Blood concentration Pharmacological response

Dtug interactions can cause serious problems in clinical practice especially when the affected dmg has the potential to be highly toxic. Furthermore, pharmacokinetic interactions are clinically important if the affected dmg has a narrow therapeutic range (i.e. small difference between the minimum effective concentration and the toxic concentration Fig. 1) and a steep concentration-response curve (i.e. significant alterations in pharmacological and/or adverse effects caused by small changes in blood concentration). 

The onset, duration, and intensity of action of a drug after administration are controlled by the rate at which the drug reaches its site of action and by the concentration of the drug at the receptor. The physiological disposition of a drug is controlled by the three major processes of absorption, distribution into and within tissues, and elimination. Pharmacokinetics is a mathematical consideration of these processes which relates the dose given, the concentration in the blood, and the pharmacological response. 

The apparently linear relationship between biophase concentration and pharmacologic response usually reflects the fact that effects have been analyzed over only a limited concentration range (14). In many caseS/ an Ej ax model is required to analyze more pronounced effects/ such as the blood pressure response of cats to norepinephrine. This was the concentration-effect relationship initially analyzed by Segre (7) when he proposed a model for the time course of biophase concentrations. For the Ej ax model/ AE in Equation 19.8 is described by... 

Once absorbed, dmg particles are transported in blood plasma. These are referred to as free dmgs because they are not bound to any receptor sites. Only free dmgs can cause a pharmacological response. Dmgs bind to proteins in plasma, usually albumin or globulins. These dmg-protein complexes decrease the concentration of free dmg in the circulation. This protein-dmg molecule is too large to pass through the membrane of a blood vessel and is not available for... 

Since the primary and secondary lymphoid organs may be the site of action of IFNs and ILs, the intensity of a pharmacological response may depend on both the systemic exposure (as measured by plasma concentration), and the route of administration. Simultaneous measmement of both the plasma and lymph concentrations allows calculation botti of the rate of absorption directly from the injection site into the blood and lymph, and of the transfer rate from the lymph to the blood. 

Pharmacology Bretylium tosylate inhibits norepinephrine release by depressing adrenergic nerve terminal excitability, inducing a chemical sympathectomy-like state. Bretylium blocks the release of norepinephrine in response to neuron stimulation. Peripheral adrenergic blockade causes orthostatic hypotension but has less effect on supine blood pressure. It has a positive inotropic effect on the myocardium. Pharmacokinetics Peak plasma concentration and peak hypotensive effects are seen within 1 hour of IM administration. However, suppression of premature ventricular beats is not maximal until 6 to 9 hours after dosing, when mean plasma concentration declines to less than 50% of peak level. Antifibrillatory effects occur within minutes of an IV injection. Suppression of ventricular tachycardia and other ventricular arrhythmias develops more slowly, usually 20 minutes to 2 hours after parenteral administration. 

Changes in pharmacodynamics further complicate the pharmacology of many drugs in the neonate and infant. The blood-brain barrier is poorly developed, allowing more rapid transfer of drugs into the central nervous system (CNS). However, the response to higher brain concentrations may be tempered by an inadequate response due to lack of receptor maturation. 

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