Alpha/Beta - Adrenergic blocking agents include-

Labetalol, Carvedilol,

 Interacting drugs- summary

Cravediol +

 Antidiabetic agents

agents with beta-blocking properties may enhance the blood sugar-reducing effect of insulin and oral hypoglycaemics. Patients taking insulin or oral hypoglycaemics, regular monitoring of blood glucose is recommended.

Calcium blockers

incr isolated instances of conduction disturbance (rarely with hemodynamic compromise) have been observed when cravediol is coadministered with diltiazem. If carvediol is to be administered with verapramil or diltiazem type, it is recommended that ECG and blood pressure is monitored

Clonidine

 concomittant administration of clonidine with agents with beta blocking properties may potentiate blood pressure and heart rate lowering effects. Discontinue beta blocking agent first. Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage.

Digoxin

digoxin concentrations are increased by about 15% during concurrent use. Increased monitoring of digoxin is recommended, when initiating, adjusting or discontinuing carvediol.

+ Carvediol

 Cimetidine

 cimetidine increased carvediol AUC by about 30% but caused no changes in C max

Rifampin

rifampin reduced plasma concentration of carvediiol by about 70%. 

Cardiovascular-

AV block, extrasystoles, hypertension, hypotension, palpitations,peripheral ischemia, syncope, angina, arrhythmia, atrial fibrillation, bundle branch block, cardiac failure, myocardial ischemia, cerebrovascular disorder

CNS-

Ataxia, hypesthesia, paresthesia, vertigo, depression, nervousness, migraine, neuralgia, paresis, amnesia confusion.

Respiratory-

Asthma, allergy, bronchospasm, respiratory alkalosis, eosinophilia.

GU-

male- Decreased libido, impotence in males.

Dermatologic-

Pruritus, rash, alopecia.

Special senses-

abnormal vision, tinnitus,decreased hearing Metabolic/nutrional- hypercholesterolemia, hyperglycermia, hyperuricemia, glycosuria, increased weight

Hematologic-

anemia, leukopenia, increased BUN, decreased HDL, hyperkalemia, hypokalemia, increased NPN,increased alkaine phosphatase, atypical lymphocytes

Miscellaneous-

asthenia,hot flushes,leg cramps, malaise, dry mouth,sweating increased, myalgia

Patients with NYHA class IV decompensated cardiac failure; bronchial asthma (two cases of death from status asthmaticus have been reported in patients receiving single doses of carvediol) or related bronchiospatic conditions;

second or third degree AV block; cardiogenic shock; severe bradycardia;

hypersensitivity to the drug.

Special Precautions:

Cardiovascular effects- since carvediol has beta blocking activity, it should not be discontinued abruptly, particularly in patients with ischemic heart disease. Discontinue over 1 to 2 weeks.

Anaphylatic reactions- while taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the uuusal doses of epinephrine used to treat allergic reaction.

Bronchospasm nonallergic- eg chronic bronchitis,

emphysema- patients with bronchospastic disease should in general not receive beta-blockers. Carvediol may use with caution.However, it is prudent to use the smallest efective dose.

Drug/Food interaction- when taken with food rate of absorpion is slowed but the extent of bioavailabiliy is not affected.

Warnings

 Cardiac failure- hypertensive patients who have CHF controlled with digitalis, diuretics or an angiotensin converting enzyme inhibitor should use carvediol with caution.

Hepatic injury- hepatic injury has been revesible and has occured after short or long term therapy with minimal clinical symptomatology. No deaths due to liver function abnormalities have been reported.

Peripheral vascular disease- betalockers can precipitate or aggravat symptoms of arterial insufficiency in patients with peripheral vascular disease. Excercise caution in such individuals.

Anesthesia and major surgery- if cardiliol treatment is to be continued perioperatively take particular care when anesthetic agents which depress myocardial function eg. cyclopropane, tricholroethylene , are used.

Diabetes and hypoglycemia- caution patients subject to spontaneous hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic agents about trhe possibilities of masking some of the manifestations of hypoglycemia, and use carvediol with caution.

Thyrotoxicosis- abrupt withdrawal of beta blockers may be folllowed by an exacerbation of the symptoms of hyperthyroidism or may precipitate thyroid storm.

Hepatic function impairment- use of carvediol in patients with clinically manifest hepatic impairment is not recommended.

Elderly- there is no notable differences in efficacy or the incidence of adverse events between older and younger patients.

Pregnancy- use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation- beceuse of the potential for adverse reactons to the nursing infants, decide whether to discontinue nursing or discontinue the drug depending on the importance of the drug to the mother.

Children- safety and efficacy in patients < 18 years of age have not been established.

Essential hypertension

Dosage:

Recommended dosage is 6.25mg twice daily. Maintain the dose for 7 to 14 days and then increase to 12.5mg twice daily

Overdosage- Symptoms

Ovedosage may cause severe hypotension, bradycardia, cardiac insufficiency, cardiogenic shock and cardiac arrest.

Respiratory problems, bronchospasms, vomiting, lapses of consciousness, and generalized seizures may also occur.

Treatment

1. Place the patients in a supine position and where necessary. Keep under observation and treat under intensive care conditions

2. Gastric lavage or pharmacologically induced emesis may be used shortly after ingestion.

3. The following agents are administered-

i. For excessive bradycardia- Atropine 2mg IV

ii. To support cardiovascular function- Glucogon 5 to 10 mg IV rapidly over 30 seconds,followed by a continous infusion of 5mg/hr sympathomimetics (dobutamine, isoprenaline, ephinephrine) at doses according to body weight and effect.

iii. For therapy-resistent bradycardia, perform pacemaker therapy

iv. For bronchospasm- give beta sympathomimetics ( as aerosol or IV) or aminophylline IV

v. In the event of seizures- slow IV injection of diazepam or clonazepam is ecommended

vi. In the event of severe intoxification where there are symptoms of shock, treatment with anitdotes must be continued for sufficiently long period of time consistent with the 7 to 10 hour, half-life of carvediol.

1. Do not interrupt or discontinue using carvediol without a physicains advice.

2. A drop in blood presure may be experienced when standing,resulting in dizziness and rarely fainting. Patients should sit or lie down when these symptoms of lowering of blood pressure occur. Consult your physician.

3. Avoid driving or hazardous tasks if experience dizziness or fatigue.

Pharmacology:

Carvediol an antihypertensive agent is a racemic mixture in which beta adrenoreceptor blocking activity is present. The mechanism by which beta blockade produces an antihypertensive effect has not been established.

Pharmacokinetics:

Carvediol is rapidly and extensively absorbed following oral administration, with bioavailability of about 25% to 35% due to significant degree of first pass metabolism. The apparent elimination half-life generally ranges from 7 to 10 hours.

When taken with food, the rate of absorption is slowed but extent of bioavailability is not affected.

Taking with food minimises the risk of orthostatic hypotension.

Pregnancy:

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation:

Because of potential for serious adverse reactions to nursing infants, decide whether to discontinue the drug or discontinue nursing.

Children-

Safety and efficacy in patients < 18 years of age have not been established.