Psychiatric Disorders Flashcards
Major Depressive Criterion
2/> Weeks w/Depressed mood most of the day, Markedly diminished interest or pleasure in most activities, Weight loss/gain, Insomnia/Hypersomnia, Agitation, Fatigue, Guilt, No concentration, Suicidal ideation;
Criterion for Manic Episode
1wk - Abnormal and persistent elevated, expansive or irritable mood
3/> Inflated self esteem, decreased need for sleep, Talkative, Flight of ideas, Distractibility, Increased goal directed activity, Excessive risky pleasure
Drugs for Treating Depression
Trycyclic Antidepressants, 2nd Generation or heterocycle, Monoamine oxidase-A inhibitors, SSRIs
-ipramine
TCA
-tyline
TCA
-xetine
SSRI
-opram
SSRI
-azadone
2nd Gen
-apine
2nd Gen
Tricyclic Antidepressants
Shotgun Drug
Blocks reuptake of NE, 5HTT in brain; Causes down regulation of postsynaptic receptors or 2nd messengers
Blocks Ach receptors, Blocks Histamine receptors, Blocks alpha adrenergic receptors, 2nd Generation (block alpha2, 5HT), Local anesthetic (chronic pain)
Tricyclic Antidepressants Indications
Depression (Delayed max action, Full therapeutic activity in 2-3wks); Enurisis - Bed wetting (Decrease REM, Increase deep sleep), Chronic pain (NE-5HT descending pain control or local anesthetic action - Potency based on Lidocaine>Carbamazepine>TCA>SSRI; beta adrenoreceptors in reducing pain, 5HT less involved)
Tricyclic Antidepressants Side Effects
Sedation
Anticholinergic Side Effects (Xerostomia, Constipation, Vagal cardio-inhibitory tone, Urinary retention, Glaucoma, Fail of temp control, Anemia/Memory dysfunction, Cardiotoxicity (Increase catecholamine duration, Direct cardiotoxicity, Orthostatic hypotension), Weight gain, Lower seizure threshold (Including second-gen agents Bupropion), BB Suicidal ideation, Mania
Tricyclic Antidepressants Drug Interactions
Agents with CNS depressing properties (Enhance sedative), NE and sympathomimetics (LA, Elevate BP, BP response to sympathomimetics) Agents substrates for CYP2D6 or CYP3A4 and P-Glycoprotein inhibitors, Many inhibit HERG K+ channels and make inhibitor (Erythromycin) worse, Chance for pQT, Other anticholinergics, Displace drugs from protein binding, Severe reaction in patients with MAO-A inhibitors, Serotonin syndrome
2nd Generation or Heterocycle
Shotgun Drugs
Bupropion (Wellbutrin/Zyban) - DAT
Buproprion
2nd Generation or Heterocycle;
Mild dopamine reuptake transport blocker, Mild block of serotonin receptors, Used to aid smoking cessation, Dry mouth, Overdosing lowers seizure threshold, Abuse potential
Selective Serotonin Reuptake Inhibitors - SSRI
NOT Shotgun Drug
Fluoxetine (Prozac, Sarafem)
Selective presynaptic 5HTT reuptake transporter blocked, Increase CNS 5-HT, Less binding NE, Ach, DA receptors, Possible neuroprotective
SSRI Use
Depression, OCD, PMS, Panic attacks, Bulimia Nervosa, Anxiety; Few side effects than TCA - Useful in patients where side effects unacceptable, Not equipotent
Fluoxetine
(Prozac, Sarafem)
All Inhibit P-Glycoprotein
Long half life and Active metabolites, Blocks metabolism of other drugs through P450 mechanism (CYP2D6, CYP2C19 - Lidocaine does CYP3A4)
Other SSRI - Paroxetine, Sertraline, Fluvoxamine
All inhibit P-Glycoprotein, Shorter action, Less P450 block
SSRI Side Effects
Nausea, Insomnia, Tremor, Headache, Sexual Side effects, Bleeding, Suicide BB, Serotonin syndrome, Antidepressant withdrawal syndrome, Teratogenicity, Parkinson like side effects;
Dental Side Effects - Mild Xerostomia, Increase jaw clenching and bruxism (Cracked teeth), Onset days-2mo after SSRI, Incidence of motor side effects, Females higher rates, Adolescent and Elders; Decrease platelet serotonin storage and platelet function - Increase bleeding
SSRI Drug Interactions
Monoamine Oxidase inhibitors - “Serotonin syndrome,” Serotonergic agonists, NSAIDs (Increased ulcers), Substrates or inhibitors of P450 metabolism, Several increase pQT or TdP and SNRI velafaxine, Displace SSRI from plasma or vice versa
Selective Serotonin/NE Reuptake Inhibitors - SNaRI and NaRI
Vary use, Side effects - Dry mouth, Hypertension, Vasoconstrictors
Monoamine Oxidase A Inhibitors
NOT Shotgun drugs
Phenelzine (Nardil), Tranylcypromine (Parnate); Block Monoamine Oxidase Type A, No action on other receptors, Irreversible blockade, Elevate free NE or 5HT
MAO-I Uses
Used where side effects of Tricyclics is unacceptable - Elderly, Cardiovascular disease, Replaced by SSRI; Possible hepatotoxicity, Orthostatic Hypotension, Tachycardia, Dry mouth
MAO-I Drug and Food Interactions
Opiates (Especially Meperidine), Tryclic antidepressants, SSRI, Barbiturates, Alcohol, Sympathomimetics
Food high in Tyramine - Precursor to NE, Displaced presynaptic NE (Cheese, Wine, Canned fish, Snails, Liver, Nuts, Beans, Citrus fruit, Coffee, Yeast) - Severe headaches and hypertension
St. John’s Wort
Naturceutical; Super reuptake blocker of bioamines, Variable amount of hyperforin, Action mediated by TRPC6 - Modulates Na, Ca for reuptake and modulates neurite growth; Induces P450 enzymes (PXR) Drug interactions!!
Mania Drug Treatment
Lithium Carbonate; Neuroprotective, Adjunct agents sometimes (Haloperidol, Anticonvulsant - Carbamazepine, Anticonvulsant - Valproate and many like thyroid, omega fatty acids, calcium channel blockers)
Lithium Carbonate Side Effects
Mania; Induces diabetes incipidus, leads to marked xerostomia and rampant caries;
Lithium Carbonate Drug Interactions
Drugs alter urinary excretion - Diuretics (Paradoxically used to control diabetes incipidus), NSAIDs, Anticholinergic drugs
Other Depression Treatment
Electroconvulsive therapy - Effective, Less side effects and toxicity, Loss of memory, Lethal in elder
Rapid MDD reversal with IV Ketamine - Low dose ketamine can reverse MDD or bipolar depression in few hour and relief lasts week, Reduce suicidal ideation; Classified dis-associative anesthetic that blocks NMDA glutamate receptors to produce amnesia and analgesia; Psychomimetic side effects
Symptoms of Schizophrenia
Diagnosis - 2 or more of following, for 6mo and 1mo active:
Positive - 1/3
Delusions, Hallucinations, Disorganized speech and behavior, Disorganized/Catonic behavior
Negative - Flattening, Alogia or Avolition
Cognitive - Memory, Judgement problem, Decreased empathy and problems, Visual tracking delay or Olfactory deficit
Therapeutic Target for Antipsychotic Drugs
Block Dopamine (D2) receptors at meso-limbic dopamine cells (Reduce positive signs of psychosis), Block dopamine at chemoreceptor trigger zone, Blocks Ach receptor and Block 5HT2a receptors reduce extrapyramidal side effects (5HT2a blocks positive and negative symptoms)
Side Effects from Blocking Dopamine
Striatal (Basal Ganglia) - Extrapyramidal effects, Tardive dyskinesia (Valbenazine helps for this)
Tubro-infundibular dopamine path - Dopamine inhibits prolactin release from ant. pituitary, Adverse reaction of blocking dopamine = gynecomastia or lactation
VMAT-2 Inhibitors
Tetrabenazine, Ingrezza (Valbenazine) - FDA approved for tardive dyskinesia, Astudeo (Deutetrabenzine) - FDA approved for Huntington’s Chorea;
Indications Huntington’s chorea, Torrette’s syndrome, Tardive dyskinesia, Hemiballismus
VMAT-2 Inhibitors Side Effects
BB for Suicidal ideation! Drowsiness, Parkinson’s like side effects, GI-Dry mouth, Diarrhea, Arthralgia, Weight gain/Diabetes, Teratogen, Prolonged QT, Hyperprolactinemia, Neuroleptic malignant syndrome, Binds melanin
VMAT-2 Inhibitors Drug Interactions
MOAIA, MOAIB, Inhibitors of CYP3A4, CYP2D6 or CYP, P-Glycoprotein inducers and Drugs that sedate
Antipsychotics Side Effects
Not approved to treat dementia (Alzheimers) related psychosis - Increased deaths due to Cardiovascular events (Prolonged QT) and increased lethal infection
-azine
Classic antipsychotic
-ixine
Classic antipsychotic
-peridole
Classic antipsychotic but DA selective
-zapine
AAP w/ side effects
-idone
AAP but SDA fewer side effects
-piprazole
AAP-Partial DA agonist/low side effects
Phenothiazine
Shotgun Drug; Early antipsychotics, Acts at many receptors - Anti-dopaminergic (D1-D2), Anti-serotoninergic (5HT2), Anti-muscarinic M1 (anti-DA and anti-Ach reduces Parkinson’s like side effects), Anti-histmainergic (H1), Anti-adrenergic (alpha block - 1-2; Epi reversal, Orthostatic hypotension), Cardiac Potassium Channel Block (Prolonged QT, Torsades de Pointes), Sigma receptors
Use for Typical Antipsychotic Drugs
Management of psychotic disorders, Antiemetics, PCP psychosis, Migraine, Tourette’s syndrome, Huntington’s chorea, Systemic Lupus Erythematosus, Dementia, Adjunct in bipolar disorder
Phenothiazine Prototype
Chlorpromazine
a1>5HT2>=D2>D1>M
Older agents reduce delusions and hallucinations
Haloperidol
Butryophenone - LESS Shotgun like
“Selective” antipsychotic; Blocks D2 receptors preferentially - sigma>D2>D1=D4>a1>5HT2; Little anticholinergic action - High incidence of EPS, Add antichoinergic agents, Switch to AAP
Classic Antipsychotic Medication Side Effects
Drowsiness, Parkinsons, Dyskinesia, Perioral tremor, Rabbit syndrome, Tardive dyskinesia, Dry mouth, Constipation, Glaucoma, Orthostatic Hypotension (alpha-blockade) - Epinephrine “reversal”, Prolonged QT, Deaths in elder, Endocrine changes - DA block prolactin secretion and gynecomastia in prolong use, Neuroleptic Malignant Syndrome, Photosensitivity, Weight gain, Pigmentation
Atypical Antipsychotics - “AAP”
Clozapine (Clozaril) - Shotgun Drug
Blocks many receptors, M>5HT2,6,7=H1=a1=a2=D4>D1=D2, Low extra pyramidal side effects, Improves “negative” signs, Improve course of disease, Strong antimuscarinic action - Increases salivation and may involve a2A polymorphic receptor, Potential for hepatic, pancreatic toxicity (Diabetogenic-related to H1 block), Cardiovascular toxicity and Agranulocytosis (5BB!! - Require REMS)
AAP with Diabetes Hyperglycemia Warning
Clozapine and Olanzapine
