Atropine

UNDER REVIEW (April 2017)

Mechanism of Action:
Muscarinic acetylcholine receptor (mAChR) antagonist [anti-muscarinic, anti-cholinergic]. mAChRs are 7TM GPCRs (7 transmembrane G-protein coupled receptors) which are activated by the endogenous neurotransmitter, acetylcholine (cholinergic receptor). Atropine is relatively selective for mAChRs, which are generally associated with the parasympathetic nervous system, and also cholinergic transmission in the CNS for atropine crosses the blood brain barrier. There are 5 subtypes of receptors, of which the function of 3 are well-established. Their excitatory functions (M1, 3) include CNS excitation (e.g. tremor, hypothermia), gastric acid secretion, glandular secretions (e.g. salivary, bronchial, sweat) and contraction of visceral smooth muscle (e.g. GI tract, eye-constrictor pupillae and ciliary muscle, bronchial). Examples of inhibitory functions (M2, 3) are cardiac inhibition (slow heartbeat) and the relaxation of smooth muscle (mainly vascular). Note that the other major class of cholinergic receptor (nicotinic) – at which atropine has little effect – is responsible for neurotransmission in autonomic ganglia and at the neuromuscular junction.

Lecture and CAL materials:

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)

Adenosine

UNDER REVIEW (April 2017)

Mechanism of Action:

Adenosine is an agonist at adenosine receptors (also known as P1 purinoceptors) which are transmembrane G protein-coupled receptors (GPCRs). There are three main types, A1, A2 and A3. Adenosine inhibits many intracellular ATP-utilizing enzymes, including adenylyl cyclase and activates potassium channels via A1 receptors. Its antiarrhythmic action does not fit easily into the Vaughan-Williams classification. The result is to slows pacemaker activity and atrioventricular conduction via A1 receptors at the atrioventricular node.

Lecture and CAL materials:

Verapamil

UNDER REVIEW (September 2016)

Mechanism of Action:

Calcium channel blocker – prevents Ca2+ entry through voltage-operated calcium channels. There are 3 classes of calcium channel blockers – all block the L-type calcium channel, but bind to different sites. Verapamil belongs to the phenylalkylamine class, and binds to the V binding site. (Other classes – dihydropyridines eg nifedipine: N binding site; benzothiazepines eg diltiazem: D binding site). Verapamil is more cardiac selective, and acts as a negative inotrope in the heart, suppressing myocardial contractility. Verapamil and diltiazem also cause the Ca+ channel to recover more slowly, thereby reducing cardiac conduction speed and automaticity. Verapamil decreases action potential duration by blocking the inward entry of calcium. This slows the propagation of impulses, leading to a longer refractory phase in the atrioventricular (AV) node.

Lecture and CAL materials:

Digoxin

UNDER REVIEW (September 2016)

Mechanism of Action:

Cardiac glycoside. Anti-arrhythmic action: not classified (or class V, recently introduced for drugs that are not class I-IV, or have unknown mechanism). Activates K+ channels and leads to hyperpolarization. Slows atrioventricular conduction – can block AV conduction. Increases the strength of cardiac muscle contractions (positive inotropic action), and is useful in the treatment of chronic heart failure.

Lecture and CAL materials:

Lidocaine

UNDER REVIEW (September 2016)

Mechanism of Action:

A sodium channel block blocker (Class 1b). Has its major effect on electrically excitable tissues such as cardiac cells and nervous tissues.

  1. Anti-arrhythmic action – reduces the rate of depolarization of cardiac action potential, increases effective refractory period and decreases atrioventricular conduction.
  2. Local anaesthetic effect. Reduces conduction in sensory neurones.

Lecture and CAL materials: