Carvedilol is a racemic mixture where the S(-) enantiomer is a beta adrenoceptor blocker and the R(+) enantiomer is both a beta and alpha-1 adrenoceptor blocker. It is currently used to treat heart failure, left ventricular dysfunction, and hypertension. The dual action of carvedilol is advantageous in combination therapies as moderate doses of 2 drugs have a decreased incidence of adverse effects compared to high dose monotherapy in the treatment of moderate hypertension.

Therapeutic Indication
● Atrial Fibrillation (AF)
● Chronic Stable Angina Pectoris
● High Blood Pressure (Hypertension)
● Left ventricular dysfunction
● NYHA Class I or II heart failure
● Chronic heart failure with reduced ejection fraction (NYHA Class III)


Mechanism of Action:
Carvedilol reduces tachycardia through beta adrenergic antagonism and lowers blood pressure through alpha-1 adrenergic antagonism. Carvedilol inhibits exercise induce tachycardia through its inhibition of beta adrenoceptors. Carvedilol's action on alpha-1 adrenergic receptors relaxes smooth muscle in vasculature, leading to reduced peripheral vascular resistance and an overall reduction in blood pressure. At higher doses, calcium channel blocking and antioxidant activity can also be seen. The antioxidant activity of carvedilol prevents oxidation of low density lipoprotein and its uptake into coronary circulation.

Absorption: Carvedilol has a bioavailability of 25-35%. Carvedilol has a Tmax of 1 to 2 hours. Taking carvedilol with a meal increases Tmax without increasing AUC.
Volume of distribution: Carvedilol has a volume of distribution of 1.5-2L/kg or 115L
Protein binding: Carvedilol is 98% protein bound in plasma. 95% of carvedilol is bound to serum albumin.
Metabolism: Carvedilol can be hydroxylated, demethylated. Carvedilol and its metabolites may undergo further sulfate conjugation or glucuronidation before elimination.
Route of elimination: 16% of carvedilol is excreted in the urine with <2% excreted as unmetabolized drug. Carvedilol is primarily excreted in the bile and feces.
The half-life of carvedilol is between 7-10 hours, though significantly shorter half-lives have also been reported.

Side Effects
Common side effects include:
● Dizziness.
● Unusual tiredness.
● Low blood pressure.
● Diarrhea.
● High blood sugar.
● Lack of energy or weakness.
● Slower heart rate.
● Weight gain

Absolute contraindications for the use of carvedilol include
● Severe hypotension
● Second or third-degree AV block
● Sick sinus syndrome
● Severe bradycardia in the absence of a functional pacemaker
● Severe decompensated heart failure requiring inotropic support
● History of a serious hypersensitivity reaction
● Clinicians should use caution in a patient with a history of asthma or reactive airway disease and should avoid use in patients with active wheezing due to beta-blocking properties.

Following medications can interact with carvedilol:
● Cimetidine 
● Clonidine 
● Cyclosporine 
● Digoxin
● Diltiazem
● Epinephrine
● Insulin
● Isocarboxazid
● Selegiline