You have learned You have learned a LOT so fara LOT so far

A few extra facts to throw inA few extra facts to throw in

No single reproducible abnormality in any NT, No single reproducible abnormality in any NT, enzyme, receptor or gene has been found to enzyme, receptor or gene has been found to cause Psychopathology (but they can contribute cause Psychopathology (but they can contribute to the risk)to the risk)

Virtually all Psychotropic drugs have been found Virtually all Psychotropic drugs have been found thru serendipity or by guessingthru serendipity or by guessing

Finally, we need to know how…Finally, we need to know how…

Drugs effect the body Drugs effect the body ((PharmacodynamicsPharmacodynamics) )

That the body effects the drugs That the body effects the drugs absorption, distribution, biotransformation, absorption, distribution, biotransformation, and excretionand excretion ( (PharmacokineticsPharmacokinetics))

AbsorptionAbsorption

Occurs in the stomach and small intestines for Occurs in the stomach and small intestines for oral medicationsoral medicationsBioavailability- How much of the drug is Bioavailability- How much of the drug is available in the bloodstreamavailable in the bloodstream

– Taken with or without foodTaken with or without food– Blood/Brain BarrierBlood/Brain Barrier– Introvenious drugs (100% bioavailable)Introvenious drugs (100% bioavailable)

Why is this necessary to know?Why is this necessary to know?

DistributionDistribution

After the drug is absorbed and reaches the blood stream After the drug is absorbed and reaches the blood stream (absorption)….(absorption)….Then it must be distributed to various organs or body Then it must be distributed to various organs or body sitessites– High blood flow 1High blood flow 1stst (liver, kidney, heart, brain) (liver, kidney, heart, brain)– Muscles and fat tissues 2ndMuscles and fat tissues 2nd

Each medication has a particular distribution pattern. Each medication has a particular distribution pattern. – For example, TCAs are distributed in the fat and muscle cells. For example, TCAs are distributed in the fat and muscle cells.

What are the implications for the prescribing physician?What are the implications for the prescribing physician?– Why might a patient not become depressed for days or weeks Why might a patient not become depressed for days or weeks

after discontinuing medications?after discontinuing medications?

Biotransformation (Metabolism)Biotransformation (Metabolism)

Toxicity IssuesToxicity IssuesMetabolizes primarily in the Liver via Metabolizes primarily in the Liver via enzymes, so that Kidneys can secrete enzymes, so that Kidneys can secrete more easilymore easilyDifferent people have different enzymes in Different people have different enzymes in the liver, thus one may metabolize Zoloft the liver, thus one may metabolize Zoloft well, but not Prozac.well, but not Prozac.What are the implications for prescribing What are the implications for prescribing physicians?physicians?

BiotransformationBiotransformation

What do you think are the cultural What do you think are the cultural implications in Biotransformation?implications in Biotransformation?

BiotransformationBiotransformation

5-10% of Caucasians are poor metabolizers via 5-10% of Caucasians are poor metabolizers via the enzyme CYP450 2D6, so they must the enzyme CYP450 2D6, so they must metabolize drugs that require this enzyme in an metabolize drugs that require this enzyme in an alternate manner, which might not be as efficientalternate manner, which might not be as efficient

20% of Japanese and Chinese individuals have 20% of Japanese and Chinese individuals have reduced activity in enzyme CYP450 2C19reduced activity in enzyme CYP450 2C19

How does this make you feel about the clinical How does this make you feel about the clinical studies that have been done with little attention studies that have been done with little attention to race/ethnicity?to race/ethnicity?

ExcretionExcretion

Drugs are eliminated from the Drugs are eliminated from the body thru the Kidneys, Intestines, body thru the Kidneys, Intestines, Respiratory, Sweat, Saliva, and Respiratory, Sweat, Saliva, and Breast MilkBreast Milk

Adequate excretion is dependent Adequate excretion is dependent on Kidney functioningon Kidney functioning

What should physicians take into What should physicians take into consideration prior to prescribing a consideration prior to prescribing a medication?medication?

Half-Life is an important factor in Half-Life is an important factor in ExcretionExcretion

Half-lifeHalf-life: The period of time required for the : The period of time required for the concentration or amount of drug in the body to be concentration or amount of drug in the body to be reduced by one-half reduced by one-half

4-5 X half-life=Steady State4-5 X half-life=Steady State– As repeated doses of a drug are administered its plasma As repeated doses of a drug are administered its plasma

concentration builds up and reaches what is known as a steady concentration builds up and reaches what is known as a steady state. This is when the amount of drug in the plasma has built up state. This is when the amount of drug in the plasma has built up to a concentration level that is therapeutically effective and as to a concentration level that is therapeutically effective and as long as regular doses are administered to balance the amount of long as regular doses are administered to balance the amount of drug being cleared the drug will continue to be active. The time drug being cleared the drug will continue to be active. The time taken to reach the steady state is about five times the half life of taken to reach the steady state is about five times the half life of a drug. a drug.

Steady State does not = onset of drug actionSteady State does not = onset of drug action

Half-life exampleHalf-life example

Some drugs like ibuprofen have very short half Some drugs like ibuprofen have very short half lives, others take much longer to eliminate from lives, others take much longer to eliminate from the plasma resulting in a long half life. So drugs the plasma resulting in a long half life. So drugs like ibuprofen that are cleared from the blood like ibuprofen that are cleared from the blood more rapidly than others need to be given in more rapidly than others need to be given in regular doses to build up and maintain a high regular doses to build up and maintain a high enough concentration in the blood to be enough concentration in the blood to be therapeutically effective. therapeutically effective.

Now that we understand Now that we understand Pharmacokinetics, we Pharmacokinetics, we want to know more about want to know more about Pharmacodynamics-how Pharmacodynamics-how and which the drugs and which the drugs effect the body. This will effect the body. This will be the focus of the rest of be the focus of the rest of the classthe class