1. Introduction to the Biological Basis for Understanding Psychotropic Drugs

2. CONTENT OUTLINE: • First: The social determinants of psychotropic 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?

3. 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)

4. First: How are neural messages transmitted?

5. 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.

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

7. 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

8. 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.

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

10. 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

12. 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)

13. 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)

14. Antidepressant drugs: Important categories • Selective Serotonin Reuptake Inhibitors (SSRIs) • TricyclicAntdepressants (TCAs) • Monoamine Oxidase Inhibitors (MAOs)

15. 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

16. TricyclicAntdepressants (TCAs) • Inhibit the reuptake of norepinephrine and serotonin by presynapticneuronsing, 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

17. 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

18. 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

19. 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.

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