Chapter 1: Principles of Pharmacology Flashcards
Movement of a drug from the site of administration to the circulatory system.
Absorption
Rapid tolerance formed during a single administration of a drug, as is the case with alcohol.
Acute tolerance
Drug interactions characterized by the collective sum of the two individual drug effects.
Additive effects
Attraction between a molecule and a receptor.
Affinity
Area in the medulla of the brain stem that is not isolated from chemicals in the blood. It is responsible for inducing a vomiting response when a toxic substance is present in the blood.
Area Postrema
Star-shaped cells of the nerve tissue that have numerous extensions and that modulate the chemical environment around neurons, metabolically assist neurons, and provide phagocytosis for cellular debris.
Astrocytes
The reduced effectiveness of a drug administered chronically that involves learning: either instumental or classical conditioning.
Behavioral tolerance
Concentration of drug present in the blood that is free to bind to specific target sites.
Bioavailability
Inactivation of a drug through a chemical change, usually by metabolic processes in the liver.
Biotransformation
Fluid that surrounds the brain and spinal cord, providing cushioning that protects against trauma.
Cerebrospinal fluid (CSF)
Repeated pairing of a neutral stimulus with an unconditioned stimulus. Eventually the neutral stimulus becomes a conditioned stimulus and elicits a (conditioned) response that is similar to the original unconditioned response.
Classical conditioning
Drug that binds to a receptor but has little or no efficacy. When it competes with an agonist for receptor sites, it reduces the effect of the agonist.
Competitive antagonist
Difference in the amount or concentration of a substance on each side of a biological barrier, such as the cell membrane.
Concentration gradient
Tolerance to a specific drug can reduce the effectiveness of a another drug in the same class.
Cross-tolerance
Class of liver enzymes, in the microsomal enzyme group, responsible for both phase 1 and phase 2 biotransformation of psychoactive drugs.
Cytochrome P450 (CYP450)
Type of drug interaction involving binding to an inactive site, such as to proteins in the plasma, to bone, or to fat.
Depot binding
Graph used to display the amount of biological change in relation to a given drug dose.
Dose–response curve
Type of experiment in which neither the patient nor the observer knows the treatment received by the patient.
double-blind experiment
Decrease in the number of receptors, which may be a consequence of chronic agonist treatment.
Down-regulation
Molecular changes associated with a drug binding to a particular target site or receptor.
Drug action
Interaction between two drugs that share a metabolic system and compete for the same metabolic enzymes. Bioavailability of one or both increases.
Drug competition
INACTIVE sites where drugs accumulate. There is NO biological effect from drugs binding at these sites, nor can they be metabolized.
Includes plasma proteins (e.g., albumin), muscle, and fat.
Drug depots
bound drug has no drug effect; drug remains in system
Alterations in physiological or psychological functions associated with a specific drug.
Drug effects
The extent to which a ligand-receptor binding initiates a biological action (e.g., the ability of an agonist to activate its receptor).
Efficacy
Drug administration by oral or rectal routes.
Enteral
Increase in liver drug-metabolizing enzymes associated with repeated drug use.
Enzyme induction
Reduction in liver enzyme activity associated with a specific drug.
Enzyme inhibition
Method that involves administration of a drug into the cerebrospinal fluid surrounding the spinal cord.
Epidural
Large pores in endothelial cells allowing rapid exchange between blood vessels and tissue.
Fenestrations
Term used to describe exponential elimination of drugs from the bloodstream.
First-order kinetics
Phenomenon in which the liver metabolizes some of a drug before it can circulate through the body, particularly when the drug has been taken orally.
First-pass metabolism
Application of DNA that encodes a specific protein to increase or block expression of the gene product to correct a clinical condition.
Gene therapy
Genetic variations in a population resulting in multiple forms of a particular protein.
Genetic polymorphisms
Time required to remove half of the drug from the blood. It is referred to as t1/2.
Half-life
Drug delivery via an implanted pump (e.g., subcutaneous) that delivers regular, constant doses to the body or into the cerebral ventricles.
Infusion pump
Method that involves administration of a drug through the lungs.
Inhalation
Small gaps between adjacent cells.
Intercellular clefts
Method that involves administration of a drug into the cerebrospinal fluid of the ventricles.
Intracerebroventricular
Method that involves administration of a drug into the brain tissue.
Intracranial
Injection technique that is the most common route of administration for small laboratory animals. The drug is injected through the abdominal wall into the peritoneal cavity—the space that surrounds the abdominal organs.
Intraperitoneal (IP)
Method that involves administration of a drug into a muscle.
Intramuscular (IM)
Topical administration of a drug to the nasal mucosa.
Intranasal administration
Method that involves administration of a drug directly into the bloodstream by means of a vein.
Intravenous (IV)
Substance that activates a receptor but produces the opposite effect of a typical agonist at that receptor.
Inverse agonist
Process involving the dissociation of an electrically neutral molecule into charged particles (ions).
Ionization
Molecule that selectively binds to a receptor.
Ligand
Type of tolerance to a drug that is characterized by a reduced amount of drug available at the target tissue, often as a result of more-rapid drug metabolism. It is sometimes also called drug disposition tolerance.
Metabolic tolerance
Area in the hypothalamus that is not isolated from chemicals in the blood and where hypothalamic-releasing hormones are secreted for transport to the anterior pituitary gland.
Median eminence
Physical or behavioral changes not associated with the chemical activity of the drug–receptor interaction but with certain unique characteristics of the individual such as present mood or expectations of drug effects.
Nonspecific drug effects
Drug that reduces the effect of an agonist, but does not compete at the receptor site. The drug may bind to an inactive portion of the receptor, disturb the cell membrane around the receptor, or interrupt the intercellular processes initiated by the agonist–receptor association.
Noncompetitive antagonist
Area of pharmacology focusing on chemical substances that interact with the nervous system to alter behavior, emotions, and cognition.
Neuropsychopharmacology
Area of pharmacology specializing in drug-induced changes to the function of cells in the nervous system.
Neuropharmacology
Enzymes in liver cells responsible for metabolizing exogenous substances such as drugs.
Microsomal enzymes
Type of learning in which animals learn to repond to obtain rewards and avoid punishment.
Operant conditioning
Method that involves administering a drug through the mouth.
Oral administration (PO)
Methods of drug administration that do not use the gastrointestinal system, such as intravenous, inhalation, intramuscular, transdermal, etc.
Parenteral
Drugs that bind to a receptor but have low efficacy, producing weaker biological effects than a full agonist. Hence they act as agonists at some receptors and antagonists at others, depending on the regional concentration of full agonist.
Partial agonists
An experimentally-derived measure of a drug’s lipid solubility used to predict its relative rate of movement across cell membranes.
Partition coefficient
Movement of lipid-soluble materials across a biological barrier without assistance based on its concentration gradient, from higher to lower concentration.
Passive diffusion
Reflexive and unconscious response to a stimulus.
Pavlovian
Type of tolerance formed by changes in nerve cell functions in response to the continued presence of a drug.
Pharmacodynamic tolerance
Study of physiological and biochemical interactions of a drug with the target tissue responsible for the drug’s effects.
pharmacodynamics
The study of the genetic basis for variability in drug response among individuals (sometimes called pharmacogenomics).
Pharmacogenetics
Factors that contribute to bioavailability: the administration, absorption, distribution, binding, inactivation, and excretion of a drug.
Pharmacokinetic
Study of the actions of drugs and their effects on living organisms.
Pharmacology
Lipid molecules that are major constituents of the cell membrane. They are composed of a polar head and two lipid tails.
Phospholipids
Drug interaction characterized by two drugs reducing each other’s effectiveness in the body.
Physiological antagonism
Type of vesicles that envelop and transport large molecules across the capillary wall.
Pinocytotic vesicles
Substance that is pharmacologically inert, yet in many instances produces both therapeutic and side effects.
Placebo
Measure of the amount of drug necessary to produce a specific response.
Potency
Drug interaction characterized by an increase in effectiveness greater than the collective sum of the individual drugs.
Potentiation
Those drugs that have an effect on thinking, mood, or behavior.
Psychoactive drugs
Area of pharmacology specializing in drug-induced changes in mood, thinking, and behavior.
Psychopharmacology
A neurochemical or drug that can bind to a particular receptor protein and alter the shape of the receptor to initiate a cellular response.
Receptor agonist
A molecule that interacts with a receptor protein and produces no cellular effect after binding, and also prevents an “active” ligand from binding.
Receptor antagonist
Group of receptors that respond to the same neurotransmitter but that differ from each other to varying degrees with respect to their structure, signaling mechanisms, and pharmacology.
Receptor subtypes
Proteins located on the surface of or within cells that bind to specific ligands to initiate biological changes within the cell.
Receptors
Drug delivery method, such as a suppository, used to deliver drugs via the lower intestine.
Rectal administration
Enhanced response to a particular drug after repeated drug exposure.
(Reverse tolerance)
Sensitization
Undesired physical or behavioral change associated with a particular drug.
Side effect
Physical or behavioral changes associated with biochemical interactions of a drug with the target site.
Specific drug effects
Condition characterized by better performance of a particular task that was learned in a drugged state in the same drugged state, rather than in a nondrugged state. Tasks learned in a nondrugged state are likewise performed better in a nondrugged state.
State-dependent learning
The desired blood concentration of drug achieved when the absorption/distribution phase is equal to the metabolism/excretion phase.
Steady state plasma level
Method that involves injection of a drug just below the skin.
Subcutaneous (SC)
Any agent including a virus, drug, or radiation that induces abnormal fetal development, causing birth defects.
Teratogen
Taking multiple blood samples to directly measure plasma levels of a drug after administration, to identify the optimum dosage for maximum therapeutic potential and minimal side effects.
Therapeutic drug monitoring
Desired physical or behavioral changes associated with a particular drug.
Therapeutic effects
The relationship between the drug dose that results in a toxic response compared to the dose required for the desired biological response. It is represented by the equation TI = TD50/ED50 where TD50 is the dose that is toxic for 50% of the population and ED50 is the effective dose for 50%.
Therapeutic index
Connection between cells characterized by a fusing of adjoining cell membranes.
Tight junctions
Decreased response to a drug as a direct result of repeated drug exposure.
Tolerance
Method that involves administration of a drug through a mucous membrane such as the oral cavity, nasal mucosa, or vagina.
Topical
Method that involves administration of a drug through the skin (e.g., with a patch).
Transdermal
Increase in the number of receptors, which may be a consequence of denervation or of chronic antagonist treatment.
Up-regulation
Use of a virus as a delivery system (called a vector) to carry a gene into the nuclei of target cells to alter protein synthesis.
Viral vector
Term used to describe a constant rate of drug removal from the body, regardless of drug concentration in the blood.
Zero-order kinetics
5 Pharmacokinetic factors
- Routes of administration
- Absorption and distribution
- Binding
- Inactivation
- Excretion
6 Routes of Administration
- Oral/Rectal
- Intravenous
- Intraperitoneal
- Subcutaneous
- Intramuscular
- Inhalation
Oral administration (PO) 3 Benefits?
2 Considerations?
Safe, self-administered, economical.
Degradation by stomach acid and enzymes.
Many factors can influence plasma concentrations
4 Factors that influence absorption
- food in stomach
- type of food
- physical activity
- metabolism
With rectal administration…
The drug may avoid first-pass metabolism depending on placement.
Intravenous (IV) injection pros
Most rapid and accurate method.
Intravenous (IV) injection cons
Rapid onset offers little time to correct an overdose or allergic reaction
Drug cannot be removed from the body
Inhalation absorption is _____ and the drug effect is _____.
Absorption is rapid
Psychoactive drug effect is rapid
Intranasal administration local effects
Relieving nasal congestion
Intranasal administration systemic effects
Allergy relief
Intranasal administration - 3 facts
By-passes the blood–brain barrier
Produces high brain concentrations.
Full absorption can occur within 15min
The most important factor in determining plasma drug levels:
The rate of passage through cell membranes.
Passive diffusion
Mean by which lipid soluble drugs can pass through the cell membrane
Movement is in a direction of higher to lower concentration.
The larger the concentration gradient, the faster the diffusion.
4 factors affecting absorption & distribution:
- Rate stomach empties.
- Size and sex of individual
A larger person has more body fluid to dilute a drug.
Females tend to have less body fluid than males. - Frequency and history of prior drug use
- Nonspecific factors characteristic of individuals and
their environment
Highest concentration of a drug will be distributed to area where blood flow is _____
greatest
Lipid-soluble drugs can _____ brain tissue
easily enter
Blood–brain barrier _____ of ionized molecules.
limits movement
Fills the subarachnoid space around the brain and spinal cord, ventricles, and canals.
Cerebrospinal fluid (CSF)
Separation between brain capillaries and the brain/CSF
Blood–brain barrier
Vomit center
Located in the medulla
Area postrema
Depot binding prevents drug from reaching the _____ or _____
target site or liver
Drugs are eliminated via _____ and metabolites are excreted.
biotransformation (metabolism)
Longer half-life could lead to accumulation, which increases potential for _____ and _____
side effects and toxicity
When does zero order kinetics occur?
When drug levels are high and routes of metabolism or elimination are saturated.
Example: alcohol
Liver enzymes that metabolize drugs.
Microsomal enzymes
Microsomal enzymes lack strict _____ and can metabolize a wide variety of foreign chemicals (xenobiotics).
specificity
_____ enzyme family are responsible for oxidizing most psychoactive drugs.
Cytochrome P450 (CYP450)
4 Factors that modify biotransformation capacity include
- Enzyme induction
- Enzyme inhibition
- Drug competition
- Individual differences in age, gender, and genetics.
Most drugs do not pass into neurons, but act on _____
surface receptors
Neuropharmacology identifies drugs that act at _____
neurotransmitter receptors
Neuropharmacology enhances or reduces _____.
normal functioning of the cell
The “anticipatory” (conditioned) response is compensatory, meaning…
The environment associated with administration of the drug elicits physiological responses opposite to the effect of the drug. Ex: shooting heroine in a green bathroom routinely - body learns to anticipate and prepares itself.
Drug dosage could be adjusted if an individual’s _____ is known.
Genetic makeup
