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Absorption-the movement of a drug from its site of administration into the blood
the AMOUNT of absorption helps determine how intense effects will be
Factors affecting drug absorption:
- Rate of dissolution- before a drug can be absorbed, it must first dissolve. the rate of dissolution helps determine the rate of absorption
- Surface Area- the larger the surface area, the faster absorption will be
- Blood flow- drugs are absorbed most rapidly from sites where blood flow is high
- Lipid Solubility- as a rule, highly lipid-soluble drugs are absorbed more rapidly. this is bc lipid-soluble drugs can readily cross the membranes that separate them from the blood
- pH partitioning- absorption will be enhanced when the difference between the pH of plasma and the pH at the site of administration is such that drug molecules will have greater tendency to be ionized in the plasma
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Distribution- the movement of drugs throughout the body
has 3 major factors: blood flow to tissues, the ability of a drug to exit the vascular system, and, to a lesser extent, the ability of a drug to enter cells
- Blood flow to the tissues: since most tissues are well perfused, regional blood flow is rarely a limiting factor in drug distribution
- two pathological conditions that can affect drug therapy- abscesses and tumors.
- an abscess if a pus-filled pocket of infection that has no internal blood vessels. abscesses must first be surgically drained for the drug to reach it
- solid tumors have a limited blood supply. this is the reason why solid tumors are resistant to drug therapy
- exiting the vascular system since most drugs do not produce their effects within the blood, the ability to leave the vascular system is an important determinant of drug actions. exiting the vascular system is also necessary for drugs to undergo metabolism and excretion. drugs in the vascular system leave the blood at the capillary beds
- typical capillary beds: most capillary beds offer no resistance to the departure of blood
- Blood-brain Barrier (BBB): there are tight junctions between the cells that compose the walls of most capillaries in the CNS. they are so tight they prevent passage. only drugs that are lipid soluble or have a transport system can cross the BBB to a significant degree.
- Placental drug transfer: the membranes of the placenta do NOT constitute and absolute barrier to the passage of drugs. drugs that have the ability to cross the placenta can cause serious harm.
- Protein binding: many drugs bind reversibly to plasma albumin. while bound to albumin, drug molecules cannot leave the vascular system
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drug metabolism-aka biotransformation; the enzymatic alteration of drug structure.
most drug metabolism takes place in the liver and is catalyzed by the cytochrome P450 system of enzymes
the most important consequence of drug metabolism is promotion of renal drug excretion (by converting lipid-soluble drugs into more polar forms)
other consequences of drug metabolism are conversion of drugs to less active (or inactive) forms, conversion of drugs to more active forms, conversion of prodrugs to their active forms, and conversion od drugs to more toxic or less toxic forms
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Drug excretion- the removal of drugs from the body
drugs and their metabolites can exit the body in urine, bile, sweat, saliva, breast milk, and expired air.
the most important organ for drug excretion is the kidney
steps in renal drug excretion: glomerular filtration, passive tubular reabsorption, and active tubular secretion
drugs that are highly lipid soluble undergo extensive passive reabsorption back into the blood, and therefore cannot be excreted by the kidney (until they are converted into more polar forms by the liver
drugs can be excreted into breast milk, thereby posing a threat to the nursing infant
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Some advantages and disadvantages of route of drug administration:
IV: aka intravenous
advantages-
1. results in rapid onset of action; clearly beneficial in emergencies
2. because the entire dose is administered directly into the blood, we have precise control over levels of drug in the blood
3. this route is the only parenteral route that permits the use of large volumes of fluid
disadvantages-
1. expensive, difficult and inconvenient
2. can be dangerous; once a drug has been injected, there is no turning back
3. embolism, which is blood vessel blockage at the site distant from the point of administration. because of the risk of embolism, you should check IV solutions prior to administration to ensure that drugs are in solution. If the fluid is cloudy or contains particles, the drug is not dissolved and must not be administered
IM: aka intramuscular
advantages-
1. used for parenteral administration of poorly soluble drugs
2. can be used to administer depot preparations (preparations from which the drug is absorbed slowly over an extended time ). depending on the depot formulation, the effects of a single injection may persist for days, weeks or even months
disadvantages-
1. discomfort, inconvenience, and painful
2. bleeding risk
3. can cause local tissue injury and possibly nerve damage
subQ: aka subcutaneous
nearly identical to those of IM administration
PO: aka oral
advantages-
1. easy, convenient, and inexpensive (by inexpensive, we dont mean that oral drugs themselves are inexpensive, but rather that there is no cost for the process of administration)
2. route is safer then injections
3. reversible
disadvantages-
1. major disadvantage is absorption can be highly variable
2. can lead to inactivation of certain drugs
3. some oral preparations cause local irritation of the GI tract
additional routes of administration of medications:
- 1. applied topically for local therapy of the skin, eyes, ears, nose, mouth and vagina
- 2. transdermal absorption into the systematic circulation
- 3. inhaled to elicit local effects in the lung
- 4. rectal suppositories for local effects or for effects throughout the body
- 5. vaginal suppositories to treat local disorders
- 6. direct injection into specific site for management of some conditions (heart, joints, nerves, CNS)
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Clinical significance of plasma drug levels
two plasma drug levels are of special importance
1. the minimum effective concentration and
2. the toxic concentration
The minimum effective concentration (MEC)- the plasma drug level below which therapeutic effects will not occur
toxic concentration- toxicity occurs when plasma drug levels climb too high
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