Drug transport and disposition are influenced by a non-specific and reversible drug binding to plasma and tissues proteins. Albumin and al acid glycoprotein are the most important transport proteins of the blood. Albumin possesses specific sites for acidic and basic drug binding and can interact with them in the plasma since a third site is trapped only by digoxin. Diseases and stress conditions induce conformational changes either in plasma or in tissue proteins by the synthesis of endogenous substances which can strong interfere with the amount of the free pharmacological effective drug ratio. This may affect the binding of drugs in target molecules inducing significant pharmacokinetic alterations. Stress conditions are associated with FFA increase in serum playing an antagonistic role with other acidic molecules (e.g. ampicillin) to the same binding site. The bounded drug is displaced and freer ratio is available to interact with various organ receptors leading to pharmacological effect enhancement and therefore to side effects manifestation such as seizures. Furthermore conjunctive tissues diseases, ageing, prolonged bleeding, starvation or diseases affecting protein profile, characterized by reduced total plasma proteins, followed by albumin decrease and lessen binding sites lead to more free drug availability enhancing its pharmacological effect. Increased a1-acid glycoprotein the acute phase protein as by heart infraction or liver morbidities (e.g CCl4 intoxication) mainly occupied from basic substances, in the case of cationic drug treatment resulted to the enhancement of them and consequently to pronounced effectiveness. In addition, renal failure reduced free fractions of many acidic drugs. It may be concluded that by narrowed therapeutic index of a medicine, and when drug/drug or drug/disease interactions are anticipated, drug monitoring seems to be necessary for its dosage adjustment.
Ultrasound technique limitations do exist. We present 2 conditions, edema and subcutaneous air, which contributed to ultrasound failure to provide a clear image of the targeted nerves.
Binding of drugs to plasma and tissue proteins is critically involved in their pharmacokinetics and pharmacodynamics. Stress affects drugs' protein binding via alterations in plasma proteins' levels and excessive increase of free fatty acids due to cortisol-induced fat mobilisation. Free fatty acids play a crucial antagonistic role to drugs for the binding sites on albumin, the major binding plasma protein, resulting in subtherapeutic or toxic levels of many medications' pharmacological classes (oral anticoagulants, beta-lactames, fluoroquinolones, local anaesthetics). Upon stress, changes in blood flow rate and vascular function are also important parameters that can alter drug distribution and pharmacokinetics. Many cases are reported where stress-induced pharmacokinetic alterations led to serious clinical consequences. However, the stress affected drug activity do not always deteriorate the clinical outcome, due to the adaptive and defensive mechanisms of healthy organism. Sensitive population as patients with serious underlying diseases or after trauma or surgery should be given special attention. Clinicians should be alert and monitor cases where stress-induced drugs' pharmacokinetic modifications can have negative impact on the clinical outcome.
IntroductionTransthoracic echocardiography (TTE) is a reliable, noninvasive imaging method that is useful in the evaluation of cardiovascular thrombosis. We conducted a retrospective study of all the echocardiograms from patients in the postoperative care unit to assess the role of TTE in thrombus identification in the left ventricle.MethodsThis retrospective database evaluation included all echocardiograms during a 14-month period. The echocardiographic examination protocol included the subcostal four-chamber view, the apical four-chamber view, the apical two-chamber view and the parasternal view, along the long and short axes in both spontaneously and mechanically ventilated patients. All echocardiograms were obtained within the 48 hours immediately following surgery.ResultsIn total, 160 postoperative echocardiograms were obtained from 160 patients and resulted in the detection of five cases of left ventricular thrombosis. Subgroup analysis showed that 21 and 35 of the 160 patients examined had either dilated or ischemic cardiomyopathy, respectively. In these patients, preoperative echocardiograms had been obtained recently prior to surgery and were negative for left ventricular thrombus. In three of 35 patients with ischemic cardiomyopathy and two of 21 patients with dilated cardiomyopathy, thrombus was identified in the left ventricle. The thrombi were mobile, uncalcified and pedunculated and were located in the apex of the left ventricle. In addition, no clinical consequences of the left ventricular thrombi were recorded.ConclusionsLow-flow conditions in heart chambers due to ischemic or dilated cardiomyopathy in conjunction with the hypercoagulability caused by perioperative prothrombotic factors may lead to thrombotic events in the left ventricle.
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