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Lecture-31 - Tolerance to drugs There are two forms of...

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Tolerance to drugs
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There are two forms of tolerance to drugs: 1. Metabolic (pharmacokinetic) 2. Functional (pharmacodynamic) Shirt in d-r curve illustrates tolerance, but not mechanism
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FUNCTIONAL Same [], different response
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METABOLIC
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After the chronic administration of many drugs, tolerance can be seen to develop. This means that higher doses of the drugs may need to be taken in order to get the same degree of effect. Metabolic tolerance This usually occurs by the drug inducing enzymes in the liver that metabolize the drug. The result is an increased metabolism rate of the drug, and thus a lower drug (area under curve) in the body. Common examples include the barbiturates and ethanol . Metabolic cross-tolerance can also occur. Eg., induction of cyt. P450 enzymes by ethanol, barbiturates & phenytoin can affect the metabolism of many other drugs.
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Functional tolerance This is the spectrum of adaptive changes that the brain or spinal cord may undergo to offset the effect of the drug. Eg., sedatives produce a depression of neuronal excitability. An adaptive compensation by the body might be an alteration in some neurochemical pathway(s) that either promotes neuronal excitability or antagonizes neuronal inhibition. The end result of this adaptive compensation is the production of a more normal state while the drug is present.
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