PCOL 350.6

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PCOL 350.6
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2012-09-13 18:10:55
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  1. Define: pharmacology.
    1.  Study of the changes produced in living animals by chemical substances, especially the actions of drugs, used to treat disease.

    2.  Branch of medicine that deals with the interaction of drugs with the systems and processes of living animals, in particular, the mechanisms of drug action as well as the therapeutic and other uses of the drug
  2. Pharmacology is derived from the Greek word ______ meaning what?
    Pharmakon, meaning magic charm for treating disease.  Over time, this Greek word has come to me a remedy or drug.
  3. What is a drug, in the broadest sense of the word?
    Any chemical agent that affects living processes.
  4. Give 3 more specific definitions of a drug.
    1.  Chemical substance that affects the processes of the mind or body.

    2.  Chemical compound used in diagnosis, treatment, or prevention of disease or other abnormal condition.

    3.  Substance used recreationally for its effects on the CNS, such as a narcotic.
  5. What are the different types of names that a typical drug is assigned?
    • 1.  Proprietary (brand) name (one or more)
    • 2.  Nonproprietary (generic) name
    • 3.  Pre-market manufacturer code
    • 4.  Chemical name
  6. What are the two major subdivisions of pharmacology?  What is the difference between these two subdivisions?
    Pharmacokinetics and pharmacodynamics.  PK is what the body does to the drug (involves ADME).  PD is what the drug does to the body (involves receptor binding, signal transduction, and biological effects).
  7. Explain the difference between an adverse effect, side effect, and iatrogenic effect.
    1.  Adverse effect: due to interactions or some unknown mechanisms.

    2.  Side effect: generally a secondary effect, which may be beneficial OR harmful.

    3.  Iatrogenic effect: adverse effect or complication caused by a physician (resulting from medical treatment or device).
  8. List some of the major routes of administration (ROA) for a drug.
    • 1.  Enteral--oral, sublingual, rectal.
    • 2.  Parenteral (route other than the digestive tract)--IV, IM, SC, intra-arterial, intrathecal, intraperitoneal.
  9. What does drug absorption refer to?
    The passage of drug from the site of administration into the general circulation (except for drugs that are applied directly to the target tissue--skin patches, for ex.)
  10. Describe absorption for a drug injected intravenously.
    IV injection results in immediate and complete (100%) absorption.
  11. In general, what types of drug molecules are better absorbed?  Which are poorly/slowly/not absorbed?
    • Better absorbed: non-ionized, small, lipid-soluble
    • Poorly absorbed: ionized, large
  12. Give some examples of drugs that are poorly absorbed and explain why these drugs are poorly absorbed.
    1.  Penicillin G, insulin, and other peptides: destroyed by stomach acid or digestive enzymes.

    2.  Tetracyclines: chelated to components of food to form insoluble complexes.

    3.  Aminoglycoside antibiotics (streptomycin, gentamycin: so polar they won't cross cell membranes.

    4.  Nitroglycerin, adrenaline, dopamine: undergo extensive metabolism.
  13. Define: pKa.
    The pKa of a drug is the pH at which half of the drug is ionized.
  14. State whether the protonated or unprotonated form of an acidic or basic drug would be better absorbed.
    Acidic drug: protonated (uncharged) form is better absorbed.

    Basic drug: unprotonated (uncharged) form is better absorbed.
  15. Describe the phenomenon of ion trapping.
    At steady state, an acidic drug would accumulate on the more basic side of a membrane and a basic drug would accumulate on the more acidic side of a membrane.
  16. Why do pregnant women need to be careful about taking basic drugs?
    A mother's blood plasma has a pH of 7.4.  In this environment, the non-ionized form of a basic drug is preferred over the ionized form.  The non-ionized form of a drug can easily pass across cell membranes.  A basic drug could pass into fetal plasma (pH 7.0-7.2) or the breast milk.  These environments are slightly more acidic than the mother's plasma.  In a more acidic environment the ionized basic drug accumulates because it can no longer cross the membrane freely.
  17. Why is the phenomenon of ion trapping clinically significant with regards to poisoning?
    We can use our knowledge of ion trapping to save someone who has been poisoned by acidification or alkinatization of the urine.  To increase excretion of acidic drugs (phenobarbital, salicylates), IV sodium bicarbonate is given.  To increase excretion of basic drugs (amphetamine) NH3Cl or ascorbic acid may be given.
  18. What is the first pass effect (first pass metabolism)?  How can first pass metabolism be combatted?
    Some drugs are ineffective when given orally because of metabolizing enzymes in the intestinal wall and/or the liver.  First, much of a drug taken orally is metabolized in the intestinal wall, decreasing the amount that reaches the portal circulation.  Then, more of the drug is metabolized in the liver, leaving very little or no drug left to reach the general circulation.

    Solutions: increase the dose, change ROA.
  19. What is the cheese-wine reaction?
    Foods such as cheese and wine containe the sympathomimetic amine tyramine, which is normally metavolized by MAO in the GI wall and liver.

    However, if a patient is taking a MAO inhibitor, tyramine will be absorbed and will reach the circulation and nerve terminals wher it will release NE.  NE stimulates adrenergic receptors causing tachycardia and high blood pressure.
  20. The enzyme MAO (monoamine oxidase) metabolizes neurotransmitters.  Give an example of a case in which we would aim to inhibit this enzyme.
    Parkinson's.  By inhibiting MAO, we can increase neurotransmitter levels endogenously.  Patients with Parkinson's have a dopamine deficiency, so MAO inhibitors are a viable solution.
  21. What is bioavailability?
    The fraction of an orally given drug that reaches the circulation.  Fractional indicates that bioavailability values are a number between 0 and 1.
  22. Acidic drugs bind to the plasma protein ____________ while basic drugs bind to the plasma protein _____________.
    albumin, a1-acid glycoprotein (a globulin)
  23. What is the effect of displacement of a drug from plasma protein binding?
    Generally this results in no change in the overall effect of a drug or its adverse effects.  However, drugs with a very small volume of distrubtion are a special case (ex. Warfarin, which is 97% bound to albumin).
  24. When most of a drug is located extravascularly, change in free plasma drug concentration caused by displacement from plasma protein binding would be ________, but if the drug is located intravascularly, displacement would be _________.
    minimal; significant--and potentially dangerous.
  25. What is distribution?
    The reversible movement of a drug between body compartments.
  26. List 4 factors that affect drug distribution.
    • 1.  ionization
    • 2.  capillary permeability
    • 3.  blood flow
    • 4.  plasma protein binding
  27. In which organs are capillaries particularly leaky?
    Liver and spleen.

    Drugs will leave these capillaries regardless of whether they are poorly lipid soluble, charged, or polar.
  28. Brain capillaries have _______  ____________.  How do glucose and amino acids cross the blood-brain barrier?  What drugs can cross the blood-brain barrier?
    tight junctions.

    -specific carrier-mediated transport systems.

    -only lipophilic drugs diffuse across brain capillaries (unless other drugs are actively transported across).
  29. The amine dopamine is administered as L-dopa to patients with Parkinson's disease.  Why?
    Because it cannot cross the blood-brain barrier (dopamine is metabolized by enzymes in the BBB).
  30. What are the clinical implications of the blood brain barrier regarding injury and tumor treatment?
    Injury: BBB does not work properly in areas of infection or injury.

    Tumors: develop new blood vessels/capillaries that have no tight junctions.  Substances like radioactive iodine-labeled albumin penetrate normal brain tissue slowly, but can enter tumor tissue and aid in diagnosis.

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