Pharmacotherapeutics Flashcards
Patient related factors affecting drug response requiring a higher dose
hyporeactivity
tolerance
tachyphylaxis (desensitization)
Patient related factors affecting drug response requiring a lower dose
hyperreactivity
supersensitivity
hypersensitivity
Types of tolerances to drugs
pharmacodynamic (cell tolerance)
immune (antibodies bind to drug)
pharmacokinetic (induction of enzymes of metabolism)
cellular distribution (changes in cell)
learned tolerance (individual)
Drug-drug intolerances are mostly
unintentional
Causes of drug-drug interaction
other drugs prescribed by clinicians
self-prescribed drugs
environmental and dietary chemicals
Types of drug-drug interaction
pharmaceutical
pharmacokinetic
pharmacodynamic
pharmacotherapeutic
Types of drug-drug interactions effects
antagonism
potentiation
summation
synergism
Combined use of antibiotics that inhibit cell wall synthesis and protein synthesis via receptor competition
Antagonism
Effects of antagonism
increased metabolic inactivation or excretion
Physiological examples of antagonism
CNS stimulants and depressants
Chelation of divalent cations in antiacids by tetracycline
example of chemical antagonism
Two drugs do not share similar effects but one drug increases the effect of the other
potentiation
Physical or chemical incompatibilities and administration
examples of pharmaceutical drug-drug interactions
Absorption
Distribution
Transport
Biotransformation
Excretion
examples of pharmacokinetic drug-drug interactions
CNS depressants
examples of pharmacodynamic drug-drug interactions
Caused by increasing active concentration of drug
potentiation
Succinylcholine neuromuscular blockage increased by administration of acetylcholinesterase inhibitor
neostigmine
example of potentiation
Local anesthetic action enhanced and prolonged
when administered with vasoconstrictor
effects of potentiation
Combination of two or more drugs
produces effect greater than summation of
drug effects
synergism
Minimize development of drug resistance
* Treatment of tuberculosis
* Treatment of cancer
synergism effects
Hepatotoxicity from alcohol and carbon
tetrachloride
synergism can cause
a more accurate dose adjustment vs age
BSA
Environmental effects
diet
temperature
indigenous microflora
How can diet effect absorption and metabolism
Insulin and meals
Grapefruit juice: inhibition of CYP 3A enzymes
Monamine oxidase inhibitors and tyramine containing foods (hypertension)
How can temperature effect drug interactions
Sunlight worsens some antibiotic hypersensitivities
Atropine and drug induced hyperthermia
How can indigenous microflora effect drug interactions
Drug metabolism by bacterial enzymes can impact absorption of drugs
Antibiotic therapy effects
At what times during pregnancy are the most susceptible to having a toxic effect on the fetus
first trimester and term
How can drug allergy be distinguished from other forms of drug toxicity
The severity of response is dose independent
Prior exposure to the drug or a closely related compound is necessary to elicit this reaction
drug allergy
What causes the effects of a drug allergy
the unfavorable effect is a function not of the drug but of the immune mechanism
Typical reaction to a drug allergy
Reaction is unpredictable; occurs in a small
portion of the population, sometimes in patients who
had been previously treated with the drug on multiple occasions without mishap
Drug allergy types
Type 1: anaphylactic responses
Type 2: cytotoxic reactions
Type 3: immune complex reactions
Type 4: cell mediated immunity
Symptoms appear in minutes of hours of
taking the drug
IgE
GI cramps, erythema, urticaria, edema,
bronchoconstriction, vasodilation, blood
vessel permeability increases.
Epinephrine to reverse
severe response
Anaphylactic response
Caused by IgG and IgM
Plasma membrane
constituent can be hapten
carrier (i.e platelets) or
complete antigen
adsorbed on membrane, Ig
binding followed by
complement fixation and
cell lysis occurs
Drug induced hemolytic
anemia, leukopenia, and
thrombocytopenia.
Delayed and manifest
from hours to days after
drug exposure
cytotoxic reactions
Antigen-antibody
complexes form in
intravascular or interstitial
spaces go onto
small blood vessel walls
Activation and migration of
neutrophils
Degranulation of immune
cells causing
lysosomal enzymes
Local tissue damage
Looks like disease states
(neuropathy,
glomerulonephritis etc)
Can be cytotoxic
immune complex reactions
T-lymphocytes
exposed to the drug hapten
or its conjugate, release
lymphokines, attracting
additional cells (lymphocytes,
macrophages, cytotoxcic T
cells).
Lysosomes and toxic
lymphokines produce tissue
damage
Dentists experience this type
of delayed reaction via
“contact dermatitis” due to
exposure to ester local
anesthetics like procaine
cell mediated immunity
Mediator of type 1 reactions
IgE
Effector of type 1 reactions
Mast-cell activation
Example of hypersensitivity rxn for type 1
anaphylaxis, allergic rhinitis, asthma
Mediator of type 2 reactions
IgG and IgM
Effector of type 2 reactions
FcR+ cells (phagocytes and NK cells)
Example of hypersensitivity rxn for type 2
hemolytic anemia and thrombocytopenia
Mediator of type 3 reactions
IgG
Effector of type 3 reactions
FcR+ cells complement
Example of hypersensitivity rxn for type 3
serum sickness, arthus reaction
Mediator of type 4 reactions
T cell
Effector of type 4 reactions
T cells
Example of hypersensitivity rxn for type 4
contact dermatitis, delayed hypersensitivity
Indirect and often unpredictable consequences of a drugs primary pharmacologic action
secondary reactions
Example of a secondary reaction
antibiotics can cause supra infection due to suppression of normal microflora
Any agent capable of altering DNA
a potential carcinogen
Example of a carcinogen (social drug mix)
tobacco and EtOH
How long does latency period of a carcinogen last
can span decades
Amount of exposure required for a carcinogen
Dose dependent but dose or
duration of exposure below which
tumors will not occur is difficult to
establish
