Carvedilol

IUPAC nomenclature

(±)-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine

Classification

Carvedilol is a mixed α/ß blocker.

Physiochemical Properties

Mechanism of Action

• Carvedilol inhibits ß-adrenoceptors which results in inhibition of the exercise induce tachycardia.
• Smooth muscles in vasculature relaxes due to the action of carvadilol on α₁-adrenergic receptors, which further results in reduced peripheral vascular resistance and an overall reduction in blood pressure.
• Calcium channel blocking and antioxidant activity can also be seen at higher doses of the drug.
• The antioxidant activity of drug prevents oxidation of low density lipoprotein and thus, prevents the uptake of same into coronary circulation. [1]

Structure Activity Relationship

• The type of N-substitutions such as N-isopropyl and N-t-butyl eliminates α₁-activity.
• Arylalkyl groups with α-methyl substituent returns back the α­₁-affinity but not the intrinsic activity.
• The ß-blocking activity is almost 10-100 that of its α₁-blocking activity. [2]

Method of synthesis

i. Condensation of 4-hydroxycarbazole with epichlorohydrin produces 4-(2,3-epoxypropoxy)carbazole.

ii. The latter compound is then reacted with 2-(2-methoxyphenoxy)ethanamine to produce carvedilol.[3]

Therapeutic Uses

Carvedilol is used for treatment of:

• Hypertension
• Prevention of strokes
• Prevention of heart attacks
• Prevention of kidney problems

Side Effects

Side effects of carvedilol are:

• Dizziness
• Tiredness
• Impotency
• Diarrhea
• Drowsiness
• Lightheadedness

MCQs

Q.1 Carvedilol inhibits exercise induce tachycardia through?

a) Agonism of α₁-adrenergic receptors

b) Agonism of α₂-adrenergic receptors

c) Antagonism of ß-adrenergic receptors

d) α-adrenergic antagonism

Q.2 Therapeutic use of drug Carvedilol is/are?

a) Glaucoma

b) Hypertension

c) Diabetes

d) All of the above

Q.3 Which amongst the following are the correct statements with respect to the SAR of drug Carvedilol-

I. The type of N-substitutions such as N-isopropyl and N-t-butyl eliminates α1-activity.

II. Arylalkyl groups with α-methyl substituent returns back the α¬1-affinity but not the intrinsic activity.

III. The ß-blocking activity is almost 1.5-folds that of its α1-blocking activity.

a) I, II

b) I, III

c) I, II, III

d) II

Q.4 The starting chemicals required for the synthesis of drug Carvedilol?

a) 2-(4-hydroxyphenyl-ethanol) and benzyl halide

b) Benzyl halide and epoxide

c) 4-hydroxycarbazol and epichlorohydrin

d) None of the above

Q.5 Correct sequence for the True/False for the physiochemical properties of the drug betaxolol-

I. Molecular weight = 307.4 gm/mol.

II. Melting point = 114.5°C

III. Octanol/water partition coefficient = 3.8

a) TFT

b) FFT

c) TTT

d) FTT

Q.6 Correct statements for the IUPAC nomenclatures of the drugs are?

I. Betaxolol: (RS)-1-{4-[2-(cyclopropylmethoxy)ethyl]-phenoxy}-3-(isopropylamino)propan-2-ol

II. Carvedilol: (RS)-1-{4-[(2-Isopropoxyethoxy)methyl]phenoxy}-3-(isopropylamino)propan-2-ol

III. Bisoprolol: (±)-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine

IV. Propranolol: (RS)-1-(1-methylethylamino)-3-(1-naphthyloxy)propan-2-ol.

a) I, II, IV

b) I, IV

c) III, IV

d) I, II, III, IV

 Q.7 Match the following drugs with their correct classifications-

 a) i-A, ii-C, iii-D, iv-B

b) i-D, ii-B, iii-C, iv-A

c) i-A, ii-C, iii-D, iv-B

d) i-B, ii-D, iii-C, iv-A

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ANSWERS

1-c

2-b

3-a

4-c

5-d

6-a

7-a

REFERENCES