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Pharmacodynamics

Terms in this set (87)

therapeutic window/index
measure of drug safety; relationship between beneficial and adverse effects
drugs with a wide therapeutic window:

narrow window:
safer

less safe, harder to dose, require closer monitoring and are associated with a higher rate of dangerous toxicities
minimal effective concentration
minimum blood level below which they are ineffective

this level varies depending upon the drug and what it is being used to treat, and can also vary per patient
term for when blood levels are below the minimum
sub-therapeutic
maximal safe concentration

when the maximal safe concentration is exceeded:
maximal level above which serious side effects and toxicities may occur

patient receives no additional efficacy/benefits, but is exposed to unnecessary and unexpected adverse effects
toxicity
used interchangeable with adverse drug reaction (ADR) or side effect

refers to more serious or unexpected ADRs that tend to occur above the maximal safe concentration or when the drug is not monitored properly
steady state

when someone starts taking a medication:
refers to the point at which drug input equals drug output

blood levels rise over time but they don't keep rising forever --> at some point they stabilize/plateau and become steady
normal dosing of all medication is designed so that the steady state will be a level
within the therapeutic range --> takes 4-5 half-lives for a drug to reach a steady state
onset of action

depends upon the:
as soon as blood levels rise to the therapeutic range, we see the drug begin to take effect (onset of action)

drug's mechanism of action and how long that takes to become physiologically visible
some medications take ____ before we see the onset of action, others:
several weeks (ex. rheumatoid arthritis medication that work by slowly resolving inflammation and quieting the immune system)

work as soon as the drug reaches the blood stream (ex. nitroglycerin SL works within minutes)
duration of action
length of time a drug can be expected to exhibit its pharmacological effects

half life specifically refers to blood levels, but duration of action is more clinically relevant
duration of action is correlated with ___ but:
half-life, they are not the same thing --> a drug with a long half-life will have a long duration of action, etc.
receptor theory

the function of the receptor or cell is:
a drug produces an effect by combining with some specific molecular constituent (receptor)

modified to produce a measurable effect
agonist
a drug that mimics some natural compound by binding with the receptor and stimulating some cellular response
antagonist
a drug that binds with a receptor, blocks the receptor from stimulation and prevents it from being triggered normally
affinity
measure of the strength of attraction between a drug and its receptor, describes the tightness of the bond
a drug with a high affinity to a certain receptor is ______ as compared to a drug with a low affinity or may:
likely to elicit that response

only do so in some patients or when used in very high doses
selectivity

usually, the more selective a drug is:
refers to the degree to which a drug acts upon one site relative to all possible sites

the fewer adverse effects it will cause
alteration of enzyme activity
many drugs work by altering the activity of various body enzymes and thus increasing or decreasing production of neurotransmitters, hormones, etc
adverse drug reaction
broad term that can encompass a variety of types of reactions
adverse effect/side effect
undesired pharmacological effect of a drug; usually dose related and usually related to how the drug works or its mechanism of action
example: a bp med that unexpectedly bottoms out the patient's bp or a sedative that makes the patient unresponsive or sedated for an extended period of time
exaggerated drug response
allergic reaction

patient is usually:
immune system mediated (IgE, antibody, IgG, or T-cell mediated)

allergic to all drugs of that same chemical class
pseudoallergic drug reactions

reactions are often due to:
these reactions resemble allergic reactions but they are not mediated by the immune system; there is no antibody production

immediate drug-induced histamine release (or other physiological causes) without antibody production
pseudoallergic drug reactions example
vancomycin red-man syndrome, morphine rash, ACE-I rash
intolerance
term used to describe any type of ADR that the patient feels is intolerable, thus limiting the drug's usefulness or acceptance to the patient
high risk drugs
those with a narrow therapeutic window, high incidence of side effects, high incidence of allergic reactions
high risk patients

these include:
patients who would be least likely to tolerate ADRs or loss of efficacy

neonates/infants, elderly, frail, malnourished, diabetes, arrhythmias, heart disease, epilepsy, those who take many medications and have many co-morbid diseases
the following criteria suggest that a drug reaction may be immunologically mediated (6)
-occurs in a small % of patients receiving the drug
-rxn does not resemble the drug's pharmacologic effect
-rxn is similar to that seen with other allergic rxns
-rxn is not dose-dependent and can be reproduced even by minute doses
-rxn is typically reproduced by agents with similar chemical structure
-rxn resolves after the drug has been discontinued
immediate allergic rxns

generally begins within:

have a high potential to progress to:

symptoms may reoccur within:
Immunoglobulin E (IgE)-mediated activation of mast cells and basophils

2 hours of exposure

anaphylaxis

6-8 hours after treatment; therefore patients must be observed for at least 12 hours after a treated episode
acute hives occurring within 2 hours of drug exposure should be
considered an immediate IgE-mediated reaction that could progress to anaphylaxis
delayed allergic reactions
generally begins 6 hours to days after exposure; these rxns tend to be mild dermatologic reactions such as itching, rash, delayed onset hives
SJS/TEN is a rare type of
delayed allergic rxn that can be life threatening
SJS and TEN: mucosal involvement occurs in...

common drug causes:
90% of cases of SJS/TEN

allopurinol, some anticonvulsants, sulfonamide antibiotics, some NSAIDS
pseudo-allergic drug reactions

for some drugs, the reaction is:

if the rxn was life-threatening:
ADRs with symptoms that mimic drug allergy

not expected to reoccur; in others it typically will

do not attempt a re-challenge
pseudo-allergic drug reactions are often due to
imemdiate drug-induced histamine release or other physiological causes without antibody production
tolerance

tolerance to _____ can develop:

may be due to:
higher doses of a drug are needed over time to elicit the same response

efficacy and/or adverse effects

alterations in numbers of receptors or homeostatic responses
physical dependence
drug is needed to function normally --> stopping the drug will cause withdrawal sx
withdrawal sx

example: stopping a bp medication suddenly may result in:
usually the opposite effects of the drug and can range from uncomfortable to life threatening

rebound hypotension
addiction or psychological dependence
deviant behavior causing an overwhelming involvement in the use of and acquisition of a drug for euphoria
addiction and physical dependence are

example:
very different!

no one is addicted to their bp medication or Afrin nasal spray although they may experience withdrawal sx when stopping it
drug interaction
the modification of the effects of one drug by the prior concomitant administration of another drug
drug interactions --> list of 4
altered GI absorption

protein displacement

altered metabolism

synergistic effects and antagonistic effects
drug interaction: altered intestinal flora

________ can alter intestinal normal flora and sometimes affect drug absorption
intestinal bacteria carry out a variety of enzymatic processes which can impact the absorption and metabolism of orally ingested drugs

antibiotics
about 10-40% of orally ingested digoxin is metabolized by GI flora --> reducing gut flora may
increase digoxin absorption and increase levels in some patients (toxicity)
bacterial enzymes may _____ absorption and activation of orally ingested estrogen (birth control) --> reducing gut flora may:
enhance

reduce estrogen absorption and activation and estrogen levels in some patients
drug interaction: altered pH

depending on the pH of the solution a drug is dissolved in:
the non-ionized (non-charged) form of a drug molecule can more easily cross lipid barriers and will have the best oral absorption

it may be more or less ionized
drugs that alter the pH of the gut may
increase or decrease drug absorption
several drugs require acidic environment for best oral absorption and therefore
cannot be taken with antacids, H2 blockers or proton pump inhibitors

calcium supplements, iron supplements, and some antifungal drugs
drugs that require alkaline pH for best oral absorption will be impacted by
acidic beverages such as orange juice or soda
drug induced mucosal damage
drugs that "tear up" the gut lining can reduce absorption of medications and nutrients leading to malnourishment
chelation interactions
chelation is a form of strong chemical bonding of two substances that reduces their solubility and thus prevents oral absorption
chelation interactions examples
quinolone antibiotics (Cipro) or tetracycline antibiotics with polyvalent cations such as calcium, iron, magnesium and aluminum
effects of food on drug absorption
presence or absence of food can play a significant role in the absorption of certain medications
effects of food: these are often _____ and may include alterations in:
multifactorial

pH, chelation interactions, composition of the meal, and changes in rate of gastric emptying
empty stomach means you should take the drug _________ or _______
1 hour before food or 2 hours after
transport protein interactions
multiple drugs competing for PGPs may reduce PGP binding of one or both drugs --> drugs may be inhibitors or inducers of PGPs thus increasing or decreasing absorption
PGPs in the gut
efflux the drug out of the body/blood stream back into the gut
PGP inhibition
inhibiting activity

reduced efflux = increased blood levels
PGP induction
inducing activity

increased efflux = decreased blood levels
drugs bound to plasma proteins are pharmacologically

there are limited number of binding sites available on:
inactive and exist in equilibrium between bound and unbound

serum albumin
taking 2 drugs, both highly protein bound, causes
one drug to displace the other, creating a situation of transient increase in free drug
protein displacement drug interaction usually only clinically relevant when
both drugs are highly bound - >90%
concurrent administration of two drugs metabolized by the same liver enzyme system can cause

most of these interactions involve the:
increases or decreases in blood levels of one or both drugs

Cytochrome p450 system (which has multiple enzyme subsets)
enzyme induction caused when
one drug induces or speeds up the shared metabolic pathway
enzyme induction: the presence of one drug can cause the liver to make more of the enzyme that normally metabolizes it =
increased rate of metabolism = lower drug and blood levels = loss of efficacy
enzyme inhibition occurs when
2 or more drugs create a "traffic jam" by all trying to use the same limited quantity of liver enzyme for metabolism
enzyme inhibition: less available enzyme lead to
decreased metabolism rate = higher drug and blood levels = increased effects, adverse effects and toxicity
_________ is the most common type of drug interaction
enzyme inhibition
examples of enzyme inhibitors
grapefruit juice, macrolites, several antifungal drugs and seizure medications, diltiazem, verapamil, erythromycin, most antidepressants
examples of enzyme inducers
St. John's Wort, several seizure medications, chronic alcohol use, cigarette smoking
cytochrome p450 system is a broad term for
certain metabolic enzymes responsible for drug metabolism
subsets of p450 enzymes are called

drugs are often metabolized by:
isozymes or isoenzymes

more than one isozyme
substrates
drugs that are AFFECTED by other drugs that either induce or inhibit a particular isozyme
ultra metabolizer
has higher than normal levels of certain isozymes and thus faster than expected drug metabolism
extensive metabolizer
has normally functioning and normal levels of that isozyme and thus metabolize drugs at expected rates
poor metabolizer
abnormally low levels of certain isozymes and thus slower/limited drug metabolism
synergistic drug interactions occurs when
the effects of two drugs together are greater than would have been predicted from each of their effects along
synergistic drug interactions:

if the additive effects are unwanted or unexpected, we would call that a:

if the additive effects are beneficial and being done on purpose to improve effectiveness, we simply call that:
synergistic drug reaction

synergy
antagonistic drug interactions occurs when
the effects of two drugs are less than predicted from their effects when given along
caffeine can
increase theophylline toxicity
grapefruit juice can cause
significant cytochrome p450 interactions
vitamin K rich food can _____ efficacy of warfarin
decrease
alcohol ________ acetaminophen toxicity
increases
nonadherence in the pediatric population is
just as high if not higher than other populations
nonadherence in the older adult population is

over ______ of older adults take > or equal to 5 medications per week
common due to multiple medications, prescribers, and complex drug regimens

40%
rates of nonadherence are high is
asthma (50%), depression, diabetes, glaucoma (even going blind in one eye), epilepsy and HTN
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