1. Introduction to the Biological Basis for Understanding Psychotropic Drugs

2. First: The social determinants of psychotropic drug prescription—critical social science meets the psychiatric system… 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?

3. First: How are neural messages transmitted?

4. How neurotransmission involved in the mechanisms of drug action…

5. 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

6. 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.

7. The transmitters that have been most consistently linked to mental activity are: norepinephrine dopamine serotonin GABA (gamma-amino-butyric acid) glutamate histamine

8. 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

10. 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)

11. 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)

12. Antidepressant drugs: Important categories Selective Serotonin Reuptake Inhibitors (SSRIs) Tricyclic Antdepressants (TCAs) Monoamine Oxidase Inhibitors (MAOs)

13. SSRIs Block neuronal pre-synaptic 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

14. Tricyclic Antdepressants (TCAs) Inhibit the reuptake of 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

15. Monoamine Oxidase Inhibitors (MAOIs) But…tyramine is toxic above a certain level…foods containing tyramine must be eliminated or avoided MAO: responsible for inactivating/breaking down monoamine transmitters (e.g. norepinephrine, serotonin, dopamine, tyramine) MAOIs increase neurotransmitter availability for synaptic release in the CNS

16. Drugs used in the treatment of Mania Lithium carbonate is a naturally occurring salt that has mood 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

17. 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.

18. Antipsychotic Drugs Conventional antipsychotics are antagonists at dopamine receptor sites--this blockage causes EPSE… atypical antipsychotics are dopamine and serotonin antagonists…less EPSE