Exam 1 pharmacodynamics Flashcards
_____ are the result of interactions between drug and a receptor on or within a cell
Most effects (beneficial and harmful)
what initiates alterations in biochemical and/or molecular activity through signal transduction?
drug-receptor complex
name a drug that doesn’t work through receptors
antacids
drug or naturally occurring molecule that acts as the signal
ligand
acts as the signal detector
receptor
Pharmacologically, this is any biologic molecule to which a drug binds and produces a measurable response
receptor
recipient of ligand
receptor
where are receptors usually located?
on cell surface
2 receptor states
inactive
active
subtypes of inactive receptor state
inactive, resting vs recovery phase.
type of receptors where Ligand binds on receptor and opens channel which allows ions through
channel-linked receptors/ Ligand-gated ion channels
type of receptors where ligand binds to receptor outside of cell, activates inside of cell and enzyme generates product.
Enzyme linked
receptor type that Usually involve second messenger systems.
g-protein coupled receptors
receptor type where Receptors are fully inside cell, and the drug molecule needs to go through membrane to get inside of cell.
intracellular receptors
4 receptor families
- Ligand-gated ion channels
- Enzyme linked
- g-protein coupled receptors
- intracellular receptors
receptor family where Response is very rapid, i.e. few milliseconds
Ligand-gated ion channels
receptor family where Ligand binding results in activation of the G proteins which causes dissociation and the subsequent interaction with other cellular effectors
g-protein coupled receptors
type of Receptors that can be down-regulated to prevent over-stimulation and they are recycled constantly
g-protein coupled receptors
receptor type that activates second messengers which cause a cellular response
g-protein coupled receptors
receptor family where Responses last several seconds to minutes
g-protein coupled receptors
can more than one G protein can be associated with each receptor to amplify the signal?
yes
receptor family where Duration of responses is minutes to hours
Enzyme-linked receptors
Most receptors of this type have a tyrosine kinase activity
Enzyme-linked receptors
receptor family that Commonly effects metabolism, growth, and differentiation
Enzyme-linked receptors
receptor family where Ligand must be lipophilic (to through membrane)
Intracellular receptors
primary targets of intracellular receptors
transcription factors
receptor family that Often takes hours-days-months to get outcomes
Intracellular receptors
examples of intracellular receptors
some hormones, corticosteroids
Three Important Features of Receptors and Signal Transduction
- Signal amplification
- Desensitization and down-regulation of receptors
- Up-regulation when receptor is blocked
what is particularly important to receptors that respond to hormones, neurotransmitters, and peptides
Signal amplification
Down-regulation can occur when what two things happen?
- Receptor undergoes endocytosis and is recycled after some period of time
- Receptor is degraded which reduces total number of receptors
dysregulation of receptors disease examples
DMII and myasthenia gravis for example
This mainly occurs when receptor-blocking drugs are given over periods of time and/or at high doses
Up-regulation when receptor is blocked
An ________ binds to a receptor and influences the normal physiologic response
agonist
Two major types of agonists
full and partial
What are full agonists?
activate the receptor to result in maximal (“normal”) physiologic response of the endogenous ligand
What are partial agonists?
partially activate the receptor to result in a response that is less than the maximal endogenous response
third uncommon type of agonist is inverse. what does inverse agonist do?
causes receptor to be inactive state so there is no biologic response
what are antagonists?
Bind to receptors but do not active them so results in blockade preventing binding of endogenous ligand
types of antagonists?
Competitive/reversible antagonists (blocks binding)
Irreversible antagonists (blocks binding)
Functional and chemical antagonism
these block adrenergic receptors
beta blockers
beta blockers are an example of ____.
antagonists
what is Competitive Antagonism
when Both antagonist and agonist can bind to receptor so they compete
What determines binding in Competitive Antagonism?
affinity
how can the effects of irreversible antagonism be overcome?
synthesis of new receptors
what happens in irreversible antagonism?
The drug binds covalently or with very high affinity to the active site of the receptor which prevents anything else from activating the receptor
what is Functional antagonism?
when the ligand acts at a completely separate receptor and initiate effects that are functionally opposite those of the agonist
what is Chemical antagonism?
when a chemical modifies or sequesters the agonist so that it is incapable of binding to and activating its receptor
examples of Functional antagonism
histamine at the H1 histamine receptors v. epinephrine at the β2-adrenergic receptors in bronchial smooth muscle
example of chemical antagonism
protamine sulfate basic (positive charge) protein binds to heparin with is acidic (neg charge)
This is sometimes referred to as “physiologic antagonism”
Functional antagonism
when does PK antagonism occur?
occurs when some change to ADME results in decreased effect
what is Therapeutic index?
ratio of dose that produces toxicity to the dose that produces a clinically desired or effective response in a population of individuals
Loss of therapeutic effects over time
tolerance
how can tolerance can be overcome?
by increased doses
what is Tachyphylaxis
Rapid tolerance that is NOT dose-dependent
Unintended, harmful reactions to medicines when given at therapeutic dose
adverse drug rxn
Among the leading cause of death in many countries
ADR
% of Americans take at least one medication
80%
% of Americans that take five or more medicines
30%
700,000 ED visits and 120,000 hospitalizations annually are caused from ____.
ADRs
Low BP after antihypertensive and
Fungal overgrowth after antibiotics
are examples of what type if ADR
Extension of therapeutic effect
type of ADR that occurs when IgE-mediated response leads to increased release of inflammation mediators
Allergy- Non-therapeutic
Extreme sensitivity
Prolonged drug effects
Resistance to drug
Unusual response
are examples to what kind of ADR?
Idiosyncratic-Non-therapeutic
medical error type of ADR
Iatrogenic
ADR caused by health provider or someone involved in care
Iatrogenic
these are examples of what type of ADR?
20 U of insulin ordered but the “U” was read as 0 and 200 units administered
10 mg methotrexate ordered daily but should be weekly
Patient’s caregiver applies 6 pain patches at one time because they were not counseled to remove each one when applying a new one
Iatrogenic
Prescriber Responsibilities regarding ADRs (5)
Ensure the “rights” Use minimally effective dose Evaluate patient and family history Evaluate possible interactions Patient education
Study of how genetic makeup affects an individual’s response to drugs
Pharmacogenomics
Difference in gene expression or single-nucleotide polymorphisms correlates with ______.
efficacy or toxicity
Several known genes which are responsible for variances in drug metabolism and response. most common variations are associated with what gene?
CYP450 genes
p-glycoprotein polymorphisms is an example of _______.
genes which are responsible for variances in drug metabolism and response
different ______ lead to variations in ability, or lack thereof, to metabolize some medications
phenotypes
