Pharmacology Flashcards
Who is Paracelsus?
father of pharmacology; worked on mercury; said every drug is a poison, the dosage determined its toxicity
what is coumadin?
aka warfarin; it’s a blood thinner.
what is the name of the first experiments in humans?
phase I clinical trials; not intended for effectiveness of drug
phase II clinical trials?
have to show that drug is actually beneficial
phase III clinical trials?
crucial phase; very expensive; multi-center trials; double blind studies
phase IV clinical trials?
NOT part of the drug approval process; after drug is approved, clinical data continues to be collected by FDA in the “real world”; able to see rare side effects due to larger # of people taking the drug
what source of drug info does our prof use the most?
The physicians desk reference
CLASS I:
a. abuse potential
b. examples
c. physical/psychological effects
d. handling
a. abuse potential: highest
b. examples: heroin, LSD, marijuana, mescaline
c. physical/psychological effects: no accepted medical use
d. handling: experimental or research only
CLASS II:
a. abuse potential
b. examples
c. physical/psychological effects
d. handling
a. abuse potential: high
b. examples: morphine, meperidine, amphetamine, methylphenidate, secobarbital, phencylcidine (PCP)
c. physical/psychological effects: may produce dependence, accepted medical uses
d. handling: prescriber’s signature required; NO refills
CLASS III:
a. abuse potential
b. examples
c. physical/psychological effects
d. handling
a. abuse potential: moderate
b. examples: codeine mixes, weaker stimulants and sedatives
c. physical/psychological effects: may produce moderate-low dependence; accepted medical uses
d. handling: prescriptions may be called in; <5 refills/6 mo; container w/ warning labels
CLASS IV:
a. abuse potential
b. examples
c. physical/psychological effects
d. handling
a. abuse potential: less
b. examples: benzodiazepines, pentazocine; phenobarbital; d-propoxyphene
c. physical/psychological effects: none
d. handling: same as C-III
CLASS V:
a. abuse potential
b. examples
c. physical/psychological effects
d. handling
a. abuse potential: least
b. examples: some codeine containing cough syrup, d-propoxyphene
c. physical/psychological effects: none
d. handling: OTC in some states
Does class II drugs have medical use? how can it be acquired?
yes; get it w/ prescriber’s signature
Does class IV drugs have medical use? how can it be acquired?
yes; prescriptions may be called in
who coined the term receptor?
Langley
occupancy theory?
higher number of receptors binding drugs means greater effect
spare receptors?
full effect of drug w/ less than 100% of receptors binding drug
What are the 4 processes of pharmacokinetics?
Absorption, distribution, metabolism, excretion
what drug is an exception to being metabolized/absorbed before being excreted?
NO
oral dose stays in therapeutic range longer than an IV dose bc ut us absorbed slower. t/f?
true!
inhalation as a method of drug administration is useful for what?
peptides (i.e. insulin)
what are some prolonged release preps for drugs?
drug coatings, drug salts, ion-exchange resin complex, drug polymer
matrix storage and reservoir storage?
matrix - drug imbedded in solid
reservoir - drug dissolved in liquid
what are specific molecular carriers?
viral envelopes, erythrocyte ghosts, liposomes (very good!)
- first 2 methods = not good
liposomes are coated in what?
coated w/ polyethylene glycol (PEG) to stabilize liposomes & evade body defenses
examples of liposomes drugs?
doxil and myocet - for delivery of doxorubicin to solid tumors
what is the lipid/water partition coefficient?
how much drug has gone in each partition (Lipid or water)
statin’s work really well bc…?
they have transporters in the liver that bring them directly to the site of action
what is the fastest method to cross membranes for drugs?
transporters
hexanoic acid?
type of alipoic acid; easy to cross memb; hydrophilic or lipid soluble; need transporter for glc
if you have a weak acid w/ ____ pH, more of the weak acids will be in charged form.
low pH
if you have low pH, more weak bases will be in ______ form.
uncharged
when is pH = pKa?
when there is an equal amt of charged/uncharged form
An acid drug in an acid compartment is going to be transferred _____ and will be present in its ____ form.
rapidly; uncharged
a basic drug in an ____ environment won’t be absorbed bc it will remain in its charged form.
acidic
What are anion drug transporters?
P-glycoprotein (MDR or MDRP–multidrug resistance proteins) & organic anion transport protein (OATP)
tl;dr: MDR/MDRP & OATP
What are cation drug transporters?
Organic cation transport proteins (OCT)
Multidrug & toxin extrusion (MATE)
Organic Cation/Carnitine Transporters (OCTN)
what promotes diffusion? (fick’s law)
larger SA, thinner memb, larger conc gradients
*Fick’s law only covers uncharged form of a drug.
if a compartment/organ is acidic, what kind of drugs will be attracted there?
BASIC
where are the highest perfusion rates? the lowest?
highest - brain, kidney, liver
lowest - bone, fat, skin
Acidic drugs bind to what plasma protein?
albumin
Basic drugs often bind to what plasma protein?
globulins
total fraction of drug bound is determined by?
drug conc, affinity of binding sites, # of binding sites
If Warfarin changed from 99 to 98 % bound, its free concentration would _____.
double
what is the most lipid soluble drug available?
thiopental
what is volume of distribution of a drug?
Vd = amt of drug administered/plasma drug concentration = mg/(mg/ml) = ml
what are the patterns of distribution for drugs?
vascular, uniform, non-uniform, conc in specific tissues
*most drugs are non-uniform
diff betw microsomal and nonmicrosomal enzymes?
microsome = enzymes for a drug found in microsomes of the SER
codeine is a prodrug that is converted to…
morphine
what is the most important site for drug metabolism?
liver
what does phase I rxns do?
phase I (nonsynthetic) rxns produce a change in a drug that can allow a synthetic rxn
what do phase II rxn do?
these are synthetic rxns and they produce a metabolite by transfer of a chemical group to the drug; aka conjugation or adduct formation
what secretes beta-glucuronidases?
microflora in the intestine; slow down the elimination of the drug
Make sure to go back to look at the glucuronide conjugation equations…
Meep.
What is the donor to drugs in the glucuronide conjugation?
UDPGA
steroids get metabolized by what type of synthetic rxns?
sulfate & glucuronide conjugation
in order to transport the sulfate, the pathway must be activated by…?
atp
What is the donor to activate the sulfate group?
PAPS
in amino acid conjugation, drug MUST be converted to ____ and then reacts w/ _____.
Co-A; glycine or glutamine
donor for acetylation synthetic rxn?
acetyl-CoA
glutathione conjugates w/ what?
itself. it conjugates w/ reduced glutathione.
donor for methylation rxn?
s-adenosyl-methionine (SAM)
The most important nonsynthetic rxn is…? What catalyzes it?
Oxidation; cytochrome p450 in the mitochondria
*name comes from strong absorption of light at 450 nm when enzymes are exposed to carbon monoxide
what do we need to know about the cyt p450 enzyme? And the process it is involved in?
binding of the drug makes Fe3+ become reduced to 2+ via reductase; then oxidized by molecular O2; product = oxidized drug & water (requires NADPH)
*DIFFERENCE OF ONE ATOM OF OXYGEN
One atom of O2 is reduced to make H2O and the other atom is added to the drug in a rxn w/ cyt p450. t/f?
ALWAYS TRUE
Demethylation/dealkylation of codeine forms what?
morphine + formaldehyde
*even though it says dealkylation rxn, it is actually an oxidation rxn.
CYP3A4 & CYP3A5 isoforms are involved in the metabolism of ~___% of drugs.
50
What happens in the nonsynthetic rxn, reduction?
add a hydrogen or remove oxygen
What happens in the nonsynthetic rxn, hydrolysis?
addition of water w/ breakdown of molecule. performed in blood plasma and liver by esterases.
What are 2 enzymes involved in hydrolysis rxns that are important for dentists?
- hydrolase (in blood)
2. amidase (in many tissues of body)
humans make mercapturic acid via what conjugation rxn?
NO, humans make glutathione conjugate rather than mercapturic acid.
what is used for tx for TB? and how is it metabolized?
isoniazid; N-acetyl-transferase
clearance times plasma conc gives ?
rate of excretion from blood
reabsorption of a weak acid is _____ in the acidotic patient.
100x faster
reabsorption of a weak base is _____ in the acidotic patient.
100x slower
if you overdose on an acidic drug, give ___ to make urine more basic.
bicarb
if you overdose on a basic drug, give ___ to make urine more acidic.
ammonia chloride
_____ is a straight line, while _____ is curved line in first order elimination of drugs.
elimination phase (beta phase); distribution phase (alpha phase)
drugs conc in blood decreases as an ______.
exponential decay
most drugs are eliminated by _____ kinetics.
first order
zero order elim of drugs?
not dictated by conc; it depends on restrictions of its metabolism; drug conc dec linearly
ex. alcohol is restricted by alcohol dehydrogenase and falls under zero order
in order to calculate pharmacokinetics of multiple dosing, we need to know what variable?
fractional bioavailability (fraction of an administered dose of unchanged drug that reaches the systemic circulation)
tell me about the plateau state of multiple dosing…
attained after 4 half lives; time required to reach state is independent of dose….
tell me about plateau conc in multiple dosing…
directly proportional to dos; indirectly proportional to dosage interval; proportional to half life
diff betw agonist and antagonist?
agonist - drug binds & has effect
antagonist - drug binds and blocks or reduces an existing effect
Km = ?
Km = half of maximum activity
ED50 = ?
effective dose for 1/2 the max effect
greater potency will have the curve more to the…?
left; potency tells us the diff in conc for 2 diff drugs; the more potent drug produces an effect at a lower conc
efficacy is a measure of?
the maximal effect of a drug; a drug with a higher efficacy will have a greater max effect (greater response)
usually what is noted about ED50, if the drug is more potent?
the more potent a drug, the lower the ED50
the therapeutic index is used for comparing..?
relative safety of similar drugs; drug companies want a low ED50 and a high LD50
what are the 2 important features of competitive antagonism?
can’t bind to both at the same time and this type is surmountable (can overcome by producing more hormone or drug)
what are the 2 important features of noncompetitive antagonism?
receptor can bind both at the same time & not surmountable (cannot be overcome by increased amount of agonist)
what are the 2 important features of uncompetitive antagonism?
agonist binds to receptor before the antagonist will bind (can’t bind to free receptor); inc conc of agonist can allow more antagonist to bind
non-equilibrium competition is similar to …?
noncompetitive antagonism but not the same bc non-eq competition is not reversible.
competitive antagonism affects…?
potency
noncompetitive affects…?
efficacy
