Psychotherapeutic Drugs PDF

Psychotherapeutic Drugs: Ch 34 Antipsychotic Drugs Ch 35 Antidepressants Ch 36 Drugs for Bipolar Disorder Ch 38 Anxiolytics Objectives Define condition related to depression, anxiety states and psychoses Discuss the prototype drugs used in the treatment of each of these conditions Discuss...

Psychotherapeutic Drugs: Ch 34 Antipsychotic Drugs Ch 35 Antidepressants Ch 36 Drugs for Bipolar Disorder Ch 38 Anxiolytics Objectives Define condition related to depression, anxiety states and psychoses Discuss the prototype drugs used in the treatment of each of these conditions Discuss the mechanism of action, indications, major adverse effects, precautions, contraindications, interactions for these classifications and the selected prototypes Describe the therapeutic effects of the agents Describe care of patients receiving these drugs Psychotherapeutic Drugs Treatment of emotional and mental health disorders Can range from occasional depression or anxiety to constant emotional distress inability to carry on normal daily living Psychotherapeutic Drugs “The therapy of emotional and mental health disorders” Naming of Drugs (good or bad?) Anti-anxiety drugs (anxiolytics) Antidepressants and mood stabilizers Antipsychotics Psychotherapeutic Drugs Inherent subjectivity in description and reporting of symptoms How to establish effectiveness of drug therapy? Verbal reports and observation Tools eg Hamilton Depression Rating Scale, self-administered rating scales, others Psychotherapeutic Drugs Three main emotional and mental health disorders Anxiety Mood (affective) disorders Psychoses Psychotherapeutic Drugs Anxiety – unpleasant emotional state Perception of real or perceived dangers Mood (affective) disorders Mania (abnormally pronounced emotions) Depression (abnormally reduced emotions) Bipolar disorder – periodic swings Psychotherapeutic Drugs Psychosis major emotional disorder that impairs the mental function of the affected individual to the point that the individual cannot participate in everyday life loss of contact with reality Schizophrenia Depressive and drug-induced psychoses Psychotherapeutic Drugs Understanding mental health disorders is very difficult Treatment of mental health disorders is complex Why? Psychotherapeutic Drugs Complex consequences drug action drugs used to treat mood disorders often take weeks to take full effect Probably reflects adaptive responses to drugs Psychotherapeutics: Pathophysiology Biochemical imbalance theory Over simplistic description underlying mental health conditions Co-ordination of neuronal activity play an important role in maintaining mental health  Mood (Affective) Disorders: Antidepressants Ch 35 Mood and Affect “mood” a sustained emotional attitude typically garnered through patient self-report “affect” the way a patient’s emotional state is conveyed relates more to others’ perception of the patient’s emotional state, responsiveness Mood (Affective) Disorders Depression Mania Or episodes of both Depression What are the symptoms of depression? Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5) Depression Persistent sad, anxious, or "empty" mood Loss of interest or pleasure in hobbies and activities that were once enjoyed, including sex Loss of appetite and/or weight loss, or conversely overeating and weight gain Insomnia or oversleeping Restlessness or irritability Feelings of worthlessness, inappropriate guilt, helplessness, hopelessness, pessimism Difficulty thinking, concentrating, remembering, or making decisions Thoughts of death or suicide or attempts at suicide Decreased energy, fatigue, feeling "slowed down" or sluggish Persistent physical symptoms that do not respond to treatment, such as headaches, digestive disorders or chronic pain Monoamine NTs and Depression Catecholamines Norepinephrine (NE) Norepinephrine Indolamines Serotonin (5-HT) Serotonin Anti-Depressant Drugs Newer-generation antidepressants Selective serotonin reuptake inhibitors (SSRIs) Mixed serotonin (5-HT) and NE reuptake inhibitors (SNRI) NE reuptake inhibitors Tricyclic antidepressants (TCA) Monoamine oxidase inhibitors (MAOIs) Anti-Depressant Drugs: SSRIs Most commonly prescribed drugs for depression sertraline (Zoloft) fluoxetine (Prozac) – original 1988 paroxetine (Paxil) fluvoxamine citalopram (Celexa) Drugs for Depression: SSRIs SSRIs may take from 2-6 weeks to have effects Keep taking the meds! Structural changes? SSRI: Mechanism of Action Selectively inhibit 5-HT reuptake increased serotonin concentration in synapse little or no effect on NE or DA reuptake Advantage over tricyclics and MAOIs little or no effect on cardiovascular system SSRI: Indications Major Depressive Disorder Bipolar affective disorder But not alone! Also Eating disorders Obsessive-compulsive disorder Panic attacks Myoclonus (quick, involuntary muscle jerk) SSRI: Adverse Effects CNS Headache, nervousness, insomnia, fatigue GI Nausea Other Sexual dysfunction, weight gain Serotonin Syndrome Within 2 – 72 Hours Cognitive confusion, agitation, restlessness Autonomic tachycardia, hypertension, hyperthermia, sweating Neuromuscular clonus, hypereflexia, tremour Drugs for Depression - SNRI SNRI (serotonin and norephinephrine reuptake inhibitor) Venlafaxine (Effexor) duloxetine Drugs for Depression – SSRI and SNRI No more effective than older TCAs and MAOIs Fewer adverse effects than TCAs eg anticholinergic action MAOIs eg ‘cheese reaction’ Few drug-drug or drug-food interactions Tricyclic Antidepressants (TCAs) Tricyclic Antidepressants No evidence that SSRIs/SNRIs more effective that TCAs for major depressive disorder Why not commonly in use? Tricyclic Antidepressant Drugs Have largely been replaced as first-line drugs for depressant by SSRIs/SNRIs Considered second-line For clients who fail with SSRIs or other newer- generation antidepressants As adjunct therapy with newer drugs Tricyclic Antidepressant Drugs: Indications Depression Childhood enuresis (uncontrolled urination; imipramine) Obsessive-compulsive disorders (clomipramine) Adjunctive analgesics Trigeminal neuralgia Tricyclic Antidepressant Drugs Amitriptyline Imipramine desipramine clomipramine without TCA with TCA TCA TCA TCAs Block TCA here Tricyclic Antidepressant Drugs Blockade of NE reuptake Blockade of 5-HT reuptake Tricyclic Antidepressant Drugs Also, receptor block of: Mucarinic (cholinergic) receptors α1-adrenoceptors H1 receptors Leads to predictable adverse effects Tricyclic Antidepressant Drugs: Adverse Effects Sedation CNS H1 receptor blockade But wears off after 1-2 weeks Anticholinergic effects blurred vision, dry mouth, constipation, urinary retention, tachycardia Orthostatic hypotension α1-adrenoceptor blockade Tricyclic Antidepressant Drugs: Serious Adverse Effects Caution in patients with existing disorders Cardiac Dysrhythmias Anticholinergic effect Slows conduction in Bundle of His Seizures (excessive excitability of brain neurons) TCAs in Overdose Can be lethal 70% to 80% die before reaching hospital Death results from seizures or cardiac dysrhythmias TCAs in Overdose No antidote for acute toxicity decrease drug absorption with activated charcoal speed elimination by alkalinizing urine manage seizures and dysrhythmias with drugs basic life support Monoamine Oxidase Inhibitors (MAOI) MAOIs First generation drugs for depression phenelzine Now treatment for depression not responsive to other drugs Disadvantage: potential to cause hypertensive crisis when taken with tyramine (cheese effect) MAOIs: Mechanism of Action Inhibit MAO enzyme In CNS and peripheral tissues Enzyme metabolizes monoamine (DA, 5-HT, NE) neurotransmitters With MAOIs, reduced breakdown of monoamines in neurones greater amounts released from neurones MAOIs: Adverse Effects Orthostatic hypotension most common dizziness/light-headedness tachycardia CNS stimulation Insomnia, anxiety MAOI and the “cheese effect” MAOIs: Food and Drug Interactions Ingestion of foods and/or drinks with tyramine may lead to hypertensive crisis Hypertensive Crisis Most serious problem with MAOIs Severe headache, hypertension, tachycardia possible cerebral hemorrhage, stroke and death MAOIs: Food and Drug Interactions Avoid foods that contain tyramine! Aged, mature cheeses (cheddar, Blue, Swiss) Smoked/pickled or aged meats: fish, sausage (salami, pepperoni), corned beef, paté Yeast extracts (Marmite) Red wines (Chianti, burgundy, sherry, vermouth) Italian broad beans (fava beans) MAOI If switching from an SSRI to MAOI must be a 2- to 5-week “wash-out” drug-free period between SSRI and MAOI therapy If switching from MAOI to a TCA/SSRI must be a 2-week “wash-out” drug-free period between drugs also maintain diet restriction 2 weeks after MAOI cessation Other Drugs for Depression Other Drugs for Depression bupropion block of DA and NE reuptake mirtazapine increase release of 5-HT antagonism at certain 5-HT receptors vortioxetine (2014) complex modulation of 5-HT neurotransmission block of 5-HT reuptake, agonist at some 5-HT receptors and antagonism at other 5-HT receptors Drugs for Depression: Client Care Implications Inform clients that it may take 2 to 4 weeks to see therapeutic effects Monitor clients closely during this time, assess for suicidal tendencies, and provide support Sedation often occurs with tricyclic therapy notify physician if this lasts more than 2 weeks Drugs for Depression: Client Care Implications Monitor for therapeutic effects: Improved sleep patterns and nutrition increased feelings of self-esteem decreased feeling of hopelessness increased interest in self and appearance increased interest in daily activities fewer depressive manifestations or suicidal thoughts or ideations Anxiety Disorders Chapter 38 Anxiety Disorders Uncomfortable state that has both: Psychologic components Fear, apprehension, dread, uneasiness Physical components Tachycardia, palpitations, trembling, sweating, shortness of breath Treatment when persistent and disabling Anxiety Disorders What are some examples of anxiety disorders? Major anxiety disorders (persistent anxiety) Generalized anxiety disorder (GAD; unfocused cause) Social anxiety disorder (human interactions) Obsessive-compulsive disorder (OCD; ritulistic) Posttraumatic stress disorder (PTSD; recall of past stressful events) Panic disorder (overwhelming fear = sweating, tachycardic) Phobia (multiple forms, specific objects or situations) Anxiolytic Drugs Benzodiazepines (BZDs) Barbiturates (similar action) no longer used Drugs initially used in depression (antidepressants) SSRIs and SNRIs for all anxiety disorders Buspirone in GAD (weeks for effect) 5-HT1 agonist non-sedating and non-habit-forming Anxiolytic Drugs Drugs used for seizures in GAD Valproate, gabapentin Antipsychotics in GAD and PTSD Olanzepine, risperidone Anxiolytic Drugs Benzodiazepines (BZDs) Depress activity in brainstem and limbic system Immediate relief Used sparingly long term Benzodiazepines CNS Depressant (see class) “Sedative-Hypnotic” Increasing Dosage 1. anxiolytic 2. sedation 3. hypnotic (promote sleep) 4. stupor (near-unconsciousness or insensibility) Benzodiazepines: Indications Anxiety BZDs also for Sedation including conscious sedation Muscle relaxation Seizure control Adjuvant therapy for depression Alcohol withdrawal Benzodiazepines Benzodiazepines used as anxiolytics lorazepam (Ativan) alprazolam diazepam (Valium) clonazepam Benzodiazepines: Mechanism of Action GABA reduces excitability of neurones Fewer action potentials in neurones Benzodiazepines enhances effect of GABA Decreased neuronal excitability =Depress CNS activity GABA-Releasing Neurone GABA Benzodiazepines Decrease Activity in Post-synaptic neurone Benzodiazepines Little respiratory depression given po contrast to barbiturates BZDs much safer in overdose Respiratory Depression IV combined with opioids, alcohol, barbiturates Benzodiazepines: Adverse Effects Decreased CNS activity Drowsiness, loss of coordination, dizziness, confusion Affects manual skills Potentially habit-forming and addictive but less than barbiturates Psychotherapeutic Drugs: Client Care Implications Monitor for anxiolytics therapeutic effects Improved mental alertness, cognition, and mood Fewer anxiety and panic attacks Improved sleep patterns and appetite Less tension and irritability, fewer feelings of fear, impending doom, and stress More interest in self and others Bipolar Disorder Chapter 36 Bipolar Disorder Mania (euphoric/hypomania) enthusiasm rapid thought and speech patterns extreme self confidence impaired judgment risk taking Different from psychosis (schizophrenia) disturbances in thoughts Bipolar Disorder Depression Similar symptoms to other depressive conditions Bipolar Disorder “Mood stablizers” Lithium carbonate Drugs used for other indications Bipolar Disorder Lithium first-line treatment of mania and manic depressive illness acute episodes and maintenance May be used with other medications to stabilize mood Poor understanding of mechanism Bipolar Disorder Narrow therapeutic range maintenance serum levels should range between 0.4 and 41OC) CV problems (BP irregularities, cardiac dysrhythmias) may end in seizures or coma Therapy removal of typical antipsychotic drug antipyretics, dantrolene, bromocriptine Typical Antipsychotics: Adverse Effects Body System Effects Neurological Extrapyramidal motor disturbances (EPD/EPS) Other CNS Sedation, delirium Cardiovascular Orthostatic hypotension, syncope, dizziness, ECG changes (Long QT) Dermatological Photosensitivity, skin rash, hyperpigmentation, pruritus Atypical Antipsychotics: Second-Generation Antipsychotics clozapine (Clozaril ) very little EPD olanzapine (Zyprexa) risperidone (Resperidal) EPD eg tremors and muscle twitching Resperidal Consta IM depot injection every 2 weeks increase compliance/steady plasma levels but expensive Atypical Antipsychotics Newer drugs in Canada lurasidone minimal anticholinergic (muscarinic) action asenapine SL only Atypical Antipsychotics: Mechanism of Action Block 5-HT receptors (5-HT2 receptors) Less effect on DA receptors than typical antipsychotics hence less motor disturbances Equal efficacy to typical antipsychotics more expensive Atypical Antipsychotics Other Receptor Effects Block histamine receptors (causing sedation) Block muscarinic (cholinergic; constipation etc) Block α1-adrenoceptors (hypotension) Also used to treat anxiety states bipolar disorder Atypical Antipsychotics: Adverse Effects Varies with drug Clozapine Hematological agranulocytosis (WBC) anemia take regular blood counts Drooling opthalmic atropine eye drops SL  Table 1 Metabolic risks associated with antipsychotic drugs De Hert, M. et al. (2011) Metabolic and cardiovascular adverse effects associated with antipsychotic drugs Nat. Rev. Endocrinol. doi:10.1038/nrendo.2011.156 All Antipsychotics Weight gain Disturbances in metabolism blood glucose management plasma lipids Extent varies with drug generally associated with atypical drugs  Antipsychotics Agents: Client Care Implications Do not take alcohol or other CNS depressants with these medications Monitor for EPD eg long-term haloperidol therapy may result in tremors or uncontrollable shaking of small muscle groups symptoms should be reported to the physician Antipsychotics Agents: Client Care Implications Monitor for therapeutic effects Improved mood and affect, alleviation of psychotic symptoms and episodes Decrease in hallucinations, paranoia, delusions, garbled speech, inability to cope