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PSYC650 Psychopharmacology

PSYC650 Psychopharmacology. Opiates, Stimulants, ADRs, and Interactions. Opiate Mechanism of Action. Binds to mu, kappa and delta receptors Increases opiate activity in frontal cortex, medial thalamus and PAG This lowers nociceptor stimuli Also affects amygdala, hypothalamus

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PSYC650 Psychopharmacology

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  1. PSYC650 Psychopharmacology Opiates, Stimulants, ADRs, and Interactions

  2. Opiate Mechanism of Action • Binds to mu, kappa and delta receptors • Increases opiate activity in frontal cortex, medial thalamus and PAG • This lowers nociceptor stimuli • Also affects amygdala, hypothalamus • This plus frontal cortex activity alters emotional aspect of pain • Medulla • Antitussive • Smooth muscle slowing • Great for treating diarrhea • Thermoregulation

  3. Withdrawal

  4. Dependence • A major concern for opiate medications • Tolerance, Withdrawal • Usually not a problem when used for acute pain, such as surgery • Chronic pain may be more problematic • Weigh against quality of life • The cautionary tale of the One-Stop Robber of Flint, Michigan

  5. Typical Opiate ADRs • Mostly related to respiratory suppression • Increased CO2 levels lead to increased intracranial pressure • Which is bad for people with acute head injury or tumor • Orthostatic hypotension • Esp. for elderly or those with lower kidney or liver function

  6. Of Note • codeine • methadone • Heroin • Oxycontin • Suboxone (buprenorphine + naloxone) • ketamine (not an opiate, but important to talk about)

  7. Methadone • The Hitler Myths • That it was created in response to an order from Hitler in response to declining morphine supplies • That it was named after him • 1st synthesized in 1938 • Invasion of Poland in 1939 is held to be the start of WWII • Trade named Polamidon • Patent filed in 1941 • After WWII, it came to Eli-Lilly, who named it Dolophine • Dolor = ‘Pain’; Fin = “End”

  8. Opiate Antagonists • Naltrexone, naloxone • Competitive, direct opiate antagonist • Can reverse overdose • If opiate dependent, can induce withdrawal • “Rapid detox” • Suppresses ETOH cravings

  9. Amphetamines • WWI: Benzedrine • WWII: Methamphetamine • Adderall (Mixed amphetamine salts) • Ritalin (methylphenidate) • Dexedrine (d-amphetamine) • Ecstasy ([+/-] methylenedioxymethamphetamine) • Desoxyn (methamphetamine)

  10. ADHD • Ritalin • Concerta • Ritalin SR • Adderall • Adderall XR • Dexedrine • Dexedrine Spansule • Wellbutrin • Strattera

  11. ADRs • Weight loss • Hence, the treatment for obesity • Insomnia • Good for narcoleptics • Growth delay or retardation • Not terribly common: • Hallucinations • Depression • Appathy • Often give ‘drug holidays’ on weekends or during summers

  12. Dose Response Effects with ADHD • Tailor to needs of the patient • Low to moderate doses • Improved learning, but not behavior • Higher doses • Improved behavior, but not learning

  13. Adverse Drug Reactions Top 8 Reasons • Failure to adjust dose for age, weight, gender, or body system (e.g., kidney, liver) • Failure to recognize individual variation in drug response • Failure to monitor narrow TI drugs • Failure to gradually discontinue long-term pharmacotherapy • Failure to acknowlege interactions • Failure to identify patients who may be susceptible to ADRs (related to #2) • Failure to consider the risk of addiction • Failure to stay in control (allowing family, drug companies or patients pressure into prescribing something potentially risky)

  14. Allergic ADRs • Exposure dose • Anaphylactic • Sudden and deadly (roughly 30 min) • Hits surface of mast cells • Breathing • Hypotension • Stomach cramps • Swollen throat • Not terribly common in psychoactives per se, but sometimes the vehicle

  15. More Allergies • Cytotoxic • Antigen attaches to cell surface • Antibodies destroy the whole cell • Most often affects liver, skin & kidney • “Serum Sickness” • Antigen-antibody combination circulates in your system, destroying tissue as it passes • Reminiscent of car chase sequence in cheap action movie • Arthritis, fever, tissue death, rash • Tissue inflammation • Antigens react to antibodies attached to lymphocytes • Insect bite, TB test, allergy testing

  16. Cardiovascular ADRs • Blood pressure • Hypertension can cause intracranial hemorrhage and strokes if susceptible • Usually stimulants • Hypotension can cause fainting • Cardiac conduction • Rhythmic/flow problems • TCAs • Usually not a problem unless there’s a preexisting condition • Other rhythm effects • Bradycardia (60bpm or less) • Tachycardia (100 bpm or more) • Fainting, dizziness, movement problems • TCAs

  17. Neuroleptic Malignant Syndrome • Antipsychotic malignant syndrome • Deadly: Kidney failure or Respiratory attack • Altered state of consciousness • ANS problems (incontinence, pulse, respiration, perspiration • Hyperthermia (104oF or more) • Muscular rigidity • Kills up to 20%

  18. NMS • Sudden extensive DA blockade in hypothalamus and nigrostriatal pathway • May need preexisting musculoskelatal metabolism deficit • Risk factors • 40 or older • Male • Injecting • High or rapidly decreasing doses • Affective disorders • Take off meds immediately • Supportive, symptomatic care • DA agonist (e.g., bromocriptine) • Skelatal muscle relaxants

  19. Serotonin Syndrome • Too much 5-HT on board • Atypicals • Esp if in conjunction with SSRIs • Agitation • Hyperthermia • Incoordination • Drooling • Can be countered with 5-HT antagonist (methysergide, Sansert)

  20. Extrapyramidal • Dystonia: intermittent or sustained muscle contractions • Strange postures and repetitive twisting movements • Occurs after or during the first few days • Will go away after you remove the drug • Can also treat with anticholinergic • Akathisia: Can’t sit still • Mostly antipsychotics (roughly 30% will get it) • Some SSRIs • Parkinsonian symptoms • Slow or no movements • rigid limbs • postural instability (shuffling, festination) • Reduce drug, change drug, or give an anticholinergic • Tardis

  21. Skin ADRs • Sudden Acne (Barbiturates) • Hair Loss • Stevens-Johnson syndrome • Photosensitivity (chlorpromazine) • The ‘antibiotic sunburn’ • Photoallergic • Within 2 days (requries ‘priming’ exposure) • Can look like anything from sunburn to lesions • Phototoxic • Almost always sunburn • Happens within 6 hours (no priming exposure) • Toxic Epidermal Necrolysis • As nasty as it sounds • Huge, painful eruptions that easily burst • Secondary infection

  22. ADRs in the Blood • Agranulocytosis • Increased risk for bacterial or fungal infection • Chills • Fever • Necrosis of mucus membranes • Mouth • Throat • Rectum • Vagina • Discontinue and things go back to normal in about 2 weeks

  23. More Bloody ADRs • Aplastic Anemia • Decrease of cells in marrow • Infection and hemorrhage results in death • Rare • Hemoitic Anemia • Decrease in red blood cells • Leukopenia • Decrease in white blood cells • Thrombocytopenia • Decrease in platelets • Easy bruising and bleeding • Possible internal bleeding • Healing is rapid after decrease

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