Medical Pharmacology – Chapter 8 – Variability in reactions to
drugs
Sensitivity differences
Effect of drugs is not always equal evet at the same dose. Large variation between
individuals but also within 1 person.
Single dose administration (as well as multiple dose administration) need to take into
account the following;
Body weight; effect is proportional to concentration.
Age; in premature children a not yet fully developed blood-brain barrier and
biotransformation and renal excretion. In elderly there is slowed metabolism
and deficient elimination
Genetic difference; inherited abnormalities alter sensitively to drugs.
Psychological factors; mood swings can affect sensitivity to drugs. Patient
expectation play also a role (placebo-effect)
Using repeated administration also other factors may come into play:
Allergies; drugs bind to body proteins and form a complex. Immune
system can interpret this as an allergen and produce antibodies
against it. In repeated contact with the drug an allergic reaction can
occur. Drugs that form allergens easily (penicillin, sulfonamides,
aspirin)
Habituation (gewenning)- or tolerance; in repeated administration
the sensitivity of the organism might decrease. Because drugs
often intervene with homeostatic regulatory processes, the
regulatory mechanism try to correct the deviation from the norm that is being
caused by the drug
Tachyphylaxis: repeated administration of the same dose of a drug results in
reduced effect of the drug over time
Desensitization: decreased ability of a receptor to respond to stimulation by a
drug or ligand
Homologous; decreased response at a single type of receptor
Heterologous; decreased response at 2 or more types of receptors
Inactivation; loss of ability of a receptor to respond to stimulation by a drug or
ligand
Refractory; after a receptor is stimulated a period of time is required before the
next drug-receptor interaction can produce an effect
Down-regulation; repeated or persistent drug-receptor interaction results in
removal of the receptor from sites where subsequent drug-receptor interaction
could take place
Elective habituation; habituation will occur for one drug but not for the other
drug
Cross tolerance; drugs with similar mechanism of action will all show reduced
sensitivity as tolerance for one of them has developed
Phenomenon of habitation lead to administration of increasingly larger doses
drugs
Sensitivity differences
Effect of drugs is not always equal evet at the same dose. Large variation between
individuals but also within 1 person.
Single dose administration (as well as multiple dose administration) need to take into
account the following;
Body weight; effect is proportional to concentration.
Age; in premature children a not yet fully developed blood-brain barrier and
biotransformation and renal excretion. In elderly there is slowed metabolism
and deficient elimination
Genetic difference; inherited abnormalities alter sensitively to drugs.
Psychological factors; mood swings can affect sensitivity to drugs. Patient
expectation play also a role (placebo-effect)
Using repeated administration also other factors may come into play:
Allergies; drugs bind to body proteins and form a complex. Immune
system can interpret this as an allergen and produce antibodies
against it. In repeated contact with the drug an allergic reaction can
occur. Drugs that form allergens easily (penicillin, sulfonamides,
aspirin)
Habituation (gewenning)- or tolerance; in repeated administration
the sensitivity of the organism might decrease. Because drugs
often intervene with homeostatic regulatory processes, the
regulatory mechanism try to correct the deviation from the norm that is being
caused by the drug
Tachyphylaxis: repeated administration of the same dose of a drug results in
reduced effect of the drug over time
Desensitization: decreased ability of a receptor to respond to stimulation by a
drug or ligand
Homologous; decreased response at a single type of receptor
Heterologous; decreased response at 2 or more types of receptors
Inactivation; loss of ability of a receptor to respond to stimulation by a drug or
ligand
Refractory; after a receptor is stimulated a period of time is required before the
next drug-receptor interaction can produce an effect
Down-regulation; repeated or persistent drug-receptor interaction results in
removal of the receptor from sites where subsequent drug-receptor interaction
could take place
Elective habituation; habituation will occur for one drug but not for the other
drug
Cross tolerance; drugs with similar mechanism of action will all show reduced
sensitivity as tolerance for one of them has developed
Phenomenon of habitation lead to administration of increasingly larger doses
