Tuesday, August 10, 2010

Drug Information Resources

Drug Information Resources



Goals: To become familiar with advantages/disadvantages, proper use, and applicability of commonly used drug information resources.

Objectives: After this discussion, the student should be able to:

1) Know the differences (structure, advantages/ disadvantages, proper use, applicability) between the following tertiary references: Physician’s Desk Reference (PDR), American Hospital Formulary Service (AHFS), and Drug Facts and Comparisons.

2) Know the differences between (structure, advantages/ disadvantages, proper use, applicability) and become familiar with the various drug information handbooks and specialty texts presented in class.

3) Know the differences between (organization, advantages/ disadvantages, content, applicability) of the secondary resources discussed in class.

4) Recognize commonly-used primary journals.


Drug Information Resources

I. General Drug Information Resources

A. Physician’s Desk Reference (PDR)

1. Contents: product labeling provided by manufacturer (manufacturer

pays a fee to be included in the PDR)

2. Publication: yearly

3. Index: generic or brand name, product category

4. Structure: arranged alphabetically by manufacturer

5. Additional features

a. Manufacturer’s index

b. Product identification section (photographs of tablets)

6. Advantages

              a. Easy to use

              b. Includes both active and inactive ingredients

              c. Good reference for SE, contraindications, warnings, dosing

             d. Information is referenced

             e. OTC, Rx, Medical Devices

             f. Updated twice a year

7. Disadvantages

            a. Not all drugs are included in PDR

            b. No unlabeled indications

8. Cost: minimal (sometimes free)

B. American Hospital Formulary Service (AHFS)

1. Contents: drug monographs

2. Publication: yearly by ASHP

3. Index: generic or brand name, product category

4. Structure: arranged by AHFS classification number

5. Additional features:

               a. Updates: quarterly

               b. Some conversion tables, nomograms

6. Advantages

             a. Good resource for pharmacokinetic information

             b. Drug classification system

c. User friendly

d. Contains unlabeled uses (other uses)

7. Disadvantages:

              a. Information not referenced

              b. Mainly drugs (not many devices)

              c. Products listed do not indicate Rx or OTC

8. Cost: minimal; cheap for students in ASHP

C. Drug Facts and Comparisons

1. Contents: drug information monographs

2. Publication: yearly (hardbound), also published in loose-leaf form

3. Index: generic or brand name, product category

4. Structure: arranged in drug categories (but no official classification system like AHFS )

5. Additional features

             a. Updates: monthly (loose-leaf)

             b. Manufacturer’s index

             c. Contains relative pricing index

6. Advantages

             a. Easy to use

             b. Contains unlabeled uses

             c. OTC, Rx, Devices

             d. Very good comparative tables!!

             e. Indicates products that are sugar or alcohol free

7. Disadvantages

             a. Must keep up with monthly updates

             b. Does become bulky

             c. Information is not referenced

8. Cost: minimal



All the above references are available in CD-ROM.

The CD-ROM for the PDR is updated quarterly



D. MICROMEDEX - Computerized database that includes several useful

sources of information. And they are...

1. DRUGDEX - Contains information on specific drugs and adverse reactions, and therapy concerning specific disease states. It is divided into Drug Evaluations (drug monographs) and Drug Consults (answers to therapeutic questions).

2. IDENTIDEX - Database which identifies both foreign and domestic tablets or capsules by imprint code or visual characteristics.

3. POISONDEX - Contains the chemical composition of drug products (foreign and domestic, OTC and RX) and household chemicals, and also includes information on the therapeutic management of these types of poisonings. Also contains a tablet identification section similar to

the one in IDENTIDEX.



II. Speciality Resources

A. Foreign Drug Information

1. Martindale: The Extra Pharmacopeia - Contains information on 4,000 domestic and foreign drugs, as well as information on herbal products. Serves as an excellent source for foreign drug identification and in some cases, their US product equivalents. Also may be used as a general drug reference.

B. Pregnancy and Lactation

1. Drugs in Pregnancy and Lactation (Brigg’s) - Complete resource for information on drug use during pregnancy and breastfeeding. Contains summaries of clinical trials (human and animal) and is updated quarterly.



C. Intravenous Compatibility/Incompatibility

1. Handbook of Injectable Drugs (Trissel’s) - Contains referenced information concerning compatibility/incompatibility of intravenous preparations. Gives specific information for IV admixture, syringe, and Y-site compatibility.

D. Drug Identification/Availability

1. American Drug Index - Lists drugs alphabetically by generic, brand, and chemical name. Manufacturer, chemical or generic name, package size, dosage form, strengths, and therapeutic category are listed.

2. Drug Topics Red Book (The Red Book) - Contains information for purchasing drug products within the United States (i.e. NDC number, package size, average wholesale price). Also has manufacturer’s index, lists of alcohol-free and sugar-free products, listing of drug information and poison centers within the US, state and national pharmacy associations, and state boards of pharmacy.

3. Med Scan Manual - Domestic medications found in this reference are listed by the tablet imprint. Gives information as to color, coating, manufacturer, strength, and shape of the medication.



4. IDENTIDEX (see also section on MICROMEDEX) - Part of MICROMEDEX Computerized Clinical Information System. Database which identifies both foreign and domestic tablets or capsules by imprint code or visual characteristics.



5. NDA Pipeline - Comprehensive book that lists all drugs currently in therapeutic trials, which have not yet been approved by the FDA. Also contains an extensive manufacturer’s listing.

E. Pharmacotherapy

1. Pharmacotherapy - A Pathophysiologic Approach (Dipiro’s) Contains information on the drug therapy of many disease states. Arranged in a lecture-type format (incidence, etiology, presentation, therapy)



2. Applied Therapeutics (Koda Kimble) - Presents pathophysiology and treatment of disease states in a case-based format.

F. Natural Products

1. The Review of Natural Products

Monthly newsletter that focuses on natural products and herbal remedies.

G. OTC Products

1. Handbook on Nonprescription Drugs - Published by the American Pharmaceutical Association.

Contains information and comprehensive tables of OTC product ingredients, strengths, availability.

H. Toxicology

1. Ellenhorn’s Medical Toxicology - Information is categorized into the treatment of poisonings

with drugs, home products, chemicals, and natural toxins. Cool pictures of venomous snakes!!



2. POISONDEX - Contains the chemical composition of drug products (foreign and domestic, OTC and RX) and household chemicals, and also includes information on the therapeutic management of these types of poisonings. Also contains a tablet identification section.

I. Drug-Drug Interactions

1. Drug Interaction Facts - Published by Facts and Comparisons. Easy-to-use index which classifies interactions according to severity (mild, moderate, major), onset of action (delayed, rapid), and documentation (established, probable, suspected, possible, and unlikely). Also

available on disk.

J. Adverse Reactions/Side Effects

1. Textbook of Adverse Drug Reactions (Davies’) - Information is indexed according to drug class and/or drug and by specific side effect (i.e. what drugs cause this side effect). Published every 4 years.



2. Meyler’s Side Effects of Drugs - This index is separated into two distinct listings: 1) Drug and/or drug classes and side effects associated with their use and 2) Side effects and the drugs most likely to cause them. Published every 4 years.

K. Patient Information References

1. USP-DI Volume II - Contains more detailed information for the patient, which may prove more confusing. Also, information about a specific drug is usually longer than one page.



2. ASHP Medication Teaching Manual - Contains concise and relative information concerning proper administration, side effects, etc. Information is usually on one page, and is easy to copy. MUSC’S computerized version of this is called MedTeach.

L. Other

1. FDC Reports (The Pink Sheets) - Published weekly by the United States Federal Government (who says your tax dollars aren’t hard at work??) The Pink Sheets provide information concerning the pharmaceutical industry side of things, i.e. FDA rulings, new drug approvals, drug withdrawals, ongoing clinical trials, and manufacturer’s financial information.

III. Drug Information Handbooks

A. Drug Information Handbook - Published annually by APhA, and alphabetized by generic name. Lists age specific dosing information, side effects, monitoring parameters, how supplied, etc. (We’ve found some errors in this!!!) In appendix: abbreviations/measurements, chemoregimens, comparative drug charts, toxicology, immunology, therapeutic recommendations.

B. Handbook of Clinical Drug Data - Pocket-size handbook that gives brief monographs for drug classes and individual pharmaceutical products including those pending FDA approval. Also has information on drugs and breastfeeding, drug elimination in renal disease (hemodialysis, peritoneal dialysis), and drug- drug interactions.

C. Pediatric Dosing Handbook - Also published annually by APhA. Contains dosing information on

drugs in guess who??...children and infants. Also provides recipes for extemporaneously compounding oral medications for pediatric use. Appendix contains ACLS guidelines, comparative drug charts, toxicology,

immunology, nutrition.

IV. Secondary Resources

A. Current Contents - Computerized database of biomedical literature which does not use a structured language similar to MEDLINE. When compared to MEDLINE, it has fewer references, but a shorter lag-time (journals are updated weekly).



B. MEDLINE - Database for biomedical information containing approximately 370,000 references from about 3,000 articles. The information therein spans from 1966 to the present. MEDLINE uses a structured language,

which is referred to as MESH Headings, and is updated monthly. (Some journals are indexed quicker than others, i.e. NEJM, JAMA)



C. IPA (International Pharmaceutical Abstracts) - Found in the DI center, this database contains information which focuses on both national and international pharmacy-related issues. Compared to other secondary resources, IPA has a much greater inclusion of pharmaceutical journals and publications. It also contains abstracts to ASHP meetings.



D. IDIS (Iowa Drug Information System) - Developed by the University of Iowa (Go Hawkeyes!!), this database which is also located in the DI center allows retrieval of complete articles from more than 180 biomedical journals. The articles themselves are found on microfiche, and therefore, more journals are able to be kept within a smaller space.



E. Reactions - Published by ADIS international, Reactions is a collection of case reports from the medical literature which focuses on the adverse reactions of drugs, and drug-drug interactions.

V. Primary Resources (Journals)

A. Journal of the American Pharmaceutical Association - Official journal of the APhA which publishes information, news, and research updates in pharmacotherapeutic management of diseases, trends in

pharmacy practice, meetings or procedures of the Association, and developments in pharmaceutical care. Formerly American Pharmacy.



B. American Journal of Health-System Pharmacy - Official journal of ASHP which is a good source of information for IV compatibility/incompatibility. Also has professional listings for pharmacy positions, and provides comprehensive schedule of ASHP Midyear Meeting.



C. Journal of the American Medical Association - One of the most-read, peer-reviewed medical journals. It is published weekly and is a good source for consensus statements (all encompassing clinical guidelines for treating diseases) from renowned medical groups.



E. New England Journal of Medicine - Another premiere medical journal (published weekly) which

includes original and review articles important to physicians and other health care professionals.



F. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy - Published weekly by the American College of Clinical Pharmacy. Focuses on pharmacotherapeutic aspects of disease-state management (i.e. pharmacokinetics, bioavailability, drug interactions, clinical trials, and pharmacology) .

Thursday, August 5, 2010

cell culture

                              Cell Culture
Eukaryotic cells are much more difficult to culture than most prokaryotes. They demand complex media and are very susceptible to contamination and overgrowth by microbes such as bacteria, yeasts and fungi. In simple terms, there are three types of eukaryotic cell culture:

Primary cells:


Primary cells are explanted directly from a donor organism, e.g. white blood cells or nasal brushings. They may be capable of one or two divisions in culture, and given the right conditions can survive for some time, but they do not continue to grow and eventually senesce and die. So why do we bother growing these demanding cells? Because they are thought to represent the best experimental models for in vivo situations, and because they may express characteristics which are not seen in cultured cells, e.g. epithelial cells with beating cilia:

Lymphoid (white blood) cells can be cultivated and made to undergo a limited number of divisions before sensecence by adding cytokines and lectins to the growth media. Lectins are proteins which react with specific sugar residues on cell surfaces, cross-linking them and often causing intracellular signalling. Different lectins stimulate the outgrowth of different types of lymphoid cells, e.g. phytohaemagglutinin (PHA) stimulates T-cells only, while conconavalin-A has mitogenic activity (inducing cell division) for both T-cells and B-cells. The following video shows primary human peripheral blood lymphocytes stimulated with conconavalin-A after one week in culture. Activation of cells causes the expression of many cell surface receptors and the formation of large clumps of cells:





Secondary cells:

Secondary cells were originally explanted from a donor organism, and given the correct culture conditions, divide and grow for some time in vitro, e.g. 50-100 generations. However, they do not continue to divide indefinitely and eventually, their physical characteristics may change, after which the cells will eventually senesce and die. The factors which control the replication of such cells in vitro are related to the degree of differentiation of the cell - in general, terminally differentiated cells are harder to maintain than less specialized cells.

MRC5 cells are secondary human lung fibroblasts which undergo between 60-70 doublings before senescence. These cells are widely used to study viruses in vitro and for vaccine production:





BEAS-2B cells are human bronchial epithelial cells, transformed by SV40 T-antigen:



Immortalized cells:

Unlike primary and secondary cells, immortalized cells continue to grow and divide indefinitely in vitro for as long as the correct culture conditions are maintained. Immortalized cell lines are also known as transformed cells - i.e. cells whose growth properties have been altered. This does not necessarily mean that these are "cancer" or "tumour" cells, i.e. able to form a tumour if introduced into an experimental animal, although in some cases they may do. Transformation is a complex process and can occur by many different routes, e.g. infection by transforming tumour viruses or chromosomal changes.

HeLa cells are the classic example of an immortalized cell line. These are human epithelial cells from a fatal cervical carcinoma transformed by human papillomavirus 18 (HPV18). (Henrietta Lacks, 1951) HeLa cells are adherent cells (they stick to surfaces) which maintain contact inhibition in vitro, i.e. as they spread out across the culture flask, when two adjacent cells touch, this signals them to stop growing. Loss of contact inhibition is a classic sign of oncogenic cells, i.e. cells which form tumours in experimental animals. Such cells not only form a monolayer in culture but also pile up on top of one another in foci. HeLa cells are not oncogenic in animals, but they may become so if further transformed by a virus oncogene: