Transcript PSYC650 Opiates Stimulants ADRs Interactions

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
– This plus frontal cortex activity alters emotional aspect of
pain
• Medulla
– Antitussive
– Smooth muscle slowing
• Great for treating diarrhea
– Thermoregulation
Withdrawal
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
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
Of Note
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codeine
methadone
Heroin
Oxycontin
Suboxone (buprenorphine + naloxone)
ketamine (not an opiate, but important to talk
about)
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”
Opiate Antagonists
• Naltrexone, naloxone
• Competitive, direct opiate antagonist
– Can reverse overdose
• If opiate dependent, can induce withdrawal
– “Rapid detox”
• Suppresses ETOH cravings
Amphetamines
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WWI: Benzedrine
WWII: Methamphetamine
Adderall (Mixed amphetamine salts)
Ritalin (methylphenidate)
Dexedrine (d-amphetamine)
• Ecstasy ([+/-] methylenedioxymethamphetamine)
• Desoxyn (methamphetamine)
ADHD
• Ritalin
– Concerta
– Ritalin SR
• Adderall
– Adderall XR
• Dexedrine
– Dexedrine Spansule
• Wellbutrin
• Strattera
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
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
Adverse Drug Reactions
Top 8 Reasons
1. Failure to adjust dose for age, weight, gender, or body system
(e.g., kidney, liver)
2. Failure to recognize individual variation in drug response
3. Failure to monitor narrow TI drugs
4. Failure to gradually discontinue long-term pharmacotherapy
5. Failure to acknowlege interactions
6. Failure to identify patients who may be susceptible to ADRs
(related to #2)
7. Failure to consider the risk of addiction
8. Failure to stay in control (allowing family, drug companies or
patients pressure into prescribing something potentially risky)
Allergic ADRs
• Exposure dose
• Anaphylactic
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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
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
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
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Bradycardia (60bpm or less)
Tachycardia (100 bpm or more)
Fainting, dizziness, movement problems
TCAs
Neuroleptic Malignant
Syndrome
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Antipsychotic malignant syndrome
Deadly: Kidney failure or Respiratory attack
1. Altered state of consciousness
2. ANS problems (incontinence, pulse, respiration,
perspiration
3. Hyperthermia (104oF or more)
4. Muscular rigidity
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Kills up to 20%
NMS
• Sudden extensive DA blockade in hypothalamus and nigrostriatal
pathway
• May need preexisting musculoskelatal metabolism deficit
• Risk factors
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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
Serotonin Syndrome
• Too much 5-HT on board
• Atypicals
– Esp if in conjunction with SSRIs
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Agitation
Hyperthermia
Incoordination
Drooling
Can be countered with 5-HT antagonist (methysergide,
Sansert)
Extrapyramidal
• Dystonia: intermittent or sustained muscle contractions
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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
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Slow or no movements
rigid limbs
postural instability (shuffling, festination)
Reduce drug, change drug, or give an anticholinergic
• Tardis
Skin ADRs
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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
ADRs in the Blood
• Agranulocytosis
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Increased risk for bacterial or fungal infection
Chills
Fever
Necrosis of mucus membranes
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Mouth
Throat
Rectum
Vagina
• Discontinue and things go back to normal in about 2
weeks
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
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Decrease in platelets
Easy bruising and bleeding
Possible internal bleeding
Healing is rapid after decrease