Cannabinoids, Psychoactive, Benzodiazepines Flashcards
What are the 2 main parts of Cannabis?
THC, CBD
Where does THC act?
It acts presynaptically but is on the postsynaptic terminal
What are the 2 types of cannabinoid receptors?
CB1 – highest in the brain and spinal cord
CB2 – highest in the immune system
What does the CB1 receptor do?
CB1 inhibit transmitter release: GABA inhibitory, glutamate excitatory, dopamine
(mainly presynaptic action)
Some found on astrocytes, microglia, not just on neurons
They have a widespread distribution creating many effects
What does the CB2 receptor do?
CB2 receptors: potential role in neural/psychiatric disorders
(mainly postsynaptic)
Types of endocannabinoids?
Anandamide (AEA)
Arachidonoyl glycerol (2-AG)
Arachidonic acid can synthesize these
CB1 receptors are what kind of channel?
CB1 – ion channels, K opens, Ca2+ closes
Cannabinoid signaling system?
(action on presynaptic, release postsynaptic)
postsynaptic enzymes produce endogenous cannabinoids but presynaptic CB1 activation inhibits transmitter release
Where are cannabinoids absorbed?
Lungs, skin, GI tract
Distribution of cannabinoids?
lipid soluble, can cross the BBB fast
Metabolism of canabis?
mainly in the liver
Excretion of cannabinoids?
Metabolites in the urine, saliva, sweat
THC induces which Cytochrome P450?
CYP 1A2 inducer
CBD inhibits which cytochrome P450?
CYP3A4 inhibitor
Of the 333 drug interactions with cannabis, which are major drug interactions?
24 major drug interactions, 309 moderate drug interactions
Toxicity of cannabinoids?
Carcinogens similar to cigarettes
Main risk is similar, cancers, heart attacks, strokes
Long term effects are still unknown
Cannabis Use Disorder (CDU)?
Tolerance and dependence (there are withdrawal effects that are not lethal, but opposite in effect of cannabis, excitation)
How long is driving impaired for after cannabis use?
5 hours, since reaction time is reduced
When were the first psychiatric drugs available?
The late 1950s. The introduction of drugs helped a lot of people able to go back to live with their family, learn again, go to university, go to work, have friends and a love life
Schizophrenia is due to?
Increased dopamine in parts of the brain
What does Phenothiazines do?
They block D2 receptors
Effectiveness of antipsychotics correlates to what?
Effectiveness of antipsychotics correlates to block D2 receptors
Dopamine receptors can excite or inhibit, D2 receptors?
D2 – major inhibitory receptors
What does Chlorpromazine do?
Chlorpromazine: inhibits many receptors/pumps (many side effects), inhibits D2, used for schizophrenia, but now looking for ones m ore selective, less side effects
Antidepressants are used to treat depression. What are the types of antidepressants?
MAOIs, Tricyclic antidepressants (TCAs), Atypical: Noradrenalin or serotonin reuptake inhibitors
How do MAOIs work?
Serotonin, dopamine, noradrenalin are broken down by Monoamine oxidases, if they are inhibited the neurotransmitters will stay around longer and prevent depression symptoms
what are SSRIs?
Selective Serotonin Reuptake Inhibitors, less side effects since they are selective, reduce depression symptoms
(most commonly prescribed antidepressants)
What are Prozac and Zoloft?
They are SSRIs (fluoxetine, sertraline)
Why are MAOIs still on the market is SSRIs are more effective and have less side effects?
the variability in people means that SSRIs are not effective for some people, MAOIs can work for them
How long does depression treatment take to seen an effect?
1-2 weeks
What ending do benzodiazepines have?
They end in “am”
What is the treatment for SAD, seasonal, Affective, Disorder?
Light box with the same wavelength as the sun
What are the major effects of benzodiazepines?
Major effects
- Anti-anxiety
- Anticonvulsant
- Muscle relaxant
- Impair memory formation (amnesia)
Most useful in acute stress related anxiety
What do beta-blockers do?
They decrease heart palpitations/arrythmias, for stage fright/tremors
What is chlordiazepoxide?
It is a benzodiazepine, used to treat anxiety and alcohol withdrawal
What is diazepam (valium)?
it is a benzodiazepine, used to treat short-term anxiety, acute alcohol withdrawal, muscle spasms
What do benzodiazepines act on?
Benzodiazepines act on benzodiazepine receptors on the alpha subunit of GABA A receptors. GABA needs to bind 2 sites to have inhibitory action (benzodiazepines act at an allosteric site)
What activity do benzodiazepines cause? (inhibitory/excitatory, how?)
Benzodiazepines bind the sites of the GABA A receptor causing more chloride ions to enter the neuron and increasing inhibition, causing antianxiety
Which direction do benzodiazepines shift GABA dose response curve?
Benzodiazepines shift GABA dose response curve to the left (positive modulator)
Therefore, you need less GABA to cause an effect
What are Barbiturates?
They are sedatives that cause sleep or prevent convulsions
How do Barbiturates act?
They are CNS depressants that activate GABA inhibition. They act on GABA A receptor’s beta subunits, they can have action without GABA binding
Why are barbiturates more dangerous than benzodiazepines?
Benzodiazepines: frequency of opening, no direct action (need GABA to have action), safer, selective
Barbiturates: duration of opening longer, act by itself on the Cl- channel, death is more easy
What are beta-carbolines?
Inverse agonists of GABA inhibition. They will cause decreased inhibition
Which way does an agonist shift the dose response curve?
Agonist: dose response curve shifts to the left
Which way does an inverse agonist shift the dose response curve?
Inverse agonist: dose response curve shifts to the right
Which way does an antagonist shift the dose response curve?
Antagonist: no shift in the dose response curve, blockage of receptors (flumazenil, not irreversible, for GABA receptor)
What is flumazenil?
Flumazenil is a benzodiazepine antagonist, it is used to counteract their effects after surgery
What is Zolpidem?
It is used to treat insomnia, it does not depress REM sleep, more selective GABA A binding, less side effects (it has a shorter half life, so will not effect waking day)
Do GABA A receptors act Post or Pre synaptic?
They act on the postsynaptic neuron
Where do GABA B receptors act? (Pre or Post synaptic)
GABA B receptor: presynaptic action, inhibit release of many transmitters
Benzodiazepines pharmacokinetics?
Benzodiazepines pharmacokinetics:
Absorption: well, absorbed orally, high lipid soluble, peak in around 1 hour
Distribution: wide distribution, variable protein binding, rapidly enter brain
Metabolism: Active intermediates, long half life,
Excretion: In the Kidneys
What is Midazolam?
It is a benzodiazepine used to relax muscles before minor surgeries
What P450 metabolizes Diazepam?
Diazepam metabolized by CYP 2C19
What P450 metabolizes midazolam?
Midazolam metabolized by CYP 3A4
Diazepam has an active metabolite nordiazepam, why is its accumulation problematic?
Diazepam – nordiazepam is an active intermediate, very long half life- 60 hours
Accumulation of active metabolite, takes long for amounts to decrease, slower metabolism in older people, can start to affect daily life if not metabolized during sleep (if take it for sleep), can also cross to fetus so need to be careful during pregnancy
Benzodiazepine toxicity? treatments?
- Low toxicity when taken alone
- In combination with other drugs can be fatal
- Flumazenil is a benzodiazepine antagonist that can be used to block adverse effects of benzodiazepines
- Stomach pump, charcoal, hemodialysis – may be needed if taken in combination with other drugs
What is the differential tolerance of benzodiazepines?
Differential tolerance
Greater tolerance to the sedative effect
Less ability to tolerate anti-anxiety
Benzodiazepine withdrawal symptoms?
Withdrawal has the opposite effect – severe anxiety, hallucinations
