1060 W2 Absorption Study Activity.docx

PHARMACOLOGY STUDY ACTIVITY Absorption of Oral Drugs I. [ADVANTAGES OF ORAL ROUTE] II\. [G.I. ABSORPTION] A. Most oral drugs must be absorbed from G.I. tract into blood before they can be used by the body. To be absorbed from the G.I. tract into the bloodstream, a drug must be dissolved in G.I....

PHARMACOLOGY STUDY ACTIVITY Absorption of Oral Drugs I. [ADVANTAGES OF ORAL ROUTE] II\. [G.I. ABSORPTION] A. Most oral drugs must be absorbed from G.I. tract into blood before they can be used by the body. To be absorbed from the G.I. tract into the bloodstream, a drug must be dissolved in G.I. fluids, pass through G.I. membrane, dissolve in interstitial fluid and then pass through capillary membrane. B. Rate and extent of absorption help determine drug's effectiveness. C. Bioavailability: Amount of administered drug that reaches the blood stream or other body system where it can be measured. D. Factors that affect bioavailability (or absorption). 1\. Drug form or preparation: dissolution rate - the degree and speed that the drug dissolves in G.I. fluids - is the major way that form effects bioavailability. a\. Capsule - how fast does it disintegrate. b\. Tablet -- starch or buffers help a table expand and break apart. c\. Film or sugar coating - dissolve fast in the stomach. d\. Enteric coating -- do not dissolve in the stomach. Dissolve in the intestine. Do not break or crush. e\. Sustained or delay release forms (waxy coat) -- do not crush, chew, break, or take with hot or alcoholic beverages as this may result in overdose from too rapid release in the stomach. f\. Soluble liquid forms of drugs usually are more bioavailable than drugs in solid forms. g\. Non-soluble liquids -- cloudy, non-translucent liquids with the drug held in suspension. Absorption does not occur or is very slow. 2\. Nature of the Absorbing Surface -- the cell membrane a\. Membranes that a drug must pass through to be absorbed: mucosal lining of the stomach or small intestine into the interstitial fluid (the fluid between cells of different tissues) and the cell membrane of the capillary of the bloodstream. b\. Membranes are composed primarily of lipid (fat) and protein molecules believed or thought to be arranged as a double layer of lipids with proteins located within the lipid layers; some proteins molecules penetrate both layers while others are found at or near only one surface. c\. Thought that pores (small openings) are within the membrane and that water can move through the pores. The size of the pores varies from one body tissue to another. d\. [Passive Transport] 1\. [Lipid] -- [soluble]: Drug dissolves in the lipid material of the cell membrane and then moves through it; moves from an area of high drug concentration. Rate and direction of diffusion (the process of dissolving and moving) is determined by the relative concentration of the drug on either side of the membrane. Increasing the dosage increases the rate of diffusion into the bloodstream. 2\. [Water] -- [soluble]: Drugs that carry and electrical charge (ionized); move through the pores; size of drug molecule determines if the drug can pass through the pores; movement through the pore also is affected by the electrical charge of the pore which tends to be the same as the drug and, therefore, repels the drug and keeps it from going through. The rate of absorption of water-soluble drugs tends to be slower than lipid-soluble drugs. 3\. Chemical and physical characteristics of G.I. system -- also influence rate and extent of absorption: a\) pH or acid-base content of the fluids in the G.I. tract 1\. Stomach -- acid. b\) A drug may be non-ionized in one form of pH and ionized in another. c\) A non-ionized drug is lipid-soluble and passes through membranes easily but is not easily dissolved in fluids. d\) An ionized drug is water-soluble and dissolves in body fluids easily but is not easily diffused. e\) Aspirin -- is a weak acid, therefore, it becomes almost non-ionized in the stomach, it is highly lipid-soluble in the stomach, it is hard to dissolve in but easily absorbed from the stomach. f\) As an acidic drug moves into an environment that is alkaline the number of drug molecules that are ionized increases and the drug becomes water-soluble and dissolves easier but passes less readily through membranes. As aspirin moves into the intestines it is easily dissolved but poorly absorbed. g\) Basic drugs act in just the opposite way. Basic drugs become more ionized in the acid environment of the stomach, water-soluble and poorly absorbed through stomach membranes. Basic drugs are more easily dissolved in stomach fluids than are acidic drugs, which is why buffering an aspirin speeds absorption -- buffering releases the acidic aspirin from the tablet faster and once released it zips through the lipid membrane. h\) Basic drugs become less ionized in an environment that is more alkaline than the drug. Basic drugs are less ionized, more lipid-soluble, less readily dissolved and more easily absorbed in the intestine. i\) [surface area available] for absorption also affects the rate at which the drugs will reach the internal circulation. 1\) Intestine has the largest surface area for absorption of oral drugs: length, folds in the mucosal lining and villi; the number of folds increase the surface area available 2\) Stomach -- relatively small area due to its size and lack of villi. 4\. Food and other materials in G.I. system. a\) Tetracycline combines with heavy metals in foods and in drugs such as some antacids or iron preparations and is inactive in this insoluble complex -- leads to a 50-80% decrease in the serum level or bio-availability of tetracycline. b\) Normal constituents of the G.I. tract may inactivate drugs. Insulin is inactivated by digestive enzymes and can never be given orally. c\) Delay in stomach emptying slows the absorption of most drugs. Causes of delayed stomach emptying: 1\) Food -- particularly hard to digest foods such as fatty acids. 2\) Lying on the left side slows emptying: lying on the right side speeds it. d\) Too rapid emptying of the G.I. tract limits contract time for absorption and, therefore, decreases absorption. Causes of too rapid emptying 1\) Laxatives e\) Changes in pH of intestine and stomach may be caused by food or drugs -- such a change will affect the location and rate of absorption of drugs taken with pH changers. 1\) Drugs that raise pH of gastric fluid (make it less acid or more alkaline): antacid drugs such as sodium bicarbonate, Maalox 2\) Food and drugs that raise the pH of gastric fluids, those with high fat content. f\) Lack of food also affects absorption rate: prolonged fasting of more than 20 hours results in vasoconstriction of the blood vessels supplying the mucosa of the tract's lumen. This delays absorption. STUDY ACTIVITY: Absorption of Oral Drugs True or False [ True] 1. Bioavailability measures the amount of drug in the blood. [False] 2. All liquid drugs are soluble in the fluid in the G.I. tract 3\. List four precautions a patient receiving a sustained-release medication should be taught concerning administration procedures. **DO NOT** a\. [ Chew ] b\. [ Crush ] c\. [ Break ] d\. [ Take with hot beverages or alcohol ] Designated with the letters A through D the order of bioavailability of these forms of medication. Use A for the most bioavailable, etc. [ A] 4 a liquid [ C] 5 a compressed tablet [ D] 6 an enteric-coated tablet [ B] 7 a gelatinous capsule After each statement, place the term [ionized] or [non-ionized] to indicate the state of the molecules under each condition. 1\. more lipid-soluble [ Non Ionized ] 2\. more water-soluble [ Ionized ] 3\. moves readily through membranes [ Non Ionized ] 4\. dissolves readily in body fluids [ Ionized ] 5\. has an electrical charge [ Ionized ] 6\. state of an acid drug in the stomach [ Non Ionized ] 7\. state of a basic drug in the intestinal tract [ Non Ionized ] Complete Statements: 8\. In the stomach, a basic drug such as codeine will be primarily in the **[water]** - soluble state and [ **Will NOT**] be absorbed readily. 9\. In the stomach, an acidic drug such as aspirin will be primarily in the [ **Lipid**] - soluble state and [ **WILL**] be absorbed readily. 10\. The stomach provides a [ **SMALLER**] area for absorption than does the intestine. 11\. List three factors which affect the amount of surface area available for absorption in the intestine. a\. [ Length of Small Intestine ] b\. [ Fold of mucosal lining ] c\. [ Presence of Villi ] 1\. List two factors which will delay stomach emptying a\. [ Food, Especially high fat ] b\. [ Lying on the left side, slows stomach emptying ] 2\. When a tetracycline drug and an antacid are administered concurrently interaction occurs? How does this impact tetracycline? **[Tetracycline combines with the heavy metals found in antacid making the\ tetracycline insoluble and inactive]** 3\. Drug absorption is [ **Decreased**] when a drug complexes with food to form an insoluble complex. 4\. The amount of drug absorbed when drugs move rapidly through the G.I. tract is [ **Decreased**] than when the movement is slower. 5\. The concurrent administration of sodium bicarbonate and an acidic drug such as phenobarbital will [ **Decrease**] the rate of phenobarbital absorption. 6\. John Jones has been ordered to take a tetracycline drug for an infection. Because he finds that the drug makes him nauseated, he takes it with a glass of milk. One week later he returns to the clinic and states that his infection has not improved under therapy. What teaching do you think would be appropriate to give at this time? [Tetracycline binds with heavy metals making it inactive: Milk contains calcium a\ heavy metal: Contact prescriber and report nausea and recommend changing\ the antibiotic:]