Learning Assessment 1 Flashcards
TD 50
The median toxic dose of a drug is the dose at which toxicity occurs in 50% of
cases.
Ed 50
The effective dose for 50% of the population (Median effective dose). The ED50 is
commonly used as a measure of the reasonable expectancy of a drug effect, but
does not necessarily represent the dose that a clinician might use.
Helps in understanding the median dose where 50% of the population has a
therapeutic response.
Ec50
The effective concentration of a drug which induces a response halfway between the
baseline and maximum after a specified exposure time. (Median effective
concentration)
It is commonly used as a measure of a drug’s potency.
Ed 50 can be used to compare the potency of two drugs, the lower the EC50 the more potent
Helps in understanding the median effective concentration of a drug. Helps in comparing potency of similar drugs in a class.
Ic50
The the concentration of an inhibitor where the response (or binding) is reduced by
half.
Therapeutic index
The therapeutic index ( also referred to as therapeutic ratio) is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity.
relationship between the TD50 and ED50
graded response
Biologic effects that can be measured continually in response to a medication: Blood pressure Heart Rate Diuresis Bronchodilation Pain
quantal response
Effects that may or may not occur (Present or absent) Seizures Pregnancy Rash Sleep Death
pharmacodynamics
(What the drug does to the body): (Mechanisms of Action)
- Interactions with Receptors
- Non-receptor mechanisms
pharmacokinetics
(What the body does to the drug) Absorption Bioavailability Distribution Metabolism Elimination
receptor mechanisms
Ion Channel Receptors G Protein Receptors Enzyme-Linked Receptors Intracellular Receptors Ion exchangers
target receptors include: enzymes ion channels cell surface receptors transporters DNA
non-receptor mechanisms
chemical action
neutralization (antacids), chelation (penicillamine), ion exchangers (cholestyramine)
physical action: osmosis, absorption, demulcents, counterfeit incorporation (sulfa drugs/ neoplastics)
ligand
A molecule (drug/hormone/neurotransmitter) that binds to a receptor forming a ligand-receptor complex. May activate or inhibit. agonist or antagonist)
substrate
molecule upon which an enzyme acts
agonist
binds to a receptor and produces an effect
antagonist
binds to a receptor and odes not produce an effect
blocks receptor and prevents endogenous compounds from binding to the receptor
competative agonist/ antagonist
morphine/ naloxone
partial agonist
binds to a receptor that stimulates only some of the receptors
ion channel receptors
Transmit signals across cell membrane by increasing the flow of ions and altering the electrical potential or separation of charged ions across the cell membrane Drugs that target ion channel receptors Amlodipine Zolpidem Alprazolam Sulfonylureas Repaglinide
g protein coupled receptor
Alpha and Beta adrenergic
drugs
Albuterol Losartan Morphine Clopidogrel haloperidol
enzyme-linked receptors
Examples of drugs that target enzyme-linked receptors: Antibiotics Atorvastatin Insulin Heparin
intracellular receptors
Examples of drugs that target intracellular receptors: Corticosteroids Glucocorticoids Mineralocorticoids Thyroid Hormones
absorption
pharmacokinetics
how the drug enters the body affects: bioavailability, onset of action, durations of action, patient adherence
first-pass effect/ metabolism
drugs are metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation
A drug is absorbed from the GI tract and passes via the portal vein into the liver where some drugs are metabolized (bypassing general circulation) Sometimes the result of first pass metabolism means that only a proportion of the drug reaches the circulation. First pass metabolism can occur in the gut and the liver.
Drugs with high first pass effect include verapamil (remember in the previous slide we said verapamil given orally had low bioavailabilty F factor? This is in part due to the high degree of first pass effect.
bioavailability
fraction of the administered drug that enters the bloodstream
f= drug administered/ drug that enters the bloodstream
parenteral has the greatest bioavailability 100%
distribution
the drug traveling to its site of action to produce a pharmacodynamic effect
passive distribution and active transport
protein binding (think physiologic states that affect protein binding such as hypoalbuminemia)
transport systems
volume of distributions
volume of distribution (Bd)= amt of drug in the body/ concentration of drug in the blood
larger distribution usually causes increased drug concentrations in the tissue and decreased concentrations in the plasma
metabolism
Metabolism is chemical alteration or biotransformation by enzymes into
new molecules (metabolites)
Sometimes metabolism is required to achieve the “active metabolite.”
The degree of metabolism can increase or decrease a drug
onset
duration of action and
toxicity of drug
metabolism mostly occurs in the liver
metabolism, in general, makes these molecules more water-soluble so they can be excreted by the kidneys (mostly n the smooth endoplasmic reticulum of liver cells)
phase I metabolism
involve oxidation, reduction and hydrolysis reactions, mixed-function oxidase system
cytochrome P 450
CYP P450 enzymes
results in metabolites with greater or lesser pharmacologic activity
some phase I metabolites are rapidly eliminate4d, others go to phase II metabolism
CYP 450 enzymes may inhibit (decrease) metabolism which leads to
higher plasma drug levels and decreased clearance
Or
CYP450 enzymes may induce (increase) metabolism which leads to
lower plasma drug levels and increased clearance
phase II metabolism
conjugation reactions
metabolites are linked into highly polar molecules making them more water-soluble and thus easily eliminated from the body
increased solubility leads to increased excretion of the drug
