Term
| What is Biopharmaceutics? |
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Definition
- Biopharmaceutics is concerned with the relationship of physico-chemical properties of the drug in a dosage form and the pharmacologic, toxicologic, and clinical response observed after its administration(of dosage form)
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Term
| What is Oral Biopharmaceutics? |
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Definition
- Study of the factors influencing oral bioavailability of the drug in man and animals and the use of this information to optimize pharmacologic or therapeutic activity of oral drug products in clinical application.
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Term
| What is Oral Bioavailability? |
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Definition
- Amount of orally administered drug which reaches the general circulation, intact (after passage through the liver) relative to direct systemic (IV) administration.
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Term
| Characteristics of IV Administration |
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Definition
- Aka directsystemic administartion - IV is always 100% bioavailable - Always calculate bioavailability relative to IV |
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Term
| What is total Oral Administration? |
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Definition
- What is the total amount of oral drug which reches systemic circulation, *after* passing through the liver. |
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Term
| Define Trancellular Passive Diffusion |
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Definition
- Through the lipid bilayer, dependent on lipophilicity
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Term
| Define Paracellular Transport |
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Definition
- Route between two cells, not based on lipophilicity, combination of diffusion and convection (fluid transport). |
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Term
| What is Carrier-Mediated Transport? |
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Definition
- Requires a carrier protein to be transported across, need a carrier protein (this process is saturable). |
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Term
| What is P-glycoprotein-mediated efflux? |
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Definition
- Opposite to absorption, P-glycoprotein is a transport protein, throws drug back out!~!~!~!~!~! |
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Term
| What is Receptor-mediated Endocytosis? |
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Definition
- Endocytosis followed by transcytosis. - Endocytosis is to bring into the cell - Transcytosis is throwing drug into other side. |
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Term
| What is Fluid Phase Endocytosis? |
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Definition
- Doesn't require other receptors that would be present in receptor mediated endocytosis
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Term
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Definition
- Smaller molecule and hydrophilic prefer paracellular transport. - MW and size important during drug absorption |
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Term
| What is Carrier-Mediated Uptake and Transport and what uses this process? |
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Definition
- For things your body needs, eg., Amino Acids, Sugars, Vitamins, etc. (These are hydrophilic). - These molecules are larger, so can't do paracellular. - Many of these carrier proteins are not on both sides of the membranes. - Amino acids have carriers on both sides of the cell. - Efflux transporter for P-glycoprotein only on one side of membrane. - High concentration of P-glycoprotein in brain, liver, kidney, intestines (lumen). - Why? To prevent toxic substances in these places. |
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Term
| Carrier Mediated Absorption |
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Definition
- If no carriers, you won't get transport. - Passive diffusion would be straight diagonal line on graph, wherease carrier mediated would curve upward until a max was reached, at which point it would plateau. - This is the circle diagram with the "tail" to the right |
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Term
| P-Glycoprotein mediated drug-efflux (detailed) |
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Definition
- Outside the cell P-glycoprotein is in form of carbohydrate with amine structure (N-Glycosamine) - Inside the cell it is in the form of a Carboxyl and amine (COOH) - P-glycoprotein has 2 regions, chemical regions (6 of them), and a membrane spanning region. - Protein will require energy for efflux (hence the ATP) - Bioavailability is influenced by efflux systems. - This is the mechanism of how the body reduces the toxicity in the liver cell; drug comes into liver, metabolized by p450, excreted out by P-glycoprotein. |
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Term
| Drug Ionization/ pH and pKa |
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Definition
- Extent of ionization controls bioavailability. - Non-ionized molecules diffuses through lipid bilayer. |
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Term
| Intestinal Absorption for Acids and Bases |
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Definition
- As pH of intestine INCREASES absorption of acidic drugs DECREASES. - As pH of intestine INCREASES absorption of basic drugs INCREASES - Remember, low pH = high acidity - Rate of absorption reflects bioavailability - Acidic and basic drugs, in general, you will see acidic drugs, because intestinal absorption will increase because of higher S.A - Higher stomach acid, higher absorption. - |
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Term
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Definition
- Don't eat pizza with hydrophobic drugs, affects bioavailability - If a patient were to take methotrexate, an anti-cancer drug, with food, absorption would decrease. - Fasting, more bioavailability - Food can affect enzymatic activity - Only after pre-hepatic metabolism can you affect bioavailability - Bacteria can affect absorption - Vitamins are transported by carrier mediated transport. Salads, fruits, will affect absorption, because carriers will be saturated, and drug bioavailability will be down. |
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Term
| Good Effects of Foods on B.A |
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Definition
- Food can protect drugs from degradation - Food can prolong absorption - Protect gastric mucosa *This is only in some cases |
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Term
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Definition
- Drug is not absorbed in stomach - Most of drug absorption occurs in.... - Duodenum - Jejunum - Ileum - So it doesn't matter if drug is acidic or basic |
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Term
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Definition
- The Villi are the anatomical structures where absorption actually occurs. - Because of the villi, we have the highest drug absorption. - There are millions of Villi, and each villi has a capillary. - Drug is absorbed, then goes to capillaries, now drug is in circulation. |
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Term
| Why are orally administered drugs not completely available to our bodies? |
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Definition
- Drugs may have low permeability; need to improve permeability using lipphilic prodrugs; administration with food can increase residence time and hence, absorption; use absorption enhancing excipients. - Drugs may have low solubility in GI fluid. Need to change dosage form; design water-soluble prodrugs; enhance drug solubility through complexation. - Drug metabolism
- Drug lost through fecal elimination and GI metabolism - Drug Degradation - Degradation of Penicillin because of acidic pH in stomach |
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Term
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Definition
- Full openings between blood and hepatocytes |
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Term
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Definition
- Opening between endothelial cells - No barrier between blood (drug) intercharge |
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Term
| Oral Drug Delivery vs. Rectal Drug Delivery |
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Definition
- Drug can bind to mucous and not be bioavailable - Hepatic portal vein (first pass effect) - Rectal absorption: You can bypass the first pass effect, this is important!~!~!~!~!~! |
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Term
| Some Factors that Influence Bioavailability of Oral Drugs (Drug Substance Physico-chemical properties) |
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Definition
- Particle size - Crystalline or amorphous form - Salt form - Hydration - Lipid or water solubility - pH or pKa |
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Term
| Some Factors that Influence Bioavailability of Oral Drugs (Pharmaceutical Ingredients) |
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Definition
- Fillers - Binders - Coatings - Disintegrating Agents - Lubricants - Suspending Agents - Surface Active agents - Flavoring agents - Coloring agents - Preservative agents - Stabilizing agents |
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Term
| Some Factors that Influence Bioavailability of Oral Drugs (Dosage form characteristics) |
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Definition
- Disintegration rate (tablets) - Dissolution time of drug in dosage form - Product age and storage conditions |
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Term
| Some Factors that Influence Bioavailability of Oral Drugs (Physiologic Factors and Patient Characteristics) |
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Definition
- Gastric emptying time - Intestinal Transit Time - Gastrointestinal abnormality or pathologic condition - Gastric contents - Other drugs - Food - Fluids - Gastrointestinal pH - Drug Metabolism (gut and during first passage through liver) |
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