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General psychopharmacology
This document provides an overview of general principles of psychopharmacology. It discusses key topics including: - Psychopharmacology is the study of how drugs affect the nervous system and behavior. Drugs can produce changes in physiological processes and behavior. - Drugs act through various sites in the body including receptors, ion channels, enzymes, and carrier proteins. Their effects depend on how the drug structure interacts with these sites. - Drugs are classified based on their structure, mechanism of action, history, uniqueness, and major clinical applications like antidepressants, antipsychotics, and anxiolytics. - Pharmacodynamics examines what the body does to the drug through processes like receptors, dose
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General psychopharmacology
- 1. GENERAL PRINCIPLES OF PSYCHOPHARMACOLOGY DrSalman Kareem 1st yr Resident Department of Psychiatry
- 2. PSYCHOPHARMACOLOGY Psychopharmacology: The study of the effects of drugs on the nervous system and on behavior. Drug effects: The changes a drug produces in patient‟s physiological processes and behavior. Sites of Action: The locations at which molecules of drugs interact with molecules located on or in cells of the body, thus affecting some biochemical processes of these cells.
- 3. CLASSIFICATION Structure- Tricyclics Mechanism of Action – MAOI History – First generation, traditional. Uniqueness – atypical antipsychotics Major clinical applications Anti depressent Anti psychotics anxiolytics
- 4.
- 5. PHARMACODYNAMICS What the body does to the drug Receptor mechanism Dose response curve Therapeutic index Development of tolerance Dependence Withdrawal phenomenon
- 6. MECHANISM • Four sitesof action o Receptors (those sites to which a neurotransmitter can specifically adhere to produce a change in the cell membranes) o Ion channels o Enzymes o Carrier Proteins • Biologic action depends on how its structure interacts with a receptor
- 7. Neurotransmitters Go through 7 steps 1. Synthesis 2. Storage 3. Enzymatic destruction if not stored 4. Exocytosis 5. Termination of release via binding with autorecptors 6. Binding to receptors 7. Inactivated Drugs are developed that address these actions as an AGONIST (mimic the NT ) or ANTAGONIST (block the NT)
- 9. RECEPTORS • Typesof Action o Agonist: same biologic action eg benzodiazepines act benzodiazepine recognition site in the benzodiazepine GABA receptor complex o Antagonist: opposite effect eg Flumazenil o Partial Agonist :Buprenorphine o Inverse agonist • Interactions with a receptor o Selectivity: specific for a receptor o Affinity: degree of attraction o Intrinsic activity: ability to produce a biologic response once it is attached to receptor o Medications treating anti psychotics - blocks dopamine 2 receptors
- 10. MECHANISM Poorly understood Drugs alter synaptic concentration of dopamine, serotonin, nor epinephrine , histamine, gamma amino butyric acid or acetylcholine Results from Receptor agonist, antagonist Interference with neurotransmitter uptake
- 11. ION CHANNELS • Drugscan block or open the ion channels • Example: benzodiazepine drugs facilitate GABA in opening the chloride ion channel
- 12. ENZYMES • Enzymes catalyzespecific biochemical reactions within cells and are targets for some drugs • Monoamine oxidase is an enzyme that breaks down most bioamine neurotransmitters (NE, DA, 5-HT) • Enzymes may be inhibited to produce greater neurotransmitter effect. • Eg Lithium binds directly to enzyme inositol 1 phosphatase
- 13. CARRIER PROTEINS • Transport neurotransmitters across cell membranes • Medications may block or inhibit this transport • Example: antidepressants (SSRI) on serotonin transporter protein /
- 14. SIDE EFFECTS Unavoidablerisks of medical treatment Probability of its occurence Impact on quality of life Cause
- 15. TCA‟s –most common side effect caused by blockade of muscarinic acetylcholine receptors or histamine 2 receptors. SSRI‟s serotonion reuptake – cause nausea and sexual dysfunction Anti psychotics – D2 blockage of drugs – Extra pyramidal side effects. Benzodiazepine – agnostic action ataxia and daytime sleepiness.
- 16. Time course adverse effects differ in terms of time of onset and duration . Some appears ate the end of the treatment Nausea occuring with SSRI‟s or venlaxafine eg Sedation occuring with mirtazapine of onset Long term complications – Dopamine and other Dopamine receptor antagonists – Tardive Dyskinesia
- 17. MOST COMMON SIDEEFFECTS Somnolence - desirable adverse effect GI Disturbances - Sertraline most likely to cause loose stools, Fluvoxamine most likely to cause nausea Movement disorder Sexual dysfunction – most commonly associated with the use of SSRI. Weight gain - atypical antipsychotics bec. of disturbance in glucose and insulin metabolism
- 18. SIDE EFFECTS Glucosechanges- atypical antipsychotics because of disturbance in glucose and insulin metabolism Hyponatremia – elderly patients more common by oxcarbamazepine Cognitive impairment Sweating Cardiovascular Rash Urinary retention
- 19. POTENTIAL ADVERSE EFFECTSOF ANTIDEPRESSANT THERAPY 10/5/2012 Central Nervous System Cardiac Dizziness, cognitive impairment, Orthostasis sedation, light-headedness, 19 hypertension somnolence, nervousness, heart block, insomnia, headache, tremor, tachycardia changes in satiety and appetite Gastrointestinal Nausea, constipation, Urogenital vomiting, dyspepsia, Erectile dysfunction, diarrhea ejaculation disorder, anorgasmia, Autonomic Nervous System priapism Dry mouth, urinary retention, blurred vision, sweating
- 20. IDIOSYNCRANTIC AND PARADOXICAL RESPONSE When a patient expresses particularly unusual or rare effects from a drug Eg some patients may be agitated when given a benzodiazepine Spontaneous orgasm instead of anorgasmia Behavioural disinhibition - benzodiazepines
- 21. SAFETY Therapeutic index relative measurement of toxicity or safety of a drug and is defined as ratio of median toxic dose to median effective dose. High therapeutic index: wide range between dose at which the drug begins to take effect and dose that would be considered toxic eg SSRI Low therapeutic index: low range eg LITHIUM
- 22. OVERDOSE Newer drugshave a wide margin of safety. Safest drug can have severe medical complication especially when combined with other drugs Suicide is a major concern Attempt made to verify that the medicine is not hoarded. Random pill container Asking family members to dispense daily might be helpful. Possible of accident ingestion of medication by children in household.
- 23. PHARMACOKINETIC ACTION What the body does to the drug Time course of drug concentration in different parts of the body such as plasma , adipose tissue and CNs. Explains or predicts the onset and duration of drug activity and intention between drugs that alter their metabolism or excretion.
- 24. ABSORPTION • From siteof administration into the plasma • Oral - (tablet and liquid) o Most Convenient o Most variable (food and antacids) First pass effect Decreased gastric motility (age, disease, medication) • IM - Short-and long acting • IV - Rarely used outside hospital
- 25. BIOAVAILABILITY • Amount ofdrug that reaches systemic circulation unchanged • Often used to compare one drug to another, usually the higher the bioavailability, the better
- 26. DISTRIBUTION • Amount ofdrug found in various tissues, especially the intended ones • Psychiatric drugs must pass through blood-brain barrier (most fat-soluble) • Factors effecting distribution o Size of organ (larger requires more) o Blood flow (more, greater concentration) o Solubility (greater, more concentration) o Plasma protein (if bound, slower distribution, stays in body longer) o Anatomic barriers (tissues surrounding)
- 27. CROSSING THE BLOODBRAIN BARRIER • Passive diffusion o Drug must dissolve in the structure of the cell o Lipid solubility is necessary for drugs passing through blood brain barrier (then, can also pass through placenta) • Binding to other molecules o Plasma protein binding o The more protein binding, the less drug activity. o Can bind to other cells, especially fat cells. Then are released when blood level decreases. Image Source Page: http://www.nanowerk.com/spotlight/spotid=19339.php
- 28. METABOLISM • Process bywhich the drug is altered and broken down into smaller substances (metabolites) that are usually inactive. • Lipid-soluble drugs become more water soluble, so they may be more readily excreted. • Most metabolism is carried out in the liver
- 29. CYTOCHROME P450 (CYP) Largestclass of enzymes catalyzing oxidation of organic substances in all living things • 11,550+ identified ; 57 in humans • High affinity for fat-soluble drugs • Involved in metabolism of most psychiatric medications • Inactivate drugs (or in some cases activate them) • Chemicals may increase or decrease CYP activity • Example: o SSRIs inhibitors of the subfamily CYP2D6 o Compounds in grapefruit juice inhibit CYP3A4 o Tobacco induces CYP1A2
- 30. ELIMINATION • Clearance: Totalamount of blood, serum, or plasma from which a drug is completely removed per unit time • Half-life: Time required for plasma concentrations of the drug to be reduced by 50% • Only a few drugs eliminated by kidneys (lithium) • Most excreted via the liver o excreted in the bile and delivered to the intestine o may be reabsorbed in intestine and “re-circulate” (up to 20%) o BILE, FECES, and URINE are major routes of excretion.
- 31. SUCCESS OF MEDICATIONS Patient related factors Diagnosis Past history of diagnosis Concurrent medical disorder Lifestyle Overall medical stats Genetic factor
- 32. Diagnosis failure to diagnose a disorder diminishes the likelihood of optimal drug selection. Produces worsening of symptoms Treatment failure for exacerbation of symptoms should promp a reassesment of diagnosis Post treatment response Response in faulty members
- 33. Concurrent medical / psychiatric illness Thyroid disease not adequately treated Sleep apnea produces depression and cognitive impairment. Kleine levin syndrome – mimics bipolar disorder Recreational drug, alcohol consumption and frequent consumption of coffee can undermine psychotropic drug treatment.
- 34. DOSING AND STEADYSTATE • Dosing: Administration of medication over time, so that therapeutic levels can be achieved. • Steady-state: o drug accumulates and plateaus at a particular level o rate of accumulation determined by half life o reach steady state in about five times the elimination half-life
- 35. Duration varies High rates of chronicity and relapse Therapeutic trial Continuation therapy Frequency of visits Determined by clinical judgment. Maintenance therapy needs monitoring.
- 36. TREATMENT OUTCOMES Remission Degree of improvement to below the syndromal threshold is defined as remission. Response 50 percent or greater decrease from baseline on a standard rating scale. Treatment failure Anticipate Prompt reassesment Intolerance to side effects Appropriate dosage for sufficient for a length of time? Drug non compliance
- 37. THREE PHASES OFTREATMENT Remission Recovery Normal Relapse Recurrence Response Relapse > 50% STOP 65 to 70% Rx STOP Rx Acute Continuation Maintenance Phase (3 months+) Phase (6-12 months) Phase (years) Time
- 38. TREATMENT RESISTANCE Somepatients fail to respond to repeated trials of medication. Tolerance Marked by a need, over time , to use increased doses of drug for it to maintain a clinical effect. Decreased responsiveness occurs after repeated doses. Sensitization Reverse of tolerance Sensitivity to a drug effect increases over time.
- 39. Withdrawal Development of physiological adaptation of a drug „side effect‟ More abruptly it is stopped and the shorter its elimination half life more likely the clinically significant withdrawal symptoms occur Gradual tapering of medication. Benzodiazepines, SSRI (paroxetine)
- 40. COMBINATION OF DRUGS “use of mutiple drugs should be avoided as possible” When two psychotropics drugs with the same approved indications are used concurrently , this is termed as combination therapy. Adding another drug with another indication is termed as augmentation. Almost all patients with bipolar disorder take more than one psychotropic agent. Medications are also given to counteract the side effects , to treat specific symptoms and as a temporary measure to transition from one drug to another.
- 41. SPECIAL POPULATION Children high metabolism, low – slow, /kg Pregnant and nursing women Avoid administering in them unless the psychiatric disorder is severe. Paroxetine – FDA warning – cardiac malformation. Lithium – ebstein‟s anomaly Carbamazepine, valproic acid – neural tube defects. Lamotrigine – oral clefts. Psychotherapeutic drugs – overly sedated at delivery ECT is good
- 42. Elderly patients – more susceptible to adverse effects and may metabolize and excrete drugs more slowly. low metabolism , 1/3 adult dose, drug interaction and medical state Medically ill patients Medical disorder should be ruled out as a cause of psychiatric symptoms Taking other medications can result in pharmacodynamic and pharmacokinetic interaction Potentially increased sensitivity to adverse effects including increased or decreased metabolism and excretion of the drug.
- 43. NON APPROVED DOSAGESAND USES Treat psychiatric disorders with drugs that are approved for non psychiatric conditions. Propanolol – social anxiety and lithium induced tremor Verapamil for mania and treatment of MAOI induced hypertensive crisis. Clonidine and guanificine for ADHD and PTSD. Levothyroxine for antidepressent augmentation
- 44. BLACK BOX WARNING Prescribing information sometimes contains a black box warning to warn physicians about potentially important safety information Strongest warning – more serious than just bolded text
- 45.