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181 Cards in this Set
- Front
- Back
Why don't we know how CNS drugs work?
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CNS research is technically difficult
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What kinds of drugs cross the BBB?
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Lipid-rich drugs
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What kind of drugs DON'T cross the BBB?
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Protein-bound or ionized drugs
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What happens with prolonged exposure to CNS drugs?
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Increased therapeutic effects
Decreased side effects Tolerance, physical dependence |
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Normal function of dopamine CNS receptors:
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Pleasure, reward, motivation, reinforcement, wide variety of behaviors and emotions
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Diseases associated with dopamine receptors:
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Parkinson's
Schizophrenia |
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Normal function of norepinephrine CNS receptors:
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Arousal, wakefulness, learning, memory, mood
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Normal function of norepinephrine PNS receptors:
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ANS "fight or flight"
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Diseases associated with norepinephrine:
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Depression
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Normal function of serotonin CNS receptors:
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Sleep, dreaming, mood, eating, pain, aggressive behavior
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Diseases associated with serotonin:
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Depression
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Normal function of serotonin PNS receptors:
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GI tract function
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Normal function of GABA CNS receptors:
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Inhibitory, with a role in sleep and eating
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Diseases associated with GABA:
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Anxiety
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Normal function of acetylcholine CNS receptors:
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Arousal, attention, memory, motivation, movement
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Normal function of acetylcholine PNS receptors:
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ANS "housekeeping"
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Disease associated with CNS acetylcholine:
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Alzheimer's
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Normal function of glutamate CNS receptors:
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Long-term memory, pain perception
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Diseases associated with glutamate:
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Alzheimer's
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Normal function of endorphin/enkephalin CNS receptors:
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Pain perception, inhibition of pain
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Diseases associated with endorphins/enkephalin:
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Addiction
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Normal function of histamine 1 CNS receptors:
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Sleep/wake cycle
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What two CNS receptors are associated with memory?
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Acetylcholine
Glutamate |
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What receptors do opiates effect?
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Endorphin
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What is a seizure?
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Widespread hyperactivity of neurons in the brain
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How do seizure drugs work?
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Suppress the discharge of neurons at the focus/propagation from the focus outward
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What four ways do seizure drugs work?
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Suppress sodium influx
Suppress calcium influx Antagonism of glutamate Potentiation of GABA |
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Which class of seizure drugs will stop a seizure fastest?
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Benzodiazepenes
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Traditional anti-seizure medications:
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phenobarbital
phenytoin valproic acid carbameazepine |
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Pros of traditional antiseizure medications:
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Cheap! Well established
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Cons of antiseizure medications:
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Not as well tolerated, drug interactions, less safe in pregnancy
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What is gabapentin usually prescribed for?
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Peripheral neuropathy
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Cons of newer anti-seizure drugs:
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EXPENSIVE
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Common side effects of anti-seizure drugs:
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CNS (sedation, uncoordination)
GI (early) Dermatologic (rashes -> SJS) Hematologic (myelosuppression) Hepatic/renal Weight changes (may increase) Risk of suicidal behavior |
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Uses of phenobarbital:
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Epilepsy, sleep/sedation
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Action of phenobarbital:
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Binds to GABA receptors
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Half-life of phenobarbitol:
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4 days (long!)
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Side effects of phenobarbitol:
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Respiratory depression, dependence, sedation
Abuse, fetal harm, depression, learning impairment, rash |
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Interactions with phenobarbitol:
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CNS depressants, valproic acid (increases levels), OCP/warfarin (decreased levels)
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Action of phenytoin (Dilantin):
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Blocks Na entry into hyperactive neurons
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Use of phenytoin (Dilantin):
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Epilepsy/seizure prevention
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PK of phenytoin (Dilatin):
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Half-life depends on dose! (This is WEIRD.) Liver has limited capacity to metabolize.
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Side effects of phenytoin (Dilantin):
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CNS (nystagmus, sedation, diplopia, cognitive impairment)
Gingival hyperplasia Skin rash Teratogenic CV effects when given IV |
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Interactions with phenytoin (Dilantin):
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CNS depressants
Decreases levels of OCP, warfarin, glucocorticoids Levels are increased by diazepam, valproic acid, cimetidine, alcohol, isoniazid Levels are decreased by carbamazepine, phenobarbital |
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IV administration of phenytoin (Dilantin):
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Give ONLY with normal saline
IV push no more than 50mg/min |
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Target serum levels of phenytoin (Dilantin):
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10-20mcg/mL
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Oral adminstration of phenytoin (Dilantin):
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With meals to lower GI side effects
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Use of carbamazepine (Tegretol):
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Epilepsy, bipolar, neuralgias
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Half-life of carbamazepine (Tegretol):
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Half-life decreases as treatment progresses
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Side effects of carbamazepine (Tegretol):
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Visual sx, ataxia, vertigo, headache
Myelosuppression Teratogenic Skin reactions |
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Use of valproic acid (Depakote):
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First line for many seizures
Bipolar disease Migraine headaches |
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Side effects of valproic acid (Depakote):
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GI effects
Hepatotoxicity Pancreatitis Teratogenic Rash, weight gain, hair loss, tremor |
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Interactions with valproic acid (Depakote):
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Increases levels of phenytoin and phenobarbital
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What is the goal of seizure treatment?
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Minimize seizures, eliminate entirely if possible
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How do we diagnose seizures?
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EEG
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Is possible to switch brands/generics of antiseizure drugs?
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Really not recommended
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Do patients ever come off anti-seizure drugs?
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Withdrawal trials can happen, but need to happen slowly (over 6 weeks)
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What cases Parkinson's?
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Loss of dopamine from the substantia nigra to striatum and the imbalance of dopamine/ACh
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Are dopamine and ACh inhibitory or excitatory?
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Dopamine is inhibitory
ACh is excitatory |
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Goal of PD treatment drugs:
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Increase dopamine
Block ACh |
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Signs and symptoms of PD:
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Resting tremor (dominant side)
Rigidity Postural instability Shuffling gait Bradykinesia Dementia Depression Memory impairment Drooling |
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Is PD reversible?
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No; therapy improves symptoms, does not reverse degeneration
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First line drugs for PD:
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Dopamine replacement
Dopamine agonists |
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Dopamine replacement drugs:
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Levodopa, levodopa/carbidopa (Sinemet)
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Dopamine agonist drugs:
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pramipexole (Mirapex)
ropinirole (Requip) rotigotine (Neupro) |
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2nd line drug for PD:
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Dopamine releaser (amantidine/Symmetrel)
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How do COMT inhibitors work?
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Block the breakdown of levodopa in the gut
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How do MAO-B inhibitors work?
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Prevent dopamine breakdown
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MAO-B inhibitor drugs:
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selegiline (Carbex/Zelapar)
resagiline (Azilect) |
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If a patient is 70 or older, how do we treat PD?
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Start with levodopa
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If a patient is younger, how do we treat PD?
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Start with dopamine agonist or MAO-B, save the levodopa
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How long is levodopa effective for?
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About 5 years
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Action of levodopa:
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Converted to dopamine in the striatum
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Time until effect of levodopa:
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Over months
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Describe fluctuation in levodopa effectiveness:
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"On-off" phenomenon
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Side effects of levodopa:
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N/V (early)
DYSKINESIAS (tics, head bobbing) Postural hypotension Somnolence Psychosis |
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Interactions with levodopa:
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Traditional antipsychotics
MAO-Is Pyridozine (vitamin B6) High-protein meals |
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How does adding carbidopa affect levodopa?
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Allows more dopamine to get to the brain
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Action of dopamine agonists:
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Binds to D2, D3 receptors
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Side effects of dopamine agonists:
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Less dyskinesia than levodopa
Nausea, dizziness, daytime sleepiness, insomnia, constipation, weakness, hallucinations When combined w/ levodopa, orthostatic hypotension, dyskinesias |
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Examples of anticholinergic agents:
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benztropine (Cogentin)
trihexyphenidyl (Artane) |
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Action of anticholinergic agents:
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Blocks activation of muscarinic (cholinergic) receptors in brain/periphery, restores DA/Ach balance
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Side effects of anticholinergic agents:
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Can't see, can't pee, can't spit, etc...
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Who should not take anticholinergic agents?
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The elderly
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Pathophysiology of schizophrenia:
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Excessive dopamine, insufficient glutamate
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Three types of schizophrenia symptoms:
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Positive, negative, cognitive
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Two major groups of antipsychotics:
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Conventional
Atypical |
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How do conventional antipsychotics work?
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Block dopamine receptors
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How do atypical antipsychotics work?
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Block serotonin (and to a low degree, dopamine)
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What are positive schizophrenia symptoms?
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Hallucinations, delusions, paranoia
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Negative symptoms of schizophrenia:
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Withdrawal, lack of insight, blunted affect, poor self-care, etc
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What's the major difference in antipsychotic classes?
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Side effects
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Uses for conventional antipsychotics:
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Schizophrenia
Bipolar disorder Tourette's Emesis Dementia Organic syndromes |
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What's the danger in using antipsychotics in the elderly?
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Doubles the rate of death from CV event or infection
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Action of conventional antipsychotics:
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Blocks dopamine, ACh, histamine, NE
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Relationship between potency and SE in conventional antipsychotics:
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High potency produces lower SE
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Classification of conventional antipsychotics:
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Low potency: chlorpromazine (Thorazine), thioridazine (Mellaril)
Medium potency: loxatine (Loxitane) High potency: haloperidol (Haldol) |
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Side effects of conventional antipsychotics, by transmitter:
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Dopamine: EPS, prolactin release
Histamine: sedation, weight gain Norepinephrine: ortho hypotension, tachycardia Serotonin: weight gain, insulin resistance Acetylcholine: dry mouth, constipation |
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Extrapyramidal symptoms:
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Acute dystonia
Parkinsonism Akathisia Tardive dyskinesia |
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Difference between drug-induced parkinsonism and PD:
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PD tends to affect dominant side first
Drug-induced tends to be bilateral |
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Symptoms of neuroleptic malignant syndrome:
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Lead-pipe rigidity
Very high fever ANS instability (BP up and down, arrhythmias) |
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Endocrine side effects of antipsychotics:
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Gynecomastia
Galactorrhea Mentrual irregularity |
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Side effects of atypical antipsychotics:
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Metabolic effects: weight gain, diabetes, dyslipidemia
Seizures, myocarditis Agranulocytosis |
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Dangerous adverse effect of atypical antipsychotics:
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Agranulocytosis
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Examples of atypical antipsychotics:
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Zyprexa (weight gain!!)
Risperdal (for bipolar, autism) Seroquel (for bipolar mania) Geodon (low metabolic SE risk) Abilify (major depression - no metabolic SE) |
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Examples of tricyclic antidepressants:
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imipramine (Tofranil)
amitriptyline nortriptyline (Pamelor) doxepin (Sinequan) |
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Action of tricyclic antidepressants:
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Block reuptake of NE and serotonin
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Use of tricyclic antidepressants:
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Depression, bipolar, neuropathic pain, insomnia, ADHD, panic, OCD
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Onset of action of tricyclic antidepressants:
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1-3 weeks initial
1-2 months max |
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Side effects of tricyclic antidepressants:
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CARDIAC TOXICITY
Lethal dose is 8x daily dose Sedation, hypotension, anticholinergic |
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Interactions with tricyclic antidepressants:
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MAOI, anticholinergics, CNS depressants
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Examples of SSRIs:
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fluoxetine (Prozac)
paroxetine (Paxil) sertraline (Zoloft) fluvoxamine (Luvox) citalopram (Celexa) escitalopram (Lexapro) |
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Uses for SSRIs:
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Major depression
Anxiety, PTSD, panic disorders |
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Time to effect of SSRIs:
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1-3 weeks
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Action of SSRIs:
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Inhibits reuptake of serotonin at synapse
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Symptoms of serotonin syndrome:
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MS changes, neuromuscular findings (tremor, hyperreflexia, myoclonus, autonomic instability), fever, mydriasis, BP fluctuations, tachycardia
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Most common SE of SSRIs:
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Sexual dysfunction
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Side effects of SSRIs:
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Sexual dysfunction
Weight-gain Nausea Nervousness, insomnia, anxiety Withdrawal syndrome |
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Examples of SNRIs:
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venlafaxine (Effexor)
desvenlafaxine (Pristiq) duloxetine (Cymbalta) |
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Uses of SNRIs:
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Major depression, GAD, social anxiety
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SEs of SNRIs:
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Very similar to SSRIs, but need to monitor BP
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Action of SNRIs:
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Block reuptake of both serotonin and NE
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Examples of MAOIs:
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isocarboxazid (Marplan)
phenelzine (Nardil) tranylcypromine (Parnate) |
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Danger of MAOIs:
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Hypertensive crisis if tyramine is consumed
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Action of MAOIs:
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Inactivates monoamine neurotransmitters (NE/serotonin/DA) and irreversible inhibition of MAO-A
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Interactions with MAOIs:
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Foods containing tyramines
Cold medicines and many others |
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Side effects of MAOIs:
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CNS stimulation
Orthostatic hypotension Hypertensive crisis |
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Drug interactions with MAOIs:
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Epinephrine
Cold meds Asthma meds SSRIs TCAs Antihypertensives Demerol levodopa |
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Tyramine-rich foods:
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Yeast extracts, cheese, aged cured fish, imported beers, Chianti wine, fava beans, figs, bananas
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The structure of buproprion is similar to:
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Amphetamines
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Time to effect of buproprion:
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1-3 weeks
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Noticably lacking side effects of buproprion:
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Sexual SE, weight loss
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Most serious SE of buproprion:
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Seizures
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Side effects of bupriprion:
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Agitation, headache, constipation, dry mouth, GI upset, dizziness, tremor, insomnia, blurred vision, tachycardia
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Examples of MAOIs:
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isocarboxazid (Marplan)
phenelzine (Nardil) tranylcypromine (Parnate) |
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Danger of MAOIs:
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Hypertensive crisis if tyramine is consumed
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Action of MAOIs:
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Inactivates monoamine neurotransmitters (NE/serotonin/DA) and irreversible inhibition of MAO-A
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Interactions with MAOIs:
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Foods containing tyramines
Cold medicines and many others |
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Side effects of MAOIs:
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CNS stimulation
Orthostatic hypotension Hypertensive crisis |
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Drug interactions with MAOIs:
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Epinephrine
Cold meds Asthma meds SSRIs TCAs Antihypertensives Demerol levodopa |
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Tyramine-rich foods:
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Yeast extracts, cheese, aged cured fish, imported beers, Chianti wine, fava beans, figs, bananas
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The structure of buproprion is similar to:
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Amphetamines
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Time to effect of buproprion:
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1-3 weeks
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Noticably lacking side effects of buproprion:
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Sexual SE, weight loss
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Most serious SE of buproprion:
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Seizures
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Side effects of bupriprion:
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Agitation, headache, constipation, dry mouth, GI upset, dizziness, tremor, insomnia, blurred vision, tachycardia
|
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Examples of MAOIs:
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isocarboxazid (Marplan)
phenelzine (Nardil) tranylcypromine (Parnate) |
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Danger of MAOIs:
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Hypertensive crisis if tyramine is consumed
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Action of MAOIs:
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Inactivates monoamine neurotransmitters (NE/serotonin/DA) and irreversible inhibition of MAO-A
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Interactions with MAOIs:
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Foods containing tyramines
Cold medicines and many others |
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Side effects of MAOIs:
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CNS stimulation
Orthostatic hypotension Hypertensive crisis |
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Drug interactions with MAOIs:
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Epinephrine
Cold meds Asthma meds SSRIs TCAs Antihypertensives Demerol levodopa |
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Tyramine-rich foods:
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Yeast extracts, cheese, aged cured fish, imported beers, Chianti wine, fava beans, figs, bananas
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The structure of buproprion is similar to:
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Amphetamines
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Time to effect of buproprion:
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1-3 weeks
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Noticably lacking side effects of buproprion:
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Sexual SE, weight loss
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Treatment of bipolar disorder:
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Mood stabilizers (lithium, valproic acid, carbamazepine)
Antipsychotics (olanzapine, risperidone) Antidepressants (SSRIs, Wellbutrin, Effexor) combined with mood stabilizer |
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Time to effect of lithium:
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Effects in 5-7 days
Full in 2-3 weeks |
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Most serious SE of buproprion:
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Seizures
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Side effects of bupriprion:
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Agitation, headache, constipation, dry mouth, GI upset, dizziness, tremor, insomnia, blurred vision, tachycardia
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Uses of buproprion:
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Depression, smoking cessation
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Drug of choice for mania:
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Lithium
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Half-life of lithium:
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Very short, needs multiple daily doses
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Therapeutic serum lithium levels:
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0.8 - 1.4 mEq/L
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When taking lithium, what intake is critical to maintain?
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SODIUM - low Na increases lithium levels
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Signs of low lithium levels:
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GI upset, polyuria, lethargy, slurred speech, muscle weakness, hand tremor, hypothyroid
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Signs of lithium toxicity:
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Muscle hyperirritability, sedation, clumsy, confusion, giddiness, ataxia, polyuria, tinnitus, blurred vision, fasciculations, seizures, clonic movements
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Interactions with lithium:
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Loop and thiazide diuretics
NSAIDs Anticholinergic agents (antihistamines, pheothiazines, antipsychotics, TCAs) |
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Uses of sedative-hypnotic agents:
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Antianxiety
Anxiolytic Tranquilizers |
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Class of sedative-hypnotic agents that directly mimics GABA:
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Barbiturates
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Big three benzodiazepines:
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diazepam (Valium)
lorazepam (Ativan) misazolam (Versed) |
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Uses of benzodiazepines:
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Anesthesia
Anxiety Seizure Insomnia Also muscle spasm, panic disorder, alcohol withdrawal |
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Action of benzodiazepines:
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Enhances inhibitory action of GABA by binding to GABA receptors
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Side effects of benzodiazepines:
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CNS depression, respiratory depression
Amnesia, abuse, "opposite" effects |
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Interactions with benzodiazepines:
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Alcohol, opioids, barbiturates
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Competitive antagonist to benzodiazepines:
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flumazenil (Romazison)
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Drugs used for insomnia:
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zolpidem (Ambien)
zaleplon (Sonata) eszopiclon (Lunesta) |
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Action of anti-insomnia drugs:
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Agonist at benzodiazepine site on GABA receptor
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Drugs used for ADHD:
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Amphetamines (CNS stimulants)
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Action of amphetamines:
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Promote release of NE, DA
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Side effects of amphetamines:
|
Weight loss, CV effects
|