topic 6 Flashcards
What are two types of dose response relationships?
Graded-Plotted with the dose increasing on the x-axis and intensity of effect on the y axis
Quantal-plotted with the dose increasing on the x-axis and the fraction of a population that a dose works for on the y-axis. Good for all or nothing effects of drugs
What does a typical dose effect curve look like? Where do most drugs aim to be on curve?
Threshhold-When the drug first starts to take effect
Slope-linear relationship where larger dose leads to larger effect. (1st order)
max effect-line evens out, larger dose doesn’t lead to greater effect
Most drugs aim to be just above the threshhold dose
What is the difference between efficacy and potency? How are they measured
Efficacy refers to the maximum effect a drug can have regardless of size or dose. It is measured by Emax
Potency refers to the quantity of drug necessary to achieve a certain effect. It is measured by ED50 or EC50, which is the amount of a drug required to cause 50% of the max. effect.
What is the importance of a slope of a dose response plot
If the slope is steep, it means that a slight change in dose could lead to large changes in response which means that it will more easily become toxic. A flatter slope is easier to dose (less chance of toxicity).
What is a full agonist? Partial agonist?
A full agonist is a drug that gives the maximum effect once bound to a receptor. A partial agonist gives a less effective response than the full agonist and thus when both are give, a partial agonist can act as an antagonist.
What is a dose-percent curve? What is the difference between a cumulative frequency distribution and a frequency distribution?
The dose-percent curve is a quantal dose-effect curve. It plots the dose vs. the percent of individuals affected. A frequency distribution plots only the percentage of people that were first affected a certain dose. A cumulative frequency distribution plots all the people that were affected at a certain dose even if they were previously affected by a lesser dose (it resembles
a graded dose response curve).
How do you calculate the therapeutic index and the margin of safety for a drug.
Therapeutic index=LD50 (lethal dose)/ED50
Margin of safety can be more accurate especially when dealing with different slopes.
Margin of safety=LD1/ED99
What are the 4 levels of drug response and mechanism?
systems-effect on system function(autonomic, etc.)
tissue-effect on tissue function
cellular-transduciton
molecular-receptor, ion channel enzyme, carrier molecule, etc.
What are 3 general ways that drugs work?
Antagonize/block inhibit endogenous proteins
activate endogenous proteins
Other unconventional ways
What are some examples of drugs with unconventional mechanisms of action?
Enzymes such a streptokinase (from bacteria) for thrombolysis
Drugs that exert actions due to physical properties (mannitol-osmotic diuretic)
Antigens (vaccines)
What are 4 ways in which drugs can selectively inhibit enzymes (examples?)
Selective toxicity through inhibition of a unique metabolic pathway-sulfonamides work on an enzyme that bacteria have but humans don’t.
Selective toxicity through species differences in enzyme selectivity-more drug is needed to inhibit the human enzyme than the bacteria enzyme (antibacterial/anti-malarial drugs-trimethoprim/pyrimethamine).
counterfeit incorporation-add an analog to a macromolecule (substrate) and make it so the enzyme doesn’t recognize it. Anti-cancer drugs.
Inhibitors of enzyme activity in specialized cells-target pathways specific to certain cells. Inhibitors of tyrosine hydroxylase
How do drugs target ion channels?
They can either directly or indirectly bind to the channel but allosterically. There are numerous places in which different drugs can bind and the effects can be numerous. They might make the opening of the channel faster or slower or might block the channel or keep the channel open longer, etc.
What are some examples of drugs affecting carrier proteins
NE uptake-Tricyclic antidepressants block the carrier molecule that brings it back into the cell, cocaine does the same.
Penicillin reuptake-Probenicid (targets the carrier protein that leads to excretion in kidney).
What are 4 key characteristics of receptors
Specificity, Affinity, Intrinsic activity (causes some affect), saturability
What are 4 types of receptors (physiological targets)? How quickly do they work?
Ionotropic-receptor operated channels-milliseconds
G-protein coupled (metabotropic)-seconds to minutes
Kinase Linked (tyrosine kinase, serine/threonine)-minutes
DNA Linked (nuclear)-hours
