1 - Cells, Diffusion, Basics Flashcards
Defines the dose of drug that is lethal to 1% of population compared with dose therapeutically effective in 99% (LD1/ED99).
Certain Safety Index
The difference of content between one side of the cell membrane and the other; the larger the difference, the faster the diffusion.
Concentration Gradient
These describe the extent of biological or behavioural effect produced by a given drug dose on a population. Plotted on a semi-log scale, it has an S-shape. At low doses, drug-induced effect is slight because very few receptors are occupied. The ____ ____ is the smallest dose that produces a measurable effect. As the dose of drug increases more receptors activate and a greater biological response occurs.
___ __ is the dose that produces half of maximal effect (the more potent drug is the one for which it is lower) and ___ ___ occurs at a dose where we assume receptors are maximally occupied.
These graphs show that with increasing doses, the effect increases steadily until the maximum effect is reached.
Dose–Response Curve | Threshold Dose | ED50 | ED100
The reduction in a cellular response to a molecule due to a decrease in number of receptors on cell surface. The process of reduces / suppresses a response to a stimulus.
Down-Regulation
Refers to specific molecular changes produced by a drug when it binds to a particular target site or receptor.
Drug Action
All drugs have multiple effects and can be sorted/identified in any of several ways depending on the trait of interest.
Drug Category
Molecular changes from drug action lead to more widespread alterations in physiological or psychological functions.
Drug Effects
Effects of drug are determined by 2 primary factors and are qualified by other issues (2)
- How muach drug reaches its target sites, where it has biological action, and
- how quickly the drug reaches those sites.
qualified by
- Nonspecific characteristics of individuals/environments;
- Frequency/history of prior use — time gap; same dose may overdose/kill
Inflammation of heart lining
Endocarditis
A network of tubules within the liver cell cytoplasm. Liver enzymes primarily responsible for metabolizing psychoactive drugs are located here.
Endoplasmic Reticulum
Drugs pass through the liver and become subject to metabolism/biotransformation
First Pass Effect
Family of proteins that act as molecular switches inside cells. Involved in transmitting signals from variety of stimuli outside cell to interior.
GNBP
Guanine Nucleotide-Binding Proteins. G proteins.
These bind to a receptor and initiate a biological action that is the opposite of what would be produced by an agonist.
Inverse Agonists
Any molecule that binds to a receptor with some selectivity.
Ligand
Concerned with drug-induced changes in the functioning of cells in the nervous system.
Neuropharmacology
Its goal is to identify chemical substances acting on the nervous system which alter behaviour that is disturbed due to injury, disease, or environmental factors. Also interested in using chemical agents as probes to gain understanding of neurobiology of behaviour.
Neuropsychopharmacology
Drugs that reduce effects of agonists in ways other than competing for receptors. May impair agonist action by binding to portion of receptor other than agonist-binding site, by disturbing cell membrane supporting the receptor, or by interfering with intracellular processes that were initiated by the agonist–receptor association.
ex: the analgesic dose–response curve of morphine is distorted and the same maximum effect is not likely to be reached.
Non-Competitive Antagonists
Demonstrate efficacy that is less than that of a full agonist but more than that of an antagonist at a given receptor.
Partial Agonist
A substance tends to move from an area of high concentration to an area of low concentration until the concentration is equal across the space.
Passive diffusion
How our cells breath; CO2 leaks out and oxygen goes in same way.
The study of physiological and biochemical interactions of drug molecules with target tissue responsible for the ultimate effects of a drug. Drugs have biological effects because they interact with receptors on target tissues.
Pharmacodynamics
Study of genetic basis for variability in drug response in individuals. Goals are identify genetic factors that confer susceptibility to specific side effects and to predict good/poor therapeutic response. It should be possible for clinician to select most appropriate drug for individual based on this study.
Pharmacogenetics
These collectively contribute to bioavailability (5)
Pharmacokinetic Factors/Components of DrugAction
- Routes of administration
- Absorption and distribution
- Binding
- Inactivation
- Excretion
Scientific Study of the actons of drugs and their effects on a living organism
Pharmacology
2 drugs act in distinct ways but interact in a way that reduce each other’s effectiveness.
One may act on receptors in heart to increase heart rate, and 2nd may act on distinct receptors in brain-stem to slow heart rate.
Physiological Antagonism
Absolute amount of drug necessary to produce a specific affect. Differences among 3 drugs can be seen by comparing each ED50.
Potency
Combination of 2 drugs produces effects greater than sum of individual effects.
Often involves issues of pharmacokinetics like altered metabolic rate/competition for depot binding, which may elevate free drug blood levels in unexpected ways.
Potentiation
Usual analogy of a lock and key suggests only a limited group of these neurochemicals or drugs can bind to a particular receptor protein to initiate a cellular response.
Receptor Agonists
A key may fit in a lock but not turn; a ligand may be recognized by a receptor but not initiate a biological action. These ligands are considered to have low efficacy and block the receptor; they bind to receptors but fail to initiate an intracellular effect, thereby reducing the effects of the agonists.
Receptor Antagonists / Competative Antagonists
Receptor proteins for a drug or neurotransmitter with different characteristics in different target tissues.
Receptor Subtypes
Large protein molecules located on cell surface or within cells that are initial sites of action of ligands.
Receptors
Where the drug does its work. May be different from site of drug effect.
Site of drug action
Morphine taken internally leads to pinpoint pupils. The ____ ____ ____ ____ is distant from the site of initial action.
Site of Drug Effect
Those based on the physical and biochemical interactions of a drug with a target site in living tissue.
Specific Drug Effects
Desired blood concentration of a drug achieved when the absorption/distribution phase is equal to the metabolism/excretion phase. Approached after a period of time queal to 5 half-lives.
Steady State
Involves taking multiple blood samples to directly measure plasma levels of drug after drug has been administered. Done to identify optimim dosage to maximize positive potential and minimize side effects. Especially important for dugs with serious side effects and when there are changes in an individual’s pharmacokinetics due to aging, hormonal shifts, stress, new medications, or other events.
Therapeutic Drug Monitoring
Desired outcome/effects of the drug’s use.
___
The drug–receptor interaction produces desired physical or behavioural changes. SSRI - more serotonin/calming
Therapeutic Effects
Calculates Drug Safety by looking at cumulative % of population experiencing particular drug-induced response.
Therapeutic Index
2 principal types of receptors
Extracellular: Most drugs and neurotransmitters remain outside cell and bind to receptors on exterior cell surface
Intracellular: Many hormones capable of entering cell before acting on an intracellular receptor that changes expression of specific genes within nucleus.
Increase in a cellular response to a molecular stimulus due to increase in number of receptors on cell surface. The process increases response to a stimulus.
Up-Regulation
Pharmacologically inert compound administered to an individual
Placebo
All effects other than the desired physical or behavioural changes
Side Effects
Explainations for Placebo Effect
- Pavlovian Conditioning
- Social Learning —Conscious expectations of outcomes
- Genetic Variants (runners who like running may ave greater natural opioid response → higher placebo response
Amount of drug in the blood that is free to bind at target sites.
Bioavailability
Expecting treatment failure when an inert substance is given along with verbal suggestions of negative outcome produces negative reporting (increased stress hormones). Warnings about side-effects can lead to greaeteer side effect occurance.
Nocebo Effect
Drug unrelated to the drug being tested but not completely innert so as to produce some side-effects. When the study drug is certain to have side-effects this helps conceal the true placebo group.
“Active” Placebo
