Chapter 2 Flashcards
Preclinical stage
Early part of drug development.
Identification of promising drugs and their testing on animals occurs in this stage.
Clinical stage
Pharmaceutical companies establish the safety and effectiveness of new products in humans during this stage.
Phase I clinical trials
Establish biological effects, as well as safe dosages and pharmacokinetics in a small number of healthy people.
Phase II clinical trials
New drugs are used to treat in small number of patients and to establish the potential of a drug to improve patient outcomes.
Phase III clinical trials
Compares the new medication to standard therapy in a larger number of patients studied by at sites across the country.
Post-marketing sureveillance
Surveillance during which health professionals are encouraged to report adverse events experienced while on the new drug.
Clinical trial
Stage where several thousand patients receive a new drug.
Post-marketing period
Larger population receives new drug. Additional adverse effects are identified, if they arise.
Pharmacogenomics
Study of how individual variations in drug targets or metabolism affect drug therapy.
Helps identify factors that are responsible for beneficial or adverse effects in individual patients.
Homeostasis
Cell, tissue, or body does not respond to drug, but instead maintains internal environment by adjusting physiological processes.
Pharmacology
Study of substances that produce biological responses.
Graded drug response
Biological effects that can be measured continually up to the maximum resounding capacity of the biological system.
- blood pressure
- heart rate
- diuresis
- bronchodilation
- FEV1
- pain
- coma
Quantal drug response
Drug responses that may or may not occur.
- convulsions
- pregnancy
- rash
- sleep
- death
Drug potency
How much drug is needed to produce a biological response.
Drug efficacy
The maximum effect a drug can produce.
Drug intrinsic activity
The ability of a drug to produce a response once it has occupied specific receptors.
Drug selectivity
A ratio of the dose or concentration producing the undesired effect to the dose or concentration producing the desired effect.
Therapeutic index
Ratio of lethal dose of the drug to the therapeutic dose of the drug.
Therapeutic index for drugs on the market is always greater than 1.
Placebo effect
Pharmacological effect that is not due to the active ingredient.
Structure-activity relationship (SAR)
Correlation of chemical structure with pharmacological activity.
Ion channel receptors
Transmit signals across the cell membrane by increasing the flow of ions and altering the electrical potential or separation of charged ions across the membrane.
Produce responses with rapid onset and short duration.
• muscle movements
Examples:
ACh (nicotinic)
Gamma-aminobutyric (GABA)
Excitatory amino acids (glycine, aspartate, and glutamate)
Receptors coupled to G proteins
Proteins that cross the cell membrane 7 times, creating a pocket in which drugs can interact. Bound drugs may stimulate the receptor to release G protein that can interact with various effector proteins to produce a physiological response.
•Heart beat
Examples:
Alpha
Beta
Gamma
Transmembrane receptors
Receptors that consist of extra cellular hormone-binding domain and intracellular enzyme domains that phosphorylates the amino acid tyrosine.
Examples:
Receptors for insulin
Receptors for epidermal growth factor
Platelet-derived growth factor
Intracellular receptors regulating gene expression
Liquid soluble hormones can pass through the cell membrane and bind to intracellular receptors. The receptor moves to the nucleus, where it controls the transcription of genes by binding to specific DNA sequences.
Example: Corticosteroids Mineralcorticosteroids Sex steroids Vitamin D Thyroid hormones
Enzymes
Biological molecules that encourage specific chemical reactions in the body.
Example:
Acetylcholinesterase breaks a chemical bond in ACh to terminate its action and make acetic acid and choline.
Agonists
Drugs that produce receptor stimulation and a conformational change every time they bind.
Antagonists
Drugs that occupy receptors without stimulating them. Antagonists occupy a receptor site and prevent other molecules, such as agonists, from occupying the same site and producing a response.
Example: Beta blockers (lol)
Non-receptor mechanisms
Drugs whose action is based on their physicochemical properties rather than interaction with receptors.
Example:
Sodium bicarbonate
Pharmacokinetics
Branch of pharmacology dealing with absorption, distribution, through the body, metabolism, and excretion of drugs.
Absorption
Once inside the body, depending on route of administration, drugs interacts with various receptors to produce physiological change that result in clinical effectiveness.
Bioavailability
The percentage of the administered dose that does enter the blood stream
Distribution
The process of drugs moving throughout the body.
Passive diffusion
Process by which drugs cross some type of biological barrier, such as a cell membrane or through a layer of cells, based on the concentration difference on the two sides of the barrier.
Protein binding
Drugs bind to a variety of proteins that are present in the bloodstream; called plasma proteins.
Example: Albumin Alpha 1 glycoprotein Cortisol-binding globulin Sex-binding globulin Lipoproteins
Plasma protein binding occurs in the plasma and encourages retention of drug in the systemic circulation.
Influx of a drug
Transport of drugs into the cell.
Efflux of a drug
Transport of drugs out of the cell.
Metabolism
The process of changing one chemical into another, and the process usually either creates or uses energy.
First-pass metabolism
Metabolism by the liver following oral administration.
Phase I metabolism
Known as non synthetic reactions.
Involve oxidation, reduction, and hydrolysis reactions, which prepare the drug molecule for further metabolism.
Phase II metabolism
Known as synthetic or conjugation reactions.
Drugs molecules are metabolized and something is added to the drug to synthesize a new compound.
Cytochrome P450
Reaction that catalyze the metabolism of a large number of diverse drugs and chemicals that are highly lipid soluble.
First order metabolism
Metabolism is related to drug concentration so that a fixed FRACTION of drug is metabolized per hour.
Characterized by a half-life.
Zero-order metabolism
Ethanol is present at concentrations well above their Km for metabolism, causing enzymes to act to their maximal metabolic capacity and metabolize a CONSTANT amount of drug each hour.
Enzyme induction
Drugs that increase the expression of drug-metabolizing enzymes.
Example:
Phenobarbital
Excretion
Process in which drugs are transferred from inside the body to outside.
Some unique sites where drugs are excreted by not absorbed:
- Kidney
- gallbladder
Principle organs for drug elimination:
- kidneys
- lung
- biliary system
- intestines
