Cardiovascular disorders

It is likely that many older patients will have one or more cardiac disorders and possibly hypertension as well. This is a huge area of therapeutics and there are many drugs available to treat these conditions. Common heart disorders are cardiac failure, ischaemic heart disease and disorders of heart rhythm (arrhythmias). Hypertension is included here because many of the dmgs used to treat heart disorders are also used in hypertension. 

A basic knowledge of the physiology of the heart, the mechanism of contraction, electrical activity and control of rate and rhythm, maintenance of blood pressure and what can go wrong is needed in order to understand how the drugs work. 

The walls of the atria and ventricles consist of cardiac muscle, with that of the left ventricle being the thickest. Collectively cardiac muscle is known as the myocardium. 

The heart functions as a double pump to circulate blood through the lungs and round the rest of the body. 

Pharmacology for the Health Care Professions Christine M. Thorp 2008 John Wiley Sons, Ltd 

Q1 Coronary arteries are the first to branch off the aorta. The heart has a large blood flow (200 ml min-1) but also has great metabolic needs and so has a relatively poor oxygen supply, with little in reserve when oxygen demands increase. At each heart beat (systole), the coronary arteries are compressed by cardiac contraction and blood flow diminishes to a low level. This effect is very marked in the left ventricle, and over 80% of coronary flow to the left ventricle occurs in the periods between beats (diastole). When heart rate increases (tachycardia), the duration of diastole decreases much more than the duration of systole, and the period available for perfusion of cardiac muscle diminishes. 

Coronary blood flows through the cardiac muscle in arteries, capillaries and veins and returns to the heart via the coronary sinus. Extraction of oxygen from coronary blood is high and, when oxygen requirements increase, blood flow must also rapidly increase to supply the extra oxygen needed. 

Q2 The heart is supplied by both divisions of the autonomic nervous system (ANS) via the vagus and sympathetic nerves. The vagus innervates the sinoatrial (SA) and atrioventricular (AV) nodes and atria, but very few fibres 

Anterior view of coronary arteries. From Tortora and Derrickson Principles of Anatomy and Physiology, Eleventh Edition 2006. Reproduced with permission of John Wiley Sons, Inc. 

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Like mAChRs, nAChRs have been implicated in the etiology of ALheimef s disease and related dementias as well as in gastrointestinal and cardiovascular disorders. Nicotine has high abuse potential and is the primary component in reinforcing smoking behaviors. Nicotine patches have been... 

An important characteristic of both classes of ion channel is that they possess multiple dmg binding sites (Table 2). Many of the channel-active dmgs have achieved particular therapeutic importance, including, for example, the Ca " antagonists, widely used for a number of cardiovascular disorders. 

Mice homozygous for an ETA receptor gene disruption show craniofacial malformations, such as cleft palate, micrognathia, microtia and microglossia. ETA (—/—) mice die shortly after birth due to respiratory failure. Mice with an ET-l-null mutation show the same cranciofacial malformations and, in addition, cardiovascular disorders (e.g. septal defects, abnormal cardial outflow tract, aortic arch and subclavian arteries). 

Cambien F, Poirier O, Nicaud V et al (1999) Sequence diversity in 36 candidate genes for cardiovascular disorders. Am JHum Genet 65 183-191... 

Older adults are especially sensitive to the effects of the CNS stimulants and may exhibit excessive anxiety, nervousness insomnia, and mental confusion. Cardiovascular disorders common in the older adult, maybe worsened by the CNS stimulants Careful monitoring is important because the presence of these reactions may result in the need to discontinue use of the drug. 

A recent patent application from Roche [352] described a 2-amino-benzothiazole series. Roche claimed that compound (605) exhibited an IC50 value of 0.73 uM at CBi, and showed in excess of 10-fold selectivity over the CB2 receptor. The compounds were described as being of potential use in the treatment of a range of diseases, including CNS and psychiatric disorders, type-2 diabetes, gastrointestinal diseases, cardiovascular disorders, infertility disorders, inflammation, cancer, atherosclerosis, cerebral vascular incidents and cranial trauma. 

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