Hartglycosiden
(digoxine) Vergroten door directe beïnvloe-ding de contractiliteit van myo-cardvezels en remmen de AV-geleiding (beide door remming van de Na+ -K+ -ATPase, waar-door meer Na-ionen beschikbaar blijven door de passieve uitwis-seling met Ca2+), induceren sinusbradycardie en doen de fil-terwerking van de AV-knoop toenemen. Verder verhogen hartglycosiden de gevoeligheid voor de baroreflex, waardoor de vagale tonus toeneemt en de sympathicus wordt geremd. Ten-slotte verlagen ze de activiteit van plasmanoepinefrine en renine
Supraventriculaire ritmestoornissen, met name boezem-fibrilleren en flad-deren chronisch hartfalen door onvoldoende krachtige ventri-kelcontracties gastro-intestinaal: opgeblazen gevoel, anorexie, misse-lijkheid, braken en buikpijn cardiaal: ventriculaire en supraventriculaire ritme-stoornissen neurologische klachten zoals moeheid, depres-sie, hoofdpijn, dui-zeligheid en visus-stoornissen Klaring geschied volledig door de nieren RAS-remmers (ACE-remmers en AT II-antagonisten) ACE-remmers:
Grijpen in op het RAS. Zij remmen de omzetting van AT I naar AT II, waardoor de aldosteronproductie wordt onderdrukt. Tevens treedt er vasodilatatie op en heeft het een diuretische werking op de nieren. Tenslotte breekt ACE
bradykinine af. Dit alles resulteert uiteindelijk in
vaatverwijding en groeiremming van de hartventrikel en de gladde spiercellen in de wand.
AT II-antagonisten:
Deze middelen blokkeren de AT II-receptor.
AT II-antagonisten hebben een vergelijkbaar resultaat als ACE remmers, maar hebben geen invloed op de hoeveelheid bradykinine Hartfalen Asymptomatische LV-disfunctie Secundaire profylaxe na een acuut myocardinfarct Essentiële hypertensie en renovasculaire hypertensie Bepaalde nieraandoeningen Alleen hypertensie Orthostatische hypertensie, duizeligheid, zwakte, syncope, prikkelhoest, afname van de nierfunctie, al-lergische huidreacties, angio-oedeem, lichte hoofdpijn en maagdarmklachten Belangrijkste gevaren: Hypotensieve reacties, risico van nierinsufficiëntie bij aanwezigheid van een renale arteriestenose, risico van
nierinsuffi-ciëntie bij risico-patienten zoals patienten met hart-falen. Prikkelhoest, angio-oedeem, revesibele smaakstoornissen en hepatotoxiciteit
Bijna alle ACE-remmers zijn prodrugs, pas na hydrolysatie in de lever ontstaan actieve metabolieten. Bijna alle ACE-remmers worden door de nier uitgescheiden, een enkeling ook nog door de lever. Klaring door de lever en nieren. Eliminatie met urine, gal, faeces.
Diuretica (thiaziden, lis-diuretica, kaliumsparend e diuretica en overigen) Belangrijkste aangrijpingspunten:
- prox. tubulus; Osmotische diuretica grijpen hieraan door verhindering van de terugresorptie van water en daarom van natrium. - Lis van Henle; De
lis-diuretica remmen de Na+/2Cl-/K+ cotransport. Dit heeft een remming van
Hartfalen Nefrotische syndroom Levercirrhose Hypertensie Stoornissen in de mineraalhuishoudi ng Oedeem Hypokaliëmie Verhoging van serumlipiden Klaring geschiedt via de nieren
het passief transport van natrium tot gevolg. Hierdoor wordt minder natrium teruggeresorbeerd en treedt er kalium en waterverlies op.
- dist. tubulus; deze diuretica zorgen voor verdere remming van de terugresorptie van Na+ - verzamelbuis; hier vindt
eventuele
waterterugresorptie plaats. Met name ADH ontplooit hier zijn werkzaamheid
7.
a) The Cardiomyopathies
The cardiomyopathies are diseases that involve the myocardium directly and are not the result of hypertension or congenital, valvular, coronary, arterial, or pericardial abnormalities.
Classifications of the cardiomyopathies on the basis of differences in their pathophysiology and clinical presentation:
Dilated Cardiomyopathy
Left and/or right ventricular systolic pump function is impaired, leading to progressive cardiac enlargement, a process called remodeling, and often producing symptoms of congestive heart failure.
Although no cause is apparent in many cases, dilated cardiomyopathy is probably the end result of myocardial damage produced by a variety of toxic, metabolic, or infectious agents. Dilated cardiomyopathy may be the late sequel of acute viral myocarditis, possibly mediated through an immunologic mechanism.
Restrictive Cardiomyopathy
The hallmark of the restrictive cardiomyopathies is abnormal diastolic function; the ventricular walls are excessively rigid and impede ventricular filling. Myocardial fibrosis, hypertrophy, or infiltration due to a variety of causes is usually responsible. The infiltrative diseases, may also show some impairment of systolic function.
The inability of the ventricle to fill limits cardiac output and raises filling pressure. Therefore, exercise intolerance and dyspnea are usually the most prominent symptoms. As a result of persistently elevated venous pressure, these patients commonly have dependent edema, ascites, and an enlarged, tender, and often pulsatile liver. The jugular venous pressure is elevated and does not fall normally, or it may rise with inspiration (Kussmaul's sign). The heart sounds may be distant, and third and fourth heart sounds are common.
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, typically of a nondilated chamber, without obvious cause such as hypertension or aortic stenosis. Initial studies of this disease emphasized the dynamic "obstructive" features, and it has been termed idiopathic hypertrophic subaortic stenosis and hypertrophic obstructive cardiomyopathy. It has become clear, however, that only about one-quarter of patients with HCM demonstrate an outflow tract pressure gradient. The ubiquitous pathophysiologic abnormality is not systolic but rather diastolic dysfunction, characterized by increased stiffness of the hypertrophied muscle. This results in elevated diastolic filling pressures and is present despite a hyperdynamic left ventricle.
b) Myocarditides
Myocarditis, i.e., cardiac inflammation, is most commonly the result of an infectious process. Myocarditis may also result from a hypersensitivity to drugs or may be caused by radiation, chemicals, or physical agents. The clinical manifestations range from an asymptomatic state, with the presence of myocarditis
inferred only by the finding of transient electrocardiographic ST-T-wave abnormalities, to a fulminant condition with arrhythmias, heart failure, and death. In some patients, myocarditis simulates acute myocardial infarction, with chest pain, electrocardiographic changes, and elevated serum levels of myocardial enzymes.
c) Cor pulmonale
Cor pulmonale is defined as enlargement of the right ventricle (RV) secondary to abnormalities of the lungs, thorax, pulmonary ventilation, or circulation. It sometimes leads to RV failure, with an elevation of transmural RV end-diastolic pressure.
Pathophysiology
The severity of RV enlargement in cor pulmonale is a function of the increase in afterload. When the pulmonary vascular resistance is elevated an elevation in cardiac output can elevate pulmonary artery pressure markedly.
The elevation of RV afterload responsible for cor pulmonale is caused principally by pulmonary vascular or parenchymal disease.
Table: Cor Pulmonale
Mechanisms Responses Characteristics
PULMONARY VASCULAR DISEASES
Emboli, large or multiple Fall in cardiac output due to acute
obstruction Acute cor pulmonale Right ventricular distention
Shock Emboli, small; vasculitis; widespread lung
damage (ARDS) Pulmonary hypertension due to widespread hypoxia and microvascular obstruction
Subacute cor pulmonale Right ventricular distention
Breathlessness and fever Emboli, medium and recurrent; primary
pulmonary hypertension; diet or drug vasopathy
Pulmonary hypertension due to vascular obstruction
Low or normal cardiac output
Chronic cor pulmonale Right heart hypertrophy Breathlessness
RESPIRATORY DISEASES
Obstructive
Chronic bronchitis and emphysema; chronic
asthma Pulmonary hypertension due to hypoxia, vascular stretching, and loss of vessels
Heart beat impeded externally by lung hyperinflation
Normal or high output
Chronic cor pulmonale "Blue bloater" or "Pink puffer" (see Chap. 258)
Restrictive
1. Intrinsic: interstitial fibrosis, lung resection Hypertension due to hypoxia, vascular distortion and loss Normal or low output
Chronic cor pulmonale Breathlessness Hyperventilation 2. Extrinsic: obesity, myxedema, muscle
weakness, kyphoscoliosis, upper airway obstruction, diminished respiratory drive, high altitude
Hypertension due to alveolar hypoxia
Normal or high output
Chronic cor pulmonale Peripheral edema Hypoventilation