Beta Blockers

PHRM 304

Blood Pressure

• Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood vessels.

Category Systolic, mmHg Diastolic, mmHgNormal 90 - 119 60 - 79

Blood Pressure

• Blood Pressure = Cardiac Output x Peripheral Vascular Resistance (PVR)

• Cardiac Output = Stroke Volume × Heart rate

β1

α1

Adrenaline or Epinephrine(Catechol amine)

Noradrenaline or Norepinephrine(Catechol amine)

Fig: Proposed binding of NE to the beta receptor

Adrenergic receptors

• The adrenergic receptors (or adrenoceptors) are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline (norepinephrine) and adrenaline (epinephrine).

• There are two main groups of adrenergic receptors, α and β, with several subtypes.

Adrenergic receptors

• α receptors have the subtypes α1 (a Gq coupled receptor) and α2 (a Gi coupled receptor).

• β receptors have the subtypes β1, β2 and β3. All three are linked to Gs proteins (although β2 also couples to Gi), which in turn are linked to adenylate cyclase.

β-adrenergic antagonist

• First line drug therapy for hypertension

β1 = β2 = Agonist

Isoproterenol or Isoprenaline

DCI

First described β-blockerHas both agonist and antagonist property

3

4

- Less intrinsic sympathomimetic activity than DCI- Formed tumor in animal

(Napthylethanolamine)

• Most thoroughly studied and widely used drugs Standard for other beta blockers

• Non-selective beta blocker- Contraindicated for asthma patient

-— OCH2 – group added between ring and side chain

- Side chain moved to C2 to C1

- First clinically useful beta blocker

*

Propranolol

• Potency improved• R enantiomer is 100 times less potent than S

enantiomer

• Para substitution of sufficient size in aromatic ring along with the absence of meta substituent.

Cardioselective (β1)Ocular toxicity

*

2o amine must be present for optimal activity

Cardioselective beta blockers

Atenolol

• Atenolol is produced as a racemic mixture of the two enantiomers.

• The S(–)-form is the active isomer with no significant pharmacological activity reported for the R(+)-isomer.

β1 selective blocker

• Do not block β2 receptor in lung- safe for asthma patients

• Absence of blockage of vasular β2 receptor and thus decrease or eliminate possibility of peripheral resistance.