ANTI-PSYCHOTIC DRUGS DON D. CUA, MD Department of Pharmacology
TYPES OF PSYCHOSIS <ul><li>SCHIZOPHRENIA </li></ul><ul><li>AFFECTIVE DISORDERS (DEPRESSION/MANIA) </li></ul><ul><li>ORGANI...
SCHIZOPHRENIA <ul><li>A clinical syndrome characterized  by profound disruption in cognition and emotion, affecting the mo...
THE NATURE OF SCHIZOPHRENIA <ul><li>1% population, begins at an early age, with strong hereditary factor </li></ul><ul><li...
<ul><li>POSITIVE SYMPTOMS </li></ul><ul><li>Delusions  Disorganized behavior </li></ul><ul><li>Hallucinations  Disorganize...
Diagnostic Criteria for Schizophrenia DSM  IV <ul><li>A. Two or more of the following  ( one-month period ) </li></ul><ul>...
THE DOPAMINE HYPOTHESIS <ul><li>SCHIZOPHRENIA:  WITH EXCESSIVE  DOPAMINERGIC ACTIVITY; NORe and GABA </li></ul><ul><li>ANT...
CLASSIFICATION OF ANTIPSYCHOTIC DRUGS: <ul><li>TYPICAL ANTIPSYCHOTICS: </li></ul><ul><li>A. PHENOTHIAZENE DERIVATIVE </li>...
ALIPHATIC DERIVATIVE: <ul><li>CHLORPROMAZINE </li></ul><ul><li>TRIFLUPROMAZINE </li></ul><ul><li>PIPERIDINE DERIVATIVE: </...
PIPERAZINE DERIVATIVE: <ul><li>FLUPHENAZINE </li></ul><ul><li>PERPHENAZINE </li></ul><ul><li>TRIFLUOPERAZINE </li></ul><ul...
B. THIOXANTHENE DERIVATIVES : <ul><li>ALIPHATIC DERIVATIVE: </li></ul><ul><li>CHLORPROTHIXENE </li></ul><ul><li>PIPERAZINE...
C. BUTYROPHENONE : <ul><li>HALOPERIDOL </li></ul>
CLASSIFICATION OF ANTIPSYCHOTIC DRUGS <ul><li>1. TYPICAL ANTI-PSYCHOTICS </li></ul><ul><li>A .  Phenothiazine Derivatives ...
<ul><li>2. ATYPICAL ANTI-PSYCHOTICS </li></ul><ul><li>CLOZAPINE </li></ul><ul><li>LOXAPINE </li></ul><ul><li>RISPERIDONE <...
DIFFERENCES AMONG  ANTI-PSYCHOTIC DRUGS <ul><li>CHLORPROMAZINE   alpha1=5HT2 > D2 >D1 </li></ul><ul><li>HALOPERIDOL  D2>D1...
DOPAMINE RECEPTORS D1 like family <ul><li>D1: CHROMOSOME 5 ; INCREASE  cAMP…> </li></ul><ul><li>activation of adenyl cycla...
DOPAMINERGIC SYSTEM <ul><li>1.  MESOLIMBIC-MESOCORTICAL  substancia nigra………>limbic system  BEHAVIOR </li></ul><ul><li>2. ...
DOPAMINERGIC SYSTEM <ul><li>4.  MEDULLARY-PERIVENTRICULAR  motor nuclei of the vagus  </li></ul><ul><li>EATING BEHAVIOR </...
ANTI-PSYCHOTIC AGENTS <ul><li>PSYCHOLOGICAL EFFECTS </li></ul><ul><li>>  sleepiness, restlessness, impaired performance & ...
ANTI-PSYCHOTIC  AGENTS <ul><li>CARDIOVASCULAR EFFECTS </li></ul><ul><li>orthostatic hypotension </li></ul><ul><li>high res...
PHARMACOKINETICS <ul><li>READILY BUT INCOMPLETELY ABSORBED </li></ul><ul><li>FIRST PASS METABOLISM </li></ul><ul><li>HIGHL...
CLINICAL  INDICATIONS <ul><li>A. PSYCHIATRY INDICATIONS </li></ul><ul><li>SCHIZOPHRENIA </li></ul><ul><li>SCHIZO-AFFECTIVE...
SIDE EFFECTTS OF NEUROLEPTIC DRUGS <ul><li>A. NEUROLOGIC EFFECTS </li></ul><ul><li>1. ACUTE DYSTONIA   : s pasm of muscles...
<ul><li>3. PARKINSONISM </li></ul><ul><li>bradykinesia, rigidity, tremor, mask facies,  </li></ul><ul><li>shuffling gait s...
<ul><li>5. PERIODIC TREMOR RABBIT SYNDROME </li></ul><ul><li>Peri-oral tremors after months or years of treatment </li></u...
ADVERSE EFFECTS <ul><li>B. BEHAVIORAL EFFECTS </li></ul><ul><li>Pseudo-depression; toxic confusional state </li></ul><ul><...
ADVERSE EFFECTS <ul><li>D. METABOLIC & ENDOCRINE EFFECTS </li></ul><ul><li>Weight gain, hyperglycemia, hyperprolactinemia,...
ANTI-MANIC AGENTS <ul><li>MANIA --  STATE OF ELEVATED MOOD & PSYCHOMOTOR ACCELERATION, </li></ul><ul><li>WITH EXCESS CATHE...
LITHIUM <ul><li>INDICATIONS: </li></ul><ul><li>BIPOLAR DISORDERS  </li></ul><ul><li>THYROTOXICOSIS </li></ul><ul><li>INAPP...
LITHIUM  PHARMACOKINETICS <ul><li>ABSORPTION : virtually complete within 6 -8 hrs; peak plasma levels in 30 min to 2 hrs <...
LITHIUM PHARMACODYNAMICS <ul><li>EFFECTS ON ELECTROLYTES & IONS   TRANSPORT :  </li></ul><ul><li>Substitute for sodium in ...
<ul><li>Lithium  inhibits several important enzymes in the normal recycling of membrane phosphoinositides. </li></ul><ul><...
LITHIUM ADVERSE EFFECTS <ul><li>CNS EFFECTS:  dizziness, mild ataxia </li></ul><ul><li>NEUROMUSCULAR EFECTS:  fine tremors...
<ul><li>The TWO most common side effects </li></ul><ul><li>UNCOUPLING OF THE  </li></ul><ul><li>VASOPRESSIN and TSH RECEPT...
LITHIUM CONTRAINDICATIONS <ul><li>A.  MARKED DEHYDRATION OR SODIUM DEPLETION </li></ul><ul><li>B . SIGNIFICANT RENAL OR CA...
LITHIUM DRUG INTERACTIONS <ul><li>THIAZIDE DIURETICS : DECREASE RENAL CLEARANCE OF LITHIUM </li></ul><ul><li>NSAID : DECRE...
DEPRESSION <ul><li>I . REACTIVE OR SECONDARY DEPRESSION </li></ul><ul><li>Core Depression Syndrome: depression, anxiety, t...
<ul><li>Pathogenesis of Major Depression </li></ul><ul><li>DECREASED FUNCTIONAL AMINE-DEPENDENT SYNAPTIC TRANSMISSION </li...
ANTI-DEPRESSANTS <ul><li>A .TRICYCLIC ANTI-DEPRESSANTS(TCA) </li></ul><ul><li>THREE-RING NUCLEUS- </li></ul><ul><li>(anti-...
ANTI-DEPRESSANTS <ul><li>C.  SELECTIVE SEROTONIN REUPTAKE INHIBITORS  (SSRI) </li></ul><ul><li>FLUOXETINE </li></ul><ul><l...
ANTI-DEPRESSANTS PHARMACODYNAMICS <ul><li>ACTION OF ANTIDEPRESSANTS ON BIOGENIC AMINE NEUROTRANSMITTERS </li></ul><ul><li>...
<ul><li>B .  RECEPTOR & POSTRECEPTOR EFFECTS </li></ul><ul><li>Increase in neurotransmitter in the synapse acting on posts...
PHARMACOKINETICS <ul><li>A.  TRICYCLICS </li></ul><ul><li>Incompletely reabsorbed </li></ul><ul><li>First pass metabolism ...
PHARMACOKINETICS <ul><li>C.  SSRI  : FLUOXETINE </li></ul><ul><li>Well absorbed </li></ul><ul><li>PPC: 4 – 8 hrs </li></ul...
CLINICAL INDICATIONS <ul><li>DEPRESSION </li></ul><ul><li>PANIC DISORDER ( Imipramine ) </li></ul><ul><li>OBSESSIVE COMPUL...
ADVERSE EFFECTS <ul><li>TRICYCLICS </li></ul><ul><li>Sedation :   sleepiness </li></ul><ul><li>Sympathomimetic :  tremors,...
Foods  that interact with MAOI <ul><li>High in tyramine content  : </li></ul><ul><li>BEER  </li></ul><ul><li>BROAD BEANS, ...
<ul><li>MAO INHIBITORS </li></ul><ul><li>headache, drowsiness, dry mouth, weight gain, postural hypotension, sexual distur...
OVERDOSE TOXICITY <ul><li>Coma with shock, metabolic acidosis, respiratory depression, sudden apnea, agitation, delirium <...
DRUGS WITH SPECIAL IMPORTANCE <ul><li>Desipramine —less sedating, low anti-muscarinic effects </li></ul><ul><li>Amitryptyl...
Drugs that Interact with MAOI <ul><li>A.  INDIRECTLY ACTING  SYMPATHOMIMETICS:  amphetamines, ephedrine, metaraminol, phen...
<ul><li>Who is wise and understanding among you? Let him show it by his good life, by deeds done in humility that comes fr...
MAJOR AFFECTIVE /MANIC DEPRESSIVE DISORDERS <ul><li>Abnormal emotion or mood </li></ul><ul><li>Disorders of affect & depre...
NEUROSES: <ul><li>Less pervasive psychiatric disorders </li></ul><ul><li>Comprehend reality, suffering & disability are so...
Upcoming SlideShare
Loading in …5
×

Anti Psychoticdoncua

1,099 views
1,044 views

Published on

Published in: Health & Medicine
0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,099
On SlideShare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
53
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Anti Psychoticdoncua

  1. 2. ANTI-PSYCHOTIC DRUGS DON D. CUA, MD Department of Pharmacology
  2. 3. TYPES OF PSYCHOSIS <ul><li>SCHIZOPHRENIA </li></ul><ul><li>AFFECTIVE DISORDERS (DEPRESSION/MANIA) </li></ul><ul><li>ORGANIC PSYCHOSES (CAUSED BY HEAD INJURY, ALCOHOLISM, OTHERS) </li></ul>
  3. 4. SCHIZOPHRENIA <ul><li>A clinical syndrome characterized by profound disruption in cognition and emotion, affecting the most fundamental attributes: language, thought, perception, affect and sense of self. </li></ul><ul><li>“ clear sensorium but marked thinking disturbance.” </li></ul>
  4. 5. THE NATURE OF SCHIZOPHRENIA <ul><li>1% population, begins at an early age, with strong hereditary factor </li></ul><ul><li>SEX : Equally prevalent in men and women </li></ul><ul><li>AGE : MEN-between 15 and 25 </li></ul><ul><li>WOMEN-between 25 and 35 </li></ul>
  5. 6. <ul><li>POSITIVE SYMPTOMS </li></ul><ul><li>Delusions Disorganized behavior </li></ul><ul><li>Hallucinations Disorganized speech/thinking </li></ul><ul><li>Thought disorder Catatonic behaviors </li></ul><ul><li>NEGATIVE SYMPTOMS </li></ul><ul><li>Withdrawal from social contacts </li></ul><ul><li>Flattening of emotional responses </li></ul><ul><li>Alogia, Avolition-Apathy, Anhedonia-Asociality </li></ul><ul><li>Attention deficit </li></ul>
  6. 7. Diagnostic Criteria for Schizophrenia DSM IV <ul><li>A. Two or more of the following ( one-month period ) </li></ul><ul><li>delusions, hallucinations, disorganized speech, grossly disorganized or catatonic behavior and negative symptoms. </li></ul><ul><li>B. Social/occupational dysfunction : one or major areas of functioning such as work, interpersonal relations, or self-care, are markedly below the level achieved prior to the onset. </li></ul><ul><li>C. Continuous signs of the disturbance persist for at least SIX months. </li></ul>
  7. 8. THE DOPAMINE HYPOTHESIS <ul><li>SCHIZOPHRENIA: WITH EXCESSIVE DOPAMINERGIC ACTIVITY; NORe and GABA </li></ul><ul><li>ANTI-PSYCHOTIC DRUGS BLOCK POSTSYNAPTIC D2 RECEPTORS IN CNS </li></ul><ul><li>DRUGS THAT INCREASE DOPA AGGRAVATE SCHIZOPHRENIA </li></ul><ul><li>DOPAMINE RECEPTOR DENSITY ↑ in schizos </li></ul><ul><li>POSITRON EMISSION TOMOGRAPHY (PETS) </li></ul><ul><li>↑ Dopamine Receptor Density </li></ul><ul><li>HOMAVANILLIC ACID (HAV) </li></ul><ul><li>CHANGE IN AMOUNT </li></ul>
  8. 9. CLASSIFICATION OF ANTIPSYCHOTIC DRUGS: <ul><li>TYPICAL ANTIPSYCHOTICS: </li></ul><ul><li>A. PHENOTHIAZENE DERIVATIVE </li></ul><ul><li>3 ring structure, 2 benzene rings are linked by sulfur & nitrogen atom </li></ul><ul><li>N position 10 is replaced by carbon atom with a double bond to the side chain </li></ul>
  9. 10. ALIPHATIC DERIVATIVE: <ul><li>CHLORPROMAZINE </li></ul><ul><li>TRIFLUPROMAZINE </li></ul><ul><li>PIPERIDINE DERIVATIVE: </li></ul><ul><li>THIORIDAZINE </li></ul><ul><li>MESORIDAZINE </li></ul><ul><li>PIPERACETAZINE </li></ul><ul><li>NOTE: Decrease incidence of EPS side effects due to  antimuscarinic activity </li></ul>
  10. 11. PIPERAZINE DERIVATIVE: <ul><li>FLUPHENAZINE </li></ul><ul><li>PERPHENAZINE </li></ul><ul><li>TRIFLUOPERAZINE </li></ul><ul><li>Most potent phenothiazene & thioxanthene antipsychotic compound NOTE :  EPS but  tendency to produce sedation or autonomic side effects. </li></ul>
  11. 12. B. THIOXANTHENE DERIVATIVES : <ul><li>ALIPHATIC DERIVATIVE: </li></ul><ul><li>CHLORPROTHIXENE </li></ul><ul><li>PIPERAZINE DERIVATIVE: </li></ul><ul><li>CHLOPENTHIXOL </li></ul><ul><li>FLUPENTIXOL </li></ul><ul><li>THIOTHIXENE </li></ul>
  12. 13. C. BUTYROPHENONE : <ul><li>HALOPERIDOL </li></ul>
  13. 14. CLASSIFICATION OF ANTIPSYCHOTIC DRUGS <ul><li>1. TYPICAL ANTI-PSYCHOTICS </li></ul><ul><li>A . Phenothiazine Derivatives </li></ul><ul><li>Aliphatic Derivative : CHLORPROMAZINE </li></ul><ul><li>Piperidine Derivative : THIORIDAZINE </li></ul><ul><li>Piperazine Derivative : FLUPHENAZINE, PERPHENAZINE, TRIFLUOPERAZINE </li></ul><ul><li>B . Thioxanthene Derivative : THIOTHIXENE </li></ul><ul><li>C. Butyrophenone : HALOPERIDOL </li></ul>
  14. 15. <ul><li>2. ATYPICAL ANTI-PSYCHOTICS </li></ul><ul><li>CLOZAPINE </li></ul><ul><li>LOXAPINE </li></ul><ul><li>RISPERIDONE </li></ul><ul><li>MOLINDONE </li></ul><ul><li>SERTINDOLE </li></ul><ul><li>ZIPRASIDONE </li></ul><ul><li>OLANZAPINE </li></ul><ul><li>QUETIAPINE </li></ul><ul><li>PIMOZIDE </li></ul>CLASSIFICATION OF ANTI-PSYCHOTIC DRUGS
  15. 16. DIFFERENCES AMONG ANTI-PSYCHOTIC DRUGS <ul><li>CHLORPROMAZINE alpha1=5HT2 > D2 >D1 </li></ul><ul><li>HALOPERIDOL D2>D1=D4>alpha1>5HT2 </li></ul><ul><li>CLOZAPINE D4=alpha1>5HT>D2=D1 </li></ul><ul><li>RISPERIDONE D2=5HT2 </li></ul><ul><li>OLANZAPINE 5HT2> or= D1, D2, alpha2 </li></ul>
  16. 17. DOPAMINE RECEPTORS D1 like family <ul><li>D1: CHROMOSOME 5 ; INCREASE cAMP…> </li></ul><ul><li>activation of adenyl cyclase </li></ul><ul><li>D5 : CHROMOSOME 4 ; INCREASE cAMP </li></ul><ul><li>D2 like family </li></ul><ul><li>D2: CHROMOSOMES 11 : DECREASE cAMP …> blocks calcium channels </li></ul><ul><li>…… > opens potassium channels </li></ul><ul><li>D3: CHROMOSOME 11 : DECREASE cAMP </li></ul><ul><li>D4: DECREASE cAMP </li></ul>
  17. 18. DOPAMINERGIC SYSTEM <ul><li>1. MESOLIMBIC-MESOCORTICAL substancia nigra………>limbic system BEHAVIOR </li></ul><ul><li>2. NIGROSTRIATAL </li></ul><ul><li>substancia nigra….>caudate & putamen VOLUNTARY MOVEMENTS </li></ul><ul><li>3. TUBEROINFUNDIBULAR </li></ul><ul><li>arcuate nuclei & periventricular neurons,> hypothalamus & post pituitary </li></ul><ul><li>INHIBITS PROLACTIN SECRETION </li></ul>
  18. 19. DOPAMINERGIC SYSTEM <ul><li>4. MEDULLARY-PERIVENTRICULAR motor nuclei of the vagus </li></ul><ul><li>EATING BEHAVIOR </li></ul><ul><li>5. INCERTOHYPOTHALAMUS </li></ul><ul><li>from the medial zona incerta to the hypothalamus and the amygdala REGULATE THE ANTICIPATORY MOTIVATIONAL PHASE OF COPULATORY BEHAVIOR IN RATS </li></ul>
  19. 20. ANTI-PSYCHOTIC AGENTS <ul><li>PSYCHOLOGICAL EFFECTS </li></ul><ul><li>> sleepiness, restlessness, impaired performance & judgment </li></ul><ul><li>NEUROPHYSIOLOGIC EFFECTS </li></ul><ul><li>> hypersyncrony focal /unilateral </li></ul><ul><li>ENDOCRINE EFFECTS </li></ul><ul><li>> amenorrhea, galactorrhea, increase libido, false(-) pregnancy test </li></ul><ul><li>>decrease libido in males, gynecomastia </li></ul>
  20. 21. ANTI-PSYCHOTIC AGENTS <ul><li>CARDIOVASCULAR EFFECTS </li></ul><ul><li>orthostatic hypotension </li></ul><ul><li>high resting pulse rate </li></ul><ul><li>increase PR, decrease stroke volume, decrease mean arterial pressure </li></ul><ul><li>decrease peripheral resistance </li></ul>
  21. 22. PHARMACOKINETICS <ul><li>READILY BUT INCOMPLETELY ABSORBED </li></ul><ul><li>FIRST PASS METABOLISM </li></ul><ul><li>HIGHLY LIPID SOLUBLE </li></ul><ul><li>LARGE VOLUME OF DISTRIBUTIION </li></ul><ul><li>PROTEIN BOUND </li></ul><ul><li>COMPLETELY METABOLIZED </li></ul><ul><li>Except mesoridazine (major metabolites of thioridazine) </li></ul><ul><li>LITTLE EXCRETED UNCHANGED </li></ul><ul><li>T ½ is 10 -24 hours </li></ul>
  22. 23. CLINICAL INDICATIONS <ul><li>A. PSYCHIATRY INDICATIONS </li></ul><ul><li>SCHIZOPHRENIA </li></ul><ul><li>SCHIZO-AFFECTIVE DISORDERS </li></ul><ul><li>MANIC EPISODES IN BIPOLAR DISORDERS </li></ul><ul><li>GILLES DE LA TOURETTE SYNDROME </li></ul><ul><li>SENILE DEMENTIA </li></ul><ul><li>B. NON-PSYCHIATRIC INDICATIONS </li></ul><ul><li>ANTI-EMETIC EFFECT </li></ul><ul><li>ANTI-PRURITIC EFFECT </li></ul><ul><li>PRE-OPERATIVE ANESTHESIA </li></ul><ul><li>NEUROLEPTIC ANESTHESIA </li></ul>
  23. 24. SIDE EFFECTTS OF NEUROLEPTIC DRUGS <ul><li>A. NEUROLOGIC EFFECTS </li></ul><ul><li>1. ACUTE DYSTONIA : s pasm of muscles tongue, face, neck, back, may mimic seizures </li></ul><ul><li>During the first 1 -5 days of Rx </li></ul><ul><li>Mechanism unknown </li></ul><ul><li>Rx: anti-parkinson’s agents </li></ul><ul><li>2. AKATHISIA : m otor restlessness </li></ul><ul><li>5 -60 days </li></ul><ul><li>Mechanism unknown </li></ul><ul><li>Rx with diphenhydramine </li></ul>
  24. 25. <ul><li>3. PARKINSONISM </li></ul><ul><li>bradykinesia, rigidity, tremor, mask facies, </li></ul><ul><li>shuffling gait seen in 5-30 days </li></ul><ul><li>Mechanism : antagonism of dopamine </li></ul><ul><li>Rx: anti-parkinson’s agents </li></ul><ul><li>4. NEUROLEPTIC MALIGNANT SYNDROME </li></ul><ul><li>catatonia, stupor, fever, unstable BP, </li></ul><ul><li>myoglobulinemia after weeks of treatment </li></ul><ul><li>Mechanism : antagonism of dopamine </li></ul><ul><li>Rx: Stop neuroleptic immediately; dandrolene; bromocriptine, Anti-parkinsons- not effective </li></ul>
  25. 26. <ul><li>5. PERIODIC TREMOR RABBIT SYNDROME </li></ul><ul><li>Peri-oral tremors after months or years of treatment </li></ul><ul><li>Mechanism : unknown </li></ul><ul><li>Rx: Anti-parkinson’s Drugs </li></ul><ul><li>6. TARDIVE DYSKINESIA </li></ul><ul><li>Supersensivity of D receptors (cholinergic def) </li></ul><ul><li>oral-facial dyskinesia, choreoathetosis, dystonia </li></ul><ul><li>After months or years of RX </li></ul><ul><li>Worse on withdrawal </li></ul><ul><li>Mechanism : excess function of dopamine </li></ul><ul><li>Rx: prevention crucial </li></ul><ul><li>Rx: unsatisfactory </li></ul>
  26. 27. ADVERSE EFFECTS <ul><li>B. BEHAVIORAL EFFECTS </li></ul><ul><li>Pseudo-depression; toxic confusional state </li></ul><ul><li>C. AUTONOMIC NERVOUS SYSTEM EFFECTS </li></ul><ul><li>urinary retention, dry mouth, loss of accomodation, constipation </li></ul><ul><li>( MUSCARINIC CHOLINERGIC BLOCKADE ) </li></ul><ul><li>orthostatic hypotension, impotence, failure to ejaculate </li></ul><ul><li>( ALPHA ADRENORECEPTOR BLOCKADE ) </li></ul>
  27. 28. ADVERSE EFFECTS <ul><li>D. METABOLIC & ENDOCRINE EFFECTS </li></ul><ul><li>Weight gain, hyperglycemia, hyperprolactinemia, amenorrhea-galactorrhea syndrome, infertility, impotence in males </li></ul><ul><li>E. TOXIC OR ALLERGIC REACTIONS </li></ul><ul><li>Agranulocytosis (clozapine) , cholestatic jaundice, </li></ul><ul><li>skin eruptions </li></ul><ul><li>F. CARDIAC TOXICITY </li></ul><ul><li>Ventricular arrythmias (thioridazine) </li></ul><ul><li>G. OCULAR COMPLICATIONS : </li></ul><ul><li>“ browning of vision” </li></ul>
  28. 29. ANTI-MANIC AGENTS <ul><li>MANIA -- STATE OF ELEVATED MOOD & PSYCHOMOTOR ACCELERATION, </li></ul><ul><li>WITH EXCESS CATHECHOLAMINES ACTIVITY </li></ul><ul><li>TREATMENT : LITHIUM CARBONATE </li></ul><ul><li>CATHECOLAMINE RELEASE FROM ADRENERGIC NERVE TERMINALS </li></ul>
  29. 30. LITHIUM <ul><li>INDICATIONS: </li></ul><ul><li>BIPOLAR DISORDERS </li></ul><ul><li>THYROTOXICOSIS </li></ul><ul><li>INAPPROPRIATE ADH SECRETION </li></ul>
  30. 31. LITHIUM PHARMACOKINETICS <ul><li>ABSORPTION : virtually complete within 6 -8 hrs; peak plasma levels in 30 min to 2 hrs </li></ul><ul><li>DISTRIBUTION : in total body water; slow entry into intracellular compartment. No protein binding </li></ul><ul><li>METABOLISM : None </li></ul><ul><li>EXCRETION : virtually entirely in urine; plasma half life is about 20 hours </li></ul>
  31. 32. LITHIUM PHARMACODYNAMICS <ul><li>EFFECTS ON ELECTROLYTES & IONS TRANSPORT : </li></ul><ul><li>Substitute for sodium in generating action potentials </li></ul><ul><li>EFFECTS ON NEUROTRANSMITTERS </li></ul><ul><li>Enhance effects of serotonin? </li></ul><ul><li>Decrease norepinephrine & dopamine turnover </li></ul><ul><li>Block dopamine receptor supersensitivity </li></ul><ul><li>Augment synthesis of acetylcholine? </li></ul><ul><li>EFFECTS ON SECOND MESSENGERS </li></ul><ul><li>effect on Inositol 1,4,5 triphospate (IP3 )/ </li></ul><ul><li>Diacylglycerol (DAG)-needed in alpha a and muscarinic transmission </li></ul>
  32. 33. <ul><li>Lithium inhibits several important enzymes in the normal recycling of membrane phosphoinositides. </li></ul><ul><li>(-) IP2----IP1 </li></ul><ul><li>(-) IP1----inositol </li></ul><ul><li>It will lead to a depletion of PIP2(phosphotidylinositol-4,5-bis-phosphate) which is the membrane precursor of IP3 and DAG </li></ul><ul><li>LITHIUM could cause a selective depression of the overactive circuits. </li></ul>
  33. 34. LITHIUM ADVERSE EFFECTS <ul><li>CNS EFFECTS: dizziness, mild ataxia </li></ul><ul><li>NEUROMUSCULAR EFECTS: fine tremors </li></ul><ul><li>CVS EFFECTS: ventricular arrythmias </li></ul><ul><li>GIT EFFECTS: nausea, vomiting, diarrhea </li></ul><ul><li>GUT EFFECTS: polyuria </li></ul><ul><li>ENDOCRINE EFFECTS: hypothyroidism </li></ul><ul><li>ALLERGIC REACTION: pruritus, rash </li></ul><ul><li>OVERDOSE TOXICITY: vomiting, drowsiness, decrease consciousness and seizures </li></ul><ul><li>Rx: dialysis </li></ul>
  34. 35. <ul><li>The TWO most common side effects </li></ul><ul><li>UNCOUPLING OF THE </li></ul><ul><li>VASOPRESSIN and TSH RECEPTORS </li></ul><ul><li>FROM THEIR G PROTEINS </li></ul>
  35. 36. LITHIUM CONTRAINDICATIONS <ul><li>A. MARKED DEHYDRATION OR SODIUM DEPLETION </li></ul><ul><li>B . SIGNIFICANT RENAL OR CARDIAC DISEASES </li></ul><ul><li>C. PREGNANCY </li></ul><ul><li>D. RENAL CONCENTRATION ABILITY </li></ul><ul><li>Nephrogenic diabetes insipidus with polyuria </li></ul>
  36. 37. LITHIUM DRUG INTERACTIONS <ul><li>THIAZIDE DIURETICS : DECREASE RENAL CLEARANCE OF LITHIUM </li></ul><ul><li>NSAID : DECREASE LITHIUM CLEARANCE </li></ul><ul><li>ANTIPYSCHOTIC AGENTS : INCREASE </li></ul><ul><li>NEUROTOXICITY </li></ul>
  37. 38. DEPRESSION <ul><li>I . REACTIVE OR SECONDARY DEPRESSION </li></ul><ul><li>Core Depression Syndrome: depression, anxiety, tension, bodily complaints, guilt (> 60%) </li></ul><ul><li>II . ENDOGENOUS DEPRESSION </li></ul><ul><li>Core Depression Syndrome plus ABNORMAL vital signs rhythm of sleep, motor activity, libido, decrease appetite ( 25%) </li></ul><ul><li>III. DEPRESSION ASSOCIATED WITH BIPOLAR AFFECTIVE DISORDER </li></ul><ul><li>(10-15%) </li></ul>
  38. 39. <ul><li>Pathogenesis of Major Depression </li></ul><ul><li>DECREASED FUNCTIONAL AMINE-DEPENDENT SYNAPTIC TRANSMISSION </li></ul>
  39. 40. ANTI-DEPRESSANTS <ul><li>A .TRICYCLIC ANTI-DEPRESSANTS(TCA) </li></ul><ul><li>THREE-RING NUCLEUS- </li></ul><ul><li>(anti-muscarinic, anti-H and @(-)adrenergic) </li></ul><ul><li>IMIPRAMINE. AMITRYPTYLINE </li></ul><ul><li>( mixedNorE and serotonin uptake inhibitors ) </li></ul><ul><li>DOXAPIN, NORTRIPTYLINE , DESIPRAMINE, CLOMIPRAMINE , PROTRIPTYLINE, TRIMIPRAMINE </li></ul><ul><li>Note: toxicity due alpha adrenergic blocking activity </li></ul><ul><li>B . HETEROCYCLIC: SECOND & THIRD GENERATIONS </li></ul><ul><li>1. SECOND GENERATIONS </li></ul><ul><li>AMOXAPINE ( dopamine receptor antagonist ) MAPROTILINE </li></ul><ul><li>TRAZODON, BUPROPION </li></ul><ul><li>2. THIRD GENERATIONS </li></ul><ul><li>MIRTAZAPINE, VENLAFAZINE,NEFAZODONE </li></ul>
  40. 41. ANTI-DEPRESSANTS <ul><li>C. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI) </li></ul><ul><li>FLUOXETINE </li></ul><ul><li>PAROXETINE </li></ul><ul><li>SERTRALINE, CITALOPRAM, FLUVOXAMINE </li></ul><ul><li>D. MONOAMINE OXIDASE INHIBITORS (MAOI) </li></ul><ul><li>PHENELZINE, TRANYLCYPROMINE </li></ul><ul><li>MOCLOBEMIDE ,SELEGILINE </li></ul><ul><li>NOTE: MAO-A —amine oxidase responsible for NORe, serotonin and tyramine </li></ul><ul><li>MAO-B ---selective for dopamine( SELEGILINE ) </li></ul>
  41. 42. ANTI-DEPRESSANTS PHARMACODYNAMICS <ul><li>ACTION OF ANTIDEPRESSANTS ON BIOGENIC AMINE NEUROTRANSMITTERS </li></ul><ul><li>TCA (-) NorE and serotonin reuptake pump </li></ul><ul><li>“ OFF-SWITCHES” of the amine transmission </li></ul><ul><li>MAO inhibitors (-) major degradation pathway resulting </li></ul><ul><li>to accumulation of amines in presynaptic stores for the amino neurotransmitters and increase release </li></ul><ul><li>Trazodone,Nefazodone and Mirtazepine (-) 5HT2a or 5HT2c </li></ul><ul><li>Mirtazepine (-) alpha 2 NorE receptors </li></ul><ul><li>( Increase therapeutic effects ) </li></ul>
  42. 43. <ul><li>B . RECEPTOR & POSTRECEPTOR EFFECTS </li></ul><ul><li>Increase in neurotransmitter in the synapse acting on postsynaptic receptor giving ultimate effect. </li></ul><ul><li>by decreasing cAMP rather than increase. </li></ul><ul><li>and decreasing postsynaptic B adrenoreceptors as clinical improvement is seen. </li></ul><ul><li>C . EFFECTS OF SPECIFIC ANTIDEPRESSANTS </li></ul>
  43. 44. PHARMACOKINETICS <ul><li>A. TRICYCLICS </li></ul><ul><li>Incompletely reabsorbed </li></ul><ul><li>First pass metabolism </li></ul><ul><li>Large volume of distribution </li></ul><ul><li>Metabolized due to transformation of tricyclic nucleus and alteration of the aliphatic side chain </li></ul><ul><li>( hydroxylation and conjugation and demethylation ) </li></ul><ul><li>B. HETEROCYCLICS </li></ul><ul><li>Variable bioavailability </li></ul><ul><li>High protein binding </li></ul><ul><li>Variable and large volume of distribution </li></ul><ul><li>Active metabolites </li></ul>
  44. 45. PHARMACOKINETICS <ul><li>C. SSRI : FLUOXETINE </li></ul><ul><li>Well absorbed </li></ul><ul><li>PPC: 4 – 8 hrs </li></ul><ul><li>Inhibits drug metabolizing enzymes </li></ul><ul><li>D. MAOI </li></ul><ul><li>Readily absorbed </li></ul>
  45. 46. CLINICAL INDICATIONS <ul><li>DEPRESSION </li></ul><ul><li>PANIC DISORDER ( Imipramine ) </li></ul><ul><li>OBSESSIVE COMPULSIVE( SSRI-Fluoxetine ) </li></ul><ul><li>ENURESIS ( TCA ) </li></ul><ul><li>CHRONIC PAIN ( TCA,Phenothiazine ) </li></ul><ul><li>OTHERS: Eating Disorder (Bulemia)( SSRI ) </li></ul><ul><li>Cataplexy associated with narcolepsy, school phobia, attention deficit syndrome </li></ul><ul><li>NOTE: Serotonin Syndrome-hyperthermia,muscle rigidity and myoclonus </li></ul>
  46. 47. ADVERSE EFFECTS <ul><li>TRICYCLICS </li></ul><ul><li>Sedation : sleepiness </li></ul><ul><li>Sympathomimetic : tremors, insomnia </li></ul><ul><li>Anti-muscarinic : blurred vision, constipation confusion, urinary incontinence </li></ul><ul><li>Psychiatric : psychoses aggravated </li></ul><ul><li>CVS : orthostatic hypotension </li></ul><ul><li>Neurologic : Seizures </li></ul><ul><li>Metabolic-Endocrine : weight gain, sexual disturbance </li></ul>
  47. 48. Foods that interact with MAOI <ul><li>High in tyramine content : </li></ul><ul><li>BEER </li></ul><ul><li>BROAD BEANS, LAVA BEANS </li></ul><ul><li>CHEESE </li></ul><ul><li>CHICKEN LIVER </li></ul><ul><li>SAUSAGES </li></ul><ul><li>RED WINE </li></ul><ul><li>YEAST </li></ul>
  48. 49. <ul><li>MAO INHIBITORS </li></ul><ul><li>headache, drowsiness, dry mouth, weight gain, postural hypotension, sexual disturbance </li></ul><ul><li>AMOXAPIN </li></ul><ul><li>Tricyclic & anti-psychotic effects </li></ul><ul><li>MAPROTILINE </li></ul><ul><li>Tricyclic effects </li></ul><ul><li>TRAZODONE & NEFAZODONE : drowsiness, dizziness, insomnia, nausea and agitation </li></ul><ul><li>BUPROPION </li></ul><ul><li>dizziness, dry mouth, tremor </li></ul><ul><li>FLUOXETINE </li></ul><ul><li>Anxiety, insomnia, tremors, decrease libido, GIT effects </li></ul>
  49. 50. OVERDOSE TOXICITY <ul><li>Coma with shock, metabolic acidosis, respiratory depression, sudden apnea, agitation, delirium </li></ul><ul><li>Hypertensive crisis </li></ul><ul><li>Cardiac conduction defects such as arrhythmias </li></ul><ul><li>DRUG INTERACTIONS </li></ul><ul><li>MAO Inhibitors and sympathomimetics and opiates </li></ul><ul><li>Anti-hypertensive drugs—exaggerated hypotension </li></ul><ul><li>TCA—increase concentration with cimetidine and phenothiazines </li></ul>
  50. 51. DRUGS WITH SPECIAL IMPORTANCE <ul><li>Desipramine —less sedating, low anti-muscarinic effects </li></ul><ul><li>Amitryptyline -more sedating and marked anti-muscarinic effects </li></ul><ul><li>Maprotiline -seizures </li></ul><ul><li>Trazodone —prolonged penile erection </li></ul><ul><li>Fluoxetine —minimal sedative effects, very low anti-muscarinic effects </li></ul><ul><li>Nefazodone -less sedating, no SSRI </li></ul>
  51. 52. Drugs that Interact with MAOI <ul><li>A. INDIRECTLY ACTING SYMPATHOMIMETICS: amphetamines, ephedrine, metaraminol, phenylpropanolamine </li></ul><ul><li>B . OTHER ADRENORECEPTOR AGENTS & RELATED AGENTS : levodopa, methyldopa, guanethidine, reserpine </li></ul><ul><li>C. OPIOID ANALGESICS & DERIVATIVES : morphine, codeine, meperidine, dextromethorphan </li></ul><ul><li>D. MISCELLANEOUS DRUGS : buspirone, fluoxetine, LSD </li></ul>
  52. 53. <ul><li>Who is wise and understanding among you? Let him show it by his good life, by deeds done in humility that comes from wisdom. </li></ul><ul><li>James 3: 13 </li></ul>THANK YOU!!!
  53. 54. MAJOR AFFECTIVE /MANIC DEPRESSIVE DISORDERS <ul><li>Abnormal emotion or mood </li></ul><ul><li>Disorders of affect & depression, dysphoria, elation or mania </li></ul><ul><li>Bipolar or non-bipolar </li></ul><ul><li>Can occur as a mild disorder or can be associated with other psychiatric or medical illnesses </li></ul>
  54. 55. NEUROSES: <ul><li>Less pervasive psychiatric disorders </li></ul><ul><li>Comprehend reality, suffering & disability are sometimes severe </li></ul><ul><li>Acute or transient, persistent or recurrent </li></ul><ul><li>Mood changes- anxiety , panic, depression </li></ul><ul><li>Limited abnormalities of thought- obsessions, irrational fears </li></ul><ul><li>Behavior – rituals, compulsions, hysterical conversions </li></ul>

×