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¡ ¡physiological movement of drugs lMoving into the body lMoving through the body lExiting the body |
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Four steps in Pharmacokinetics |
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lAbsorption lDistribution lMetabolism/Biotransformation lExcretion |
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¡movement from an area of high concentration to an area of low concentration |
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¡passive movement with carrier molecules; still to an area of lower concentration from an area of high concentration |
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¡movement of molecules across membranes using a carrier molecule that pumps against a concentration gradient using energy (ATP) |
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¡- fat loving l - Lipophilic drugs dissolve in fats or oils (or phospholipid cell membrane) ¡- Intestinal mucosa has a lipid rich cell membranes and so lipophilic drugs are well absorbed from the gut using diffusion - tend to be nonoionized |
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¡- water loving l- Hydrophilic drugs dissolve in water ¡
- Do not pass through cell membranes as easily as lipophilic drugs, but dissolve well in body water (extracellular fluid, blood, etc) ¡- Ideally, IM injections should be hydrophillic for rapid absorption - tend to be ionized |
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¡- having a positive or negative charge l - Depends on the pH of the liquid that carries the drug as well as the pH of the drug l - Ionized drugs tend to be hydrophilic |
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¡- no charge/neutral l- Depends on the pH of the liquid that carries the drug as well as the pH of the drug l- Nonionized drugs tend to be lipophilic |
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¡movement of drug from the site where it was administered to the fluids of the body that carry it to the site(s) of action |
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¡percentage of a drug that is absorbed and reaches the circulation |
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¡ability to dissolve, and in this case allow for absorption to occur |
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¡Oral drugs lMust be in lipophilic form to penetrate the GI mucosa lTablets must dissolve into smaller particles; liquids tend to have a quicker onset of action lEnteric coating or drug formulation (sustained-release) may change the dissolution or absorption rate lChanges in GI motility may change time available for absorption lPresence of food may interfere with dissolution and absorption |
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¡Parenteral drugs lBetter absorbed if hydrophilic lAlteration of blood flow to the site of administration will alter absorption ¡Ie: temperature, presence of some drugs, medical conditions may alter blood flow lFormulation of the drug may change absorption rate |
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the physiological movement of drugs from the systemic circulation to target tissues (the intended site of action) |
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distribution is affected by 4 things...
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lMembrane permeability lTissue perfusion lProtein binding lVolume of distribution |
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¡Capillaries in the CNS have no fenestrations and have additional cells (glial cells) adding to the thickness of the cell walls lDrugs that enter the CNS typically have to be highly lipophilic lSome diseases may alter the blood brain barrier |
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¡relative blood supply to a tissue lAffects how rapidly a drug may be distributed lWell perfused tissues will have more rapid distribution of drug ¡Brain and heart tend to be very well perfused ¡Fat tends to have poor perfusion |
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¡- how well a drug is distributed throughout the body based on the concentration of the drug in the blood ¡- The larger the volume into which the drug may be distributed, the lower the drug concentration in the blood after distribution |
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¡the chemical alteration of drug molecules by the body ¡May produce lActive drug lInactive drug lToxic form |
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Four main pathways of metabolism |
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lOxidation (loss of electrons) lReductions (gaining electrons) lHydrolysis (adding water molecules and splitting the drug) lConjugation (adding a glucoronic acid molecule and increasing water solubility) |
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Primary site of metabolism |
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¡enzyme located within hepatocytes (liver cells) which alter the structure of drug molecules |
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lWhen a drug is absorbed from the GI tract and enters the circulation, it passes through the portal system before it goes to the rest of the body. This allows the liver to metabolize the drug before the rest of the body is exposed. |
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5 Patient Factors That Affect Metabolism |
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Age Tissue types Disease status Nutritional status Species |
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¡Excretion: elimination for the body ¡Typically occurs in... |
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lKidneys lLiver lIntestine lLungs lMilk lSaliva lSweat |
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¡period of time after a drug is administered during which drug residues persist in the animal/animal products lOf particular concern for food animals; the meat and products of these animals must be discarded and not consumed lCalculated based on the half life of the drug |
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¡Time required for the amount of the drug in the body to decrease to half of the original level lGives an idea of the speed of elimination |
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the point at which drug accumulation equals that of elimination |
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¡how drugs produce physiologic changes lDrugs alter existing cellular functions, they do not create new ones ¡Depress function ¡Alter affect of another agent ¡Induce function |
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interaction of two agents such that the effect of the two together is greater than the sum of their individual effects |
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