Block 1 Flashcards
what are relative contradictions
caution should be taken
what are absolute contradictions
drug should not be used
what is the national formulary
information on the product available to prescribers
what is the pharmacopoeia
contains a list of drugs with all there chemical information
what is another name for brand name of a drug
proprietary
aspirin is an example of it’s chemical name, non-proprietary name, or proprietary name
non-proprietary
what are the 7 stages of drug development
- discovery
- animal studies
- IND application
- clinical studies
- submission of NDA
- approval of NDA
- post-marketing surveillance
what are the 3 purposes
of animal studies
beneficial/harmful effects on organs
mechanism of action
pharmokinetics
what is the dosage for acute toxicity
single dose
what is the dose for sub-acute toxicity
3 doses, 2 weeks to 3 months
what is the dose for chronic toxicity
more than 6 moths (2 species)
what is involved in phase I of a clinical trial
evaluation of safety
healthy volunteers
both investigator and subjects know what drug is being administered
what is involved in phase II of a clinical trial
patients with the disease
single or double blind
“does the drug work in patients with the targeted condition”
what is involved in phase III of a clinal trial
large group of patients with the disease
double blind
“does it work, how safe is it”
what is off-label drug use
medication is being used for something other than what is was originally approved for
in what schedule of drugs can medication not be refilled
II
in what schedule of drugs are they not accepted for medical use
I
schedule III, IV, and V drugs can be refilled but only for a maximum of __ times
5
what is first pass metabolism
the drug is metabolized before it has reached systemic circulation
(absorption through intestinal mucosa to liver portal system for processing before reaching systemic circulation)
what 2 type of drug administration have no first class metabolism, therefor have a greater bioavailability
IV
sublingual/buccal
what drugs move by way of simple or passive diffusion
lipid soluble
non-ionized
what is the equation for oral bioavailability if equal dose is given
AUCoral/AUCiv
AUC= area under curve
what is the equation for intramuscular bioavailability if equal dosage is given
AUCim/AUCiv
what equation is used to calculate bioavailability if an equal dosage is not given
(AUCoral x Doseiv)/(AUCiv x Doseoral)
non-ionized forms of drugs are lipid soluble or water soluble and are easier or harder to absorb
lipid
better
ionized drugs are poorly absorbed so they are eliminated in what way
renally excreted
weakly acidic drugs are best absorbed in the ___, while weakly basic drugs are best absorbed in the ___
stomach
intestine
milk reduces the activity of what drug
tetracycline
food reduces the activity of what drug
ampicillin
fatty foods increase the absorbance of what drug
griseifulvin
does first pass metabolism increase or decrease bioavailability
decrease
what 3 factors delay rate of drug absorption
increased speed though GIT
delayed transport from stomach to intestines
presence of food in the stomach
what is the effect of P-glycoprotein on rate of drug absorption
decreases
(pumps drugs out of cell)
what is the definition of drug distribution
drug reversibly leaves the bloodstream and enters interstitium/tissues
what makes up the central compartment for drug distribution
highly blood perfused compartments (blood, heart, lungs, liver, kidneys)
what makes up the peripheral compartment for drug distribution
lower blood flow, less vascularized (fat tissues, muscle, CSF)
what does a high volume of distribution tell us
more of the drug is in tissue than in plasma
what is the equation for volume of ditribution
amount of drug in the body/plasma concentration at time 0
what does a low volume of distribution tell us
the drug mostly remains in the blood
A drug with a volume of distribution of __ L is low Vd drug
4-8L
A drug with a volume of distribution of __ L is medium Vd drug
14-16
A drug with a volume of distribution of greater than__ L is high Vd drug
42
what are 3 characteristics of low Vd drugs
only in blood/plasma
large weight/charged
bound to plasma proteins (hydrophilic)
what are 4 characteristics of medium Vd drugs
distribute to interstitial fluid/intravascular
small weight
hydrophilic
not bound to plasma proteins
what are 2 characteristics of high Vd drugs
drugs distributes to all tissues
small, uncharged (hydrophobic or lipophilic)
lipophilic or lipophobic drugs have a greater drug distribution
lipophilic
the greater the plasma protein binding, the greater or lower drug distribution
lower
the greater the blood flow, the greater or lower drug distribution
greater
the greater the capillary permeability the greater or lower drug distribution
greater
highly protein bound drugs have a longer or shorter duration of action
longer
what increases the risk of drug toxicity
if 2 highly plasma bound drugs are given together and both drugs bind to the same site
the blood brain barrier restricts __ soluble drugs while __ soluble drugs cross more easily
(lipid or water)
water
lipid
do liver and kidney disease increase or decrease Vd
increase
(less protein binding in plasma)
does heart failure increase or decrease Vd
decrease
(less distribution to organs)
does obesity increase or decrease Vd
increases
(highly lipid soluble drugs get distributed to the adipose tissue)
does pregnancy increase of decrease Vd
increase
(increase body weight/adipose)
what is redistribution
highly lipid soluble drugs are rapidly distributed to highly blood perfused tissues (brain, heart, kidney) but get redistributed into less vascularized tissues at the end of the drug action
the greater the lipid solubility the drug, the slower or faster redistribution
faster
what is an example of a drug that is terminated by drug redistribution
anesthetic effect of thiopental
what are 3 possible effects of drug metabolism
inactivation
conversion to an active metabolite to lengthen drug action
activation
what is the definition of a pro-drug
a drug needs to go through metabolism to become active
microsomal enzymes such as cytochrome P-450 and oxidases are primarily associated with what location
ER of liver
nonmicrosomal enzymes such as monoamine oxidase, esterases, amidases, and transferases are primarily associated with what 3 main locations
cytoplasm
mitochondria of liver cells
plasma
characteristics of microsomal enzymes (4)
mostly catalyze phase I reactions
non-specific
can be induced or inhibited
metabolize only lipid soluble drugs
in the nomenclature of cytochrome P450:
ex: CYP3A4
3= __
A=__
4=__
family name
subfamily
isozyme
what are the 3 most important cytochrome Ps for drug metabolism
CYP3A, CYP2D, and CYP2C
2 characteristics of nonmicrosomal enzymes
non-inducible
phase II reactions
what is the difference between the types of reactions involved in phase I vs II reactions
phase I- nonsynthetic
phase II- synthetic/conjugation
phase I and II metabolism is used to metabolize __ soluble agents into more polar substances because the kidneys can’t effectively secrete __ drugs
lipid
lipophilic
phase I reactions are mostly catalyzed by ___ system
cytochrome P450
phase I reactions convert the drug to a __ soluble metabolite
water
the reactions involved in phase I reactions are __, __, and __
oxidation
reduction
hydrolysis
the drug metabolite after phase II is mostly __, __ soluble, and __
polar
water
inactive
can phase II metabolism occur before phase I
yes
what are the 6 reactions of phase II metabolism
glucuronidation
glutathionylation
glycination
acetylation
methylation
sulfation
enterohepatic recycling is between what 3 organs
GIT
liver
kidneys
what is the effect of enterohepatic recycling
prolong half-life
what classification of drugs interfere with enterohepatic recycling
antibiotics
antibiotics that interfere with enterohepatic circulation have what affect on contraceptives
failure
