Pharmacokinetics I Flashcards
How many half-lives does it take to reach steady state concentration or to eliminate the drug?
5 half-lives
What is the main goal when determining dose?
The goal is to determine the lowest effective dose (~68% of population)
What factors influence dose?
Maturing organ function (BBB in children) Age of the patient (decreased kidney function, increased fat) Organ pathology (Liver, Kidney, etc.)
What are other terms for “oral”
Enteral, PO
What is the most common, convenient, safest and economical method of drug administration?
Oral (enteral, PO)
What is the main disadvantage of oral drug administration?
First pass effect- the absorbed drug is exposed to the liver first
When are parenteral routes of administrations used?
Used when drugs cannot be administered orally
What is the most direct route of administration?
Injections
How are gaseous anesthetics, agents that readily vaporize, and aerosol drugs administered?
Inhalation
When is rectal drug administration used?
When oral ingestion is precluded by emesis (vomiting) or unconsciousness
Does buccal/sublingual drug administration have high or limited first pass effect?
Limited
Absorption of topical drugs is proportional to what?
The surface area exposed and lipid solubility of the drug
How do inflammation and conditions that increase cutaneous blood flow effect absorption?
Enhance absorption
What is absorption?
Process whereby a drug gains entry into bodily fluids, typically the blood, that distribute it throughout the organism.
Drugs that have a high degree of lipid solubility are most likely absorbed by which mechanism?
Simple diffusion
What mechanism of absorption do small, water soluble drugs; concentration gradients use?
Aqueous pores
What mechanism of absorption do drugs use when drugs get engulfed by vesiculation of cell membrane followed by endocytosis?
Vesicular transport
What factors modify absorption?
Route of administration Solubility (aqueous vs. oil) Dissolution Concentration of drug Blood flow/Circulation Absorbing surface area and contact time pH
Are most drugs strong acids/ strong bases or weak acids/weak bases?
Weak acids or weak bases
Are acids proton donators/acceptors?
Proton donators (HA ↔ A- + H+)
Are bases proton donators/acceptors?
Proton acceptors (B + H+ ↔ BH+)
What affects a drug’s ability to permeate biological membranes and exert its effect?
Degree of ionization
To cross a membrane, a drug must be what?
Non-ionized and lipid soluble
Why are ionized drugs not able to be absorbed?
Ionized drugs are surrounded by a water molecules that increase
hydrophilicity and prevent it absorption
What kind of acids/bases cannot be absorbed?
Strong acids and bases
An acid in an acidic environment is what?
Non-ionized and readily absorbed
A base in a basic environment is what?
Non-ionized and readily absorbed
What is ion-trapping?
Acid in basic environment or base in acidic environment will become ionized and and will accumulate in that environemnt
When an acid is pronated, is it ionized or non-ionized?
Non-ionized
When a base is pronated, is it ionized or non-ionized?
Ionized
In an acidic environment (stomach), a weakly acidic drug is predominately _____, more lipid soluble and _____ absorbed.
Non-ionized (protonated; HA)
Rapidly
In a basic environment (intestine), a weakly acidic drug is predominately _____, and _____ absorbed.
Ionized (unprotonated; A-)
Not rapidly
In an acidic environment (stomach), a weakly basic drug is predominately _____, and is _____ absorbed.
Ionized (protonated; BH+)
Not rapidly
In a basic environment (intestine), a weakly basic drug is predominately _____, more lipid soluble and _____ absorbed.
Non-ionized (unprotonated; B)
Rapidly
What can ion trapping be used for?
To increase the elimination of drugs
If you make urine basic, ____ drugs will be trapped and excreted.
What can you use to make the urine more basic?
Acidic
Sodium bicarbonate or acetazolamide
If you acidify the urine, ____ drugs will be trapped and excreted.
What can you use to make the urine more acidic?
Basic
Ammonium chloride
What does the Henderson-Hasselbalch equation tell you?
Degree of ionization of weakly acidic or basic drug at different pHs
What is pKa?
pH at which the amount of
ionized vs. non-ionized forms of a drug are equal
If pH < pka
a) Does the protonated/unprotonated form dominate?
b) An acid will be ionized/non-ionized and rapidly/slowly absorbed
c) A base will be ionized/non-ionized and rapidly/slowly absorbed
a) Protonated
b) Non-ionized (HA), rapidly
c) Ionized (BH+), slowly
If pH > pka
a) Does the protonated/unprotonated form dominate?
b) An acid will be ionized/non-ionized and rapidly/slowly absorbed
c) A base will be ionized/non-ionized and rapidly/slowly absorbed
a) Unprotonated
b) Ionized (A-), slowly
c) Non-ionized (B), rapidly
Weak acid in acidic environment.
pKa = 5.4
pH = 4.4
What is A-/HA?
pH < pKa = Protonated dominates
More non-ionized (acid + protonated)
1 degree difference = 10 fold
A-/HA = 1 ionized/10 non-ionized
Weak acid in basic environment.
pKa = 4.4
pH = 7.4
What is A-/HA?
pH > pKa = Unprotonated dominates More ionized (acid + unprotonated) 3 degree difference = 1,000 fold
A-/HA = 1,000 ionized/1 non-ionized
Weak base in acidic environment.
pKa = 5.4
pH = 3.4
What is B/BH+?
pH < pKa = Protonated dominates More ionized (base + protonated) 2 degree difference = 100 fold
B/BH+ = 1 non-ionized/100 ionized
Weak base in basic environment.
pKa = 4.4
pH = 8.4
What is B/BH+?
pH > pKa = Unprotonated dominates
More non-ionized (base + unprotonated)
4 degree difference = 10,000
B/BH+ = 10,000 non-ionized/1 ionized
Drug A is a weak organic acid, pKa = 6.4. What is the ratio of ionized to non-ionized drug in the urine with pH = 6.4?
1:1
Drug B is a weak acid, pKa = 6.4. What is the ratio of non-ionized to ionized drug in the blood with pH = 7.4?
pH > pka = Unprotonated dominates More ionized (acid + unprotonated) 1 degree difference = 10 fold
A- (ionized) / HA (nonionized) = 10/1
HA (nonionized) / A- (ionized) = 1/10
HA/A- ratio = 1:10
Drug B is a weak base, pKa = 5.4. What is the ratio of non-ionized to ionized drug in the blood with pH = 7.4?
pH > pKa = Unprotonated dominates
More more non-ionized (base + unprotonated)
2 degree difference = 100 fold
B/BH+ ratio = 100:1
