Pharmacodynamics III Flashcards
What kind of curves provide information about potency/EC50 of drugs?
Graded curves
What are Quantal dose response curves used for?
To indicate variability/frequency among individuals, and to determine the therapeutic index and margin of safety
What is tolerance?
When a response to a drug diminishes with repeated or chronic administration
What is pharmacokinetic tolerance? Do drug levels change? What are some examples?
Response decreases because the enzymes that metabolize the drug are induced; drug levels change
Ex: barbiturates, ethanol, warfarin
What is pharmacodynamic tolerance? Do drug levels change? What is an example?
Response decreases due to changes in receptor number or function (desensitization; receptor down regulation); drug levels do not change
Ex) Chronic exposure to B adrenergic agonists (asthma) results in down regulation and decreased response
What is physiologic tolerance? What is an example?
Occurs when two agents with opposing physiological effects are administered together
Ex: histamine a vasodilator and epinephrine a vasoconstrictor
What is competitive tolerance?
Occurs when a receptor antagonist is administered with an agonist
What is tachyphylaxis?
Very rapid development of tolerance following repeated dose over short period of time
What is the mechanism through which ion channel desensitization occurs? What is an example?
Continuous exposure to an agonist results in the conversion of an ion channel to an altered state that remains closed
Ex: succinylcholine on the nicotinic acetylcholine receptor
What is the mechanism through which G protein desensitization occurs? What is an example?
Receptor coupling effector is phosphorylated to an inactive form (GRK, beta-arrestin)
Ex: beta-receptor
What is down regulation?
Process of ligand-induced endocytosis and degradation of receptors. In general, agonist cause down regulation of receptors if chronically administered.
What factors influence variability in response?
- Differences in absorption of drug (age, sex, metabolism)
- Differences in concentration of endogenous ligands
- Differences in number or function of receptors (down and up regulation)
- Differences in post receptor effects
What is summation?
Two drugs elicit a similar response through different mechanisms and the effect of combining the drugs equals the sum of the two individual effects
What is the difference between summation and additive?
Summation- two drugs act through different mechanisms
Additive- two drugs act through the same mechanism
What is synergism? Give an example
Drugs that produce similar effects through different mechanisms are administered simultaneously enhancing the response to either agent administered alone.
Ex: depression of CNS produced by diazepam plus ethanol; act on GABA receptor but at different sites
Is the effect of synergism greater than or less than the sum of the two individual agents alone?
Greater than the sum
What five things can cause enhanced drug effects/super sensitivity?
- Administration of antagonist
- Chemically induced
- Denervation super-sensitivity
- Deficiency of metabolic enzymes
- Competition for plasma binding sites
How can administration of antagonist produce a supersensitive response?
Up regulation due to prolonged presence of antagonist
How can a supersensitive response be chemically induced?
Catecholamine sensitivity may be enhanced with general anesthetics
How can denervation super-sensitivity produce a supersensitive response?
Develops when the synaptic nerve has been destroyed, resulting in a loss of endogenous ligand and an increase in receptors
How can a deficiency of metabolic enzymes produce a supersensitive response? What is an example?
Decrease in number or activity of metabolic enzymes that would normally degrade the drug
Succinylcholine in patients with low cholinesterase
How can competition for plasma binding sites produce an enhanced response? What is an example?
Drugs may displace one another from plasma albumin binding sites
If a drug is displaced, the response to that drug is intensified
If the drug is eliminated, the duration of action is shortened
Ex: warfarin must be decreased in patient taking phenytoin, an anticonvulsant
Adverse effects from multiple receptor activation is due to what?
A drug acting on a different type of receptor than that responsible for the desired effect
Adverse effects mediated by the same mechanism as the therapeutic effect are termed what?
Overextension of the therapeutic effect
Overextension-type toxicity from sedative hypnotics can lead to what?
Excessive CNS depression
Overextension-type toxicity from antiarrhythmic agents can lead to what?
Arrhythmias
Overextension-type toxicity from insulin can lead to what?
Hypoglycemia
Overextension-type toxicity from aspirin, warfarin, or heparin can lead to what?
Hemorrhage
Organ directed toxicity from aminoglycoside antibiotics can lead to what?
Renal and ototoxicity
Organ directed toxicity from acetaminophen can lead to what?
Hepatotoxicity
Organ directed toxicity from tetracycline can lead to what?
Teeth discoloration, retardation of bone growth
Organ directed toxicity from thalidomine, methotrexate, phenytoin, and warfarin can lead to what?
Teratogenic effects
Organ directed toxicity from acetaminophen and isoniazid hepatotoxicity can lead to what?
Metabolite toxicity
What is a drug idiosyncrasy?
An abnormal response to a drug that is not immunologically mediated
Usually genetically determined (mutations)
What is an example of a drug idiosyncrasy?
Apnea a caused by succinylcholine in patients with abnormal serum cholinesterase
Explain the mechanism of hypersensitivity reactions.
Abnormal response to an antigen resulting from previous exposure (sensitization phase)
Activates an immunologic mechanism (effector phase)
Being small molecules, most drugs by themselves are not immunogenic. They must bind to a macromolecule or alter the structure of a macromolecule to evoke the production of antibodies.
Which type of drug allergies are antibody mediated?
Types I-III
Which types of drug allergies are cell mediated?
Type IV
In a type I drug allergy will the response be immediate or slow acting?
Response is immediate
In a type I drug allergy what type of antibody will the drug bind to?
IgE antibody
What are the target tissues and symptoms of a type I drug allergy?
GI tract
Skin - uticaria (hives)
Lung - asthma
Vasculature - anaphylactic shock
What is an example of a drug that causes a type I-III drug allergy?
Penicillin
In a type II drug allergy what type of antibody will the drug bind to?
IgM or IgG antibody
A type II drug allergy is what type of reaction?
Cytolytic or cytotoxic reaction
What are the major target for type II drug allergies?
Red blood cells
A type III drug allergy is what type of reaction?
Arthrus reaction
What are the major targets for a type III drug allergy?
Blood vessels, skin, joints*, kidney
What type of drug allergy causes an inflammatory response called serum sickness?
Type III
What are the symptoms of a type III drug allergy?
ARTHRITIS, uticaria, lymphadenopathy, and fever
A type IV drug allergy is what type of reaction?
Delayed hypersensitivity reaction
A type IV drug allergy is mediated by what type of cells?
T cells
What is the main symptom of a type IV drug allergy
Contact dermatitis
What is placebo toxicity?
Subjective effects such as stomach upset, insomnia, and sedation
How would you treat a type 1 drug allergy?
IV or IM injection of epinephrine; corticosteroids
What type of drug reaction is SJS and erythema multiforme?
Type IV- delayed hypersensitivity reactions
What type of drug reaction is penicillin induced hemolytic anemia?
Type II- Cytolytic/Cytotoxic reactions
What kind of drugs are commonly known to be associated with drug allergies?
Penicillin, heparin
Smoking and charbroiled foods can increase the metabolism of many drugs including warfarin. What is this type of tolerance called?
- Pharmacodynamic
- Cross
- Physiological
- Pharmacokinetic
- Competitive
Pharmacokinetic
