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Lecture 3

Terms in this set (24)

drug-receptor interactions mediate dose-response
-as the does of a drug increases so does the amount of drug at the site of the receptor and thus the biological response (effect) resulting from the drug-receptor interaction
- D (drug) + R (receptor) <---> (DR) ---> Effect
How do antidepressants work?
- goal: alter brain biochemistry- serotonin levels
-serotonin (5-HT) is a neurotransmitter (brain
messenger) that regulates happiness and
well-being
-Drug: selective serotonin reuptake inhibitor (SSRI)
-example: prozac and lexapro
-why are they called selective?
-receptor: serotonin reuptake transporters (proteins)
- found in the brain, mediate effects of
serotonin
-effect: increases serotonin levels in brain, improved mood
dose-response: Law of mass action
-paul ehrlich and JN langley
-formualtion of receptor theory at end of 19th/beginning of 20th century
-""the mode of action of drugs on cells" developed mathematical relationship of drug-receptor interactions that follow the law of mass action and was based on the reversible absorption of a gas to a metal surface
-illustrated by a hyperbolic curve (total concentration of substance, concentration of substance absorbed)
-plateau- all receptors maxed out
drug receptor binding
-DR complexes are reversible
-reversible interaction: drug receptor interactions involve weak chemical bonds
-good- biological effects of drugs are not permanent
dose-response curve
-graph describing the response of a receptor, organism, population, or biological community to a range of concentration of a drug, toxicant or xenobiotic
-DR relationship can be used to describe manydifferent types of biological resonses
-DR interaction: SSRI drug
- lethal response: death
- behavioral changes: sleepiness
Graded dose: Response curve
- individuals
-measured effect if continuous over a range of doses
-the majority of driugs produce a grade response
-the intensity of the effect increases with the dose of drug
- Ex: sleeping pill dose vs amount of time asleep
Quantal dose response
- response is all or none (dead or alive) binary
-measures # of individuals responding in a population (frequency)
- cumulative frequency distribution is similar to graded dose response curve
- ex- dose of sleeping pill vs # of people that slept through the night
Dose response curve characteristics
-potency
-efficacy
-slope
-variability
potency
amount needed for effect
efficacy
maximal effect
slope
"therapy window" medicine thats beneficial
variability
differences in response in a population of individuals
ED50
effective dose level
TD50
toxic dose level
LD50
lethal dose level
therapeutic index
-TD50/ED50
- small TI- toxic, not safe
Warfarin
-low TI
-anticoagulant
- "sweet clover disease" in cattle caused by warfarin analogue in moldy sweet clover
- used as a rodenticide
- used therapeutically to prolong blood clotting time
-potential for toxic interaction with other drugs
drugs with low therapeutic indices
- acetaminophen (Tylenol)
-causes liver damage- hepatoxic
-liver toixcity caused by formation of a reactive metabolite
-some patients have a low therapeutic index due to increased activity of enzyme that forms the toxic metabolite (alcoholics)
-What drug whould have a large TI
antibiotics
Agonist
-ligand (drug) that binds to a receptor and produces a biological effect (direct acting)
-or indirectly produces the same effect as the ligand (indirect acting)
antagonist
ligand that binds to a receptor but does not produce a biological effect (direct acting) (blocking, inhibitor)
direct acting agonist
-binds directly to and activates receptors
-opiates
indirect acting agonist
- release or enhance the action of an endogenous substance
-Ex: cocaine inhibits re uptake of monoamine neurotransmitters
-increases amount of neurotransmitter at receptor leading to CNS simulation
direct acting antagonist
-binds to the same receptor population as an agonist but fails to activate the target receptors
- little or no efficiency- ability to elicit a response
receptor based antidotal treatment
- opiate (morphine, heroin overdose)
-cause life threatening CNS and respiratory depression (stop breathing)
- naloxone binds at the opiate receptor, blocking action of heroin or morphine and reversing sedation and respiratory depression
-IV injection of naloxone will almost instantaneously revers effects
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