HOW DO DRUGS GET

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HOW DO DRUGS GET INTO THE BODY?
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WHY BE CONCERNED ABOUT HOW DRUGS GET INTO BODY?
This issue importantly affects

• 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

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HOW DO DRUGS GET INTO THE BODY?
Unless injected directly into the blood
stream, drugs must be absorbed.
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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 System
Site of Administration
DRUG
BIOLOGICAL BARRIER
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WHAT AFFECTS DRUG ABSORPTION?
The rate of drug absorption will be affected by

• 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

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WHAT DETERMINES RATE OF RELEASE OF DRUG
FROM PHARMACEUTICAL PREPARATION?
A DOSAGE FORM

• Solutions No Delay, Immediate Release
• Capsules Tables Delay (Dissolution) Followed
  by Rapid Release
• Creams, Ointments Suppositories No Delay, but
  Slow Release

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WHAT DETERMINES RATE OF RELEASE OF DRUG
FROM PHARMACEUTICAL PREPARATION?
B ADDITIVES (EXCIPIENTS)

• Decrease Rate of
• Dissolution
• Binders
• Lubricants
• Coating Agents

• 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?
C MANUFACTURING PARAMETERS

• Tablet Compression - Hard tablets dissolve more
  slowly
• Tablet Shape - Round tablets dissolve more
  slowly
• Tablet Size - Large tablets dissolve more slowly

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WHAT DETERMINES RATE OF RELEASE OF DRUG
FROM PHARMACEUTICAL PREPARATION?
D DELAYED RELEASE PREPARATIONS

• Enteric Coating - Dissolve in intestines, not
  stomach

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WHAT DETERMINES RATE OF RELEASE OF DRUG
FROM PHARMACEUTICAL PREPARATION?
E SUSTANED RELEASE PREPARATIONS

• 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

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WHAT DETERMINES MEMBRANE PERMEABILITY OF DRUGS?
A LIPOPHILICITY increases membrane permeability

• Presence of Aliphatic and Aromatic Structures
• Absence of Polar Groups

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WHAT DETERMINES MEMBRANE PERMEABILITY OF DRUGS?
B IONIZATION decreases membrane permeability

• 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)

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WHAT DETERMINES SURFACE AREA FOR ABSORPTION?
ANATOMY

• Low Surface Area
• eyes, nasal cavity, buccal cavity, rectum,
  stomach, large intestines
• High Surface Area
• small intestines, lungs

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WHAT DETERMINES TISSUE BLOOD FLOW?
A. PHYSIOLOGY

• Low Blood Flow
• eyes, stomach, large intestines,
• rectum, subcutaneous tissue
• High Blood Flow
• small intestines, lungs, muscle, buccal cavity,
  nasal cavity

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WHAT DETERMINES TISSUE BLOOD FLOW?
B. PHARMACOLOGY

• Some Drugs Are Vasoconstrictors
• Some Drugs Are Co-Administered With
  Vasoconstrictors
• Some Drugs Are Vasodilators

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WHAT DETERMINES WHETHER A DRUG IS DESTROYED AT
OR NEAR SITE OF ADMINISTRATION?
BIOCHEMISTRY

• Liver - hepatic enzymes (first pass effect)
• Colon - intestinal microflora
• Stomach - digestive enzymes and acids

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WHAT ARE THE ROUTES OF ADMINISTRATION FOR DRUGS?
PARENTERAL
ENTERAL

• Oral
• Sublingual
• Rectal

• Intravenous (IV)
• Intra-arterial (IA)
• Subcutaneous (SC)
• Intradermal (ID)
• Intramuscular (IM)
• Intraperitoneal (IP)
• Lungs (Inhalation)
• Skin (Topical)

• Nose (Intranasal)
• Eye (Opthalmic)
• Ear (Otic)
• Vagina
• Urethra
• Urinary Bladder
• Intrathecal
• Epidural
• Directly Into Target Tissue

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WHAT ARE THE ADVANTAGES AND DISADVANTAGES
OF ORAL, IV, IM AND SC ADMINISTRATION?
SAFETY
High
Low
Oral gt SC gt IM gt IV
CONVENIENCE
High
Oral gt SC gt IM gt IV
Low
COST
Low
High
IV gt IM gt SC gt ORAL
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WHAT ARE THE ADVANTAGES AND DISADVANTAGES
OF ORAL, IV, IM AND SC ADMINISTRATION?
BIOAVAILABILITY
High and Reliable
Low and/or Variable
IV gt IM SC gt ORAL
ONSET OF ACTION
Delayed
Immediate
IV gt IM gt SC gt Oral
PATIENT COMPLIANCE
Low
High
IV gt IM gt SC gt Oral
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WHAT ARE THE ADVANTAGES AND DISADVANTAGES
OF ORAL, IV, IM AND SC ADMINISTRATION?
INTERACTIONS WITH FOOD
Risk
No Risk
Oral gt IV IM SC
COMMERCIAL AVAILABILITY OF DOSAGE FORMS
Low
High
Oral gt IM SC IV
VOLUME OF DRUG
Low
High
Oral IV gt IM gt SC
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WHAT ARE THE ADVANTAGES AND DISADVANTAGES
OF ORAL, IV, IM AND SC ADMINISTRATION?
AVAILABILITY OF SUSTAINED RELEASE DOSAGE FORMS
High
Low
IM gt Oral gt SC gt IV
TOLERANCE TO FUNKY VEHICLES
Low
High
Oral IM SC gt IV
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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

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WHY CONSIDER OTHER ROUTES OF ADMINISTRATION?
IS OFTEN DESIRABLE TO CONCENTRATE MEDICATION AT
TARGET SITE TO INCREASE EFFICACY AND DECREASE
TOXICITY

• Lungs (Inhalation)
• Skin (Topical)
• Nose (Intranasal)
• Eye (Opthalmic)
• Ear (Otic)
• Vagina

• Urethra
• Urinary Bladder
• Intrathecal
• Epidural
• Directly Into Target Tissue

(The purpose here is to limit systemic absorption)
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HOW DO DRUGS GET INTO THE BODY?
Now you know!!