Psychopharmacology

Psychopharmacology • Therapeutic vs. toxic dosage levels • Side effects • Adverse effects • Interactions • Use with the elderly, during Use during pregnancy • Patient teaching • nonpsychopharmacological interventions

Neuroscience • Nervous system • Limbic system – emotional control, memory, & learning • Hypothalamus – releasing hormones ->affect human behavior and keep body’s homeostasis • Basic unit – Neuron, contains cell body, nucleus, organelles, dentrites, and axons • Neurotransmitter

Function of the Brain • Maintenance of homeostasis • Regulation of autonomic nervous system (ANS) and hormones • Control of biological drives and behavior • Cycle of sleep and wakefulness • Circadian rhythms • Conscious mental activity • Memory • Social skills

Cellular Composition of the Brain - Neuron • Respond to stimuli • Conduct electrical impulses • Release chemicals • Neurotransmitters • Presynaptic neuron ->synapse -> postsynaptic neuron • Transmitter destruction • Enzymes • Reuptake

Neuronal Action Neurons can release more than one chemical at the same time • Neuropeptides • Long-term changes in cells • Neurotrophic factors • Proteins • Gases • Effect of steroid hormones

Neurotransmitter • Neurotransmitter - combine with a specific receptor; Relay a chemical message to the receptor cell • Drugs act on neurotransmitters • Agonist – activating cell function; to accelerate or slow cellular processes • Antagonist – prevent natural or other substances from activating cell function • Affinity – binding between drug and receptor • Refractoriness - desensitization of cells to a drug over time

Dopamine  Norepinephrine  Serotonin  Acetylcholine  Gamma-aminobutyric acid (GABA)  Schizophrenia Depression Depression Alzheimer’s disease Anxiety Neurotransmitters and Related Mental Disorders

Pharmacokinetics - Absorption • PO, IV, IM,…- Absorption • qid, tid, bid, … - drug level in the blood • Individual condition - sex - female: fat age - older: health - congestive heart failure, GI, • Others - exercise

Pharmacokinetics - Distribution • Target tissue • Cardiac output - electric imbalance, CHF, chr pulmonary dis • Serum protein binding • Half-life of the drug • Pregnancy

Pharmacokinetics - Metabolism • Break down or metabolize into other compound - liver • convert into other active substance – liver

Pharmacokinetics - Excretion • Proper excretion = less toxicity • Kidney - main excretion organ • Others - GI, skin, lungs, sweat glands Tissue perfusion rate - shock, hemorrhage Diseases - renal, liver ... Urinary pH - acidic urine -amphetamine alkaline urine- barbiturates

Phases of Treatment • Initiation • Stabilization • Maintenance • Medication-free

Nursing Responsibilities • Monitor the S & S of the disease state • Monitor for common, expected or worrisome side effects of medications • Preventing adverse drug reactions • Evaluate compliance • Judge the appropriateness of the regimen • Recommend needed changes • Provide pt & family education

Patient Education • Compliance - effectiveness, symptom control • Side-effect - inevitable, unpleasant, temporary; only a few are life threatening • Education - encourages compliance; Medications are not magic bullet • Balance with information - too much or inappropriate • Health beliefs model- what is the benefit of taking med • Regular checkups and test

Classes of psychotropic medication • Antipsychotic medications • Antidepressant medications • Mood-stabilizing drugs • Anti-anxiety medications • Psychostimulants

Antipsychotics - typical • 1950 - Chlorpromazine (Thorazine) • Mechanism - Block dopamine receptors • effective in treating (+) symptoms ie. alterations of perception- hallucinations thought disturbance - delusion activity - agitation

Atypical agents • 1980’s - • Targets dopamine and serotonin, may work on both (+) & (-) symptoms • Better tolerated, less side effects, better compliance, less cognitive impairment, better efficacy in negative symptoms of schizophrenia

Phenothiazines Thorazine 200-800 mg qd half-life: 30 hours Peak 2-4 hours Non-phenothiazines Haldol 1-15 mg qd half-life: 21-24 hours Higher risk of EPSs Clozaril 150-450 mg qd, watch for fever, agranulocytosis Risperdal 2-8 mg qd Less sedation Zyprexa 5-10 mg qd smaller dose for the elderly & liver dis. pt Typical & Atypical

Neurological complications of antipsychotics • Pseudoparkinsonism - muscle rigidity • Extrapyramidal Side Effects (EPSEs)- Akathisia* - motor restlessness Dyskinesia - jerky motion Dystonia -muscle rigidity; life-threatening • Tardive dyskinesia – facial grimacing tics, tongue writhing, lip smacking, puckering… - irreversible, high dose, older, females,

Other adverse effects (I) • Anticholinergic effect – dry mouth, blurred vision, constipation, • Neuroleptic maliganant syndrome (NMS) - rare, life-threatening • altered consciousness, hyperthermia, muscle rigidity, tachycardia, sweating • discontinue the medication • reverse the dopamine-blocking effects of antipsychotics (ie bromocriptine) or muscle relaxant (ie dantrolene)

Other adverse effects (II) • Seizures - threshold  • Hyperprolactinemia - breast engorgement, falactorrhea, amenorrhea, impotence, azospermia • Hepatic changes - jaundice, nausea, fever, chill, general malaise, itching • Photosensitivity • Weight gain - 3-9 lbs

Interventions for EPSEs • Tolerance usually ↑ by the 3rd month • Lower dose of drug • Add a drug to treat EPSE, then taper after 3 M on the antipsychotics • Use a drug with a lower EPSE profile • Pt education and support

Interventions for Dystonia • Occur suddenly; frightening; painful • Common in children and young males • With high potency drugs • Medication - IV > PO; • Have respiratory support available • taper antipsychotics gradually to prevent withdrawal dyskinesia

Neuroleptic Malignant Syndrome • Drug-induced disorder; • Be recognized in 1980s • Incidence – 0.2%; uncommon but potentially life-threatening • Risk factors- dehydration, agitation, catatonia, mood disorders, organic brain syndromes, drug or alcohol withdrawal states, previous NMS episodes, drugs given by injection

Characteristics of NMS • Disturbances in mental status, temperature regulation, & autonomic and extrapyramidal functions • Mental Status – catatonia • Vital signs – tachycardia, unstable BP • Extrapyramidal functions – tremors, dysarthria, dysphagia, drooling • Lab – increased WBC, elevated blood enzymes ie. Creatine phosphokinase,

Interventions for NMS • Potential fatal - tachycardia, fever, sweating, muscle rigidity, incontinence, stupor, aspiration pneumonia, leukocytosis, renal failure, • Common with high potency drugs and in dehydrated pts • Discontinue all drugs, • supportive symptomatic care (H2O; BT↓; hemodialysis) • antipsychotics can be reintroduced later

Interventions for Agranulocytosis • Emergency case; occur abruptly • Fever, malaise, ulcerative sore throat, leukopenia • High incidence with clozapine (1-2%) - 1wk prescription a time - check CBC • Discontinue drug immediately • May need isolation and antibiotics

Interventions for Photosensitivity • Use sunscreen and sunglasses • Cover body with clothing • Reassurance normal vision typically returns in a few days tolerance develops

Interventions for Anticholinergic effect • S/S: constipation, dry mouth, blurred vision, orthostatic hypotension, tachycardia, urinary retention, nasal congestion • Avoid hazard task • Fluid, mouth rinse, hard candy, sugar-free gum. Check mouth sore • Fluid, fiber, exercises, monitor BM habits, use stool softeners,

Interventions for Weight Gain • Increase exercises • Reduce calorie diet if indicated • May need to change class of drug

AIM- Abnormal Involuntary Movement • incidence of TD has been relatively low in recent years, changes in prescribing may result in increased occurrence. • AIMS (Abnormal Involuntary Movement Scale) • http://www.psychiatrictimes.com/scales/movement_disorders/AIMS_LandingPage.jhtml

Drug interactions • Central nervous system depressants i.e. opiates, barbiturates, alcohol -> sedative effective  • Antihypertensives - hypotensive effects  • Caffeine - antipsychotic drug effect  • Cigarette smoking -blood level of antipsychotics  • Lithium - possible additive toxic effect • Anticholinergic - absorption of antipsychotics 

Anticholinergic drugs - for EPSEs • Benztropine (Cogentin): 1-4mg, qd or bid. PO or IM • Biperiden (Akineton): 2-6mg, qd, bid, tid • Trihexyphenidyl (Artane): 5-15mg/d • Procyclidine (Kemadrin): 6-20mg/d • Ethopropazine (Parsidol): 600mg/d Anticholinergic drugs → acetylcholine↓

Other drugs to treat EPSEs • Antihistamine Diphenhydramine (Benadryl) 25-300/d; PO, IM, IV • Dopamine Agonist Amantadine (Symmetrel) 100-3000mg/d; PO • Benzodiazepines Diazepam (Valium) 2-6 mg/d; PO, IV Lorazepam (Ativan) 0.5-2 mg/d; PO, IM Clonazepam (Klonopin) 1-4; PO

Types of Antidepressants • Monoamine Oxidase inhibitors (MAO inhibitors) • TCAs (Tricyclic Antidepressants) • SSRI (Selective Serotonin Reuptake inhibitor) • Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) • Serotonin-Norepinephrine Disinhibitors (SNDIs) • Mirtazapine (Remeron)

Antidepressants - MAO Inhibitors Drug Trade name Daily dose Isocarboxazid Marplan 45-90 mg Phenylzine Nardil 10-30 mg Tranylcypromine Parnate 10-30 mg

Side Effects of MAO Inhibitors Common Less common Constipation Agitation Dizziness Blurred vision Dry mouth Headache Hypotension Hypertension Insomnia Hypomania Nausea Impaired muscle Sexual difficulties coordination Weight gain Muscle cramps

Foods & Drugs to be avoided Foods Drugs Aged cheeses Amphetamine Beer Cocaine Broad-bean pods Decongestants Caffeined beverages Epinephrine Canned figs L-dopa

S/S of Hypertensive Crisis on MAOIs • Warning S - BP↑; palpitations; Headache • Symptoms - sudden BP↑; • Explosive occipital headache • Head and face are flushed & feel full • Palpitation, chest pain • Sweating, fever, nausea, vomiting • Dilated pupils, photophobia

TX of Hypertensive Crisis on MAOIs • Hold MAOIs doses • Do not lie down (elevates BP in head) • IM chlorpromazine 100mg, repeat if necessary (to block norepinephrine) • IV phentolamine, (to bind with norepinephrine receptor sites, blocking norepinephrine) • Manage fever by external cooling techniques • Evaluate diet, adherence, and teaching

Cyclic Antidepressants Drug Trade name Daily dosage Amitriptyline Elavil* 100-200 mg Clomipramine Anafranil 150-200 mg Imipramine Tofranil* 100-200 mg Nortriptyline Aventyl* 75-150 mg

Common Side effects of TCAs • Mechanism – blockade of acetylcholine • Drowsiness, dizziness, tachycardia, skin rashes, dry moth, constipation, and urinary retention, • Risk of mortality with overdose is high

Drug Interactions with Cyclic Antidepressants Drug Possible effect Alcohol Sedation, antidepressant blood level  Antiparkinsonians Additive anticholinergic effects Antipsychotics Sedation Fluoxetine(Prozac) Antidepressant blood level  Phenobarbitol Antidepressant blood level  Sedatives Sedation  Antidepressant blood level ,

The SSRI antidepressant Drug Trade name Daily dosage/starting Bupropion Wellbutrin 100-300 mg/150 mg Fluoxetine Prozac 10-80 mg/20 mg Paroxetine Paxil 10-60 mg/ 20 mg Sertraline Zoloft 50-200 mg/50 mg

Side effects of the SSRI • Anxiety & restlessness • Constipation • Dry mouth • Headache • Nausea & vomiting • Sedation • Sexual dysfunction

Serotonin-Norepinephrine Reuptake inhibitors (SNRIs) • Venlafaxine (Effexor) 150-200 mg/day • Common side effect: Changes in vision, such as blurred vision, headache, high blood pressure • Less common : Chest pain, fast or irregular heartbeat, mood or mental changes, ringing or buzzing in the ears • Duloxetine (Cymbalta) • nausea, dry mouth, sleepiness, fatigue, constipation, dizziness, decreased appetite, and increased sweating

Serotonin-Norepinephrine Disinhibitors (SNDIs) • Mirtazapine (Remeron)

Overview of antidepressants • 1st choice – SSRI, NSRI • Take 2-4 weeks to be effective of TCAs • Abrupt withdrawal of TCAs →headache, nausea, malaise • MAOIs uses could not take “tyramine” related food → hypertensive crisis • 14 days - change drugs from TCAs to MAOIs

Mood-stabilizing medications Drug Trade name Daily dosage Lithium Lithium carbonate 900-2100 mg Lithonate Valproic acid Depakote 1200-1500 mg Depakene Carbamazepine Tegretol* 400-1600 mg *can’t be used with Lithium

Side Effects of Lithium Carbonate Common Less common Potential serious (toxic) Confusion Acne Diarrhea(severe) Diarrhea Edema Dizziness Fatigue Hair loss Drowsiness (severe) Hand tremor Muscle weakness Increased thirst Nausea/vomiting(severe) Increased urination Slurred speech Muscle weakness Marked tremor/twitching Nausea/vomiting Spastic movements in limbs Weight gain* or face muscles

Psychopharmacology