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Drug Fate

Drug Fate. Some substances are very difficult to eliminate – heavy metals such as lead and mercury The body very efficient at removing most unwanted substances such as drugs. Removing substances from the body. Exhaling air – lungs function as chemical exchange unit

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Drug Fate

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  1. Drug Fate

  2. Some substances are very difficult to eliminate – heavy metals such as lead and mercury The body very efficient at removing most unwanted substances such as drugs Removing substances from the body

  3. Exhaling air – lungs function as chemical exchange unit Also perspiration, saliva, feces and even mother’s milk Major job of eliminating drugs and other unwanted substances is done by the liver and kidneys Liver responsible for breaking down chemicals Kidney responsible for excreting chemicals, but some water soluble chemicals are directly filtered out and excreted by kidneys Ways of drug elimination

  4. Largest organ in the body after skin Located high in the abdomen next to the stomach Function is to take molecules and modify them to new molecules In this case, toxic chemicals are modified into less harmful substances The liver receives 2 blood supplies One from the digestive system Second directly from the heart The liver

  5. Drugs taken orally (alcohol) begin to be metabolized, or altered prior to being distributed to the sites of action Referred to as first-pass metabolism – drugs taken orally must be given at higher dosages than those injected Blood from the digestive system

  6. Most lipid soluble substances cannot be filtered out and excreted by the kidneys. They pass through the kidneys and back into the bloodstream The liver must metabolize these substances into a form the kidneys can filter out Metabolism in the liver

  7. The liver produces enzymes that use oxygen to alter molecule structure These enzymes are called mixed function enzymes because they act on a variety of chemicals Drug interaction and mixed – function enzymes Alcohol and barbiturates Metabolism through oxidation

  8. Liver enzymes add chemicals to a drug molecule inactivating it by preventing its ability to be absorbed This is usually a second step in the metabolism process Oxidation occurs to alter the molecule, then conjugation inactivates the resulting molecule Metabolism through conjugation

  9. Metabolism of Alcohol • Ethanol (CH3CH2OH) is oxidized by P450 or alcohol dehydrogenase into acetaldehyde • Acetaldehyde then conjugated by other enzymes (mainly aldehyde hydrogenase) into acetyl-coenzyme • Acetyl-coenzyme conjugated into water, citric acid, carbon dioxide, and energy

  10. Used to discourage alcoholics from drinking Acts during the conjugation phase It competes with acetaldehyde for the aldehyde dehydrogenase Levels of acetaldehyde rise because it isn’t being broken down as quickly Acetaldehyde is a toxin causing sickness and discomfort Action of disufiram or antabuse

  11. Slowing metabolism by introducing a second drug that competes for the same enzyme Stimulating increased enzyme production due to past history Interspecies differences – animal research has to account for metabolic differences Age- enzyme systems not fully functional at birth – can be a problem Factors that effect liver metabolism

  12. Anesthesia given to mother during birth; it crosses the placental barrier Mother’s liver metabolizes anesthesia – fetus can’t Umbilical cord cut; drug remains in baby for a long time Theophyline, a stimulant used to treat asthma Baby’s liver converts theophyline to caffeine, mother’s doesn’t Baby metabolizes caffeine very slowly Drugs given to mother at delivery

  13. Filters out chemicals metabolized by the liver and water soluble chemicals the liver cannot metabolize It does not act like a sieve or a swimming pool filter Kidney function

  14. Blood pumped through kidney at high pressure Most of the fluid in the flood and substances in the fluid absorbed by the cell membranes of the kidneys Blood cells and large proteins are not absorbed Most of the fluid and substances reabsorbed back into the bloodstream Substances not absorbed are excreted in urine All lipid soluble substances diffuse back into the blood Needed non-lipid soluble substances, like glucose, are transported back into the blood Kidney function

  15. Water, drugs and other substances diffuse through the pores in the kidney cells out of the blood Water is reabsorbed or diffuses back into the bloodstream faster than other substances Concentrations of drugs increase in the kidneys and decreases the concentration in the blood There now exists a concentration gradient If the drug has not been metabolized and if it is lipid soluble, it diffuses back into the bloodstream This is critical for nutrients and other needed substances to not be excreted The role of diffusion in excretion

  16. One of alcohols effects is dehydration- it inhibits ADH or antidiuretic hormone that signals the kidneys to retain water Urination and dehydration increases as less water is reabsorbed and more alcohol is returned to the bloodstream Only reasonable way to decrease period of intoxication is drinking large amounts of water Reabsorption of alcohol

  17. Excretion curve Absorption curve Combine to form “therapeutic window” Therapeutic window – a constant level that is high enough to be therapeutic, but not toxic Interaction of absorption and excretion

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