Pharmacokinetics (J1)

Pharmacokinetics: How Drugs Are Handled by the Body

Drug Absorption
1. Orally
2. Rectally (suppository)
3. Parenterally (injection)
4. Inhaled
5. Absorbed through the skin
6. Abosrbed through mucus membranes (snorting or sniffing)


Oral Administration
*The drug must be soluble and stable in stomach fluid.
*Most psychoactive drugs are soluble enough to readily cross all cell membranes & enter the brain. Most common form of administration.
*About 75% of an orally administered drug is absorbed by 2 - 3 hours after administration.
*Disadvantages: GI distress; idiosyncratic amount of absorption.

Rectal Administration
*Typically in suppository form.
*Alternative when NOT able to swallow.
*Disadvantages: Absorption is irregular, unpredictable & incomplete; often irritates membranes.

Inhalation Administration
*Popular with recreational drugs.
* Rapid administration (within seconds) with fast onset.
*Mucous Membrane Admin.
*Through mouth or nose.
*Only in occasional use medically.

Skin Administration
*Transdermal patch, continuous controlled slow release.
* Predictable.

Injection
*Intravenous (fastest) , intramuscular (slower), or subcutaneous.
* Rapid rate of absorption.
*Accurate dose.
*Disadvantages: Leaves little time for corrective measures; requires sterile environment.

Drug Distribution
*Bloodstream > evenly distributed throughout body; passing barriers > receptors.
*Only a very small % of the drug is in contact with the receptors. The larger % of the drug in the body can cause Adverse Effects (aka side effects).

Action of the Bloodstream
*On average, each minute the heart pumps all the blood once through the body.
*Blood-Brain Barrier: Tightly joined capillaries, covered by a fatty sheath (most capillaries are made of membranes with pores).
*Rate of passage into the brain is determined by lipid solubility. Psychoactive drugs are lipid soluble; they can reach brain receptors.
*Psych drugs easily pass the Placental Barrier; Mo drug % = fetus drug %.

Termination of Drug Action
*Primary route = renal excretion of drug metabolites (drugs processed by the liver) via urine.
*Other routes: lungs, bile, skin, saliva, breast milk.

Kidneys & Drug Elimination
*In 1 minute the kidneys filter 1 liter of blood plasma.
99.9% of the filtered plasma (including some of the drug) is reabsorbed; 0.1% is excreted.
*The kidneys require help for drug elimination.

Liver & Drug Metabolism
*The liver’s enzymes metabolize (reabsorbed) drugs that are less capable of reabsorption (less fat soluble).
*Infants (more so premature infants) have great difficulty metabolizing and excreting drugs (immature kidney & liver).

Drug Half-Life
*Elimination half-life = Time for plasma level of the drug to fall by 50%. (1/2 life longer in geriatrics.)
* *1 half-life = 50% eliminated, 50% remaining.
*2 half-lives= 75% eliminated, 25% remaining.
*6 half-lives=98.4%eliminated, 1.6%remaining.

Steady State
*Time to reach steady-state concentration = 6 times elimination half-life.
*Time to reach steady-state concentration is dosage independent.
*Steady, regular-interval dosing > predictable accumulation; determined by comparing blood levels with observed therapeutic results.

TDM (Therapeutic Drug Monitoring/ Pharmacokinetics)
*Established via large-scale clinical trials.
*Indirect measure: (plasma concentrations aprox. = receptor concentrations).
*Helps: 1) measure compliance, 
 2) establish individual’s dose requirements.

Drug Tolerance
*Tolerance: a state of progressively decreasing responsiveness to a drug.
*Cellular-Adaptive or Pharmaco-dynamic Tolerance:
*Down Regulation - reduction in brain receptor sensitivity or number available.
* Behavioral Conditioning: set & setting effect the reaction to a drug. Environmental cues become conditioned stimuli that elicit conditioned responses.

Drug Dependence
*Physical Dependence or abstinence syndrome: the drug is needed in order to avoid withdrawal symptoms.