Cardiotonicity

When, aiming at its cardiotonic activity (stimulant), the 2,5-dioxo-l,2,5,6,7,8-hexahydro-3-cyano-6-bromoquinoline is made to react with different thioamides, the appropriate 6-substituted 8,9-dihydro- (R = cyanomethyl-, 2-oxopyrrolidinyl-methyl-, 2-oxohexahydroazepinomethyl-, and thioxopyrrolidinylmethyl-) (94KFZ43) or (R = H, Me, NH2, NH/S ) (86JAP(K)1, 89H1517) thiazolo[4,5-/Iquinolines 37 or oxidized products (89H1517) are produced. 

Phthalazines commonly possess adrenergic activity. One such, carbazeran (77), is a cardiotonic agent. Its patented synthesis involves nucleophilicaromatic displacement of chiorophthal-azine derivative 7 with piperidinyl carbamate 76 to give carbazeran (77)... 

Enoximone (113), an imidazdinone-containing molecule, is a cardiotonic molecule like imazodan above. Its mechanism of action is still not established but it is repotted to be a potent... 

The narrow therapeutic range of digitalis related cardiotonic agents has resulted in an extensive effort to identify compounds in other structural classes which will improve cardiac function. The discovery of the heterocyclic cardiotonic drug, amrinone, led to research on other heterocyclic compounds for that indication. The imidazopyridine, isomazole (57), is representa-... 

K.-M. Chu, S.-M. Sliieh, S.-H. Wu and O. Y.-P. Hu, Enantiomeric separation of a cardiotonic agent pimobendan and its major active metabolite, UD-CG 212 BS, by coupled achiral-cliiral normal-phase high-performance liquid chromatography , 7. Chromatogr. Sci 30 171-176(1992). 

Therapeutic Function Cardiotonic Chemical Name See structural formula... 

Therapeutic Function Cardiotonic Chemical Name 9-/3-D-ribofuranosylhypoxanthine Common Name Hypoxanthine riboside Structural Formula ... 

Assay results with the two new 1,2-cis (ft-d) cardenolides show enhanced activity as compared with the two unnatural, a-D-rhamnosides. They have potencies that fall well within the range for those of the naturally occurring cardenolides. These results support the postulate that the a-D-glycosidic linkage in cardenolides containing D-sugars is unfavorable for cardiotonic activity. 

The Na+/K+-ATPase as the Molecular Target for Cardiotonic Steroids (CIS) and Palytoxin... 

Discuss the uses, general drug action, general adverse reactions, contraindications, precautions, and interactions of the cardiotonic and inotropic drugs. 

Discuss important preadministration and ongoing assessment activities the nurse should perform on the patient taking a cardiotonic or inotropic drug. 

Discuss ways to promote an optimal response to therapy, how to manage common adverse reactions, and important points to keep in mind when administering a cardiotonic drug. 

The cardiotonics are dm used to increase the efficiency and improve the contraction of the heart muscle which leads to improved blood flow to all tissues of the body. The drug s have long been used to treat congestive heart failure (CHF), a condition in which the heart cannot pump enough blood to meet the tissue needs of the body. While the term congestive heart failure continues to be used by some, a more accurate term is simply heart failure. ... 

Until recently, the cardiotonics and a diuretic were the treatment of choice for HE However, other dragp such as the angiotensin-converting enzyme (ACE) inhibitors, and beta blockers have become the treatment of choice during the last several years. See Figure 39-1 for an example of a method of determining treatment for left ventricular systolic dysfunction. See Chapters 23, 42, and 46 for more information on the beta blockers, ACE inhibitors, and diuretics, respectively. 

Cardiotonic drugs increase the force of the contraction of the muscle (myocardium) of the heart. This is called a positive inotropic action. When the force of contraction of the myocardium is increased, the amount of blood leaving the left ventricle at the time of each contraction is increased. When the amount of blood leaving the left ventricle is increased, cardiac output (the amount of blood leaving the left ventricle with each contraction) is increased. 

When a cardiotonic drug is administered, die positive inotropic action increases the force of die contraction, resulting in an increased cardiac output. When cardiac output is increased, the blood supply to die kidneys and otiier vital organs is increased. Water, electrolytes, and waste products are removed in adequate amounts, and tiie symptoms of inadequate heart action or HF are relieved, hi most instances, the heart rate also decreases. This occurs because vital organs are now receiving an adequate blood supply because of the increased force of myocardial contraction. 

The cardiotonics affect the transmission of electrical impulses along the pathway of the conduction system of tiie heart. The conduction system of die heart is a group of specialized nerve fibers consisting of die SA node, die AV node, the bundle of His, and die branches of Purkinje (Fig. 39-2). Each heartbeat (or contraction of tiie ventricles) is tiie result of an electrical impulse tiiat normally starts in tiie SA node, is tiien received by die AV node, and travels down die bundle of His and through tiie Purkinje fibers (see Fig. 39-2). The heartbeat can be felt as a pulse at the wrist and otiier areas of die body where an artery is close to the surface or lies near a bone When the electrical impulse reaches the... 

The cardiotonics are used to treat HF and atrial fibrillation. Atrial fibrillation is a cardiac arrhythmia characterized by rapid contractions of the atrial myocardium, resulting in an irregular and often rapid ventricular rate. See Chapter 40 for more information on various arrhythmias and treatment. 

The cardiotonics are contraindicated in patients with known hypersensitivity, ventricular failure, ventricular tachycardia, or AV block and in the presence of digitalis toxicity. 

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