Pharmacokinetics:

ADME

Absorbing

Distributing

Metabolizing, and

Excreting the drug

Defined as what the body does to the drug

The chemical and physiologic changes that the drug causes

Drug effect at a cellular level

"What the drug does to the body"

Drugs are typically acids or bases.

Weak acids: Easier and faster to absorb in acidic environments (e.g., stomach)

Weak bases: Easier to absorb in alkaline environments (i.e., intestine)

Chemical properties:

Ionized (polar) form is usually water soluble.  Most weak bases are also ionized

Non-ionized (nompolar) form: more lipid soluble, apt to cross cell membrane

Absorbing surface (e.g., intestine – microvilli provide a TON of surface area; vs skin)

Blood flow to site of administration

Drug solubility:

- Water: must dissolve in water to be absorbed in GI tract

- Lipid: affects all ADME

Ionization - Ionized solutions do not cross membrane easily

Stability of drug in acid or alkaline environment

pH

- Local environment (e.g., acidic stomach) enhances or retards diffusion of acid/base drugs

- In general, drugs are weak acids or weak bases

ETOH in stomach - changes dissolution

Nicotine - Lowers plasma enzymes

 - can increase or decrease metabolism

Caffeine - increases stimulation, including gastric motility

Most at room temp

 - cannot handle heat of a car in summer

Some need refridgeration

Some are light sensitive

 - dark-color containers

Air/humidity sensitive

- require tight sealed containers

Oral—

 - 80% of drugs are given orally   swallowed, buccal, sublingual

Enteral  

 - nasogastric or gastric tubes, rectal

Parenteral  

 - SC, IM, IV, intrathecal, epidural, other fluids

Pulmonary  

 - gases, mists

Topical   

- skin, eyes, ears, nose

Rich blood supply in GI tract

Presence of food in stomach

GI motility - can affect whether drug even stays down

Oral cavity - slightly acidic pH

Stomach - highly acidic (pH 1.4)

Upper portion of small intestine - highly alkaline (pH 7-8)

SC (subcutaneous) - into adipose & connective tissue.  Slow absorption

IM (intramuscular) - into skeletal muscle, absorption more rapid than SC (because of blood supply)

IV (intravenous) - directly into blood stream, direct absorption

Must have correct diluents: Water & saline are not interchangeable!

Protective, many drugs can't enter, or are absorbed very slowly.

Heavy in lipid composition

Drug administration:

Pulmonary Route

Lungs provide large surface area for absorption, rich capillary network

Nearly instantaneous effect - fast as IV

Drug must reach alveolar level, aerosolized with propellants

Examples:

Inhalants, nebulizers, endotracheal tubes

Drug Administration:

Topical Route

Local or systemic effect (depending on skin factors)

Only lipid-soluble compounds are absorbedb

Precutaneous absorption is erratic:

 - Massaging enhances absorption

 - Heat can increase it

 - "washed" away with sweat or friction

 - dependent on intact capillary system

"fluffy" people - skin is farther from their major vessels than less "fluffy" people.  Topical drugs will not travel well into capillaries because of high amount of adipose tissue surrounding them.

Distribution

(Pharmacokinetic Activities)

• Usually easier than absorption, more rapid
• Depends on permeability of capillaries to the drug molecules, cardiac output, regional blood flow (most of drug is first distributed to major organs, then muscles and fat)