Term
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Definition
| How the body handles drugs by drug absorption, distribution, metabolism (biotransformation) and excretion |
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Term
| What does the body do to the drug? What processes determine the intensity and duration of dug action? |
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Definition
Site of Administration of soluble drug - ionized vs. non-ionezed (uncharged)
Absorption - inactive (bound) vs. active (free)
Distribution - special barriers to drug entry (b3, placental brrier); specialized sites of drug uptake/storage - fat/bone; target organ; eterohepatic recirculation; active metabolite; inactive metabolite
Excretion
The balance between four processes determines the level of the active drug |
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Term
| Drug Movement Across Cell Membranes |
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Definition
Passive Diffusion - ionized vs. non-ionized. Most drugs cross cell membranes by passive diffusion. Only nonionized (uncharged), lipid-soluble drug molecules can diffuse well.
Active Transport by specialized proteins or pumps - requires ATP; kidney
Pinocytosis
Filtration trough pores - kidney |
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Term
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Definition
| Process by which a drug moves across one or more cell membranes from its site of administration into the bloodstream. |
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Term
| Factors which influence absorption |
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Definition
Drug chemistry (i.e. drug solubility)
Route of administration
Coating of the drug |
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Term
| Comparison of drug admin routes as they r/t absorption |
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Definition
Oral- absorp variable, depending on composition of drug, gut pH & mobility, simultaneous use of other drugs that interact to alter absorp, timing of dose with respect to meals; convenient, economical, best for self-admin; requires pt compliance/assurance that med was taken; unsuitable for drugs that are insoluble, poorly or erratically absorbed; usually unsuitable for infants; may be unsuitable for children, adults with dysphagia, other problems with swallowing; unsuitable for unconscious patients, patients with frequent vomiting
Parenteral-IM:Rapid if aq, slow & prolonged if oily/depot preparation/suspension, absorption speed depends on local blood flow; admin by HCP/trained pt; SE:pain; may cause muscle damage that can inc bleeding risk during anticoag therapy, or can interfere w/ some diagnostic tests that measure organ/tissue damage; risk of infection, incompatibility with dilutents, other drugs; IV:immediate, emergency use; large vol of drug, or irritating drugs if suitably diluted;AE (overdose or otherwise) appear rapidly = short duration, requiring frequent administration; insoluble substances (eg, suspensions) cannot be given; risk of infection, pain, vasculitis, extravasation; not suitable for self-administration; SubQ:Rapid if aq, slow & prolonged if oily/depot preparation/suspension, absorption speed depends on local blood flow; admin by HCP/trained pt; SE:pain, irritation, tissue necrosis, esp if irritating, risk of infection, limited to small vol, risk of incompatibility with other drugs, sols as noted for intramuscular injection.
Inhalation - Rapid unless formulated for local effects in respiratory tract (eg. Steroids used for asthma); route for bronchodilators/anesthetics; self-administration -requires manual dexterity, coordination for optimal effect and patient teaching is essential; SE: coughing, wheezing
Percutaneous or transdermal-Incomplete, erratic unless formulated for this route; offer convenience for and acceptance by many pt, and availability of a product w/ stand amnt of drug; limited volume unless...
Rectal - erratic; small children or unconscious patients, for either locally or systemically acting drugs; require effort to retain suppository until it dissolves
Sublingual, Buccal - rapid, complete; Preferred route for some drugs that are inactivated by first-pass metabolism (eg. Nitroglycerin;Efficacy, speed, duration of effects depend on retaining tablet at administration site; eating, drinking may interfere with absorption
Topical (on skin)- incomplete, erratic;tx dermatologic problems; prolonged admin,SE-rash/allergic rxn,ASE-due to chronic or excessive use; consistent and precise dose difficult to achieve |
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Term
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Definition
Drug solubility in water and lipids:The rate and amount of drug absorbed from site of admin depends partly on the chem nature of the drug itself. Drug needs to be soluble in water and to a certain extent lipid soluble. Drug must dissolve in aq contents of digestive tract.
Stability of Drugs in Acid:Hormones and proteins are destroyed by acid in stomach. Enteric coated/time-release capsules= drugs that are protected from dissolving in the stomach
Drug Ionization and the Effects of pH:ionized (charged or polar)= adding a base - poorly diffusible anion/proton or nonionized (neutral or nonpolar)= adding an acid - diffusible
Other factors:Motility- fast(diarrhea and vomiting)= drug can’t be absorbed, (constipation)= too slow or toxic.
Drugs which irritate stomach can be taken with food.Some foods can inhibit absorp—milk products bind to tetracycline. |
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Term
| After entrance into the bloodstream, the drug is distributed by the blood to almost all regions of the body. |
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Definition
Local Blood Flow: Flow affects the amount of blood reaching organs.
Plasma Protein Binding: Only those drug molecules that are not bound to plasma proteins are able to produce pharmacologic effects. Likewise, only unbound (free) drug molecules can be metabolized or excreted.The percentage of total drug molecules that are bound or free depends on the drug itself and on the availability of protein binding sites. Effects of one drug displacing another from protein binding may lead to excessive or toxic effects due to increased concentration although dose wasn't changed.
Special Barriers to Drug Distribution:Organs that specialize in preventing some drugs from crossing the capillary network (b3/placental barrier)
Sites of Preferential Drug Accumulation: Organs that tend to accumulate certain drugs(fat/bones/teeth/kidney)
Drug Metabolism or Biotransformation:Some drugs are excreted without any prior metabolism. Others are inactivated by various metabolic reactions and then eliminated. Most drugs are partially metabolized to other compounds, while the rest of the unmetabolized drug is eliminated unchanged. Some drugs are either totally inactive or cause only week effects in the body; metabolism may change them to more active compounds.The “first pass” effect. Some drugs that are absorbed from the GI tract and pass through the liver via the portal circulation are extensively metabolized before reaching the systemic circulation. Therefore, drug concentrations in the systemic venous and arterial systems are much lower than those in the portal vein, and drug effects are minimal. Initial administration of large doses may overcome this first-pass effect, or it can be avoided altogether by using alternate administration routes.
Organs involved in metabolism: primarily the liver and to a lesser extent the lungs, GI mucosa, kidneys, and blood. |
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Term
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Definition
| Metabolic reactions (Figure 6) can result in products that are less active or less toxic (detoxification reactions). The reaction may convert the parent compound to a drug metabolite that is more active (e.g. codeine to morphine). In addition, an inactive drug, a prodrug such as cyclophosphamide, may be metabolized by the liver to an active substance. Finally, the microsomal enzymes can convert an active drug to a toxic metabolite that when present in sufficient quantities will cause fatal liver damage (e.g. acetaminophen [Tylenol]) |
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Term
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Definition
| Hepatocytes contain microsomal enzymes that metabolize drugs. |
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