true or false. There are absolutely no safe biologically active agents
true
What are 4 factors that that prescribers must take into consideration when selecting drugs?
diagnosis of the problem - what will the drug be used for?
Individual variations in physiologic status
Variations in desease states (i.e. pregnancy)
drug related pharmacodynamic and pharmacokinetic variables - exaggerated response, expected but undesired response etc.
Who approves drugs for specific indications or uses?
FDA
When a drug is prescribed for other conditions than what the FDA approved it for; e.g. antihistamine used to treat insomnia
"off-label" use
What drug is contraindicated in individuals with peptic ulcer disease?
aspirin
occur when other biologically active chemicals compete with a drug at the receptor site or during the pharmacokinetic phases of medication action
drug-related pharmacodynamic and pharmacokinetic variables
__________ during the reveiw of drugs listed on the health history should include monitoring for potential side effects
follow-up questioning
What are 6 factors that can influence the effect of a drug?
pt noncompliance
psychologic factors (placebo effect)
tolerance to medecation (tachyphylaxis)
time of administration
sex of client
age and weight
The placebo effect results from what 3 things?
doctor-patient relationship
significance of the therapeutic effect to the pt
mental setting imparted by the clinician
true or false. all drugs can produce a placebo effect. The placebo effect can significantly contribute to the success of therapy
both are true
What can develop when a drug is taken for a long period of time?
tolerance to the medication
What can solve the problem when tolerance to a drug arises?
changing to another drug with the same effect
Is it more likely for women or men to be sensitive to certain drugs requiring lower doses?
women
Which of the following would require a higher dose of a drug?
a lean but muscular 200 lb man
a lean 150 lb man with a smaller muslce mass
200 lb man who is more muscly
What percent of office visits to medical practitioners are associated with the initiation or continuation of pharmacotherapy?
75%
What percent of hospital admissions could be attributed to ADE's?
3-11%
The incidence of ADE's during hospitilization ranges from what percentages depending on the type of hospital, definition of an ADE, and study methology?
.3%-44%
What are the two classifications of ADEs?
Type A or Type B
associated with administration of therapeutic dosages of a drug (rather than high doses) usually are predicatable and avoidable, and are responsible for most ADE's
Type A ADE's
The following reactions usually occur in what type of ADE?
cytotoxic reactions
drug-drug interactions
drug-food interactions
drug-disease interactions
Type A
ADE's that are generally independant of the dose and are rarely predictable or avoidable
Type B
The following reactions occur in what type of ADE?
Idiosyncratic reactions
immunologic/allergic reactions
pseudoallergic reactions
teratogenic effects
oncogenic effects
Type B
Which type of ADE is uncommon, but are among the most serious and potentially life threatening of all
Type B
Type B ADEs usually affect which certain organ systems?
liver
hematopoietic system (spleen and bone marrow)
skin and mucosa
How long does it usually take for Type B ADEs to show clinical effects?
often up to 12 weeks, with the exception of immediate hypersensitivity reactions
What is an important example of a type B ADE with relevance to dentistry?
Osteonecrosis of the jaw (ONJ) following bisphosphonate administration
What is bisphosphonate used to treat? And what is an ADE that may result from taking it?
prevention of bone density changes during chemotherapy
to treat osteoperosis
may cause ONJ
Which mechanisms are associated with type A ADE reactions?
cell damage and vary from minor side effects to severe organ damage
What are the most adverse effects of overdose?
extensions of the drug's therapeutic effect
reactions that are most commonly caused by the formation of unstable or reactive metabolites following biotransformation and are related to some abnormality that interferes with the normal metabolism and/or excretion of therapeutic dosages of a drug; events which lead to the saturation of hepatic enzyme systems
cytotoxic reactions
What are the 2 main mechanisms that lead to the formation of intermediate compounds during biotransformation, or cytotoxic reactions?
oxidative pathway
reductive pathway
can produce compounds capable of binding covalently with cellular macromolecules
oxidative pathway
gives rise to the formation of such substances as free radicals
reductive pathway
substances that react with oxygen and produce reaction metabolites do what?
overwhelm normal antioxidant defense systems
covalent binding to proteins and the oxidation of biologic macromolecules lead to what?
direct cytotoxic effects
two or more drugs administered in therapeutic dosages at the same time or in close sequence may have what three interactions?
act independantly
interact to increase or diminish the magnitude or duration of action of one or more drugs
interact to cause an unintended reaction
all drug-drug interactions all seem to have a _____________ or a ____________ basis; the same pharmacologic mechanisms that account for a drugs efficacy also can account for many if its adverse effects
pharmacodynamic
pharmacokinetic
in pharamcodynamic interactions, of drug-drug interactions, the intended effect produced by a given plasma level is altered in the presence of a second drug; what are 4 different characterizations of these type of ineractinos?
pharmacologic interactions
physiologic interactions
chemical interactions
drug-related recepter alterations
What type of pharmacodynamic drug-drug interaction mechanism is described:
drug A and drug B compete for the same receptor site and, as a function of their repective concentrations, either produce (an agonist) or prevent (an antagonist) an effect
pharmacologic
What type of pharmacodynamic drug-drug interaction mechanism is described:
drug A and drug B interact with different receptor sites and either enhance each other's action or produce an opposing effect via different cellular mechanisms
physiologic
What type of pharmacodynamic drug-drug interaction mechanism is described:
drug A competes with drug B and prevents drug B from interacting with its intended receptor
chemical
What type of pharmacodynamic drug-drug interaction mechanism is described:
drug A, when administered long term, may either increase, or decrease the number of its own receptors or alter the adaptability of receptors to physiologic events
receptor alterations
What are 3 examples of drugs that will result in a pharmacologic drug-drug interacion mechanism?
opiods vs. naloxone
acetylcholine vs. atropine
epinephrine vs. adrenergic receptor blocking agents
What are 3 examples of drugs that will result in a physiologic drug-drug interaction mechanism?
cholinergic agents enhance the action of diazepam
epinephrine opposes the action of histamine
epinephrine opposes the action of lidocaine
What is one example of drugs that will result in a chemical drug-drug interaction mechanism?
protamine sulfate inhibits heparin
What are 2 examples of drugs that will result in a receptor alteration drug-drug interaction mechanism?
alpha 1-adrenergic receptor agonists down-regulate their own receptors
beta 1-adrenergic receptor antagonists up-regulate their own receptors
The duration and intensity of a drug's action is based on what? Which is also called what?
the amount of drug in the circulation
plasma level of drug
The plasma level of the drug is directly related to what 4 things?
The concept of affinity illustrates what type of drug-drug interaction when 2 drugs are together and the drug with the greater overall affinity for the plasma protein will in crease in the free unbound molecules of the second drug
pharmacokinetic drug-drug interaction
When a drug with greater affinity for the plasma protein causes an increased in the free, unbound molecules of the second drug, what results?
toxic effects (overdose) of the second drug
(a pharmacokinetic drug-drug interaction)
The following mechanism describes what type of pharmacokinetic drug-drug interaction?
When Drug A interferes with the absorption of Drug B
interactions that affect absorption
The following mechanism describes what type of pharmacokinetic drug-drug interaction?
When Drug A competes for plasma protein binding with Drug B
interactions that affect distribution
The following mechanism describes what type of pharmacokinetic drug-drug interaction?
When Drug A interferes somehow with enzyme activity responsible for Drug B
interactions that affect metabolism
The following mechanism describes what type of pharmadokinetic drug-drug interaction?
Drug A increases or decreases the plasma level of drug B by somehow reacting with urine or transport mechanisms
interactions that affect renal excretion
The following mechanism describes what type of pharmacokinetic drug-drug interaction?
Drug A decreases the plasma level of drug B by affecting bioflow or enterohepatic circulation
interactions that affect biliary excretion
The following mechanism is describing a pharmacokinetic drug-drug interaction that affects absorption; what are the drugs that use this mechanism?
Drug A, by causing vasoconstriction, interferes with the systemic absorption of drug B
epinephrine vs. lidocaine (or other LA agents)
The following mechanism is describing a pharmacokinetic drug-drug interaction that affects absorption; what are the drugs that use this mechanism?
drug A, by forming a complex with Drug B, interferes with the systemic absorption of drug B
calcium vs. tetracycline
The following mechanism is describing a pharmacokinetic drug-drug interaction that affects absorption; what are the drugs that use this mechanism?
Drug A, by delaying gastric empying, delays the systemic absorption of Drug B, which is absorbed primarily in the intestine
opioids vs. acetominophen
The following mechanism is describing a pharmacokinteic drug-drug interaction that affects absorption; what are the drugs that use this mechanism?
Drug A, by elevating gastric pH, prevents the absorption of drug B (a weak acid)
antacids vs. acetylsalicylic acid
the following mechanism is describing a pharmacokinetic drug-drug interaction that affects distribution; what are the drugs that use this mechanism?
Drug A (a weak acid), by compensating for plasma protein binding with Drug B, increases the plasma level of Drug B.
acetylsalicylic acid vs. sulfonylureas and many other drugs
The following mechanism is describing a pharmacokinetic drug-drug interaction that affects metabolism; what are the drugs that use this mechanism?
Drug A, by increasing or decreasing hepatic microsomal enzyme activity responsible for the metabolism of Drug B, increases or decreases the plasma level of Drug B, respectively
macrolides, azole antifungals, and ethanol (chronic use) increase the plasma level of many drugs
H2-receptor antagonists decrease the plasma level of many drugs
the following mechanism is describing a pharmacokinetic drug-drug interaction that affects metabolism; what drugs use this mechanism?
Drug A, by decreaseing hepatic nonmicrosomal enzyme activity responsible for the metabolism of drug B, increases the plasma level of Drug B
MAO-inhibitors increase the plasma level of benzodiazepines
The following mechanism is describing a pharmacokinetic drug-drug interaction that affects metabolism; what drugs use this mechanism?
drug A, by inhibiting the enzyme acetaldehyde dehydrogenase, interferes with the further metabolism of intermediate metabolites (oxidation product) of Drug B
disulfiram and metronidazole inhibit the metabolism of intermediate metabolites of ethanol
The following mechanism is describing a pharmacokinetic drug-drug interaction that affects renal excretion; what drugs use this mechanism?
Drug A, which competes with Drug B for the same excretory transport mechanisms in the proximal tubules, increases the plasma level of drug B
acetylsalicylic acid and probenecid increase the plasma level of penicillin and other weak acids
The following mechanism is describing a pharmacokinteic drug-drug interaction that affects renal excretioin; what drugs use this mechanism?
Drug A, by alkalizing the urine, decreases the plasma level of drug B
sodium bicarbonate decreases the plasma level of weak acids
The following mechanism is describing a pharmacokinetic interaction that affects renal secretion; what drugs use this mechanism?
Drug A, by acidifying the urine, decreases the plasma level of Drug B
ammonium chloride decreases the plasma level of weak bases
The following mechanism is describing a pharmacokinetic interaction that affect biliary excretion; what drugs use this mechanism?
drug A, by increasing bile flow and the synthesis of proteins, which function in biliary conjugation mechanisms, decreases the plasma level of drug B
phenobarbital decreases the plasma level of many drugs
the followin mechanism is describing a pharmacokinetic interaction that affect biliary excretion; what drugs use this mechanism?Drug A binds to Drug B, which would undergo extensive enterohepatic recirculation, and decrease the plasma level of drug B
activated charcoal and cholestyramine decreases the plasma level of many drugs
What are the 5 different types of pharmacokinetic drug-drug interactions?
interactions that affect absorption
interactions that affect distribution
interactions that affect metabolism
ineractions that affect renal excretion
interactions that affect biliary excretion
True or false. nutrients may may reduce the efficacy of or increase the duration of certain medications (a drug-food interaction)
true
Why would it benefit us to be aware of certain drug-food interactions?
to educate patients on foods to avoid while taking a drug, and optomized the pharmacotherapy
What food product should be avoided while taking tetracycline?
milk products
drug-food interactions can affect what 3 things?
absorption
metabolism
excretion
a meal with high fatty acid content will __________ the absorption of lipid soluble drugs
increase
The interaction of tetracycline with calcium in milk and other dairy products is an example of a __________ reaction
a reaction that can produce inactive complexes that cannot cross the intestinal mucosa during the absorption phase
chelating reaction
ferrous or ferric salts in liver or organ meats can bind with tetracycline and fluoroquinolonge antibiotics, preventing what?
their absorption
Components in grapefruit juice inhibit what? Causing what?
the CYP450 3A4 isoenzyme in the liver
plasma levels of drugs metabolized by this isoenzyme to greatly increase and relust in overdose or toxicity
What are 3 examples of drugs used in dentistry that are affected by the affects of grapefruit juice?
calcium channel blockers
benzodiapines
warfarin
What drug class is clarithromycin? And what is it's affect if taken with grapefruit?
antibiotic
arrhythmia
What drug class is diazepam, midazolam, and triazolam? And what are their affects when taken with grapefruit?
benzodiazepines
decreased psychomotor function and increased sedation
What drug class is amlodipine, felodipine, and nifedipine? And what are their effects when taken with grapefruit?
clacium channel blocking agents
tachycardia and hypotension
What drug class is warfarin? And what is its effect when taken with grapefruit?
oral anticoagulants
increased bleeding
Can changes in the pH of kidney fluids inhibit excretion of some drugs? What is an example of this?
yes
large dose of Vitamin C (ascorbic acid) can lower pH in glomerulus and cause acidic drugs to be reabsorbed in the kidney, delaying excreation and placing vitamin back in circulation
drug-disease interactions can involve mechanisms related to both ___________ and ____________ principles
pharmacodynamic
pharmacokinetic
this drug-disease interaction; nonselective beta-adrenergic receptor antagonists such as propranolol, can induce an asthma attack in susceptible individuals by blocking beta 2-adrenerbic receptors that aid in bronchodilation; is what type of interaction?
pharmacodynamic
this drug-disease interaction; beta 1-adrenergic receptor antagonists can adversely effect glycogen metabolism and inhibit an endogenous epinephrine-mediated hyperglycemic response to excessive insulin levels, thus placing the diabetic pt at risk; is what type of interaction?
