G7iv: Define the MoA + A/E of metoprolol & GTN when used to treat MI
- Myocardial ischaemia = occurs when O2 supply to myocardium does not meet demand
- O2 demand of heart determined by 2 factors:
- Work required to eject blood
- Body’s metabolic requirements (exercise ↑O2 consumption x 5)
- Factors required to meet CO: CO = HR x SV
- All these factors contribute to myocardial O2 consumption:
- HR
- PreL
- After L (SVR, LV wall tension, LVOT, Aortic Root P, Aortic compliance)
- Contractility
- Any ↑in these factors = ↑myocardial work = ↑myocardial O2 consumption
- Aim of pharmacotherapy is to ↓myocardial O2 demand to prevent ischaemia
Definition
Metoprolol
Cardioselective β1-blocker sympatholytic
GTN
Organic nitrate vasodilator
MoA
Metoprolol
Competitive β1 adrenergic antagonist
∴binds β1 receptors of heart
↓
Competing with NA/Adr for binding sites
↓
∴GS protein not activated
↓
∴↓cAMP formation
↓
∴↓HR & FoC
GTN
Organic nitrates → denitrated to produce NO
NO → diffuses into smooth m. cells
- Potent activator of guanylyl cyclase
↓
GTP cGMP
↓
↑cGMP
↓
Inhibits Ca2+ entry into smooth m.
↓
∴
Smooth m. relaxation
- Activates K+ channel
↓
Hyperpolarisation & relaxation of smooth m. cell
- Stimulates cGMP – dependent protein kinase
↓
↑MLC phosphatase
↓
Dephosphorylates MLC
↓
Smooth m. relaxation
PD – CVS
Metoprolol
- ↓LV wall tension
- ↓Force of contraction
- ↓HR
→ All ↓myocardial O2 demand
GTN
- Venous dilation: ↓VR, ↓LVEDP
- Arterial dilation: ↓SVR, ↓afterL
- ↓coronary BP
→ ↓myocardial O2 demand + ↑supply
Adverse Effects
Metoprolol
- Bradycardia
- Hypotension
- Bronchoconstriction
- Heart block
GTN
- Tachycardia (reflex)
- Hypotension
- Headache
- N&V
- Tachyphylaxis