Pharmcokinetics Flashcards
Drug efficacy is defined as
A drug in its therapeutic concentration.
Pharmacokinetics
Gets the drug there so pharmacodynamics (drug action) happens
Pharmacokinetics in Four easy Pieces
- Absorption
- Distribution
- Metabolism (drug molecule altered: activated/inactivated, made toxic or nontoxic).
- Elimination (broken down or excreted)
Non-absorption, why would you want this?
Drug given for localized effect, don’t want it to be absorbed.
May be well tolerated b/c it doesn’t have systemic effects
**GI infection drugs, skin and mucosal infections, lung infections (inhalants), or local anesthetics
Basic pharmacokinetic plot
X-axis is time
Y axis is [drug] (C) in blood (expressed as a log)
Absorption is the up slope: the appearance and increase of drug in blood
Factors that affect absorption:
- Drug Molecule
- Site of Administration
- Patient Factors
- Miscellaneous Factors
Chemical nature of the drug determines what?
Absorption, elimination, distribution, and metabolism.
Most important property of the drug:
Lipophilicity
- Lipophilic=fat-soluble=hydrophobic (goes better through cell membrane)
- Hydrophilic=water soluble=lipophobic
Lipophilic drug life cycle
Easily pass through cell membranes and tissue barriers.
Are generally more readily absorbed and better distributed throughout the body.
Generally must be metabolized before elimination by the kidneys.
***Easy in, easy around, hard out (stored in body fat)
Weak Acids/Weak Bases
60% of drugs
Can exist in either charged or uncharged forms.
Charged or uncharged weak acids/bases: What determines this?
The its pKa and the pH of the environment
Henderson-Hasselbach for weak acids/bases
- Weak acid: log HA/A-=pKa-pH
weak acid @low pH=more unionized so more cross the barrier. - Weak base: log H+A/A=pKa-pH
weak base @high pH=more unionized so cross barrier
Example of a weak acid with a pKa of 7.3
- In breast milk (pH 6.3): log HA/A-=7.3-6.3=1
- Log 10^1 HA/A=10 parts HA (unionized), 1 part ionized
Basically, a weak acid in a strong acid has more unionized, and vice versa.
Ion trapping
When drugs are charged they have difficulty passing through tissue barriers, they are trapped.
**Will be trapped in an environment opposite its pKa
Ion trapping of a weak acid
(Amphetamines)
Will be trapped in a basic environment.