Pharmacokinetics Flashcards
(44 cards)
What are the main use of pharmacokinetics ?
A drug should be able to reach its site of action after administrstion
In few situations a drug is directly applied to its target tissue
Example: topical application of an anti-inflammatory agent to inflamed skin
-Much more commonly, a drug is given into one body compartment, e.g. the gut, and must move to its site of action in another compartment, e.g. the brain
If a drug is given orally to produce an effect in the CNS, what are the barriers to include?
- the wall of intestine
- The walls of capillaries that perfume the gut
- The blood-brain barrier
And after bringing about its effect, the drug should be eliminated
What are the methods of drug permeation?
- Aqueous diffusion( paracellular pathway)
- Lipid diffusion(transcellular pathway)
- Special carriers
- Endocytosis & exocytosis (transcytosis)
Summarize drug absorption
Absorption= transfer of a drug from its site of administration to the bloodstream
- The rate and efficiency of absorption depend on the route of administration
- For IV delivery, absorption is complete: the total dose reaches systemic circulation
- Drug delivery by other routes may result in only partial absorption
What are the enteral routes?
Oral
Sublingual
Rectal
What is the oral route?
Maximum convenience, but absorption may be slower and less complete than with parenteral routes
-Ingested drugs suffer first-pass effect: a fraction of the drug is metabolized in the gut wall and the liver before reaching systemic circulation
What is the sublingual route?
The drug enters systemic circulation directly. The drug bypasses first-pass effect
What is the rectal route?
Partial avoidance of the first-pass effect
What are the parenteral routes?
- intravaneous
- Intramuscular
- Subcutaneous
- Intradermal
What are the other routes, aside from enteral, and parenteral routes?
- Oral inhalation
- Nasal inhalation
- Topical
- Transdermal
What are the factors that influence drug absorption?
- Effect of pH on drug absorption
- Surface area available for absorption
- Blood flow to absorption
- Contact time at absorption surface
- P-Glycoprotein
What is the effect of pH on drug absorption?
Most drugs are weak acids or bases that are present in solution as both the nonionized and ionized species
The nonionized molecules are usually liposoluble and can diffuse through the cell membrane
-The ionized molecules are usually unable to penetrate the lipid membrane because of their low liposolubility
Summarize the ionization of weak acids
For a weak acid the ionization. Reaction is:
HA —> A- + H+
The uncharged form HA (ie the protonated form) will permeate through membranes
The charged form A- (ie the unprotonated form) will not
Example:
R-COOH —> R-COO- + H+
Weaj acids diffuse the phospholipid bilayer in the HA state
Summarize the ionization of weak bases
For a weak base the ionization reaction is:
BH+ —> B + H+
The uncharged form B (ie the unprotobated form) will penetrate through the cell membrane
-The charged form BH+ (ie the protonated form) will not
Example:
R-NH3^+ —> R-NH2 + H+
Weak bases diffuse across the phospholipid bilayer in the unprotonatef form (B)
Summarize pH effect on drug absorption
The protonated form of a weak acid is the more liposolubke form
The unprotonated form of a weak base is the more liposolubke form
What is the purpose of Henderson-HasselBach equation?
The ratio between the protonated and unprotonated forms is a function of the pH and of the pK of the ionizable group
What is the Henderson hassalbach equation?
pH-pK= log[unprotonated form]/[protonated form]
According to the Henderson hasselbach equation, what happens when pH= pK?
When pH= pK, [unprotonated]= [protonated]
For each unit of pH above the pK, the [unprotonated] will be ten times the [protonated]
For each unit of pH below the pK, the [protonated] will be ten times the [unprotonated]
What is ion trapping?
The most important application of this equation(H-H) is in the manipulation of drug excretion by the kidney
If a drug is in a liposoluble form during its passage down the renal tubule, a significant fraction will be reabsorbed by passive diffusion
If the goal is to accelerate excretion of the drug, it’s important to prevent its reabsorption from the tubule
This can be accomplished by adjusting urine pH to ionize the drug
As a result the drug will be trapped in the urine
Weak acids are excreted faster in alkaline urine; weak bases are excreted faster in acidic urine
Most drug absorption occurs at the small intestine because of its large surface area
Why is the absorption favored in the small intestine over the stomach?
Blood flow to the intestine is much greater than the flow to the stomach: absorption from the intestine is favored over that from the stomach
How does contact time affect absorption surface?
If a drug moves through the GI tract very quickly, as in severe diahhrea, it is not well absorbed
What is the P-Glycoprotein?
P-Glycoprotein (MDR1) is a transporter protein responsible for transporting several drugs across cell membranes
P-glycoprotein reduces drug absorption
What is bioavailability(F)?
Fraction of administered dose of a drug that reaches the systemic circulation
What is the determination of bioavailability?
By plotting plasma concentrations of the drug vs. time, the area under the curve (AUC) can be measured
Bioavailability is determined comparing the AUC after a particular route of administration with the AUC after IV injection
- The AUC reflects the extent of absorption of the drug
- For drugs administered IV, bioavailability is 100% by definition
