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CHEM 182 (11)

Lecture 5

5 Pages

Course Code
CHEM 182
Joe Schwarcz

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Lecture November 5 th Mental Illness Part 2: Ways Neurotransmitter can transmitter can send message: 1. Nerve cell- interfere by drugs to bind to receptor, cause nt to leak out of vesicles, block reuptake, can interfere with enzymes that are responsible in reuptake. Ex. Reserpine causes norepinephrine to leak out of vesicles. Amphetamines squeeze norepinephrine and dopamine out of vesicles (are stimulants). Tricyclics prevent the reuptake of neurotransmitters.- increase []of certain nt in synapse- increasing their activities. MAO inhibitors prevent the breakdown of nts. Neuroleptics block receptors for dopamine (lack and excess of this nt can cause illness) Schizophrenia: -loss of contact with reality, visual and auditory hallucinations, delusions of persecution Straight jackets not used anymore, though meds not much better Chemical treatment started with Henri Laborit (1952, France)- noticed that patients would sometimes have heart attacks before surgery-blamed anxiety. At this time, antihistamines (used for treatment of allergies and side effect of drowsiness ie calm down) had just been introduced. Used this on patients before surgery (promethazine ie Phenergan) which worked at calming patients. Started thinking of other drugs that work.  Chlorpromazine (thorazine)-calming effect. Very strong. Used on schitzo patients and worked (other antihistamines not strong enough) and worked but side effect of causing Parkinson-like symptoms.  Nathan Klein (psychiatrist) experimented with reserpine on schitzophrenics. Snakeroot, used in India, was used as an antihypertensive, but also had tranquilizing effects. Had same effect as Thrazine, same Parkinson-like side effects as well, but VERY different structuresChlorpromazine blocked dopamine receptors (schitzo-excess dopamine, most studied nt). Reserpine caused dopamine to leak out of vesicles where nt is produced ie low influx of dopamine in synapse. Parkinson is the opposite of schitzophrenia since caused by dopamine deficiency. Therefore need to watch dosage- trial and error with individual patient.  Perphenazine- main drug today for schitzo-improvement of chlorpromazine- patients can lead relatively normal lives  Haldol still used today- calming effect on schitzo and other agitated patients- used in hospitals, senior homes- controvercy of overuse (dope to not have to deal with patients).  Clozapine (clozaril), risperidone (Risperdal), olanzapine (zyprexia)-neuroleptics  Everytually 25% of schiophrenics achieve remission with appropriate medications  Study finding that older drugs work just as well as newer ones, but new ones have patent protection so make more money. Depression: hopelessness, pessimism, uselessness for NO REASON-> antidepressants Tricyclics (3 rings): resulted from a search for an “improved” version of chlorpromazine to treat schizophrenia= imipramine (ineffective for schizo but elevated mood). Trade name became tofranil and found that it blocked reuptake of serotonin and norepinephrine. Deprex-amitriptyline-> one of best in mood elevating substances Anafranil Different one better to each individuals (psychiatry often trial and error). Side effects: “anticholinergic”(block action of achetylcholine-dry mouth, blurred vision) and “antiadrenergic”(block adrenalin-irregular heart rate) How to increase serotonin and norepinephrine in synapse without the side effects of the tricyclics? Prozac(fluoxetine)- selective serotonin reuptake inhibitors (SSRIs) – doesn’t interfere with ach or adrenalin. It has a similar, but not identical, structure to serotonin. Then followed others: Sertraline (Zoloft), fluovoxamine (luvox), maprotiline(ludiomil), paroxetine (paxil), trazodone (desyrel), citalopram (celexa) There are many since made by different companies that try to make similar compounds different enough to have patent (given by patent attorneys). None are preferred. Side effects include, nausea (foreign matter in stomach), anxiety, sleep disturbances, sexual dysfunction. Many give up drug due to side effects and others don’t feel any side effects. 1989, Louisville, Joseph Wesbecker- worker on Prozac went on murderous spree and claimed that Prozac made him do it. Suicide was another side effect, especially in children under 18. In controlled trials there was no difference in the frequency of suicidal thoughts in subjects taking Prozac, a tricyclic or a placebo. Scientology: against medications for mental illness. Tom Cruise is one. Obsessive-Compulsive Disorder (OCD) 2% of population (large number)- Person knows they are obsessive but can’t stop. Chemistry student graduate obsessed by thought of cats getting stuck in laundry (check dozens of times during laundry). Need to check up to 350 times that door is locked. Need to do a set number of sit ups in fear that something bad will happen otherwise. About 20% of first degree relatives of people with ocd have the disease. About 20% of ocd patients have tics and 50% of patients with tourette’s syndrome (have tics- a neurological disease that causes verbal or physical tics- need to make sounds ex. Barking sounds. Sometimes inability to prevent shouting obscenities) have ocd. Obsession: unwanted, unreasonable, intrusive thoughts; contamination concerns, harm to self or others, symmetry concerns (ex. Books lined up), saving concerns, “perfection” concerns Compulsion: rituals performed to gain relief from obsessive thoughts. Ex. Howard Hughes-engineer, built airplanes, and philanthropist, but obsessed with cleanliness so became recused though rational in every other ways. NOT caused by deep roo
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