1. HOW DO DRUGS GET INTO THE BODY?

2. WHY BE CONCERNED ABOUT HOW DRUGS GET INTO BODY? Bioavailability - % of dose that gets into body Bioequivalence - similarity between two formulations of same drug Speed of Drug Onset - how long it takes the drug to begin working Dosing Interval - how often the drug should be given Site of Action - whether the drug stays local or acts systemically This issue importantly affects:

3. HOW DO DRUGS GET INTO THE BODY? Unless injected directly into the blood stream, drugs must be absorbed.

4. WHAT IS DRUG ABSORPTION? The movement of drug molecules across biological barriers (mostly layers of cells) from the site of administration to the blood stream. BIOLOGICAL BARRIER Vascular SystemSite of Administration DRUG

5. WHAT AFFECTS DRUG ABSORPTION? Rate of release of drug from pharmaceutical preparation Membrane permeability of drug Surface area in contact with drug Blood flow to site of absorption Destruction of drug at or near site of absorption The rate of drug absorption will be affected by:

6. WHAT DETERMINES RATE OF RELEASE OF DRUG FROM PHARMACEUTICAL PREPARATION? Solutions: No Delay, Immediate Release Capsules & Tables: Delay (Dissolution) Followed by Rapid Release Creams, Ointments & Suppositories: No Delay, but Slow Release A: DOSAGE FORM

7. WHAT DETERMINES RATE OF RELEASE OF DRUG FROM PHARMACEUTICAL PREPARATION? Decrease Rate of Dissolution Binders Lubricants Coating Agents B: ADDITIVES (EXCIPIENTS) Increase Rate of Dissolution Disintegrants Variable Effects on Rate of Dissolution Diluents Coloring Agents Flavoring Agents

8. WHAT DETERMINES RATE OF RELEASE OF DRUG FROM PHARMACEUTICAL PREPARTAION? Tablet Compression - Hard tablets dissolve more slowly Tablet Shape - Round tablets dissolve more slowly Tablet Size - Large tablets dissolve more slowly C: MANUFACTURING PARAMETERS

9. WHAT DETERMINES RATE OF RELEASE OF DRUG FROM PHARMACEUTICAL PREPARATION? Enteric Coating - Dissolve in intestines, not stomach D: DELAYED RELEASE PREPARATIONS

10. WHAT DETERMINES RATE OF RELEASE OF DRUG FROM PHARMACEUTICAL PREPARATION? Reservoir Diffusion Products - Drug diffuses from pill core through membrane shell Matrix Diffusion Products - Drug diffuses through matrix in which it is embedded Matrix Dissolution Products - Drug released as matrix dissolves Osmotic Tablets - Drug pumped out of tablet by osmotic forces Ion-Exchange Products - Drug bound to resin exchanges with endogenous ions E: SUSTANED RELEASE PREPARATIONS

11. WHAT DETERMINES MEMBRANE PERMEABILITY OF DRUGS? Presence of Aliphatic and Aromatic Structures Absence of Polar Groups A: LIPOPHILICITY increases membrane permeability

12. WHAT DETERMINES MEMBRANE PERMEABILITY OF DRUGS? Weak acids in intestines are mostly ionized (intestinal pH ranges from 6.6 to 7.5) Weak bases in stomach are mostly ionized (stomach pH ranges from 1 to 2) B: IONIZATION decreases membrane permeability

13. WHAT DETERMINES SURFACE AREA FOR ABSORPTION? Low Surface Area: eyes, nasal cavity, buccal cavity, rectum, stomach, large intestines High Surface Area small intestines, lungs ANATOMY

14. WHAT DETERMINES TISSUE BLOOD FLOW? Low Blood Flow: eyes, stomach, large intestines, rectum, subcutaneous tissue High Blood Flow small intestines, lungs, muscle, buccal cavity, nasal cavity A. PHYSIOLOGY

15. WHAT DETERMINES TISSUE BLOOD FLOW? Some Drugs Are Vasoconstrictors Some Drugs Are Co-Administered With Vasoconstrictors Some Drugs Are Vasodilators B. PHARMACOLOGY

16. WHAT DETERMINES WHETHER A DRUG IS DESTROYED AT OR NEAR SITE OF ADMINISTRATION? Liver - hepatic enzymes (“first pass” effect) Colon - intestinal microflora Stomach - digestive enzymes and acids BIOCHEMISTRY

17. WHAT ARE THE ROUTES OF ADMINISTRATION FOR DRUGS? Oral Sublingual Rectal ENTERAL Intravenous (IV) Intra-arterial (IA) Subcutaneous (SC) Intradermal (ID) Intramuscular (IM) Intraperitoneal (IP) Lungs (Inhalation) Skin (Topical) PARENTERAL Nose (Intranasal) Eye (Opthalmic) Ear (Otic) Vagina Urethra Urinary Bladder Intrathecal Epidural Directly Into Target Tissue

18. LowHigh WHAT ARE THE ADVANTAGES AND DISADVANTAGES OF ORAL, IV, IM AND SC ADMINISTRATION? SAFETY HighLow Oral > SC > IM > IV CONVENIENCE Low COST IV > IM > SC > ORAL

19. LowHigh DelayedImmediate WHAT ARE THE ADVANTAGES AND DISADVANTAGES OF ORAL, IV, IM AND SC ADMINISTRATION? BIOAVAILABILITY High and ReliableLow and/or Variable IV > IM = SC > ORAL IV > IM > SC > Oral ONSET OF ACTION PATIENT COMPLIANCE IV > IM > SC > Oral

20. LowHigh LowHigh WHAT ARE THE ADVANTAGES AND DISADVANTAGES OF ORAL, IV, IM AND SC ADMINISTRATION? INTERACTIONS WITH FOOD RiskNo Risk Oral > IV = IM = SC Oral > IM = SC = IV COMMERCIAL AVAILABILITY OF DOSAGE FORMS VOLUME OF DRUG Oral = IV > IM > SC

21. LowHigh WHAT ARE THE ADVANTAGES AND DISADVANTAGES OF ORAL, IV, IM AND SC ADMINISTRATION? AVAILABILITY OF SUSTAINED RELEASE DOSAGE FORMS HighLow IM > Oral > SC > IV TOLERANCE TO “FUNKY” VEHICLES Oral = IM = SC > IV

22. WHY CONSIDER OTHER ROUTES OF ADMINISTRATION? Sublingual - Rapid absorption that bypasses liver Rectal - Great for patient that is vomiting or cannot (will not) swallow medication

23. WHY CONSIDER OTHER ROUTES OF ADMINISTRATION? Lungs (Inhalation) Skin (Topical) Nose (Intranasal) Eye (Opthalmic) Ear (Otic) Vagina Urethra Urinary Bladder Intrathecal Epidural Directly Into Target Tissue IS OFTEN DESIRABLE TO CONCENTRATE MEDICATION AT TARGET SITE TO INCREASE EFFICACY AND DECREASE TOXICITY (The purpose here is to limit systemic absorption)

24. Now you know!! HOW DO DRUGS GET INTO THE BODY?