Bisoprolol

Indications:

  • Chronic heart failure
  • Angina pectoris
  • Myocardial infarction
  • Cardiac arrhythmias
  • Hypertension

Mechanism of Action:

Bisoprolol is a highly beta1-selective-adrenoceptor blocking agent. It has little affinity to beta2-receptors of the smooth muscle of bronchi and vessels as well as the beta2-receptors involved in metabolic regulation. Therefore bisoprolol is not likely to influence the airway resistance or has beta2-mediated metabolic effects.

Lecture and CAL materials: (under review)

Nicorandil

UNDER REVIEW (September 2016)

Mechanism of Action:

Potassium channel activator (opener) with a nitrate component. K+ passes from smooth muscle cell resulting in hyperpolarization of the plasma membrane (increased negative charge intracellularly as a consequence of K+ moving from inside to outside of the cell). Hence, normal membrane depolarization is prevented, preventing entry of Ca2+ through voltage-dependent calcium channels. Inhibits smooth muscle contraction i.e. causes vascular relaxation. Nicorandil also has nitrovasodilator properties, and dilates both arteries and veins.

Lecture and CAL materials:

Diltiazem

UNDER REVIEW (September 2016)

Mechanism of Action:

Benzothiazepine calcium channel blocker (CCB), sometimes less correctly called ‘calcium-antagonists’. Blocks voltage-dependent L-type Ca2+ channels in vascular smooth muscle, cardiac muscle and cells within the specialized conducting system of the heart. This interferes with the inward displacement of calcium ions responsible for the plateau phase of the action potential. Hence, CCB’s give rise to vascular smooth muscle relaxation leading to diminished coronary and systemic vascular tone (vasodilation), and cardiac depressant effects (decreased force and rate of contraction-reduced myocardial contractility, depressed formation and propagation of electrical impulses through the SA and AV node). Another class of CCB’s, dihydropyridines (e.g. nifedipine, amlodipine) are more selective for calcium channels in blood vessels whereas phenylalkylamines (e.g. verapamil) are more selective for calcium channels in the myocardium. Vasodilatory CCB’s tend to cause reflex tachycardia. Subsequently, they are used for lowering blood pressure but are not suitable for angina (tachycardia increases myocardial oxygen demand). Diltiazem is intermediate in terms of selectivity and hence has marked vasodilator and cardiac depressant effect. This is important as diltiazem reduces arterial blood pressure without triggering the same degree of reflex tachycardia as with dihydropyridines. Note that the action of CCB’s on myocardial tissue is potentially detrimental when cardiac function is impaired.

Lecture and CAL materials:

Isosorbide

UNDER REVIEW (September 2016)

Mechanism of Action:

A long-acting organic nitrate (compare with short-acting organic nitrate, glyceryl trinitrate). Nitrates are reduced to nitric oxide (NO), which activates soluble guanylate cyclase to increase cGMP formation. cGMP in turn activates protein kinase G. Myosin-LC phosphatase, an enzyme which dephosphorylates myosin light chain, is activated. Hydrolysis of ATP, resulting in phosphorylation of myosin, is the energy source for contractile proteins myosin and actin to form a cross-bridge. Hence, myosin dephosphorylation reduces the contractility of actin-myosin in vascular and other smooth muscles, causing them to relax. Protein kinase G causes potassium to be removed from the cell, resulting in hyperpolarisation of muscle cells and subsequent relaxation. It also affects calcium regulation, causing calcium sequestration and relaxation of vascular smooth muscle. Potassium is also removed from the cell. Nitrates are vasodilators, and can dilate both arteries and veins.

Lecture and CAL materials:

Simvastatin

Indications

  • Treatment of hypercholesterolaemia or mixed dyslipidaemia
  • Reduction of cardiovascular morbidity and mortality in patients with a risk
  • Management of peripheral vascular diseases

Mechanism of Action

Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. HMG-CoA reductase is the rate-determining enzyme in cholesterol synthesis. Reduced intracellular cholesterol concentrations activate a cellular signaling cascade that results in the up-regulation of the gene coding for synthesis of LDL receptors. Increased LDL receptors (mainly in hepatocytes) cause increased LDL uptake into cells, resulting in lower plasma LDL levels. Simvastatin is an inactive pro-drug which is metabolized to its active form in the liver.

Lecture and CAL materials:

Glyceryl trinitrate

UNDER REVIEW (September 2016)

Mechanism of Action:

A rapid-acting organic nitrate. Nitrates are reduced to nitric oxide (NO), a gas which activates the enzyme guanylate cyclase, increasing cyclic GMP formation. cGMP in turn activates protein kinase G. Myosin-LC phosphatase, an enzyme which dephosphorylates myosin light chain, is activated. Hydrolysis of ATP, resulting in phosphorylation of myosin, is the energy source for contractile proteins myosin and actin to form a cross-bridge. Hence, myosin dephosphorylation reduces the contractility of actin-myosin in vascular and other smooth muscles (e.g. in the oesophagus), causing them to relax. Protein kinase G causes potassium to be removed from the cell, resulting in hyperpolarisation of muscle cells and subsequent relaxation. It also modifies calcium entry, causing calcium sequestration and relaxation of vascular smooth muscle. Nitrates are vasodilators, and can dilate both arteries and veins.

Lecture and CAL materials:

 

Ephedrine

Mechanism of Action

Ephedrine is a sympathomimetic amine – its principal mechanism of action relies on its indirect action on the adrenergic receptor system. Although it may have weak agonist activity at α;- and β;-adrenergic receptors, the principal mechanism is to displace noradrenaline from storage vesicles in presynaptic neurons. The displaced noradrenaline is released into the neuronal synapse where it is free to activate the aforementioned postsynaptic adrenergic receptors. Phenylephrine is an alpha adrenoceptor agonist which constricts nasal blood vessels when applied to the nasal mucosa via spray or drops, and hence reduces nasal congestion (decongestant).