Principles of psychopharm[1]


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Principles of psychopharm[1]

  1. 1. CHAPTER 36
  2. 2. Principles of Psychopharmacology <ul><li>Advances in the understanding of brain functions have resulted in: </li></ul><ul><ul><li>More effective treatments </li></ul></ul><ul><ul><li>Less toxicity </li></ul></ul><ul><ul><li>More specifically targeted therapeutic agents </li></ul></ul>
  3. 3. Classification <ul><li>Psychotropic drugs </li></ul><ul><ul><li>Antidepressants </li></ul></ul><ul><ul><li>Antipsychotics </li></ul></ul><ul><ul><li>Mood stabilizers </li></ul></ul><ul><ul><li>Anxiolytics </li></ul></ul><ul><ul><li>Hypnotics </li></ul></ul><ul><ul><li>Cognitive enhancers </li></ul></ul><ul><ul><li>Stimulants </li></ul></ul>
  4. 4. Pharmacological Actions <ul><li>Environmental and genetic factors that determine the body ’s response to medications </li></ul><ul><li>Pharmacokinetics </li></ul><ul><ul><li>What the body does to the drug </li></ul></ul><ul><li>Pharmacodynamics </li></ul><ul><ul><li>What the drug does to the body </li></ul></ul>
  5. 5. Pharmacological Actions <ul><li>Drug-neuron interaction </li></ul><ul><ul><li>Effect on neurotransmitter secretion </li></ul></ul><ul><li>Profile of efficacy </li></ul><ul><li>Tolerability </li></ul><ul><li>Safety </li></ul><ul><li>Risk-to-Benefit Ratio </li></ul>
  6. 6. Drug Selection <ul><li>Drugs for particular disorders are similar in overall effects but differ in: </li></ul><ul><ul><li>Pharmacology </li></ul></ul><ul><ul><li>Efficacy Side/Adverse effects </li></ul></ul><ul><ul><li>Effects on individual patients </li></ul></ul><ul><li>See table 36.1-1, pgs 977-979 </li></ul>
  7. 7. Drug Selection cont. <ul><li>Drug selection decisions are made on a case-by-case basis </li></ul><ul><li>Effectiveness of drugs depends on patient variables </li></ul><ul><li>Some drugs are uniquely helpful for certain subgroups of patients </li></ul><ul><li>No drug is universally effective </li></ul><ul><li>No evidence indicating unambiguous superiority of any agent as Tx for major psychiatric disorders </li></ul><ul><ul><li>Clozapine- Tx-refractory schizophrenia </li></ul></ul>
  8. 8. Drug Factors: Pharmacodynamics <ul><li>Pharmacodynamic considerations </li></ul><ul><ul><li>Receptor mechanisms </li></ul></ul><ul><ul><li>Dose-response curve </li></ul></ul><ul><ul><li>Therapeutic index </li></ul></ul><ul><ul><li>Development of tolerance </li></ul></ul><ul><ul><li>Dependence </li></ul></ul><ul><ul><li>Withdrawal phenomena </li></ul></ul><ul><li>Pharmacogenetic studies are beginning to identify factors linked to individual differences in Tx response and sensitivity to side effects </li></ul>
  9. 9. Drug Factors: Mechanisms <ul><li>Psychotropic drugs: </li></ul><ul><ul><li>Poorly understood mechanisms of action </li></ul></ul><ul><ul><li>Based on the drug ’s alteration of synaptic concentrations of neurotransmitters like: </li></ul></ul><ul><ul><ul><li>Dopamine </li></ul></ul></ul><ul><ul><ul><li>Serotonin </li></ul></ul></ul><ul><ul><ul><li>Norepinephrine </li></ul></ul></ul><ul><ul><ul><li>Histamine </li></ul></ul></ul><ul><ul><ul><li>GABA (GammaAminobutiric Acid) </li></ul></ul></ul><ul><ul><ul><li>Acetylcholine </li></ul></ul></ul>
  10. 10. Drug Factors: Mechanisms <ul><li>Results based on: </li></ul><ul><ul><ul><li>Agonist/antagonist-Receptor interactions </li></ul></ul></ul><ul><ul><ul><li>Interference with neurotransmitter reuptake </li></ul></ul></ul><ul><ul><ul><li>Enhancement of neurotransmitter release </li></ul></ul></ul><ul><ul><ul><li>Enzyme inhibition </li></ul></ul></ul><ul><ul><li>Some Drugs have mixed action </li></ul></ul><ul><ul><li>Some drugs can be agonists at one receptors and antagonists at other receptors </li></ul></ul><ul><ul><li>Some drugs are partial agonists </li></ul></ul>
  11. 11. Drug Factors: Mechanisms <ul><li>Some psychotropic drugs produce clinical effects through mechanisms other than receptor interaction </li></ul><ul><ul><li>Lithium </li></ul></ul><ul><ul><ul><li>Inhibits the enzyme: Inositol-1-phosphatase </li></ul></ul></ul><ul><li>Some effects are linked to specific synaptic effects </li></ul><ul><ul><li>Antipsychotics block Dopamine-2 receptors </li></ul></ul><ul><ul><li>Benzodiazepine agonists- bind benzodiazepine and GABA receptor complex </li></ul></ul>
  12. 12. Side Effects <ul><li>Side effects considerations </li></ul><ul><ul><li>Probability of its occurrence </li></ul></ul><ul><ul><li>Impact on patients quality of life </li></ul></ul><ul><ul><li>Time course </li></ul></ul><ul><ul><li>Cause </li></ul></ul><ul><li>Regardless of how common a side effect is it won ’t necessarily occur in every patient. </li></ul><ul><li>Side effects can result from: </li></ul><ul><ul><li>Same pharmacological action responsible for it ’s therapeutic activity </li></ul></ul><ul><ul><li>From an unrelated property </li></ul></ul>
  13. 13. Side Effects <ul><li>Side effects can vary according to: </li></ul><ul><ul><li>Pharmacological properties </li></ul></ul><ul><ul><li>Dosage </li></ul></ul><ul><ul><li>Patients health </li></ul></ul><ul><ul><li>Interactions with concurrent therapies </li></ul></ul><ul><ul><ul><li>Including OTC/Natural Dietary Supplements </li></ul></ul></ul><ul><ul><li>Other factors </li></ul></ul><ul><ul><ul><li>With or without food </li></ul></ul></ul><ul><ul><ul><li>Mixed with Alcohol </li></ul></ul></ul><ul><ul><ul><li>Recreational drugs </li></ul></ul></ul>
  14. 14. Side Effects <ul><li>Common side effects of psychotropic medications </li></ul><ul><ul><li>Somnolence </li></ul></ul><ul><ul><li>GI disturbances </li></ul></ul><ul><ul><li>Movement disorders </li></ul></ul><ul><ul><li>Sexual dysfunction </li></ul></ul><ul><ul><li>Weight gain </li></ul></ul><ul><ul><li>Weight Loss </li></ul></ul><ul><ul><li>Glucose changes </li></ul></ul><ul><ul><li>Hyponatremia </li></ul></ul><ul><ul><li>Cognitive imopairment </li></ul></ul><ul><li>Cont. </li></ul><ul><ul><li>Sweating </li></ul></ul><ul><ul><li>CV disease </li></ul></ul><ul><ul><li>Rash </li></ul></ul>
  15. 15. Side Effects <ul><li>Idiosyncratic and paradoxical drug responses </li></ul><ul><ul><li>Rare- Happen in a very small percentage of patients </li></ul></ul><ul><ul><li>Not related to the pharmacological properties of the drug </li></ul></ul><ul><ul><li>Might be related to a gentically based abnormal sensitivity </li></ul></ul>
  16. 16. Therapeutic Index <ul><li>Relative measure of the toxicity or safety of a drug </li></ul><ul><ul><li>The ratio of the median toxic dose to the median effective dose </li></ul></ul><ul><li>Median toxic dose </li></ul><ul><ul><li>Dose at which 50% of the patients experience a specific toxic effect </li></ul></ul><ul><li>Median effective dose </li></ul><ul><ul><li>Dose at which 50% of the patients have a specifies therapeutic effect. </li></ul></ul>
  17. 17. Safety: Overdose <ul><li>Safety is always a consideration in drug selection. </li></ul><ul><li>Most newer agents have a wide margin of safety </li></ul><ul><li>Clinicians must recognize that some medications can be used to commit suicide </li></ul><ul><li>In cases where suicide is suspected, medications should not be prescribed in large numbers. </li></ul><ul><li>Accidental ingestion by other members of the family should also be a safety consideration. </li></ul>
  18. 18. Patient-Related Factors <ul><li>Diagnosis </li></ul><ul><ul><li>Poor diagnosis affects optimal drug selection </li></ul></ul><ul><ul><li>Misdiagnosis can worsen the symptoms </li></ul></ul><ul><li>Past-treatment response </li></ul><ul><ul><li>Selection of specific drug according to the patient ’s history of drug response </li></ul></ul><ul><ul><ul><li>Compliance, therapeutic response, side effectsI </li></ul></ul></ul><ul><ul><ul><li>If a drug has previously been effected it should be prescribed again. </li></ul></ul></ul>
  19. 19. Patient-Related Factors <ul><li>Past-treatment response </li></ul><ul><ul><li>For unknown reasons some patients fail to respond to a previously effective agent </li></ul></ul><ul><li>Response in family members </li></ul><ul><ul><li>Drug responses tend to cluster in families </li></ul></ul><ul><ul><li>This might be an indicator of agent effectiveness on the patient ’s relatives. </li></ul></ul>
  20. 20. Patient-Related Factors <ul><li>Concurrent Medical or Psychiatric Disorder </li></ul><ul><ul><li>Obtain information about coexiting medical disorders </li></ul></ul><ul><ul><li>Some non-psychiatric disorders may mimic psychiatric disorders. </li></ul></ul><ul><ul><ul><li>Patients with thyroid disease may appear depressed </li></ul></ul></ul><ul><ul><ul><li>Sleep apnea produces depression and cognitive impairment </li></ul></ul></ul><ul><ul><ul><li>Klein-Lever syndrome can mimic bipolar disorder </li></ul></ul></ul>
  21. 21. Patient-Related Factors <ul><li>Concurrent Medical or Psychiatric Disorder. Cont. </li></ul><ul><ul><li>Addiction or substance abuse (recreational drugs or alcohol) can complicate or undermine psychotropic drug treatment </li></ul></ul><ul><ul><li>These substances can possess significant psychoactive properties and might even be the source of the patient ’s symptoms </li></ul></ul>
  22. 22. Informed Consent and Patient Education <ul><li>Trust and motivation to comply with medication regimen are essential components of successful treatment. </li></ul><ul><li>Inform patients about </li></ul><ul><ul><li>Treatment options </li></ul></ul><ul><ul><li>Possible side effects </li></ul></ul><ul><ul><li>Unique benefits of each treatment </li></ul></ul><ul><li>Always consider risk-benefit ratio </li></ul><ul><li>Thoroughly explain to the patient the reason for treatment choice </li></ul>
  23. 23. Informed Consent and Patient Education <ul><li>Important to develop strong clinician/patient therapeutic alliance </li></ul><ul><li>Document discussion and drug selection </li></ul><ul><ul><li>No need for signed informed consent </li></ul></ul><ul><li>Successful engagement of patient and family in the treatment plan influences the success of the treatment </li></ul><ul><li>Instruct patient ’s relatives about the reasons for treatment as well as expected and potential risks. </li></ul>
  24. 24. Dosing, Duration and Monitoring <ul><li>Dosing </li></ul><ul><ul><li>Plasma concentrations of many psychotropics can vary up to tenfold </li></ul></ul><ul><ul><li>Optimal dose for individuals is ultimately determined by trial and error </li></ul></ul><ul><ul><li>Some drugs demonstrate a relation between increase in dose and clinical response </li></ul></ul><ul><ul><li>Dose –response curve </li></ul></ul><ul><ul><li>Potency </li></ul></ul><ul><ul><ul><li>Relative dose required to achieve certain effects </li></ul></ul></ul>
  25. 25. Dosing, Duration and Monitoring <ul><li>Dosing, cont. </li></ul><ul><ul><li>Drugs must be used in effective dosages for sufficient periods </li></ul></ul><ul><ul><li>Inadequate dosing increases risk of side effects and no therapeutic benefits </li></ul></ul><ul><ul><li>Time dosing, based on plasma half life of drug </li></ul></ul><ul><ul><li>Dosing of psychotropic drugs, based on measurements of plasma concentrations rather than receptor occupancy in the brain </li></ul></ul><ul><ul><li>Psychotropic drugs should be used continuously </li></ul></ul><ul><ul><ul><li>Except: drugs for insomnia, acute agitantion, and severe situational anxiety </li></ul></ul></ul>
  26. 26. Dosing, Duration and Monitoring <ul><li>Duration of treatment </li></ul><ul><ul><li>Depends on multiple variables </li></ul></ul><ul><ul><ul><li>Nature of the disorder </li></ul></ul></ul><ul><ul><ul><li>Durantion of symptoms </li></ul></ul></ul><ul><ul><ul><li>Family history </li></ul></ul></ul><ul><ul><ul><li>Patient ’s tolerance </li></ul></ul></ul><ul><ul><ul><li>Medication ’s benefits </li></ul></ul></ul><ul><li>3 phases of treatment </li></ul><ul><ul><li>Initial therapeutic trial </li></ul></ul><ul><ul><li>Continuation </li></ul></ul><ul><ul><li>Maintenance phase </li></ul></ul>
  27. 27. Dosing, Duration and Monitoring <ul><li>Frequency of Visits </li></ul><ul><ul><li>Visits should continue until optimal response to treatment is achieved </li></ul></ul><ul><ul><li>Frequency of follow-up or monitoring is determined by clinical judgment </li></ul></ul><ul><ul><li>Monitoring is important even in stable patients </li></ul></ul><ul><ul><li>3 months reasonable interval, 6 months for long standing treatment. </li></ul></ul>
  28. 28. Laboratory Tests and Therapeutic Blood Monitoring <ul><li>Based on clinical circumstances and drugs being used </li></ul><ul><li>Routing testing is not required for most commonly used psychotropic drugs </li></ul><ul><li>No currently available laboratory test can confirm the diagnosis of a mental disorder </li></ul><ul><li>Pretreatment tests are used to establish baseline values to rule out medical problems that could be causing psychiatric disorders </li></ul>
  29. 29. Treatment Outcomes <ul><li>The goal of Psychotropic treatment is to eliminate all manifestations of the disorder, enabling the patient to regain the ability to function well and enjoy life as fully as before he or she became ill. </li></ul><ul><li>Response and Remission </li></ul><ul><ul><li>Remission </li></ul></ul><ul><ul><ul><li>Preferred outcome of a treatment </li></ul></ul></ul><ul><ul><ul><li>Less likely to experience a relapse or recurrence </li></ul></ul></ul><ul><ul><li>Response </li></ul></ul><ul><ul><ul><li>50% or greater decrease from baseline on a standard rating scale </li></ul></ul></ul>
  30. 30. Treatment Outcomes <ul><li>Treatment Failure </li></ul><ul><ul><li>Medication ineffectiveness should be anticipated as part of initial treatment plan </li></ul></ul><ul><ul><li>A next-step strategy should be in place at initiation of treatment </li></ul></ul>
  31. 31. Treatment Outcomes <ul><ul><li>Repeated drug failures should prompt patient reassessment. </li></ul></ul><ul><ul><ul><li>Was original diagnosis correct? </li></ul></ul></ul><ul><ul><ul><li>Are observed symptoms related to original disorder? </li></ul></ul></ul><ul><ul><ul><li>Are they adverse effects of treatment? </li></ul></ul></ul><ul><ul><ul><li>Were drug dosage and length of treatment appropriate? </li></ul></ul></ul><ul><ul><ul><li>Did a pharmacokinetic or pharmacodynamic interaction with another drug the patient was taking reduce the efficacy of the newly prescribed drug? </li></ul></ul></ul><ul><ul><ul><li>Did the patient take the drug as directed? </li></ul></ul></ul>
  32. 32. Treatment Outcomes <ul><li>Treatment Failure, cont. </li></ul><ul><ul><li>Most common reason for treatment failure is intolerance of side effects </li></ul></ul><ul><ul><li>Absorption and metabolism of drugs can vary greatly among patients. </li></ul></ul>
  33. 33. Treatment Outcomes <ul><li>Treatment Resistance </li></ul><ul><ul><li>Some patients fail to respond to repeated trials of medication. </li></ul></ul><ul><li>Tolerance </li></ul><ul><ul><li>The need over time to use increased doses of a drug to maintain a clinical effect </li></ul></ul>
  34. 34. Treatment Outcomes <ul><li>Sesitization </li></ul><ul><ul><li>Increased Sensitivity to a drug </li></ul></ul><ul><ul><ul><li>The reverse of tolerance </li></ul></ul></ul><ul><li>Withdrawal </li></ul><ul><ul><li>Physiological adaptation to a drug with a subsequent risk of withdrawal symptoms. </li></ul></ul>
  35. 35. Combination of Drugs <ul><li>Acording to the American Psychiatric Association (APA) </li></ul><ul><ul><li>Avoid, if possible, the use of multiple psychotropics. </li></ul></ul><ul><ul><li>Even so simultaneous use of multiple psychotropics is commonplace </li></ul></ul><ul><ul><li>Inpatient prescription </li></ul></ul><ul><ul><ul><li>Average 3 simultaneous psychotropics </li></ul></ul></ul><ul><ul><ul><li>Fixed combinations have also become common </li></ul></ul></ul><ul><ul><ul><ul><li>More than one medication contained in a single tablet </li></ul></ul></ul></ul>
  36. 36. Combination of Drugs cont. <ul><li>One of the advantages of fixed combinations is: </li></ul><ul><ul><li>Patient treatment compliance </li></ul></ul><ul><li>A disadvantage of fixed combinations: </li></ul><ul><ul><li>Clinician has less flexibilitiy in adjusting dosages </li></ul></ul>
  37. 37. Special Populations <ul><li>Children </li></ul><ul><ul><ul><li>ADHD and OCD are the only two disorders for which there are drugs labeled for pediatric use </li></ul></ul></ul><ul><ul><ul><li>Commonly used psychotropics have no labeling for pediatrics </li></ul></ul></ul><ul><ul><ul><li>Evidence of effectiveness of psychotropics on children are mostly based on clinical findings rather than large clinical trials. </li></ul></ul></ul><ul><ul><ul><li>Higher metabolic rates in children may suggest higher doses than for adults. </li></ul></ul></ul><ul><ul><ul><li>It is always best to start with lower dosages and adjust as needed. </li></ul></ul></ul>
  38. 38. Special Populations <ul><li>Pregnant and Nursing Women </li></ul><ul><ul><li>No assurances of risk free drugs administered during pregnancy or lactation </li></ul></ul><ul><ul><li>No psychotropic drug is absolutely contraindicated during pregnancy </li></ul></ul><ul><ul><ul><li>Except those with known risks of birth defects, premature births or neonatal complications. </li></ul></ul></ul><ul><ul><ul><ul><li>Paroxetine- Risk of cardiac malformations </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lithium- Ebstein ’s anomaly </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Carbamazepine & Valproic acid: neural tube deffects </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Lamotrigine: Oral-Clefts </li></ul></ul></ul></ul>
  39. 39. Special Populations <ul><li>Pregnant and Nursing Women </li></ul><ul><ul><li>Administration of psychotropics on or near to delivery can cause oversedation in the newborn </li></ul></ul><ul><ul><li>Virtualy all psychotropics are secreted in milk </li></ul></ul><ul><ul><ul><li>No breast feeding recommended </li></ul></ul></ul><ul><li>Elderly Patients </li></ul><ul><ul><li>2 concerns with elderly patients </li></ul></ul><ul><ul><ul><li>1- increased succeptibility to adverse effects (cardiac) </li></ul></ul></ul><ul><ul><ul><li>Decreased metabolism, requiring dosage adjustment. </li></ul></ul></ul>
  40. 40. Special Populations <ul><li>Elderly Patients </li></ul><ul><ul><li>Account for 1/3 of all prescription drug use </li></ul></ul><ul><ul><li>High incidence of polypharmacy </li></ul></ul><ul><ul><li>Nearly ½ of patients in long-term care facilities are prescribed more than on psychotropic agent. </li></ul></ul><ul><ul><li>Psychotropics have been shown to be casually related to falls in patients </li></ul></ul><ul><ul><ul><li>Discontinuation reduces risk of falls about 40% </li></ul></ul></ul><ul><ul><li>Psychotropic agents with possible adverse effects such as hypotension, cardiac conduction abnormalities, anticholinergic activity and respiratory depression should not be used </li></ul></ul>
  41. 41. Special Populations <ul><li>Medically Ill Patients </li></ul><ul><ul><li>Rule out medical disorder as a cause of the psychiatric disorder </li></ul></ul><ul><ul><ul><li>Ex: neurological or endocrine disorders, HIV/AIDS patients </li></ul></ul></ul><ul><li>Substance Abuse </li></ul><ul><ul><li>Discontinuation of substance abuse can result in cravings and clinically significant psychological withdrawal symptoms </li></ul></ul>
  42. 42. Placebos <ul><li>For mild psychiatric disorders like mild to moderated depression and some anxiety, 30% of patients exhibit significant improvement or remission of symptoms on a placebo. </li></ul>