Class I drugs

Antiarrhythmic drugs are antagonists of the fast Na+ channel, which slow the propagation of the cardiac action potential. Class I drugs suppress the fast upstroke of the action potential. 

The absorption of class III drugs is limited by their permeability over the intestinal wall. Thus, as this process is not at all modeled by the classical in vitro dissolution test, no IVIVC should be expected. When drug dissolution becomes slower than gastric emptying, a reduction in the extent of bioavailability will be found in slower dissolution rates as the time when the drug is available for permeation over the gut wall in the small intestine will then be reduced. Thus, the same type of relationship can be expected between bioavailability and in vitro dissolution, as shown in Fig. 21.12 for a class I drug. 

The FDA currently allows biowaivers (27) (drug product approval without having to show bioequivalence in vivo) for formulations that contain Class I drugs and can demonstrate appropriate in vitro dissolution (rapidly dissolving). 

Class I — Drug is highly soluble and highly permeable... 

Class I drugs have a local anaesthetic-like action, blocking the inward current in sodium channels. This depresses the fast depolarisation (phase 0) which initiates each action potential (Figure 8.5). This membrane-stabilising effect makes them valuable for the treatment of ectopic and tachycardic arrhythmias, such as atrial and ventricular fibrillation, extrasystoles, supraventricular and ventricular tachycardia. Class I drugs also decrease contractility. A sub-classification is made according to the effects on... 

Class I antiarrhythmic drugs are essentially sodium channel blockers.5,27,29 These drugs bind to membrane sodium channels in various excitable tissues, including myocardial cells. In cardiac tissues, class I drugs normalize the rate of sodium entry into cardiac tissues and thereby help control cardiac excitation and conduction.8,27 Certain class I agents (e.g., lidocaine) are also used as local anesthetics the way that these drugs bind to sodium channels is discussed in more detail in Chapter 12. 

Q Class I drugs Dose less than available binding sites... 

Quinidine is considered the prototype class I drug, although it is now quite rarely used. In addition to its class lA activity, quinidine slightly enhances contractility of the myocardium (positive inotropic effect), and reduces vagus nerve activity on the heart (antimuscarinic effect). At therapeutic doses there is lengthening of ventricular systole which is positively inotropic. 

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