Chapter 2 Part II Flashcards
what are the types of penetration
transcellular
intercellular
transappendageal
the major route of permeation is around the
corneocytes
the larger the corneocytes the ___ the route for permeation
longer
transcellular penetration is
across the cells
intercellular penetration is
between the cells
transappendageal penetration is
via hair follicles, sweat, and sebumglands, and pilsebaceous apparatus
what is the ideal log P for transdermal applications
1-3
SC/IM injections are more ___ and ___ thank oral and rectal administration
fast and predictable
which is slow absorption, SC or IM??
SC is slower
unionized drugs have better or worse absorption through the cornea than ionized drugs
better
what is an example of an unionized drug
physostigmine
what is an example of ionized drug
neostigmine
what are the three major types of factors that affect a drug from reaching its delivery site to target site
physiochemical property of drugs
physiological factors
formulation factors
why are drugs most frequently taken by oral administration
most natural
uncomplicated
pain free
safe
economical
no sterilization needed
many drugs are not administered orally primarily due to
instability of the drug in the GI tract or drug degradation by the digestive enzymes in the intestine
give two examples of drugs that are not administered orally due to instability
erythropoietin/ human growth hormone - IM
insulin - subQ or IM
absorption takes place across the ___ layer
epithelial
how many ml of gastric fluid is in an empty stomach
100
what is the pH range of the stomach
1-3
What is the primary function of the stomach
to grind the solid dosage form and facilitate release and dissolution
what are some reasons for minimal drug absorption from the stomach
thick mucus
limited surface area for absorption
what is the most important region for oral drug absorption
small intestine
why is the small intestine the most suitable for drug absorption
extremely large surface area and long residence time
what is the residence time in the small intestine
4 hours
most drugs are absorbed into the blood stream via capillaries by the
portal vein
what is found on the epithelial cell surface that has contact with food
microvilli
what is the function of microvilli
to increase the surface area by 20 fold
the microvilli in the epithelium is known as the
brush border epithelium
T or F microvilli are present in the large intestine
F, none in the large intestine/colon
what is absorbed in the large intestine
water
electrolyes
part of the drug that is unabsorbed and reaches the colon is
excreted in the feces
in which portions of the small intestine are villi most abundant
jejunum
ileum
ionization of the drug depends on its ____ and the ___ of the medium
pka
pH
a weak acid will be ____ ionized when the pH is above its pKa
more
a weak base will be ____ ionized when the pH is below its pKa
more
what are the two environments that orally administered drugs pass through
gastric and small intestinal
gastric pH is highly acidic in the
fasting state
after a meal, gastric pH becomes more _____
alkaline
why does the gastric pH become more alkaline
because of the buffering effect of food
T or F alkaline environment of the small intestine remains essentially consistent
T
T or F weakly basic and acidic drugs remain ionized form in the stomach and intestine
T
gastric emptying is the process in which
a swallowed drug quickly reaches the stomach which empties its content into the itnestine
the time required for gastric emptying is called
gastric emptying time
any delay in gastric emtpying time for the drug to reach the duodenum means that
the rate of absorption will slow, and the extent of absorption
what is MMC
migrating motor complex
what does MMC mean
pattern of peristaltic movement that occurs int eh GI tract during fasting
how does peristaltic movement affect drug absorption
mixes the contents of the duodenum and brings the drug particles in contact with the duodenum
when a drug is in the intestine, what is needed for optimum absorption
sufficient time
what happens to absorption to a drug in case of diarrhea and why>
reduced absorption due to shorter and brief residence time
What factors effect gastric emptying and intestinal motility
amount of food
caloric content
temperature
viscosity
an increase in the amount of food, _____ the emptying rate
decreases
which has the smallest to highest caloric content
carb < protein < fat
the higher the caloric content of the meal the _____ the delay to GE and delay to drug absorption
longer
for which drugs is gastric emptying rate limiting?
paracetamol
busulfan
ampicillin
riboflavin
levetiracetam
T or F hot solid meals significantly accelerate gastric emptying compared to room temperature meals
T
a hgih viscosity within the intestinal lumen can ___ the diffusion rate of a drug and reduce its absorption
reduce
T or F the physical form of food alters absorption
T
an increase in the solid content of food ______ the emptying rate
decreases
an increase in acidic content ___ the emptying rate
decreases
why does an increase in acidic content decrease the emptying rate
acid has to be neutralized by pancreatic juices, intestional juices, and secretions after is is emptied
T or F young people have a faster emptying rate than elderly
T
what hormone increases GI transit time
progesterone
progesterone increases GI transit time but decreses
esophageal sphinction tone
stomach contents are emptied faster when ____ than ___
standing up
lying down
drugs absorbed after oral administration are transported via the _____ to the hepatic portal vein
mesenteric vessels
first pass metabolism is when drugs that are highly metabolized by the liver or the intestinal mucosal cells have
poor systemic availability when given orally
what two effects can food have
positive - enhanced cmax, higher F
negative - reduced cmax, low F
a drug can exhibit negative food effects if when coadministered the AUC
decreases
which drugs does absorption decrease when given with food
penicillins
erythromycin
tetracyclines
which drugs when given with food have delayed absorption
aspirin
paracetamol
diclofenac
which drugs when given with food increase drug absorption
griseofluvins
diazapam
which drugs are unaffected in their absoprtion with food
methyl dopa
propylthio uracil
which drugs have no food effects
prednisolone
hydrochlorothiazide
ibuprofen
which drugs have negative food effects
furosemide
nadolol
tacrine
atenolol
lipid soluble drugs are better absorbed with foods with
high fat content
should lovastatin be taken with food
yes to increase F
should rosuvastatin be administered with food
no taken on an empty stomach
T or F high fiber diets may lower the efficacy of simvastatin, ezetimibe, pravastatin, and fluvastatin
T
which drugs may or may not be taken without food
simvastatin
ezetimibe
pravastatin
fluvastatin
the binding of drugs also known as _____ to components in teh GI lumen can reduce their absorption
chelation
ciprofloxacine F is reduced as a result of the presence of _______
enteral nutrition formula
chelation to ____ is a food interaction reported with fluroquinolones, tetracyclines, and oral cephalosporins which limits absorption
metal ions
_____ in the gut also affects absorption and metabolism of various drugs
microbiodata
________ diet may decrease the absorption of TCA
high fiber
T or F absorption may be influenced by circadian rhythyms
T
lipophilic or water soluble drugs have better absorption rate when taken in the morning compared to evening
lipophillic
the absorption of ketoconazole was ___ in the presence of omeprazole induced achlorhydria
reduced
what two enzymes work synergistically to reduce bioavailability fo drugs
p glyco protein
P450
P glycoprotein is a
efflux transporter
what drugs are affected by the synergy of p gp and CYP450
felodipine
midazolam
cyclosporine
ritonavir
digoxin
intraconazole
____ may inhibit the activity of CUP2C9
cranberry juice
the primary enzyme involved in the metabolism of warfarin is
cyp2c9
celiprolol is inhibited when taken with
orange juice
what does the interaction between amiodarone and grapefruit lead to
increase in QT prolongation and vtach
what are the three major disease state classes that influence the rate and extent of drug absorption
GI diseases
cardiovascular disease
hepatic disease
what GI conditions alter drug absorption
crohns
celiac
GI surgery
how does crohsn affect drug absorption
altered gut transit time, decreased gut SA and intestinal transit rate
how does celiac disease affect drug absorption
destruction of villi and microvilli, increase gastric emptying time and altered intestinal drug metabolism
how does GI surgery affect drug absorption
may cause drug dumping in the intestine
patients with CHF have
reduced intestinal motility which decrease drug absorption
patients with hepatic disease have altered drug absorption due to
liver cirrhosis affecting F
which neurologic disease affects drug absorption due to diminished GI motility
parkisons disease
