M1s3- Drug Action Flashcards
What to look at when considering a drugs action
-drug target
-drug response
-efficacy and potency
-therapeutic range
- Drug Target
-drugs designed to interact with selected target in body
-most are receptors however a few classes of drugs bind to other targets in body
Receptors:
-a molecule or complex of molecules located on outside or inside of cell which have regulatory or functional role
-many copies of same receptor exist on or within a single cell
-many of same cell types exist in an organ that all work together- means thousands of same receptors in organism
-normally bound to and activated by endogenous ligands (substances ordinarily found in body like hormones and neurotransmitters)
Location of receptors:
-many types distributed throughout body
-location determines where drug act and whether response that results from drug-receptor interaction is beneficial or detrimental
Ex. Activation of opioid receptors in brain causes pain relief however activation of opioid receptors in gastrointestinal tract causes constipation which considered an adverse effect
Other drug targets:
-less common
-some directs interact non-specifically with the biological system and not via receptors
Chemical runs- commonly used antacids neutralize stomach acid through a simple acid-base neutralization rxn
Physical chemical forces- cholestyramine (a drug used to lower cholesterol in body) works by chemically binding to bile acids in gastrointestinal tract, preventing reabsorption and increasing elimination of bile salts that used to make cholesterol
Drugs and receptors
-most drugs mimic action of or block the effects of he endogenous ligand at receptor
-drug that bind to stimulate receptor called agonists fit lock
- drug that bind to but block response at a receptor called antagonists key fit lock but couldn’t open it
-lock and key method drug key that turns and set events in motion
-drug and receptor have certain degree of compatibility of fit and while bins to receptor, does not activate it
True or false: drugs can either increase or decrease in the activity of the receptors
True
Look at good notes to see a drug and receptor interaction!!!!
- Drug response
-generally intensity of pharmacological effects produced by a drug increases in proportion to the dose
-called dose-response relationship where does defined as amount of drug taken (fundamental concept in pharmacology)
Ex. Cannabis and alcohol
-study shows marijuana safer than alcohol (when looking at driving impairment)
Drug response cannabis verse alcohol example
1 of 3: What are the main conclusions of the study? How did the authors arrive at those results?
Feedback:
In this study, several subjects were given a small dose of cannabis and asked to perform a simulated
automobile driving task. No significant impairment of the ability to perform this task was found.
The subjects were later asked to consume a large dose of alcohol, equivalent to six ounces of whisky in
half an hour, and asked to perform a simulated automobile driving task. Their ability to perform the
driving task was found to be impaired and it was concluded that cannabis was a safer drug than
alcohol.
Dosages
2 of 3: What doses of the drugs were used? Did the researchers specify why they used these
doses?
• Cannabis dose: The subject was allowed to smoke until they stated that they experienced a “social
high”. This was validated by a previously determined minimum dose, as well as a pulse rate
measurement.
• Alcohol dose: The subjects received a dose of alcohol required to produce a 0.10 blood alcohol
content (B A C). For reference, the B A C to be considered legally impaired in Canada is 0.08.
Valid Comparison
3 of 3: Do you think it is valid that the researchers compared these two doses of drugs?
The comparison between the two drugs is invalid due to the wide discrepancy between the doses of
the two drugs used. The outcome of the experiment would likely have been different if the effects of
one ounce of whisky had been compared with the effects of smoking several cannabis cigarettes.
Comparing the Effects of Cannabis and Alcohol
It has now been shown that the intensity of the pharmacological effects produced by cannabis
increases in proportion to the dose, and that large doses of cannabis do impair motor vehicle
performance. Thus, it is insufficient to just ask whether cannabis is more or less harmful than alcohol
without further specification of context. Several other questions need to be asked to accurately
compare these two drugs
-other factors
Turns out large amounts of cannabis do impair driving
What questions to ask when accurately comparing two drugs
Quality- how much alcohol was compared to cannabis?
Frequency of use- used how often?
User demographics- by what people?
Environmental factors- under what circumstances?
*critical importance of dose
- Drug Response: Dose-response relationships
-for drug to achieve its desired response, many receptors need to be activated at once
Low doses- at low dose of drug, little response is observed as not many receptors are being activated
Threshold- as dose increases, more receptors activated until desired response seen. Threshold exists where a certain number of receptors need to be activated before an effect will be seen
Therapeutic doses- once this threshold reached, a small increase in dose results in a large increase in response
Maximal effects- increase in response not indefinite however our bodies have a maximal effect.once reached continuing to increase amount of drug will have no further increase in therapeutic response
*this relationship commonly illustrated using a dose response curve
Dose-response curve
-depicts relationship between dose of drug in body and percent response
X-axis-dose of drug
Y-axis-percent response (max 100%)
Normally get curve line going up
When do log dose transformation though, line looks more like first have bell shape curve with linear relationship (increase drug in body get proportional increase in response)
-want dosing within linear region
-at start in log called threshold of effect (increasing dose but no increase in body) at beginning not enough receptors activated to get body response
-on log graph above linear region little Plato (horizontal line) max effect if give more drug still not greater response
-if keep doing with increasing drug after max effect actually cause adverse effects
At 50% response, what dose is equals ED50 = effective dose 50% so what dose give 50% effectiveness in body
Dose response curved graph explained
*check goodnotes for visual of graph
-a graphical representation of how much drug you need in the body to see a specific effect
1. Y-axis- effect of the drug on y-axis and plotted on a linear scale. Max response the body can produce is set at 100%
2. X-axis- dose of the drug is on x-axis of graph and is plotted on a logarithmic scale
3. Low doses- increase in dose not corresponding to increase in response. Receptor threshold not yet been reached
4. Receptor threshold- in this region of curve, receptor threshold has been reached and dose of drug is directly proportional to response. Small changes in dose result in large changes in response. Linear portion of curve allows for accurate determination of drug effectiveness
5. ED50- dose of drug results in 50% of maximal effect. Can also be interpreted as the dose of drug that is effective in 50% of a population
6. Maximal response- once reached here and further dose increase has no effect on response level
- Efficacy and Potency
-consider both as are properties of a drug that describes its ability to produce a response
Efficacy
Maximum pharmacological response that can be produced by a specific drug in the biological system
Potency
Dose of a drug that is required to produce a response of a certain magnitude, usually 50% of the maximal response for that drug
-refers only to amount of drug that must be given to obtain a certain response
Ex. Saying drug A is more potent than drug B simply means that one needs to take less of drug A (ex 10 mg) to achieve the same effects obtained from drug B (20 mg)
More drug need to produce effect=less potency it is
Efficacy verse potency
In efficacy amount of drug don’t matter, amount of effect does. Says what drug relieve pain better. More important as max effect determine which drug used
In potency dose can be adjusted to receive desired response
