CHAPTER 2: PHARMACOKINETICS AND FACTORS OF INDIVIDUAL VARIATION

Drug Forms
 Drugs usually contain the drug itself and other ingredients that facilitate administration
and absorption
 Aqueous Preparations (such as syrups)
 Alcoholic Preparations
 Solid/Semisolid Preparations
 Powders
 Tablets (powders compressed into tablet)
 Troches and Lozenges (meant to dissolve in mouth)
 Gelatin capsules
 Delayed-Release Products
 Enteric-Coated Products (for those drugs destroyed by stomach acid)
 Suppositories (insertion into rectum)
 Ointment (soft and oily)
 Transdermal (administered through bandage or patch)
 Parenteral Injection
Routes of Administration
 Oral Administration
o Safe and convenient
o 30-60min before there is significant absorption
o Food and water delays absorption and can prevent gastric irritation
o Can be removed by induced vomiting
 Parenteral Administration: any route that doesn’t involve GI tract
o IM Injections: usually to gluteus or deltoid muscles
o IV Injection: fastest, most direct
o Inhalation: useful for administration to respiratory system
Absorption
 Drugs must get to circulatory system
 Usually pass through cell membranes by passive transport (law of diffusion)
Lipid Solubility
 Because of lipid bilayer of cells, the more lipid soluble the substance, the faster it passes
thru the membrane
 Most drugs are primarily water soluble, except general anesthetics
Drug Ionization
 Drugs can be ionized (have a charge)
 Those that are ionized cant readily cross the membrane
 Acid drugs are mostly unionized in acidic fluid (such as gastric juice), absorption favored
o Acid drugs mostly ionized in alkaline fluid and absorption is slower
 Basic drugs unionized in alkaline fluid (lower GI tract)
o Ionized in acidic fluid
 Helps determine route of administration and how to increase excretion of ionized forms
Drug Formulation
 Liquid absorbed faster than solids
 Also, the smaller the particle, the faster the absorption

Distribution Factors
 Plasma Protein Binding
o Circulating proteins in blood help control osmotic pressure and carry vitamins and
hormones and drugs
 However, only unbound, free drugs can exert their effect
 Ratio of bound/unbound varies b/w drugs
o If drugs compete for a binding spot, concentration of free drug of one of them can
increase and cause adverse effects
 Blood Flow: organs like liver, kidneys, and brain that receive a lot of blood will receive a
lot of drug
 Blood-Brain Barrier: lipid barrier, keeps out electrolytes and water-soluble substances
Drug Metabolism
 Body tries to eliminate all foreign substances
 Drug metabolism: chemical alteration of drugs in the body (must occur before some can
be eliminated from body)
 DMMS enzymes in liver primary site
o Redox reactions on drugs to make them water-soluble, which are excreted by
kidneys
 Enzyme induction: repeated use of certain drugs that increase trigger an increase in the
amount of enzymes in the system (creates faster metabolism and decreases period of drug
action)
 Enzyme inhibition: repeated use of certain drugs can inhibit DMMS action
 First-pass metabolism: process when some drugs metabolize significantly on their first
pass thru the liver
Drug Excretion
 Renal: once drugs are made water-soluble by metabolism
 GI Tract: unabsorbed parts of oral drug excreted in feces
o Some lipid-soluble drugs can enter intestines thru bile, which are then reabsorbed
into blood
 Respiratory: not a huge part, but can get rid of some metabolized wastes
 Also sweat, saliva, and lactation

Half-Life
 Time required for blood or plasma concentration to drop by 50%
 Determined by metabolism and excretion rates
Blood Drug Levels
 Level must be at a certain point to maintain effect
 Loading dose: an initial higher dosage in order to quickly reach the therapeutic drug level
 Maintenance dose: smaller and used to maintain therapeutic level
Bioavailability: % of dose of a drug that is actually absorbed into bloodstream
 Influenced by many factors
Individual Variation Factors
 Age: infants and elderly more sensitive to drugs
 Weight: usually more weight = higher dose
 Sex and % Body Fat: greater effect in females due to their higher body fat and less body
fluid
 Genetic Variation
 Emotional State
 Placebo Effect: the influence of one’s mind of the effect and treatment
 Presence of Disease
 Patient Compliance

Pharmacokinetic Considerations for Pediatrics

 Fetal Period of Pregnancy
o Most drugs aren’t teratogens, but should be avoided

 Drugs can also easily pass into breast milk

 Infants have lower skeletal mass and less blood flow to muscle, so IM injection should be
avoided
 Thinner skin: faster topical absorption
 Less acidic stomach: decreased bioavailability of acidic drugs
 More body water/less fat: decreased distribution and higher drug blood levels
 Less plasma protein; higher absorption
 Slower excretion

Drug Tolerance
 Decreased drug effect that occurs after repeated administration
 Common in drug abusers
 Metabolic tolerance: due to increased DMMS enzymes
 Pharmacodynamic tolerance: due to drug decreasing number of drug receptors
Drug Dependence
 When reliance on administration of a drug becomes extremely important to the well-
being of an individual
 Psychological or physical
 Deprivation can lead to withdrawls