Principles of Pharmacology Flashcards
what does a mechanism of action help us understand?
expected pharmacological effects
how do beta blockers affect BP and HR?
cause hypotension and bradycardia
what can be a contraindication of a beta blocker?
exacerbate asthma
what does a beta blocker block?
activation of sympathetic nervous system
what does cardio-selectivity mean in regards to a beta blocker?
it would only affect the heart, not other parts of the body
what is the exception on dosages?
dose-limiting toxicity (DLT)
what is a proprietary (brand) name adopted by a manufacture?
trade name (patented)
Non-proprietary name assigned and approved by the USAN council
generic name (official)
which type of name gives us an idea of what family the drug belongs to?
generic name
beta blockers end in _____ and _____
-olol; -lol
benzodiazepines end in _____ or _____
-lam; -pam
what the body does to the drug is called?
pharmacokinetics
what is the drug does to the body is called?
pharmacodynamics
which organs are the primary eliminators of drugs?
kidneys and liver
what is the quickest route of administration into the system?
IV administration
when is the rate of drug absorption higher than drug metabolism and excretion?
at the beginning
when is the rate of drug metabolism and excretion higher than drug absorption?
at the end
the rate at which a drug leaves the site of administration and the extent to which this occurs
drug absorption
what are 4 things that affect drug absorption?
- route of administration
- drug formulation
- chemical nature of drug
- blood flow
the rate and extent to which an administered drug reaches the systemic circulation
systemic bioavailability
which form of administration has a higher systemic bioavailability than oral administration?
sublingual administration
why is the alveolar surface a good site of absorption?
extensive blood flow and large surface area
the alveolar surface is used primarily for the administration of _____ and _____ compounds
volatile; non-volatile
what is an example of a volatile compound?
general anesthetics
what is an example of a non-volatile compound?
bronchodilator (aerosols)
why would epinephrine be used with local anesthetics?
to prolong the effects of local anesthetics
what are 4 routes of administration that are enteral?
- sublingual
- oral
- buccal
- rectal
what is the onset of response for drug administration? (11)
IV
inhalation
buccal, SL
IP, IM, SC
rectal
oral
topical
transdermal
what are the 3 main parenteral routes of administration?
- IV
- IM
- SC
what must drugs, administered extravascularly, cross in order to reach systemic circulation?
cell membrane
what is any route administration called that is not IV
extravascular
why is it important for a drug in tablet form to disintegrate?
exposes active substances
will a drug in tablet form, in granules (aggregates), or in small particles have optimal dissolution?
a drug in small particles
what state must a drug be in for it to be absorbed?
solution
what is the absorption rate between tablet, capsule, sustained release (SR), and solution?
- solution
- capsule
- tablet
- SR
what is the difference between a solution and a suspension?
a suspension separates into 2 layers after it sits
drug molecules are either _____ or _____
weak acids; weak bases
a portion of the drug will be _____ and a portion will be _____
ionized; unionized
the ionized portion of the drug is _____ soluble
water
the unionized portion of the drug is _____ soluble
lipid
a water soluble drug must be _____ to be _____ in urine
charged; excreted
a lipid soluble drug must be _____ to _____ a membrane
uncharged; cross
a majority of weak acidic compounds will be _____, AKA _____ soluble
unionized; lipid
what can weak acidic compounds do since they are unionized and lipid soluble?
diffuse across stomach lumen and into systemic circulation
a majority of weak basic compounds will be _____, AKA _____ soluble
ionized; water
why must weak basic compounds go from the stomach into the small intestines?
to become unionized and then be absorbed into systemic circulation
why are most drugs absorbed in the small intestines?
large surface area
a certain portion of a drug being ionized vs unionized depends on what 2 factors?
pH and pKa
what value changes as a drug moves through the GI tract?
pH
what can prolong drug absorption and delay the effects of drugs?
slow GI tract emptying
what 4 characteristics that favor drugs transferring to breast milk?
- low protein binding
- low molecular weight
- unionized
- lipid solubility
what type of drug is more likely to transfer into breast milk?
weak bases
once in systemic circulation, where do drugs go? (2)
- target sites
- organs of elimination
a drug will get to ___-____ organs faster than ____-______ organs
more-perfused; less-perfused
how do drugs primarily transport across biological membranes?
passive diffusion from high to low concentration
what are 2 other ways a drug can transport across biological membranes?
- facilitated transport
- active transport
a drug that moves from high to low concentration using a protein transporter is using what kind of transport?
facilitated transport
a drug that moves from low to high concentrations using a protein transporter and ATP is using what kind of transport?
active transport
what do drugs bind to in blood?
proteins
albumin binds to _____ drugs
acidic
alpha-1-acid glycoprotein binds to _____ drugs
basic
a drug with _____ protein binding will have a more difficult time getting through the biological membrane
high
even if a drug is bound to proteins, it will go through _____ capillaries easier than _____ capillaries
systemic; CNS
drug distribution after absorption is affected by what? (2)
- protein binding
- solubility
if we want a drug to go around the body, it should be ____ protein-bound and _____ lipid soluble
low; high
in a patient with ascites, will a water-soluble or lipid-soluble drug work better?
water-soluble
in regards to a specific person, drug distribution after absorption is affected by: (2)
- body size
- body composition
what enzyme does the liver produce to remove the drug from the body, by converting it from lipid-soluble to water-soluble?
CYP450
what occurs in phase 1 of drug excretion?
biotransformation (metabolism)
what does drug metabolism or biotransformation increase?
polarity
what occurs in phase 2 of drug excretion?
synthesis
the combination of a drug with endogenous substances to make the drug more water-soluble, is what phase?
phase 2
what happens if there are multiple drugs in the body?
they compete for CYP450 to be excreted
what increases the duration of a drug (parent compound) in the body?
active metabolite
when a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation
first pass effect
anything that is absorbed in the GI tract must go through what before getting to systemic circulation?
liver
what is the relationship between first pass effect and bioavailability?
inverse relationship
why is nitroglycerin, which is an anti-anginal, administered sublingual?
goes directly into capillaries and does not get “lost”
why is there an issue with oral dosing?
it can get “lost” in other parts of the body before reaching its target site
drugs must go through which organ to be removed from the system?
kidney
reabsorption of fluid occurs in the ____ _____, making it very _____
renal tubule; concentrated
the glomerulus ability to filter depends on: (2)
- protein binding
- molecular size
why is tubular secretion considered an active process?
fluid moves from low to high concentration (from blood vessels to renal tubules)
why is tubular reabsorption considered a passive process?
drug/fluid goes from high to low concentration (from renal tubules to blood vessels)
why is amphetamine excreted faster in acidic urine?
acidic environment makes amphetamine unionized
why is amphetamine excreted slower in alkaline urine?
alkaline environment makes amphetamine ionized
why does enterohepatic circulation lead to a longer duration of a drug?
increases reabsorption
a drug can bind to what 4 targets?
- ion channels
- G-protein coupled receptors
- enzymes
- intracellular receptors
drugs use what 2 things to encourage an electrical stimulation that causes changes?
- signal transduction
- secondary messengers
drugs can ___ or ____ action of an endogenous ligand or another foreign compound
enhance; block
what is an example of an enhancer that increases BP and HR?
beta agonist
what is an example of a blocker that decreases BP and HR?
beta blocker
what would decrease the affect of angiotensin II?
angiotensin II receptor blockers (ARBs)
what is an example of a drug that replaces natural body chemicals?
insulin
when a drug is given, it goes through _____ biological levels to produce the wanted response
multiple
what is a good example of a drug going through multiple biological levels to produce the wanted response?
drug given for poor urine flow to relax bladder will also relax neck and prostate
how right a drug attaches to the target
affinity
how well the drug fits with the target (physical characteristics)
specificity
how much of the drug is specific for that particular target vs a non-intended target
selectivity
what effects results from altered cellular activity and/or physiological function?
active effector mechanism
what inhibits the transmission of pain signals in the body?
endorphins
what would happen if naloxone (reverses opioid overdose) were to bind to the receptor at the same site as the morphine/agonist?
“replaces” the agonist/morphine and would not allow pain relief
what produces 100% of the response and has a high affinity for dopamine-2 (D2) receptor?
full agonist
what combines to the receptor but differs in magnitude of efficacy in which we get some intensity for the therapeutic effect?
partial agonist
what would reduce the effect of dopamine and produces 0 intensity for a therapeutic effect?
antagonist
what are the two groups of antagonists called?
- competitive antagonist
- irreversible antagonist (noncompetitive)
what kind of antagonist fights with morphine at the receptor and is reversible by applying a higher dose of the morphine/agonist to reverse the effects of the antagonist?
competitive antagonist
what kind of antagonist binds irreversibly to the target and we cannot give enough amounts of agonist to reverse the effects of the antagonist
irreversible antagonist (noncompetitive)
what is cimetidine considered when it takes up the H2 receptor from histamine to prevent histamine’s ability to lead to peptic ulcers, and does not require the presence of an agonist (histamine) for a pharmacological effect?
inverse agonist
an increased dose will lead to an increased _____ effect and increased _____ in the system
pharmacological; time
what is the amount of drug divided by the space it is in, called?
concentration
what happens if I try to increase the dose after 100% therapeutic effect has been reached?
toxicity will occur
concentration of the drug that produces a response equal to 50% of the maximal response
ED50
the amount of drug necessary to produce an effect
potency
if angiotensin receptor blocker candesartan has a therapeutic range of 4-32 mg, and irbesartan has one of 75-300mg, which one is more potent?
candesartan
the magnitude of response a drug causes when it interacts with a receptor
efficacy
a drug that produces a greater maximal effect is more _____
efficacious
what is the dose response that goes beyond efficacy?
toxicity (LD50)
why do we want ED50 to be far away from LD50?
increases the margin of safety
relationship between the dose of the drug and the proportion of a population that responds to it
quantal dose-response relationship
what is the measure of safety of a drug?
therapeutic index
do we want a large or small therapeutic index?
large
what does it mean when stated that warfarin has a small/narrow therapeutic index?
a great number of patients respond, but warfarin can cause hemorrhage at higher doses
what does a smaller therapeutic index (TI) mean?
increased toxicity incidence
what does a larger therapeutic index (TI) mean?
decreased toxicity incidence
what happens to the efficacy curve when we increase drug levels in a patient?
the curve moves closer to the toxicity curve
what happens to the ED50 curve and potency when a beta blocker antagonizes the effect of beta agonists in managing asthma?
curve has a right-shift
potency is decreased
why is there a right- shift when a beta blocker antagonizes the effect of beta agonists in managing asthma?
we need more of the agonist to override the antagonists effect
when the sum of two drugs given in combination equals the sum of their individual effect
additive
when the combined effect of two drugs is greater than the sum of their individual effects
synergistic
what happens to potency when two drugs with different mechanisms of action are used to treat the same thing? (whether it is additive or synergistic)
potency is increased
what happens to the ED50 curve when two drugs with different mechanisms of action are used to treat the same thing? (additive or synergistic)
left-shift
why is there a left-shift in the ED50 curve when two drugs with different mechanisms of action are used to treat the same thing? (additive or synergistic)
we need less of the first drug to reach efficacy
what happens to the efficacy curve if a patient is tolerant to the therapeutic effect?
right-shift
what does a right-shift of the efficacy curve mean if a patient is tolerant to the therapeutic effect?
more of the drug is needed to reach therapeutic effect
only 95% of acetaminophen can be conjugated by the body, what happens to the other 5%?
goes through CYP2E1, which leads to toxicity to the hepatocytes
what does the gene CYP2E1 do?
causes hepatotoxicity
what is the duration of pharmacological action affected by? (2)
- metabolism
- excretion
what is the time necessary for drug concentration to decrease by 50% called?
elimination half-life
why is elimination half-life important?
helps determine dosing interval
what is reached when the rate of drug elimination is equal to the rate of drug administration, such that plasma and tissue levels remain relatively constant?
steady state
what is steady state also known as?
full effect
how many half-lives get you to a steady state?
5
what is the elimination process in which drug elimination is proportional to the drug dose/concentration
first order
what is the elimination process in which drug elimination is constant and independent of the drug dose/concentration?
zero order
how does increasing the dose in first order kinetics affect the plasma concentration?
proportional increase of plasma concentration
how does increasing the dose in zero order kinetics affect the plasma concentration?
plasma concentration increases out of proportion
what is it called when a drug is administered to achieve a desired plasma level rapidly, and is then followed by a maintenance dose to maintain the steady state?
loading dose
the fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma
volume of distribution
what three pharmacological factors determine distribution?
- volume of distribution
- lipid-soluble drug
- non-protein bound
what does a high volume of distribution mean?
drug is more distributed to the rest of the body, not just the target tissue
how does Vd (volume of distribution) affect half-life?
increased Vd can increase half-life
if phenobarbital has a Vd of 0.8L/kg and a patient comes in with a level of 15mg/L. What will be the dose required to get to the desired concentration of 35mg/L?
16 mg/kg
what is the area under the curve?
systemic exposure - how much the body is exposed to that particular drug
what is the relationship between the area under the curve/systemic exposure and dose?
proportional
what is the relationship between the area under the curve/systemic exposure and elimination capacity (clearance)?
inversely proportional
what is the elimination rate of a drug?
clearance
what kind of relationship does clearance have with steady state concentration?
inverse relationship
what does clearance help determine?
maintenance dose (MD)
how does competition for, or inhibition of, an enzyme by a concurrent medication affect therapeutic outcome?
one drug will be lost and the other drug that fits the enzyme better and has a higher affinity will be metabolized
how does induction of an enzyme by concurrent drugs affect therapeutic outcome?
the drug that the enzyme targets will be eliminated faster
how do concurrent hepatotoxic drugs affect therapeutic outcome?
damaged liver cannot eliminate drug effectively
in CYP1A2, what does the 1 indicate?
family
in CYP1A2, what does the A indicate?
subfamily
in CYP1A2, what does the 2 indicate?
specific enzyme within subfamily
what results in increased biotransformation of drugs and can lead to significant decreases in plasma concentrations of drugs metabolized by CYP isozymes, often with concurrent loss of pharmacologic effect?
CYP inducer
what leads to significant increases in plasma drug concentration and resultant adverse effects or drug toxicity?
CYP inhibitors
what is the most common form of inhibition?
competition for the same isozyme
what does it mean when a drug given orally has the same concentration over time as a drug give IV?
drug has good bioavailability
what type of bioavailability compares one non-IV route with IV administration?
absolute bioavailability
what type of bioavailability compares one non-IV route with another non-IV route?
relative bioavailability
if grape fruit juice inhibits CYP3A4-mediated metabolism, what happens if a patient drinks grape fruit juice while taking a medication?
drug cannot be metabolized and excreted = can lead to toxicity
what happens to patients with poor metabolizers of the CYP2D6 that converts codeine to morphine?
patient will not have enough pain relief
what happens to patients with ultra-rapid metabolizers of the CYP2D6 that converts codeine to morphine?
codeine will be converted to morphine more intensely - increases toxicity
