Bisoprolol

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Bisoprolol
Systematic (IUPAC) name
1-[4-[2-(1-methylethoxy)ethoxymethyl]
phenoxy]-3-(1-methylethylamino)propan-2-ol
Identifiers
CAS number 66722-44-9
ATC code C07AB07
PubChem 2405
DrugBank APRD00257
Chemical data
Formula C18H31NO4 
Mol. mass 325.443 g/mol
Pharmacokinetic data
Bioavailability >90%
Metabolism Hepatic
Half life 10-12hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.

C(AU) C(US)
Legal status

℞ Prescription only
Routes oral

Bisoprolol is a drug belonging to the group of beta blockers, a class of drugs used primarily in cardiovascular diseases. More specifically, it is a selective type β1 adrenergic receptor blocker [1].

Contents

[edit] Pharmacology and biochemistry

[edit] β1 Selectivity

In comparison with other β1-selective β-blockers (atenolol, metoprolol, betaxolol) Bisoprolol proved to be the compound with the highest β1-selectivity in all in vitro and in vivo experiments and in all animal species investigated[2][3][4][5][6][7][8][9][10][11]

Image:Bisoprolol_selectivity.jpg

[edit] Antihypertensive effect

Bisoprolol had an antihypertensive effect in all hypertension models investigated. Bisoprolol reduced the blood pressure in conscious dogs with renal hypertension, accompanied by only a slight decrease in heart rate. In comparison with bisoprolol, propranolol had a weaker antihypertensive effect even at a considerably higher dose level [12]. Bisoprolol also reduced the blood pressure in rats with renal hypertension. In rats with spontaneous hypertension, the development of high blood pressure could be clearly reduced by chronic treatment with 7.5ug/ kg bisoprolol [13].

[edit] Cardioprotection

Myocardial ischaemia was induced by coronary occlusion in anaesthetised open-chest dogs. The changes in the epicardial ECG typical of myocardial hypoxia (ST segment elevation) were attenuated by bisoprolol. A dose of 4 μg bisoprolol per kg i.v. inhibited the ST segment elevation, induced by coronary occlusion, by 60%. This cardioprotective effect of bisoprolol was still present 40 minutes after injection [14].


[edit] Renin-angiotensin system

Bisoprolol inhibits basal and stimulated renin secretion. The release of renin was inhibited by about 65% and tachycardia by about 35% [15].

[edit] Duration of action

Bisoprolol has a long duration of action. The duration of action of bisoprolol was investigated in anaesthetised guinea pigs after i.v. administration; the inhibition of isoprenaline-induced tachycardia was measured at various times after the administration of the b-blocker. The drop in the action duration curve was flatter for bisoprolol than for propranolol [16]. The results indicate a long duration of action for bisoprolol.

[edit] Pharmacology of side-effects

The performed animal experimental investigations indicated for bisoprolol no unexpected or serious side-effects. Even at high doses [30 and 100mg/ kg, single oral administration (rats)], the sedative effects ascribed to b-blockers are less marked with bisoprolol than, for instance, with propranolol. Glucose tolerance was investigated in rats and was only slightly reduced at very high doses of bisoprolol, whereas it was considerably reduced with comparable doses of propranolol [17]. Bisoprolol did not influence the lipid metabolism of adult normolipemic rats after repeated administration nor was there any quantitative change in the serum lipoprotein pattern in young hyperlipemic rats with increased plasma cholesterol and decreased alpha-lipoprotein.

[edit] Pharmacokinetics

[edit] Bioavailability

The bioavailability of bisoprolol from film-coated tablets is about 90%.

[edit] Distribution

Only 30% of the bisoprolol in the blood is bound to plasma proteins [18]

[edit] Metabolisation and excretion

Bisoprolol is removed from the plasma via two equally effective routes of clearance – half of the dose is metabolised to inactive metabolites in the liver and the other half is excreted as the unchanged substance via the kidneys.

Image:Clearance_of_bisoprolol.jpg

[edit] Elimination half-life

Bisoprolol is removed from the plasma with a half-life of 10-12 hours [19]

[edit] Indications

Bisoprolol (Concor[20], Zebeta[21], Concore[22], Monocor[23]) can be used to treat cardiovascular diseases such as hypertension, coronary heart disease, arrhythmias, ischemic heart diseases and treatment of myocardial infarction after the acute event. Patients with compensated congestive heart failure may be treated with Bisoprolol as a comedication (usually together with an ACE inhibitor, a diuretic and a digitalis-glycosid, if indicated). In patients with congestive heart failure, it reduces the need for and the consumption of oxygen of the heart muscle. It is very important to start with low doses, as bisoprolol reduces also the muscular power of the heart, which is an undesired effect in congestive heart failure.

The drug is also used to treat other conditions, including dysautonomia, anxiety and hyperthyroidism (overfunction of the thyroid gland).

Bisoprolol will give a positive result in doping tests. [24]

[edit] References

  1. ^ FASS (Swedish official drug catalog) (labeling as "Selektiv beta1-blockerare" = selective beta1-blocker)
  2. ^ Harting J et al. Pharmacodynamic profile of the selective β1-adrenoceptor antagonist bisoprolol. Arzneimittel-Forsch 1986; 36: 200.
  3. ^ Häusler G et al. High β1-selectivity and favourable pharmacokinetics as the outstanding properties of bisoprolol. J Cardiovasc Pharmacol 1986; 8 (Suppl 11): 2.
  4. ^ Kaumann A J et al. Direct labelling of myocardial β1-adrenoceptors. Comparison of binding affinity of 3H- (–) - bisoprolol with its blocking potency. Naunyn Schmiedeberg’s Arch Pharmacol 1985; 331: 27.
  5. ^ Klockow M et al. Studies on the receptor profile of bisoprolol. Arzneimittel-Forsch 1986; 36: 197.
  6. ^ Manalan AS et al. Characterization of [3H] (±) carazolol binding to b-adrenergic receptors; Circ Res 1981; 49: 326.
  7. ^ Schliep H-J et al. Antagonistic effects of bisoprolol on several b-adrenoceptor-mediated actions in anaesthetised cats. Eur J Pharmacol 1986; 123: 253.
  8. ^ Schliep H-J et al. β1-Selectivity of bisoprolol, a new b-adrenoceptor antagonist in anesthetised dogs and guinea gigs. J Cardiovasc Pharmacol 1984; 6: 1156.
  9. ^ Schnabel P et al. Binding properties of ß-adrenoceptor antagonists used in heart failure at recombinant β1, β2 and β3-adrenoceptors. Eur Heart J 1999; 20 (Suppl): A 28.
  10. ^ Smith C, Teitler M. Beta-blocker selectivity at cloned human beta1 and beta2-adrenergic receptors. Cardiovasc Drugs and Ther 1999; 13: 123.
  11. ^ Wellstein A et al. Affinity and selectivity of b-adrenoceptor antagonists in vitro. J Cardiovasc Pharmacol 1986; 8 (Suppl 11): 36.
  12. ^ Harting J et al. Pharmacodynamic profile of the selective β1-adrenoceptor antagonist bisoprolol. Arzneimittel-Forsch 1986; 36: 200.
  13. ^ Harting J et al. Pharmacodynamic profile of the selective β1-adrenoceptor antagonist bisoprolol. Arzneimittel-Forsch 1986; 36: 200.
  14. ^ Harting J et al. Pharmacodynamic profile of the selective β1-adrenoceptor antagonist bisoprolol. Arzneimittel-Forsch 1986; 36: 200.
  15. ^ Harting J et al. Pharmacodynamic profile of the selective β1-adrenoceptor antagonist bisoprolol. Arzneimittel-Forsch 1986; 36: 200.
  16. ^ Harting J et al. Pharmacodynamic profile of the selective β1-adrenoceptor antagonist bisoprolol. Arzneimittel-Forsch 1986; 36: 200.
  17. ^ Lettenbaur H. EMD 33 512 (Bisoprolol): Prüfung der Wirkung auf die Serumglukosekonzentration an Ratten im Vergleich zu Propranolol. Merck KGaA, Darmstadt, 1979.
  18. ^ Bühring KU et al. Pharmacokinetics and metabolism of bisoprolol-C14 in three animal species and in humans. J Cardiovasc Pharmacol 1986; 8 (Suppl 11): 21.
  19. ^ Leopold G. Balanced pharmacokinetics and metabolism of bisoprolol. J Cardiovasc Pharmacol 1986; 8 ( Suppl 11): 16.
  20. ^ Bisoprolol at Merck Serono [1]
  21. ^ Prescription Drugs: Zebeta. Physicians' Desktop Reference. Retrieved on 2007-12-23.
  22. ^ Pharmaceuticals. Merck Philippines. Retrieved on 2008-01-01.
  23. ^ Products: Monocor. Biovail Corporation. Retrieved on 2007-12-23.
  24. ^ Ratiopharm packing slip, dated 03.08.2006
v • d • e
Beta blockers (C07)
Non-selective β antagonists
β1 antagonists (cardioselective)
Atenolol • Acebutolol • Celiprolol • Betaxolol • Bisoprolol • Esmolol • Metoprolol • Nebivolol
Mixed α1/β antagonists