| the process by which a drug
reversibly leaves the bloodstream and
enters the instertitium (extracellular
fluid) and the tissues. | DRUG DISTRIBUTION |
| In Drug distribution, many drugs bind to __, including albumin, with an equilibrium between bound and free molecules
Competition between drugs for plasma protein binding sites
may increase the "__,“ possibly enhancing the effects
of the drug displaced | plasma proteins, free fraction |
| What are the Special Barriers to Distribution? | 1 Placental (most small molecular weight drugs cross the
placental barrier; fetal blood levels are usually lower
than maternal)
2 Blood-brain (permeable only to lipid-soluble drugs or those of very low molecular weight) |
| • Concentration of drug at the receptor site
• Commonly measured in the blood (Exception for
topical agents) | EFFECTIVE DRUG CONCENTRATION |
| Plasma concentration is a function of | – the rate of input of the drug (by absorption)
into the plasma
– the rate of distribution
– and the rate of elimination |
| Pharmacokinetics
TWO BASIC PARAMETERS | 1 CLEARANCE
2 VOLUME OF DISTRIBUTION |
| the measure of the ability of the body to eliminate the
drug | CLEARANCE |
| the measure of the apparent space in the body available
to contain the drug. | VOLUME OF DISTRIBUTION |
| The ratio of the amount of drug in the body
to the drug concentration in the plasma or
blood | Volume of distribution
-Can be affected by liver and kidney disease |
| METABOLISM OF DRUGS
Three major routes: | – Hepatic metabolism
– Biliary metabolism
– Urinary metabolism |
| Metabolism (Biotransformation) PHASES | 1) Phase I (Functionalization) – Redox Reactions and
hydrolysis.
2) Phase II (Conjugation) – Attacks certain drugs
with existing functional groups and attaches
conjugate molecules |
| What kind of reaction is common for neonates? | Sulfation |
| Metabolism (Biotransformation) May be affected by | • Drug Interactions due to inducers,
inhibitors, and substrates
• Genetic factors
• Disease states
DRUG WITH INDUCER - FASTER
DRUGS WITH INHIBITOR - SLOWER |
| an inactive precursor chemical that is readily absorbed and distributed and then converted to the active drug by biologic
processes inside the body
Can be Active to Active,
Inactive to Active | Prodrug |
| EXCRETION; Renal elimination of drugs: | – Glomerular filtration
– Proximal tubular secretion
– Distal tubular reabsorption |
| Excretion process | 1 Glomerular filtration of water and unbound drugs and metabolites
2 Active tubular secretion of acidic and basic drugs and metabolites
3 Active reabsorption of acidic and basic endogenous compounds and passive reabsorption of lipophilic drugs
4 Urinary excretion of drugs and metabolites that are filtered and or actively secreted and not reabsorbed |
