Lab 6 Flashcards
Pharmacology includes…..
The biochemical and physiologic study of drug effects related to mechanisms of drug action, absorption, distribution, metabolism, elimination, adverse effects, and toxicity
What is first studied in pharmacological studies?
The chemical and physical properties of the molecule
_____ are used to conduct the non clinical experiments
Animals
When are clinical studies in humans conducted?
Before use in the general population
Pharmacokinetics relates to….
The action of the BODY on the drug such as drug absorption, distribution, metabolism, and excretion
Pharmacodynamics relates to…..
The action of DRUGS ON THE BODY based on its biochemical, physiological, and pharmacological mechanisms of action
How do most drugs produce their effects?
By binding to specific receptors present in the tissue cells
As mentioned, most drugs produce their effects by binding to specific receptors present in tissue cells.
The predicted effect is unlikely to occur if what?
If the receptor is not present in the tissue OR if the drug is not present in the effective concentration
What is an agonist
An endogenous molecule or a drug that interacts with the specific receptor and produces its intrinsic activity
What is an antagonist
A chemical that can bind to the specific receptor and BLOCK its intrinsic activity
What can you say about partial agonists and partial antagonists
They may not produce the full effects in their effective concentrations
what is the dose-response relationship?
it combines the principles of pharmacokinetics and pharmacodynamics to determine the therapeutic dose and frequency and evaluate toxic effects
how is the dose response curve plotted?
measured response vs log dose
What is another name for a cholinergic agonist
cholinomimetics
cholinomimetics have agonist activity where?
at muscarinic acetylcholine receptors. They augment (add to) parasympathetic nervous system activity
cholinergic agonists aument activity of the parasympathetic nervous system.
what is the result of this?
INCREASED GI motility and DECREASED intraocular pressure
the anticholinergic agent works to…
inhibit PSNS (parasympathetic nervous system) activity
explain the mechanism of anticholinergics
they are ANTAGONISTS of muscarinic receptors, resulting in increased heart rate, increased conduction velocity, and stimulates bronchodilation
name 3 cholinomimetics and their uses
bethanechol – neurogenic ileus and urinary retention
pilocarpine - glaucoma and alleviating the symptoms of
Sjorgen’s syndrome
nicotine - in smoking cessation regimens
name 4 anticholinergics and their uses
oxybutynin - urge incontinence and postoperative bladder spasm
scopolamine - prevent motion sickness and postoperative nausea/vomiting
atropine - used in ACLS guidelines to treat bradyarrythmia and retinal dilator (in ophthalmic surgery)
ipratropium and tiotropium - correct acute exacerbations of bronchospasm (asthma, COPD) and exacerbation prophylaxis for these conditions
what is dopamine?
a monoamine catecholamine neurotransmitter and hormone
what does dopamine bind to? what is its function?
D1 and D2 dopamine receptor
D1 - memory, attention, impulse control, regulate renal function, locomotion
D2 - locomotion, attention, sleep, memory, learning, emesis
name a dopaminergic agonist
Levodopa - the precursor of dopamine
name a dopaminergic antagonist class of drugs
in which dosage forms are they available?
phenothiazine class of drugs
-prochlorperazine
-chlorpromazine
IV. rectal, PO
dopaminergic antagonists can block which 3 receptors?
histaminergic
cholinergic
noradrenergic
what does GABA stand for
Gamma-aminobutyric acid
explain what GABA is
an amino acid that is the primary inhibiter neurotransmitter for the CNS
what is the function of GABA
to reduce neuronal excitability by INHIBITING NERVE TRANSMISSION
what are GABA receptors?
receptors that respond when GABA is released into the post-synaptic nerve terminal
what are the chief inhibitory receptors for the central nervous system?
GABA receptors
how are GABA receptors subdivided?
GABAa
GABAb
GABAa = ligand gated ion channel. inotropic receptor
name 3 GABA receptor agonists
alcohol (ethanol), barbiturates, benzodiazepines
name 3 barbiturates
phenobarbital
pentobarbital
sodium thiopental
between benzodiazepines and barbiturates – which are used more frequently now? why?
benzodiazepines are used more frequently because barbiturates have high addiction potential and lack of antidote
what are GABA antagonists
drugs that bind to GABA receptors but do NOT increase the amount of GABA
give 2 examples of GABA antagonists
picrotoxin
bicuclline methiodide
the 2 GABA antagonists mentioned – picrotoxin and bicuclline methiodide – are mainly used for what?
research
GABA antagonists are ___ and ____
proconvulsants and stimulants
volume drug solution (normal saline) to be injected formula
mL = body weight (kg) * Dose (mg/kg)
/concentration (mg/mL)
why is non-clinical testing performed during drug development?
to assess the safety profile and PK/TK (pharmacokinetic and toxicokinetic) characteristics of the drug candidate
non-clinical testing is performed how?
both in vitro and in vivo
name 4 types of non clinical studies
pharmacodynamics
safety studies
pharmacokinetics
toxicokinetics
what is the purpose of non-clinical testing: pharmacodynamics? how is it performed?
to test the effect of the drug on the body
can be done in vivo and/or in vitro
safety studies are generally conduced how?
in vitro
in vivo vs in vitro
in vivo = in a living organism
in vitro = in a test tube or equivalent
safety studies identify what?
undesirable effects on the respiratory, CNS, and cardiovascular functions (within the recommended dose AND higher doses)
toxicokinetics evaluates what
ADME under condtions that produce toxicity
how are toxicology studies performed
initially in rodents, and then studies in a larger animal species (dogs for ex)
toxicity studies evaluate the toxicity profile of the compound using…..
single dose and repeated doses
-genotoxicity
-carcinogenity
-development and reproductive toxicity
animals are critical in…..
evaluating potential usefulness and safety of new drugs prior to trial in humans
what 3 guidance and regulatory documents outline the use of animals to evaluate pharmacology and safety risk of drug candidates?
-institutional animal care and use committee (IUPAC)
-OSH guidelines (occupational safety and health)
-international conference on harmonization
define a drug
a substance that brings about a change in biologic functions through its actions on the body
how do most drugs produce their effects
by binding to a receptor
define diluent
substances or solutions added to drug to obtain required drug concentration and/or dosage form
the PHARMACOLOGIC CLASS is based on what 3 things
mechanism of action
physiologic effect
chemical structure
define mechanism of action
the pharmacologic action at the receptor, membrane, or tissue level
define physiologic effect
the pharmacologic effect at the organ, system, or whole body level
what is the mechanism of action of diazepam
GABAa - increase the frequency, but not duration of openings at GABA-activated Cl- channels
what is the physiologic effect of diazepam
increased GABA activity
what is the chemical structure of diazepam
benzodiazepine
the pharmacokinetic properties of a drug are important when selecting what?
the route and dose of the drug (as ADME is affected by age, disease, etc)
drug-receptor interactions
-pharmacokinetics or pharmacodynamics
pharmacodynamics
define drug dose
the specific amount of drug administered at one time or at defined intervals to obtain a therapeutic effect
the drug dose varies with what 3 factors
route
weight
age
in toxicology, what is the “toxic dose”
the amount of drug that causes harmful or toxic effects
what is the difference between side (adverse) effects and toxic effects?
side effects are an unexpected effect when the drug is administered in the RECOMMENDED dose
toxic effects are the result of harmful effects when greater than the therapeutic dose is given
what is the therapeutic window
safe range between the minimum therapeutic concentration and the minimum toxic concentration
when does systemic action occur
when the drug is absorbed into the circulatory system and affects organs and tissues away from the site of administration
true or false
systemic absorption can affect multiple organs
true
local action is to the area ______ to the application
proximal
where local action is intended, systemic absorption is…….
not typically desired and is unnecessary for therapeutic effect
what are the primary routes of administration for pharmaceutical products (as defined by USP)
enteral
parenteral
topical
mucosal
volume administered =
body weight (kg) * dose (mg/kg)
/
concentration (mg/mL)
normal saline injection volume =
10mL/kg
