how to drugs get into the body presentation.ppt

drug design

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.
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
High
WHAT ARE THE ADVANTAGES AND DISADVANTAGES OF
ORAL, IV, IM AND SC ADMINISTRATION?
SAFETY
High LowOral > SC > IM > IV
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 Reliable Low and/or VariableIV > 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
Risk No RiskOral > 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
High LowIM > 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?