Transcript How is neurotransmission involved in the mechanisms of drug action?

Introduction to the Biological Basis for
Understanding Psychotropic Drugs
CONTENT OUTLINE:
 First: The social determinants of psychotropic
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drug prescription—critical social science meets
the psychiatric system…
The cellular composition f the brain
How are neural messages transmitted?
How is neurotransmission involved in the
mechanisms of drug action?
What is a neurotransmitter and how is it related
to psychotropic drug action?
The cellular composition of the brain
 The brain is composed of approximately 100 billion neurons
 Neurons are nerve cells that conduct electrical impulses.
 Most functions of the brain, from regulation of blood pressure to
cognitive processes such as learning how to play the piano, are
thought to result form the actions of individual neurons
and the interconnections between them
 Neurons carry out 3 types of physiological actions
 1. they respond to stimuli
 2. they conduct electrical impulses
 3. they release chemicals called neurotransmitters. These
neurotransmitters (here is where we will focus our attention)
First: How are neural messages
transmitted?
SO…
THE FOLLOWING SEQUENCE OCCURS TO TRANSMIT
NEUTRAL ‘MESSAGES’
 1. Nerve cell sends electrical signal along axon (e.g. that you have
touched something hot
 2. The nerve axon carries the electrical signal (as in your previous
learning…)
 3. The myelin sheath protects axon and facilitates transmission of
the electrical signal
 4. The electrical signal continues to travel along the axon and reaches
the pre-synaptic knob
 5. Once the electrical impulse reaches the end of a neuron, a
neurotransmitter is released. The neurotransmitter (neural
message) then crosses the space or synapse (from the pre-synaptic
knob to the post-synaptic knob).
 6 . Then receptor cells on the post-synaptic knob are activated and the
neurotransmitter attaches to these receptor cells on the
neuron’s surface.
How neurotransmission involved in the
mechanisms of drug action…
What is a neurotransmitter and how is it
related to psychotropic drug action?
A neurotransmitter is a chemical
substance that functions as a
neuro-messenger.
On excitation, neurotransmitters
are released from the axon
terminal at the site of the
presynaptic neuron (terminal).
The transmitter then diffuses across
the narrow space of the
synapse…
And arrives the postsynaptic
neuron, where it attaches to
specialized receptors on the post
synaptic neuron….
Where it attaches to specialized
receptors and either EXCITES or
INHIBITS the post synaptic
neuron
After attaching to the receptor and exerting its influence, the
neurotransmitter is destroyed (in two different possible
ways…more later)
It is believed that some mental illnesses are caused by either
TOO MUCH (excess) or NOT ENOUGH (deficit) of a
particular neurotransmitter (see text diagrams).
Therefore, psychotropic drugs are designed modulate
neurotransmitter concentration at the neural synapse.
The transmitters that have been most consistently linked to
mental activity are:
 norepinephrine
 dopamine
 serotonin
 GABA (gamma-amino-butyric acid)
 glutamate
 histamine
Anxiolytic (anti-anxiety) drugs
Anxiolytic (anti-anxiety) drugs e.g. diazepam, alprazolam,
lorazepam, temazepam, triazolam (the benzodiazepines):
 the neurotransmitter GABA “seems to play a role in modulating
neuronal excitability and anxiety” (Varcarolis, 2004, p. 47)
 Most anti-anxiety drugs act by increasing the effectiveness of
GABA. This is accomplished primarily through increasing
receptor responsiveness
Adverse effects of anxiolytics
 dependence
 therapeutic dose dependence
 high dose dependence
 ‘recreational’ use
tolerance
oversedation
drug interactions
memory impairment
depression, emotional blunting
Adverse effects in the elderly (ataxia, confusion; ½ adult dose and
for two weeks only!!!!!!!!!!!!!!!!!!!!!!!!)
 Adverse effects in pregnancy (benzodiazepines cross the placenta)
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Handout:
Manufacturing Addiction: The Over-Prescription of
Tranquilizers and Sleeping Pills to Women in
Canada (Canadian Women’s Health Network, 2011)
(http://www.cwhn.ca/en/print/en/node/39526)
Antidepressant drugs: Important
categories
 Selective Serotonin Reuptake Inhibitors (SSRIs)
 Tricyclic Antdepressants (TCAs)
 Monoamine Oxidase Inhibitors (MAOs)
SSRIs
 Block neuronal pre-synaptic
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reuptake receptors such as
5-HT serotonin
First line drug: least adverse
effects; low cardiotoxicity
Low lethality rate in suicide
Common adverse reactions:
increased CNS serotonin may
also induce agitation, anxiety,
sleep disturbance
Potential toxic effects: rare,
but life threatening: serotonin
syndrome
Tricyclic Antdepressants (TCAs)
 Inhibit the reuptake of
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norepinephrine and
serotonin by presynaptic
neuronsing, thus increasing
the time they are available
to the post-synaptic
receptor
Sedative effects: blockade
of histamine receptors
Anticholinergic effects
Postural hypotension
Potential cardiovascular
toxicity
Monoamine Oxidase Inhibitors (MAOIs)
 MAO: responsible for
inactivating/breaking down
monoamine transmitters
(e.g. norepinephrine,
serotonin, dopamine,
tyramine)
 MAOIs increase
neurotransmitter
availability for synaptic
release in the CNS
 But…tyramine is toxic
above a certain
level…foods containing
tyramine must be
eliminated or avoided
Drugs used in the treatment of Mania
 Lithium carbonate is a naturally occurring salt that has mood
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stabilizing effects in the treatment of bipolar disorder.
Lithium is a naturally occurring element (salt), like potassium or calcium. In the
1800s, scientists thought that lithium might be an effective treatment for gout,
although it was found to be ineffective for this use. Later, in the 1940s, it was
used as a salt substitute, until it was withdrawn from the market due to several
deaths that were caused by lithium toxicity. Later, it was discovered that lithium
can be used to treat mania.
Because lithium is a salt, it is dissolved in body’s water. If the person is
dehydrated or if they take medications that reduce body water, thenlithium
levels can go up.
It is important that the amount of lithium in a person's body be monitored by a
simple blood test. Typically the blood test is drawn 12 hours after the last dose
of lithium.
Very narrow therapeutic window: levels should not exceed 1.5 mEq/L---q5
days/ q3 months assessment; Side effects and signs of toxicity—p. 293
Drugs used in the treatment of Mania
 Anticonvulsants—in the 1980s researchers hypothesized
that mood instability could be viewed much the same as
epilepsy and that a chain reaction of sensitivity, or kindling
was responsible for the worsening of bipolar symptoms over
time (Ostacher&Tilley, 2008).
 This hypothesis led to the use of carbamazepine and valproate
as a treatment for mania and the incorporation of
anticonvulsant therapy.
 Subsequent research did not support the kindling theory,
however. It is likely that symptom improvement for bipolar
disorder is based on a different mechanism of action than
seizure prevention.
Antipsychotic Drugs
 Conventional antipsychotics
are antagonists at dopamine
receptor sites--this blockage
causes EPSE…
 atypical antipsychotics are
dopamine and serotonin
antagonists…less EPSE