Pharmacology quinidine

Pharmacology Quinidine, a class lA antiarrhythmic, depresses myocardial... 

Quinicine (quinotoxine), 419,425, 442,448 Quinidine, 419, 424 configuration, 443 constitntion, 435 isomerides, 453-4 pharmacological action, 479 transformaticn products 448 Quinidine, 419, 4 ... 

Qninidine exhibits all of the pharmacological properties of qninine, including antimalar-ial, fever-redncing, and other properties. Quinidine is used in varions forms of arrhythmia for preventing tachycardia and atrial fibrillation, and particularly for preventing ciliary fibrillation, paroxysmal snpraventricnlar tachycardia, extrasystole, and ventricular tachycardia. However, it is a toxic drug and is nsed relatively rarely. 

Other pharmacological effects - Clinical effects, in addition to antidepressant effects, include sedation, anticholinergic effects, mild peripheral vasodilator effects and possible quinidine-like actions. 

Quinidine Quinidex) was one of the first clinically used antiarrhythmic agents. Because of the high incidence of ventricular proarrhythmia associated with its use and numerous other equally efficacious agents, quinidine is now used sparingly. Quinidine shares all of the pharmacological properties of quinine, including an-timalarial, antipyretic, oxytocic, and skeletal muscle relaxant actions. 

Concurrent administration of propafenone with digoxin, warfarin, propranolol, or metoprolol increases the serum concentrations of the latter four drugs. Cimetidine slightly increases the propafenone serum concentrations. Additive pharmacological effects can occur when lidocaine, procainamide, and quinidine are combined with propafenone. 

In pharmacodynamic interactions, the pharmacological effect of a drug is changed by the action of a second drug at a common receptor or bioactive site. For example, low-potency antipsychotics and tertiary amine TCAs have anticholinergic, antihistaminic, a-adrenergic antagonist, and quinidine-Kke effects. Therefore, concurrent administration of chlorpromazine and imipramine results in additive sedation, constipation, postural hypotension, and depression of cardiac conduction. 

The increase in heart muscle excitability induced by some natural quinuclidine derivatives (quinidine, ajmaline), suggesting pharmacological activity of some synthetic quinuclidine compounds and the possibility of using quinuclidines as catalysts for production of polymers,17 stimulated further interest in the ring system. 

Po SS, Wang DW, Zang ICH, Johnson JP, Nie L and Bennett PB (1999) Modulation of hERG potassium channels by extracellular magnesium and quinidine. Journal of Cardiovascular Pharmacology 33 181-185... 

Muir W W 1995 The haemodynamic effects of milrinone HCI In halothane anaesthetized horses. Equine Veterinary Journal Supplement 19 108-113 Muir W W, Mcguirk S M 1985 Pheirmacology and pharmacokinetics of drugs used to treat cardiac disease in horses. Veterinary Clinics of North America Equine Practice 1 335-352 Muir W W D, Mcguirk S 1987 Cardiovascular drugs. Their pharmacology and use In horses. Veterinary Clinics of North America Equine Practice 3 37-57 Muir W W D, Reed S M, Mcguirk S M 1990 Treatment of atrial fibrillation in horses by intravenous administration of quinidine. Journal of the American Veterinary Medical Association 197 1607-1610... 

HttMercoisomer, quinidine. is schizonlicidal. but its pri-nuiy indication is cardiac anhythmias. It is a good example i ite importance of slercochemistry because il provides a epiificanllydiffeienl pharmacological spectrum. Quinidine iidncnssed further in Chapter 19. 

Perez-Mateo, M. Erill, S. (1977) Protein binding of salicylate and quinidine in plasma from patients with renal failure, chronic liver disease and chronic respiratory insufficiency. European Journal of Clinical Pharmacology, 11, 225-231. 

Otton, S.V., Crewe, H.K., Lennard, M.S., Tucker, G.T. and Woods, H.F. (1988) Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P-450 in metoprolol oxidation by human liver microsomes. The Journal of Pharmacology and Experimental Therapeutics, 247, 242-247. 

Nielsen, T.B., Buur Rasmussen, B., Flinois, J.-P., Beaune, P. and Brosen, K. (1999) In vitro metabolism of quinidine the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-450 3A4 activity in human liver microsomes. The Journal of Pharmacology and Experimental Therapeutics, 289, 31-37. 

Greenblatt, D.J., Pfeifer, H.J., Ochs, H.R., Franke, K, MacLaughlin, D.S., Smith, T.W. and Koch-Weser, J. (1977) Pharmacokinetics of quinidine in humans after intravenous, intramuscular and oral administration. The Journal of Pharmacology and Experimental Therapeutics, 202, 365-378. 

Darbar, D., Dellorto, S., Morike, K., Wilkinson, G.R. and Roden, D.M. (1997) Dietary salt increases first-pass elimination of oral quinidine. Clinical Pharmacology and Therapeutics, 61, 292-300. 

From a variety of X-ray crystal studies (e.g., didehydro-QCI/QCD and didehydro-quinidine), we have established that alkyne quinuclidines are twisted consistently less than the vinyl and ethyl analogues. Overall torsion angles, that is, the sum of the three torsion angles, vary from 26 to 49° compared with up to 65° for ethyl and 60° for ethenyl derivatives, respectively (Figure 12.3). Fine-tuning of nitrogen polarity (and basicity), which may be important for catalysis and perhaps pharmacological activity, is thus possible ([28] R. Wartchow, personal communication). 

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