011924a.pptx

PSYCHOLOGY 335 SECTION 001 – 011924A PHARMACOKINETICS ZACH WALSH PH.D. Pharmacokinetics Pharmacokinetics: “what the body does to a drug”  Administration  How  Absorption  How  a drug gets into the blood Distribution  How  a drug gets into the body it travels Binding at Sites of Action  Where...

PSYCHOLOGY 335 SECTION 001 – 011924A PHARMACOKINETICS ZACH WALSH PH.D. Pharmacokinetics Pharmacokinetics: “what the body does to a drug”  Administration  How  Absorption  How  a drug gets into the blood Distribution  How  a drug gets into the body it travels Binding at Sites of Action  Where  the drug needs to go Inactivation and Excretion  How the drug leaves Pharmacokinetics Pharmacokinetics Administration Routes – Parenteral – Under the skin  Vehicle is needed  Liquid  Subcutaneous  Injected  Intramuscular  Needle  inserted into the muscle Intravenous  Injected  to form a bolus just under the skin (skin popping) into the vein (mainlining) Other Parenteral Routes  Intraperitoneal (gut), Intraventricular (brain), Intrathecal (spine) Pharmacokinetics Administration  Absorption from Parenteral Sites  Reliant on blood flow  IV  is direct Enters blood stream via capillaries  Tiny vessels from with pores (porous)  # capillaries in an area influences speed of absorption  Diffusion  Substances  moves from are of high to low concentration until equal Depot Injections  Slowly dissolves into the body over a long period of time Pharmacokinetics Administration  Inhalation of Gases  The Lungs  Efficient gas exchange system  Oxygen  Carbon Dioxide  Artery from heart to brain without the liver  Diffusion allows for control of blood levels  Anesthesia Pharmacokinetics Administration  Inhalation of Smoke and Solids  Burning of dried plant material  i.e. tobacco  Vapor & tiny particles of ash  Not exhaled like gasses  Popular among humans but under-studied  Difficult with animals Pharmacokinetics Administration  Inhalation of Smoke and Solids  Vaporization – Reduced Carbon monoxide/ hydrocarbons Pharmacokinetics Administration  Sniffing of drugs  Intranasal administration  i.e.  Oral Administration   Peroral (p.o.) Buccal membranes  i.e.  cocaine chewing tobacco Suppository   Unconscious Vomiting Pharmacokinetics  The Digestive System  Drugs absorbed in intestines  Faster on empty stomach  To reach capillaries must pass intestinal membranes   made of lipid bilayer Lipid Solubility  Olive  How much in water/oil  Ions   oil partition coefficient are not lipid soluble Level of ionization determines degree of absorption Can take place in the gut via metabolism - onset of effects Pharmacokinetics Administration  Transdermal Administration  Absorbed through the skin  Epidermis  Outer layer of the skin  Keratin   Lipid soluble (but waterproof!) i.e. nicotine patch Pharmacokinetics Administration Pharmacokinetics - Absorption/ Distribution  Distribution of Drugs  Active and Passive Transport Across Membranes   Need to allow passage of non-lipid-soluble materials Passive Transport Mechanism   Active Transport Mechanism     Like diffusion i.e. ion pumps Many in blood-brain barrier Takes energy The Placental Barrier   Intermediary organ between the fetus and the wall of the uterus Little protection Pharmacokinetics- Excretion/Metabolism  Excretion and Metabolism  The Liver  Enzymes     Catalysts - change molecular structure i.e. Alcohol Dehydrogenase Restructuring molecules aka Metabolism Metabolites  > useful / < toxic  > ionized = easily excreted  Detoxification  The metabolic process Pharmacokinetics- Excretion/Metabolism  First-Pass Metabolism    Any drug absorbed from the digestive system will pass through the liver before going anywhere else in the body. Subjected to liver enzymes Rate of excretion  Excretion  Half-life most efficient at higher blood levels PharmacokineticsExcretion/Metabolism First-Pass Metabolism - Rate of Excretion (Half Life)  The top panel shows a typical excretion curve for a drug like nicotine, which has a half-life of about 30 minutes. The bottom panel shows the excretion function for alcohol, which is excreted at a constant rate (about 15 mg/100 ml of blood per hour). Because the excretion function for alcohol is a straight line, the concept of half-life does not apply. Pharmacokinetics- Excretion/Metabolism  Excretion and Metabolism  The Kidneys  Filter everything from blood and reabsorb what is needed    Lipid soluble passed back to blood  Unless actively transported out Ionized / non lipid-soluble substances passed to bladder  Unless actively reabsorbed Ph influences – blood basic/ urine acid = bases excreted Pharmacokinetics- Excretion/Metabolism   Factors That Alter Drug Metabolism Important determinant of individual differences in effects  Stimulation of Enzyme Systems  Enzyme induction  Responsible for development of metabolic tolerance  >Alcohol Dehydrogenase  > metabolism Pharmacokinetics- Excretion/Metabolism  Factors That Alter Drug Metabolism  Depression of Enzyme Systems  Metabolism of Alcohol  Disulfiram (Antabuse)  Used to prevent drinking Pharmacokinetics- Excretion/Metabolism  Factors That Alter Drug Metabolism  Age  Young not able to metabolize the dose of an adult   Incomplete enzyme development Infant with drugs in system at birth  Elderly  – less efficient liver & kidneys Species  Alcohol  dehydrogenase rats (60%) vs. guinea pig (160%) vs. humans Pharmacokinetics Combining Absorption and Excretion Functions Time Course    absorption curve, assuming no excretion excretion curve, assuming instantaneous absorption and distribution the resultant of these two theoretical processes. The resultant curve is typical of the time course for blood level of most drugs Pharmacodynamics Therapeutic Window  The therapeutic window is a range of blood concentrations of a medicine above a level that is ineffective (therapeutic level) and a level that has toxic side effects (toxic level).  Complicated by absorption / excretion curves Pharmacokinetics