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, mmHg Normal 90 - 119 60 - 79

Blood Pressure
Blood Pressure = Cardiac Output x Peripheral Vascular Resistance (PVR) Cardiac Output = Stroke Volume Heart rate

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, and , with several subtypes.

Adrenergic receptors
receptors have the subtypes 1 (a Gq coupled receptor) and 2 (a Gi coupled receptor). receptors have the subtypes 1, 2 and 3. All three are linked to Gs proteins (although 2 also couples to Gi), which in turn are linked to adenylate cyclase.

-adrenergic antagonist
First line drug therapy for hypertension

Isoproterenol or Isoprenaline 1 = 2 = Agonist

DCI

First described -blocker Has both agonist and antagonist property

(Napthylethanolamine)

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

- OCH2 group added between ring and side chain - Side chain moved to C2 to C1 - First clinically useful beta blocker

Most thoroughly studied and widely used drugs Standard for other beta blockers Non-selective beta blocker- Contraindicated for asthma patient

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

Cardioselective (1) Ocular toxicity

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

Cardioselective beta blockers

2o amine must be present for optimal activity

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.

1 selective blocker
Do not block 2 receptor in lung- safe for asthma patients Absence of blockage of vasular 2 receptor and thus decrease or eliminate possibility of peripheral resistance.