Pharmacokinetics I, lect 5 Flashcards
what biological processes does the body employ to handle drugs after they are administered (ADME)
A: absorption
D: distribution
M: metabolism
E: elimination
what is the “steady state” of a drug
- when a patient is taking a medication on a regular basis, there is an ongoing process of drug absorption in the form of each dose and an ongoing process of removal with the drug’s metabolism and clearance
- steady state= when the amount of drug going in is the same amount of drug getting taken out
how many half lives does it take for a drug to reach steady state
5
what is the first pass effect?
orally administered drugs enter circulation almost exclusively by the way of the hepatic portal system
- exposed to the liver first and may be metabolized in liver
- can significantly decrease bioavailability
What are some disadvantages to oral drug administration?
- first pass effect
- irritation of intestinal mucosa -> emesis
- desctruction by GI enzymes or low pH
- binding to food
- irregularities in absorption and gastric emptying time
bioavailability of a drug given through IV
- 100%
this type of parenteral (non-oral) route generally results in drugs being absorbed more slowly than with IV or IM injection and is often used for implantation of drugs in solid pellets
subcutaneous injection
this type of parenteral route is useful for drugs in aqeous solution and drugs are usually absorbed fairly rapidly in this method
intramuscular injection
this type of parenteral route is used for gaseous anesthetics
inhalation
Why use buccal or sublingual route of administration
used for drugs that extensively degraded by the first pass effect (nitroglycerin)
- rapid absorption but limited amount absorbed due to small surface area
What affects absorption on the skin
- absorption is proportional to the surface area exposed and lipid solubility of drug
- inflammation and conditions that increase cutaneous blood flow enhance absorption
lipid soluble drugs are absorbed via?
simple (passive) diffusion
- concentration gradient or electrochemical gradient
Acids and Bases: which is a proton donator? Which is a proton acceptor?
acids: proton donator
base: proton acceptor
is an ionized acid or base more or less likely to be absorbed?
- less likely: affects drug’s ability to permeate biological membranes and exert its effect
- ionized drugs are surrounded by water molecules that increase hydrophilicity and prevent it from diffusing through lipid bilayers
why is a drug that is a weak acid absorbed in the stomach?
- stomach has low pH, very acidic: more protons
- weak acid will not donate proton in very acidic environement; therefore it stays protonated, non-ionized which means it is more lipid soluble and rapidly absorbed
why is a weakly acid drug not absorbed in the intestine?
- intestine has high pH; few floating protons
- weak acid will donate H and become unprotonated (A-) and ionized therefore not readily absorbed
why won’t a weakly basic drug be absorbed in the stomach?
- stomach has low pH, lots of protons
- weak base (B) is a proton acceptor and accepts a proton to become (BH+) which is ionized and therefore not readily absorbed
why is a weakly basic drub absorbed in the intestine
- intestine has a high pH, few floating protons
- weak base is predominately unprotonated (B) which is non-ionzed, more lipid soluble and rapidly absorbed
how does ion trapping work to increase the elimiation of drugs
- can trap a weakly basic drug in an acidic medium or a weakly acidic drug in a basic medium because both in scenarios, the drug will become ionized and will accumulate in that environment
- ex: urine can be made basic (sodium bicarbonate or acetazolamid) so that acidic drugs will be trapped and excreted
what is the pka
pH at which the amount of ionized vs. non-ionized forms of a drug are equal
if pH < pKa, what form of acids and bases will dominate?
Protonated
- acid will be non-ionized (HA)
- base will be ionized (BH+)
if pH>pKa, what form of acid and base will dominate?
- unprotonated form
- acid will be ionized (A-)
- base will be non-ionized (B)
what is the henderson-hasselbalch equation
pH - pKa = log (A-)/HA
- for an acid
- A-: ionized
- HA: non-ionized
ex: weak acid in acidic environment
- pKa=5.4
- pH= 4.4
- what is the ratio of ionized/non-ionized
- pH < pKA therefore weak acid will be protonated (nonionized)
- pH-pKa = log (A-/HA)
- OR 4.4 to 5.4 is 1 degree of difference which is 10x difference in proportion
- A-/HA = 1 ionized / 10 non-ionized
ex: weak acid in basic environment
- pKa = 4.4
- pH = 7.4
- what is the proportion of ionized/non-ionized drug?
- pH > pkA therefore weak acid will be deprotonated (A-) and ionized
- 7.4-4.4 = 3
- 3 = 1000
- A-/HA = 1000 ionized / 1 non-ionized
Ex: weak base in an acidic environment
- pKa= 5.4
- pH = 3.4
- pKa > pH therefore weak base will be protonated (BH+) and ionized
- 3.4-5.4 = [2]
- 2=100
- 1 non-ionized / 100 ionized
- weak base in basic environment
- pKa = 4.4
- pH = 8.4
- ionized/ non-ionized ?
- pH > pKa therefore weak base will not be protonated (B) and be nonionized
- 8.4-4.4 = 4
- 4=10,000
- 1 ionized / 10,000 non-ionized
