Chapter 3: How Drugs Act Flashcards
It is a basic principle of pharmacology that…
the pharmacological, physiological, or behavioral effects induced by a drug follow from their interaction with receptors.
how is pharmacokinetics different from pharmacodynamics?
pharmacokinetics (the study of what the body does to drugs), pharmacodynamics is the study of what a drug does to the body (AKA “drug action”)
three different types of receptors?
1.ionotropic
2.metotropic
3. transporter carrier proteins
as a rule, receptors are usually…
large molecules (usually protein)
-involves hundreds of known receptor types
where are receptors located?
Located in site(s) where naturally occurring compounds (transmitters or modulators) produce biological effect
how many receptors can a neurotransmitter have?
more than one and sometimes many different types
why is a drug more specific than an neurotransmitter?
so they can act on the correct receptor type in order to produce the correct effects
what metaphor aligns with drugs and receptors?
lock and key
a general rule of psychopharmacology is that drugs do not create any unique effects.. how is this?
they merely modulate normal neuronal functioning, mimicking or antagonizing the actions of a specific neurotransmitter.
Drug binding may mimic or facilitate neurotransmitter action Or drug occupation of a receptor might block access of the neurotransmitter to that receptor and so prevent endogenous molecules from attaching, activating, and producing an effect at these sites.
what are ionotropic receptors?
function as ion channels
-activation opens channel (or pore) in membrane of cell, allowing flow of ions to trigger or inhibit neural firing
-it is typically closed until a drug sits on the activation site where the channel then opens
what is an excitatory signal and an inhibitory signal to the cells?
chloride flowing in is an excitatory signal
potassium flowing out is inhibitory
how do Benzodiazepines work on GABA receptors?
Bind to nearby sites and facilitate GABA, flooding neurons with chloride ions, inhibiting neural actions
Used as sedative, antianxiety, amnestic, antiepileptic
considered allosteric agonists
how does Flumazenil a a benzodiazepine antagonist?
binds to benzodiazepine site and prevents the benzo from occupying this site, but does not have an effect on GABA
what are G-Protein-Coupled Receptors (metabotropic receptors)?
Induce the release of intracellular protein which triggers second messengers (mediate the synaptic effects of many neurotransmitters that are involved in the action of psychoactive drugs)
Constitute a large and diverse family of proteins whose primary function is to change extracellular stimuli (transmitters and drugs) into intracellular signals
how is metatropic different than ionotropic?
produce effects much more slowly, and long-lasting
they look very different (they still have transmembrane; however, they have seven membranes and there is no ion channel in the middle)
what are first and second messengers?
first: drug or neurotransmitter
second: refers to something occuring within the cell, cellular processes such as ion channel function, energy metabolism, cell division/differentiation, neuron excitability
they mediate the synaptic effects of many neurotransmitters that are involved in the action of psychoactive drugs
describe the activation of metotropic receptors?
Process starts when hormone, neurotransmitter, or drug attaches to receptor
Receptor shapes changes and three-chain G protein on inside of cell membrane
Component of G protein is released and directly or indirectly activates ion channel
Ion channels opened, alteration of enzyme activities, or changes in gene activation may be produced
Communication between neurotransmitter-receptor complex and intracellular enzyme produce ultimate biological response
What is this a picture of?
of a G-protein-coupled (metabotropic) receptor
why are G-protein-coupled receptors considered the “middlemen,”
they are able to effect communication between the neurotransmitter-receptor complex and intracellular enzymes , the second messengers, to produce the ultimate biological response
explain the illustration of the G-protein activating an enzyme, which then produces a second messenger that opens the channel or causes other biochemical reactions
what are the Carrier Protein/Transporter Protein receptors?
Bind to neurotransmitters to transport them back to presynaptic neuron
They bind across cell membranes against concentration gradients.
Most important in psychopharmacology are the presynaptic transporters that bind dopamine, norepinephrine, or serotonin (and other neurotransmitters) in the synaptic cleft and transport them back into the presynaptic nerve terminal, terminating their synaptic action
probability of binding of transporter protein to neurotransmitter?
depends on two things
- how much neurotransmitter there is in the synapse
- how many receptors there are for the neurotransmitter
The fourth protein category relevant to the action of drugs is that of
enzymes
how do enzymes regulate neurotransmitters?
Function to break down neurotransmitters in synaptic cleft and presynaptic terminal
Monoamine oxidase inhibitors inhibit breakdown of NE and DA (used as antidepressants)
drugs that inhibit the action of enzymes do what?
increases transmitter availability and neurotransmission
Irreversible acetylcholine esterase inhibitors are used as
pesticides and nerve gases
explain what is occuring in this photo
Left: Transporter open to the synaptic cleft. Center: Transmitter “trapped” inside the transporter. Right: Inward-facing state with transmitter “released” into the cytoplasm of the neuron.
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Receptors exhibit high specificity for…
- neurotransmitters
- certain drug molecules
*the shape and configuration of these molecules matter such that they are able to lock into the receptor and produce an effect
what are Enantiomers ?
molecules which have the same shape but are rather like mirrors of each other
-one of them will typically produce the biological effect and the other will produce little to none
-therefore, the FIT matters more than the shape
what does a dose-response curve look like?
x-axis: dose of drug
y-axis: any type of effect you expect the drug might have
you are looking for the shape and nature of corresponding response
this is a very common dose curve
discuss efficacy and potency in response to this graph.
shows theoretical dose-response curves for three psychostimulants
-equal efficacy of methamphetamine and dextroamphetamine
-increased potency of methamphetamine (because curve is more to the left)
-reduced potency and efficacy of caffeine.
describe what is occuring in this graph.
shows the dose-response functions produced by different types of drugs
-the agonist can produce the maximum possible effect by binding to the receptor
-the partial agonist has affinity to the receptor but is not able to elicit the maximum effect at any dose
-the antagonist binds to the receptor, has affinity for it, but does not produce an overt effect
-the inverse agonist produces an effect opposite to that of an agonist
explain what is going on in these graphs?
shows the agonist dose-response curves in the presence of competitive (Part A) and noncompetitive/irreversible (Part B) antagonists.
The effect of a competitive antagonist is to shift the dose-response curve to the right. It takes a larger dose of the agnost to produce the same effect.
The noncompetitive/irreversible antagonist shifts the agonist curve down. Dose curve stays in the same place but the maximum effect is reduced.
explain this graph
the red curve is the standard dose response curve
the blue curve is the number of patients displaying a response against the curve
it shows HUGE variability
people who are insensitive are on the right hand of the red line
people who have no tolerance will be on the left end
the POINT: the red curve is the ideal curve, however there is considerable human variability shown by the blue curve
explain what this graph is
illustrates LD50 to ED50
shows it wouldn’t be a safe drug because at the dose, 50% of patients display desired effect, but it is already hitting the lethal dose
the curves should be separated very far on X-axis and they should not overlap
