ocular pain/pressure, abnormal lacremation.

Respiratory-

Bronchospasm, dyspnea, cough, bromncial obstruction, rales, wheezing, nasal stiffness,  pharyngitis, laryngospasm with respiratory distress, asthma, rhinitis, sinusitis, pulmonary problem,upper respiratory tract infection.

Musculoskeletal-

Joint pain, arthalgia, muscle cramps/pain, back.neckpain, arthritis, twitching/tremor,
localized pain, extremirty pain, myalgia.

Miscellaneous-

Facial swelling, weight gain, weight loss, decreased excercise tolerance, lupus
syndrome, Raynauds phenomenon, speech disorder, rogoors, earache, gout, asthenia, malaise,  fever, death.

Lab test abnormalities-
Propranol may elevate urea levels in patients with severe heart disease.
Propranol and metoprolol may cause elevated serum transaminase , alkaline phostase and LDH.
Tomol may produce slight increaes in BUN, serum potassium and serum uric acid and slight increases in hemoglobin hematocrit and HDL chloesterol, increase in liver function tests have  been reported.
Minor persistenet elevations in AST and ALT have occured in patients treated with Pinodol.

Beta -Adrenergic Blockers
Sinus,bradycardia,heart-block greater than 2nd degree untreated cardiac failure,  cardiogenic shock.
 
Special precautions:
Variant angina,acute MI, bronchospamic diseases,diabetic melitus,peripheral vascular disorders, hepatic & renal dysfunction,elderly patients.

Diabetes/hypoglycemia- beta blockers may blunt premonitory signs and symptoms (eg tachycardia,blood pressure changes)  of acute hypoglycemia. Atenolol does not potentiate insulin-induced  hypoglycemia and unlike nonselective blockers,does not delay recovery of blood glucose to normal  levels.

Thyrotoxicosis-

Beta blockers may mask clinical signs (eg tachycardia) of developing or continuing
 hyperthyroidism.Abrupt withdrawal may exacerbate symptoms of hyperthyroidism.

Serum lipid concntrations-

Beta blcokers may alter serum lipids including an increase in the
 concentration of total triglycerides, total cholesterol and LDL and VLDL cholesterol and a decrease  of HDL cholesterol.

Muscle weakness- beta blockade has potentiated muscle weakness consistent with certain myasthenic symptoms ( eg. diplopia, ptosis, generalized weakness). Timolol rarely increased  weakness in some patients with myasthenic symptoms.

Drug /Lab interactions-

These agents may produce hypoglycemia and interfere with glucose
or insulin tolerance tests.
Propranol may interfere with the glaucoma screening due to a reduction intraocular pressure.

Warnings-

Mortality- an exceesive mortality was seen in patients traeted with encainamide of flecanide, and a similar excess had been seen with moricizine.

Proarrhythmias- like other antiarrhythmic agents, solatol can provoke new or worsened
 ventricular arrhythmias,in some patients including sustained ventricular fibrillation, with potentially  fatal consequences.

Cardiac faliure- sympathetic stimulation is a vital component supporting circulatory function in CHF,  and beta blockade carries the potential hazard of further depressing myocardial contracttility and precipating more severe failure.
Administer cautiously in hypertensive patients who have CHF controlled  by digitalis and diuretics.

Wolff-Parkinson -White syndrome- in several carse tachycardia wss replaced by a severe bradycardia requiring a demand pacemaker after Popranolol administeration with as little as 5mg.

Abrupt withdrawal- occurence of beta-blocker withdrawal syndrome is contraversial. however,  hypersenitivity to catecholamines has been observed in patients withdrawn from beta-blocker therapy.

Peripheral vascular disease- treatment with beta antagonists reduces cardiac output and precipitate  or aggrevate the symptoms of arterial insiufficiency in patients with peripheral or mesentric vascular  disease..

 Excercise caution with such patients and observe closely for evidence of progression of aterial  obstruction.  

Nonallergic bronchospasm- (eg chronic bronchitis, emphysema)- in general do not administer  beta blockers to patients with bronchospastic diseases. Administer Nadolol, Timolol, Penbutrol,  Propranol, Solatol, Pinodol with caution, since they may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of B2 receptors.

Bradycardia- Metoprolol produces a decrease in sinus heart rate in most patients, this decrease  is greatest among patients with high initial rates and least among patients with low initial heart rates.

Phochromocytoma- It is hazardous to use propranol unless alpha adrenergic blocking agents are  in use. since this would predispose to serious blood pressure elevation.

Sinus bradycardia- Heart rate (< 50bpm) occured in 13% of patients receiving solatol in clinical trials. and lead to discontinuation in in about 3%.

Electrolyte disturbances- do not use Sotalol in patients with hypokalemia or hypomagnesmia prior  to correction of imbalace, as these conditions can exaggerrate the degree of QT prologation and  decrease the potential for torsades de pointes. 

Hypotension- if hypotension (systolic blood pressure < 90 mm Hg ) occurs, discontinue drug and carefully assess patients hemodynamic status and extent of myocardial damage.

Anaphylaxis- has occured and may include symptoms such as profound hypotensiuon , bradycardia with or without AV nodal block, severe sustained bronchospasm.and angioedema.  Deaths have occured.

Anesthesia and major surgery- necessity or desirability of withdrawing betablockers prior to major  surgery is contraversial. Beta blockade impairs the hearts ability to respond to beta adrenergically  mediated reflux stimuli.

AV block- Metoprolol slows AV conduction and may produce significant first (PR interval, second , or third degree heart block. Acute MI also produces heart block. If heart block occurs, discontinue  metoprolol.

Sick sinus syndrome- use sotalol only with extreme caution in patients with sick sinus syndrome  associated with symptomatic arrhythmias, because it may cause sinus bradycardia, sinus pauses or sinus arrest.

Renal /hepatic function impairment- use with caution.

Pregnancy- Safety for use during pregnancy has not been established. Use only when clearly needed.

Lactation- Although adverse effects in the infants have not been demonstrated in general, nursing  should not be undertaken by mother s receiving these drugs

Children- safety and efficacy for use in children have not been established

Indications:

Angina pectoris, hypertension,  acute myocardial infarction.

Dosage:
Initial dose- 50mg daily. Increase upto 100mg daily if required. Dosage  more than 100mg
unlikely to produce any additional benefit.

Overdosage-

Symptoms                                                                                                                Patients underlying disease state may contribute significantly. The main features are bradycardia   and hypotension                          

Cardiovascular- bradycardia, hypotension, CHF, cardiogenic shock,intravenrticular conduction,  AV Block (all degrees) asytole, pulmonary edema tachycardia and hypertension (pinodol) ststemic   vascular resistence ( propranalol)                               

CNS- depressed consciousness, coma, seizures, respiratory depression        

                                   
Other- bronchospasm, especially in persons with  obstructive pulmonary disease, hypoglycemia,  hyperkalemia.                                                               

Treatment

 1. Place patients in supine ositionand raise legs if necessary  to improve blood supply to the brain.
 2. Measure blood glucose and serum potassium levels
3. Conitinously monitor blood pressure and ECG.
4. Chest X-Rays may demonstrate pulmonary edema.
 5. Employ respiratory support, emesis (using syrup of Ipecac)  or lavage and administer charcoal if necessary.
 6. Treatment includes usual supportive measures
 7. Administer IV glucose to treat hypoglycemia
 8.Seizures respond to IV diazepam or if necessary phenytoin.
 9. Nadolol and atenolol can be removed by hemodialysis
 10. Propranol, labetolol, metoprolol , bisoprolol and timol are  not significantly                        dialyzable.
 11. In determining the duration of corrective therapy, consider their long duration of                effect
 12. Bradycardia- if hemodynamically stable no specific therapy s indicated.
       If hypotensive, give 0.6mg IV or epinephrine
  13. Ventricular premature contractions- are best treated with lidocaine or if                       necessary phenytoin.
  14. Cardiac failure- administer a  digitalis glycoside and oxygen
  15. Hypotension- place patient in trendelburg position, treat bradyarrhytmias.
       Administer IV fluids unless pulmonary edema  is present
  16. Heart block(secondary or third degree ) use isoproterenol or transvenous cardiac           pacemaker.
  17. Bronchospasm- administer a beta 2 stimulating agent, epinephrine or theophylline        derivative.

Missed dose-
1. Do not miss any doses.This is specially important when yountaking one dose per day. Some conditions may become worse oif not taken regularly.
2. If you do miss a dose take it as soon as possible.
3. However, if it is within 4 hours of your next dose ( 8 hours when using atenolol, betaxolol.bisoprolol,
    Cartteolol, labetalol, nadolol, pnbutolol,solatol, or extended release (longacting) metoprolol, oxprenonol, or  propranolol) skip the missed dose and go back to your dosing schedule
4. Do not double doses.

As per US FDA guidelines as per USPDA 1997

It is the intention to bring out the salient features. Hence relevent details as prescribed by US FDA guidelines as per USPDA 1997  are brought out clearly in the following chapters. 

Descriptons are detailed only to the Group Head and the indiviual items can be seen by visiting the Web Site

-Beta-adrenergic blockers include-

Atenolol, Acebutol, Betaxolol, Bisoprolol,Cartelol,Esmolol, Labetatol,Metoprolol, Nadolol, Oxypeprenol, Penbutolol, Pinodol, Propranolol, Solatol, Timolol,

Refer - Atenolol 

1. Do not discontinue medication abruptly, except on advise of physician. Sudden cessation of   therapy may precipitate or exacerabate angina.

2. Consult pharmacist or physician before using other products which may contain alpha  adrenergic stimulants (eg. nasal decongestants, otc cold preparations)

3. Notify physician if symptoms of CHF occur (eg. difficult breathing, especially on exertion or when lying down., night cough, swelling of the extremities).

4. Notify physician if any of these occur; slow pulse rate, dizziness, lightheadedness, confusion or   depression, skin rsh, fever, sore throat or unusual bleeding or bruising.

5. May produce drowsiness, lightheaedness, blurred vision, patient should observe caution while  driving or performing tasks requiring alertness, coordination or physical dexterity.

6. Allergies- Tell your doctor if you had any unusual or allergic reactions to bet-blockers.
    Tell your doctor if you are allergic to any other substances such as foods, or drink

7. Pregnancy- use of beta-blockers during  pregnancy has been associated with low blood sugar,   breathing problems, a slower heart rate, low blood pressure in the new born infant.

8. Breast-feeding- it is not known whether bisoprolol, carteolol or pentbutol pass into breast milk.  Mothers who are taking beta blockers and who wish to breast feed should discuss with the doctor.

9. Children- some of these medicines have been used in children and in effective doses, have not shown to cause side effects.

10. Elderly- Side effects are more likely to occur in elderly. Beta blockers may reduce tolerance to   cold temperature in elderly patients

11. Other medicines- Tell your doctor if you are taking any other  medicines-
    
      Allergy shots or  Allergy skin tests - betablockers may increase the risk of serious       allergic reactions

 12. Other medical problems- Tell your doctor if you have other medical problems-
     
    Allergy or  Bronchitis or Emphysema - betablockers may increase trouble in                 breathing  of this medicine may be increased because of slow removal from the body
 
   13. Missed dose-
      If you miss of this medicine take it as soon as possible.
      However, it it is within 4 hours of your next dose ( 8 hrs if you are using atenolol,              labetolol, madolol, penbutol, solatolol or extended release metoprolol,oxeprenol, or          propranol,)  skip the next dose and go back to your dosing schedule     

      Do not double doses.

Food enhances the bioavialabilty of Metoprolol andPropranol . This effect is not noted with Nadolol, Bisoprolol or Pinodol. Sotalol absorption is reduced approximately by a standard meal.

Pregnancy:
Safety for use during pregnancy has not been established. Use with caution in pregnant woman.

Lactation:
Known to be excreted in breast milk. Nursing should not be undertaken by mothers receiving these drugs.

Children:
Safety and efficacy for use in children have not been established.