Pharm Exam 2-lecture 4 +5 +6

Card Set Information

Author:
lhoyman
ID:
154201
Filename:
Pharm Exam 2-lecture 4 +5 +6
Updated:
2012-05-23 23:59:32
Tags:
Pharm Exam
Folders:

Description:
Pharm Exam 2
Show Answers:

Home > Flashcards > Print Preview

The flashcards below were created by user lhoyman on FreezingBlue Flashcards. What would you like to do?


  1. Bipolar Disorder
    • exhibit sx on both ends of mood continuum-manic and depressed
    • 2.3 M + Americans over 18 (1%)
    • first episode usually seen in early 20s
    • as many as 20% die from sucicide
    • M/F equal #s
  2. manic phase-psychological sx/signs
    • elated mood (or irritability)
    • sense of grandiosity
    • racing thoughts
    • pressured speech
    • impulsivity-hypersexuality, shopping spree
  3. manic phase-biological sx/signs
    • increased motor activity
    • restlessness
    • need little to no sleep
  4. Bipolar I
    • once the person has had a manic epidosode, diagnosis BD
    • can see either manic, depressed or mixed
  5. Bipolar II
    • there is not a manic episode but a HYPOMANIC episode
    • some manic sx but not as extreme as in bipolar I
    • still see fluctuations characteristic of BD
  6. medical d/os that can cause a manic episode
    • infections of brain
    • infections of whole body
    • metabolic d/os
    • seizure s/os
    • brain tumors
    • damage to brain
    • degenerative d/os of CNS
  7. mania-infections of brain
    • encephalitis
    • caused by bacteria, viruses or fungi
    • ex. CNS (tertiary) syphilis
  8. mania-metabolic disorders
    • hyperthyroidism
    • kidney failure
  9. mania-brain tumors
    • primary cancers of the brain
    • metastic (secondary) brain tumors
  10. mania-damage to brain
    • stroke
    • TBI
  11. mania-degenerative disorders of CNS
    MS
  12. certain drugs that cause manic episodes
    • psychostimulants
    • thyroid horomones
    • some antihypertensive meds
    • corticosteroids
    • isoniazid
    • procarbazine
    • s-adenosylmethionine
    • antidepressants
  13. mania-psychostimulants
    amphetamine, methamphetamine, coke, crack
  14. mania-thyroid horomones
    • levothyroxine
    • if taken in large amounts
  15. mania-corticiosteroids
    • prednisone
    • used for inflammatory illness such as systematic lupus erythematosus and for body building
  16. mania-isonazid
    used to treat turberculosis
  17. mania-procarbazine
    anticancer agent
  18. mania-s adenosylmethionine (SAMe)
    • herbal preparation for depression
    • can trigger mania in vulnerable ppl
  19. mania-antidepressants
    • manic induction/manic push
    • SSRI abrupt withdrawal
    • manic induction (false mania)
    • approach to tx
  20. manic induction/manic push
    • tricyclics and SSRIs can trigger mania
    • genetic vulnerability to BD
  21. SSRI abrupt withdrawal
    manic induction
  22. manic induction/false manic
    • induced episode that will resolve and is not BD
    • called withdrawal induced mania
  23. mania-antidepressants-approach to tx
    • if return to normal after stopping SSRI with no return to manic or hypomanic state-NOT BD
    • may cause the misdiagnosis and mistx of MDD as BD
  24. BD med tx
    • mood stabilizers
    • lithium
    • anticonvulsants
    • atypical antipsychotics
    • antidepessants
    • tx depression sx in that phase
    • antipsychotics
    • for brief psychotic sx
    • agitation, haullucinations, delusions
  25. BD and polypharmacy
    • see combo of several classes of drugs at one time...
    • SSRIs and mood stabilizers
    • SSRIs and atypical antipsychotics
    • SSRIs and anticonvulsants
  26. BD tx-extreme agitation/psychotic sx
    • lithium or valproate
    • + an atypical antipsychotic
  27. BD tx-typical/classic mania
    use lithium or valproate
  28. BD tx-for dysphoric manic or mixed mania (mixed mood episodes)
    use valproate
  29. BD tx-w/ dep sx
    • first line drug tx is with a mood stabilizer such as lithium, valproate, lamotrigine
    • if dep sx do not subside within 2-3 wks, add second mood stabilizer
    • usually an antidpressant is added to original mood stabilizer
  30. goals of psychopharmacologic tx of BD
    • reduction of mood sx
    • lessening and control of presenting manic and/or dep sx
    • prevention of relapse
    • reduction of risk for suicide
    • tx of bipolar pts does not end w/ Rx of mood stabilizing meds
    • need to learn to copew/ life not just take meds
  31. Prevention of BD relapse
    • BD is recurring prob
    • propylactic preventative interventions are essential if # and severity of mood episodes is reduced
    • appropriate tx can reduce #, freq, severity and length of mood episodes
    • failure to continue tx after acute sx are controlled can lead not only to relapse but also to progressively worsening conditions
  32. BD-reduction of risk for suicide
    • major risk in BD
    • 15-20% of BD commit suicide
    • clinicians play major role in suicide prevention
  33. Litihium Carbonate (Li+)
    • most effective med for most BD ppl
    • 40-50% response rate
    • stay on for 6-12 mo after manic episode
    • available in sustained release (lithobid)
    • acute antimanic effects
  34. Litihium Carbonate (Li+) (2)
    • useful for reducing freq and severity of recurrent bipolar episodes
    • prevented relapse in 64% of BD ppl vs. 21% placebo
    • less effective in preventing recurrence of depression than mania
  35. Lithium-pharmacodynamics
    • no known biological function
    • three hypotheses for action
    • biogenic amine
    • electrolyte
    • 2nd messenger system
  36. Electrolyte Hypothesis-Lithium
    • may modify membrance excitability via an ionic mechanism
    • based on its relationship to other electrolytes (Na+ and K+)
    • similar ionic radius to magnesium and calcium
    • inconsistent evidence that Li+ competes for CA2+ binding sites
    • could affect...dependent release of neuotransmitters
    • alter CA2+ dependent cAMP production
    • modify CA2+ mediated second messenger function
  37. Biogenic Amine Hypothesis
    • Lithium’s actions may be related to its ability to modulate serotonin and/or norepinephrine function
    • In Vitro Studies: Lithium modulates 5-HT actions
    • Li+ elevates brain tryptophan and 5-HT levels
    • Li+ increases 5-HT release in brain slices
    • Li+ may lead to down-regulation of 5-HT autoreceptors
    • Li+ may decrease the affinity of 5-HT at certain receptor subtypes
    • Li+ also enhances the uptake of NE and 5-HT
    • This may suggest a basis for the acute antimanic effects
  38. Second Messenger System Hypothesis
    • lithium alters transduction of neurotransmitter initiated signal by modifying function of second messengers
    • ex. adenyly, phosphoinoositide (PI) or G protein actions
  39. Lithium may reduce post synaptic actions of 5HT and NE on second messenger systems
    • At clinically relevant doses, lithium reduces the ability of NE to stimulate adenylyl cyclase activity
    • Lithium pretreatment prevents reserpine-induced changes in enzyme system mediated by NE
    • Lithium may reduce receptor-initiated activation of G proteins
    • Lithium may directly inhibit the enzymes necessary to activate the PI second messenger system
  40. Lithium pharmacokinetics
    • members of the alkali metal family (ion)
    • ex. includes NA, K, rubidium, Celsium and francium
  41. Lithium absorption
    • readily absorbed from both stomach and small intestine
    • reaches peak blood levels within 6 hrs
    • steady state levels reached in 6-10 days
  42. Lithium-distribution
    • depot binding to proteins is minimal
    • highest tissue levels found in brain and kidney
  43. Lithium-metabolism
    • Li+ is not metabolized
    • processed and cleared by KIDNEYS
    • excreted in intact form via kidney (95%), sweat, saliva and breasy milk (5%)
    • half life=1 day
    • increases with age and renal dysfunction
  44. Lithium-TI
    • narrow Therapeutic-tixic ratio (low TI)
    • must do blood monitoring
    • very lethal drug
    • Therapeutic range=0.6-1.2 mM (plasma levels)
    • toxicity occurs at 2.0 mM
    • BLOOD LEVEL more important than dosage
    • dosage is adjusted according to age, renal function, lithium level and clinical response
    • acute mania=1200-1800 mg daily
    • maintenance=900-1200 mg daily
  45. Lithium side effects
    • gastrointestinal sx
    • CNS sx
    • dermatologic sx
    • cardiac sx
    • endocrine sx
  46. Lithium side effects misc
    • polydipsia/polyuria
    • weight gain (water retention)
    • cold extremeties, nasal stuffiness, sluggishness
    • kidney damage (processed and cleared through kidneys)
    • CNS depressant
    • psychomotor impairment
    • CAN NOT be pregnant on this drug
  47. Lithium-gastrointestinal sx
    • nausea
    • vomiting
    • upset stomach
    • diarrhea
    • weight gain
  48. Lithium-CNS sx
    • muscle weakness
    • fine motor tremor
    • cog slowing
    • headache
    • lethargy
  49. lithium-dermatologic sx
    • rash
    • hair loss
    • acne
    • psoriasis
  50. lithium-cardiac sx
    • change in electrical activity of the heart (ECG)
    • disturbances in heart rhythm
  51. lithium-endocrine sx
    • hyperthyroidism
    • more likely among older adults and women than men
  52. Lithium-toxic effects
    • overdose sx
    • flu-like sx
    • worsened nausea, vomitingm diarrhea, muscular weakness
    • muscle twitching, drowsiness, confusion, arrythmia, coma, convulsions, death
    • CNS effects
    • disorientation, confusion, tonnitus (ringing in ear), worsening of hand tremor, slurred speech, ataxia (gait incoordination), delirium, seizures, coma, muscle twitching
    • inadequate fluid intake increases likelihood of toxicity
    • diuretics will do this as well
    • MUST discontinue drug immediately
  53. Lithium-Na interaction
    • processed and cleared through kidneys
    • diuretics will increase lithium levels by retaining lithium and eliminating water
    • NA trade off with Li
    • give up NA-->increase retention of Li
    • diuretics (sodium loss)-->more Li-->more toxic
    • coffee and alochol-diuretic effect
  54. lithium and coffee
    • diuretic effect
    • diuretics (sodium loss)--> go toxic
  55. lithium and tobacco
    • nictotine accelerates metabolism of caffeine (coffee)
    • while still smoking, need to drink more coffee to get caffeine effects
    • get increased diuretic effect from fluids alone-->go toxic
    • if quit smoking, can have dramatic rise in caffeine levels-->go toxic
    • can increase rate of caffeine in system up to 200% upon cessation of nicotine
  56. lithium drug interactions
    • SSRIs
    • TCAs
    • muscle relaxants
    • phenothiazines
    • non-steroidal and anti-inflammatory drugs
  57. lithium and SSRIs
    combo will increase risk of serotonin syndrome
  58. lithium and TCAs
    • neurotoxic effects
    • even at normal doses
  59. lithoum and muscle relaxants
    prolongs effects of lithium-->go toxic
  60. lithium and phenothiazines
    decreases levels of phenothiazines
  61. lithium and non-steroidal/anti inflammatory drugs
    increase lithium retention-->go toxic
  62. althernative therapies to lithium
    • lithium
    • serious potential for toxic side effects
    • rapid cycling bipolar ppl (more than 4 cyclic episodes per year)
    • resistant to therapeutic effects of lithium
  63. BD and off label drugs
    • NOT approved by the FDA for tx of BD
    • off label drugs are only an option after all other traditional tx has failed
    • new drugs work diff for diff ppl and each has its own side effects
  64. Lamictal (lamotrigine)
    • on label-2003 for BD
    • controls rapid cycling and mixed bipolar states for those who do not respond to lithium, carbamazepine and/or valproate
    • more antidepressant potency than carbamazepine or valproate
    • fewer side effects than lithium
    • sometimes used w/out antidepressant due to own antidpressant properties
    • side effects=headaches, rash, dizziness
  65. Stevens-Johnson Syndrome
    • lamictal side effect
    • rare but dangerous rash
    • skin sloughing, electrolyte imbalance, infections
    • MUST discontinue med
    • more avoidable with slow dose increase
    • increased risk w/ valproic acid
  66. Lamictal interactions
    • w/ ETOH
    • psychomotor impairment
    • lower seizure threshold
    • CNS depression
    • w/ carbamazepine
    • decrease Lamictal levels
    • increase likelihood of cog. probs
  67. Depakote
    • FDA approval (on label)
    • fewer side effects
    • linked to polycystic ovarian syndrome
    • contraindicated for women by some MDs
    • black box warning for pancreatitis now
    • less effective than lithium
    • used to augment lithium for "break through" manic episodes
  68. Valproic Acid
    • mechanism of action is unclear
    • seems to involve...
    • inhibit metabolism of GABA thus facilitating the inhibitory effects of GABA on the brain
    • blockage of cell firing induced by NMDA-type glutamate receptors
    • attenuation of second messenger systems
  69. advantages of Depakote (divalproex sodium)
    • strong acute efficacy data
    • some long term data
    • broad activity spectrum
    • less toxic than Li+
  70. disadvantages of Depakote (divalproex sodium)
    • nausea (acute)
    • weight gain (chronic)
    • nuisance side effects
    • possibly less effective for pure bipolar depression
    • neural tube defects (5-7%)
  71. Tegretol (carbamazepine)-anticonvulsant
    • experiemental/off label
    • rapid cycling for BD
    • side effects like TCAs
    • do NOT use with SERZONE-dangerous interaction
    • Serzone causes liver toxicity
    • Negative interactions with Prozac, Luvox, and lithium
    • mandatory regular blood count monitoring and periodic liver function tests
    • several adverse interactions can occur when combined with other drugs due to induction of liver enzymes
  72. Advantanges of Tegretol (carbemazepine)
    • strong acute efficacy data
    • broad activity spectrum
    • possible antidepressant effects in BD
    • long history of use
    • no weight gain
  73. Disadvantanges of Tegretol (carbemazepine)
    • may loss effectiveness over long term
    • drug interactions
    • blood d/os
    • narrow TI
    • acute side effects
  74. Tegretol (carbemazepine)-mechanism of action
    • unclear mechanism
    • chemically related to TCAs
    • seems to involve...
    • reduction of cellular activity via blockage of Na+ channels
    • may inhibit second messenger systems (IP)
    • may facilitate actions of inhibitory neurotransmitter GABA in brain
  75. carbamazepine vs. lithium
    • extenet and time course of efficacy in reducing manic sx is identical to lithium
    • pts unresponsive to lithium improved on carbamazepine
  76. Neurontin (gabapentin)-anticonvulsant
    • experimental/off label
    • helpful for manic states but may have antidepressant properties
    • fewer side effects
    • sleepiness, fatigue, nausea
    • may be useful for BDI and II
    • may be good for rapid cycling
    • may be used w/ or w/o lithium
    • drug clearance may be altered
    • needs to be taken up to 4x a day
    • compared to 2x for other anticonvulsants
  77. Topamaz (topiramate)-anticonvulsant
    • off label
    • seems to help regulate mood in those w/ manic dep
    • does not seem to cause weight gain
    • may help ppl lose weight
    • appears to cause more cog. side effects than new drugs
    • Does not seem to interact neg. w/ MAOIs, lithium, Lamicatal, or Neuontin
    • combo w/ Depakote or Tegretol can lower plasma levels of Topamax
  78. side effects of carbamazepine
    • sedation
    • weight gain
    • gastrointestinal distress (upset stomach)
    • hand tremors
    • Nystagmus (involuntary mvmt of eyes)
  79. side effects of Valproate
    • alopecia (hair loss)
    • weight gain
    • gastrointestinal distress
    • nausea
    • sedation
  80. signs of toxicity/overdose w/ anticonvulsants
    • CNS signs
    • somnolence, seuizures, coma
    • gastrointestinal sx
    • severe nausea and vomiting
    • cardiac signs
    • arrhythmias
  81. side effects of newer anticonvulsants
    • less research supports use of newer anticonvulsants to treat BD
    • blood level monitoring is usually used when anticonvulsants are prescribed
  82. side effects of newer anticonvulsants (2)
    • gastrointestinal sx
    • nausea, vomiting, weight gain
    • CNS sx
    • sedation, headache, fine hand tremor
    • Dermatologic sx
    • rash
    • endocrine sx
    • menstrual irregularities
  83. signs of newer anticonvulsant toxicity/overdose
    • CNS signs
    • confusion
    • renal signs
    • urinary retention
    • hematological signs
    • bone marrow suppression
  84. antiepileptic drugs (FDA)
    • 2x suicide risk
    • suicidal ideation/beh can be seen as early as 1 wk after drug taken, and cn last through 24 wks
    • higher suicide in pts with epilepsy compared to drug given for only psychiatric reasons
  85. classic antipsychotics
    • used for very short term control of excessive psychotic beh
    • agitation
    • hallucinations
    • delusions
    • bc of side effects and probs of longer term use-MUST be used w/ great caution
  86. atypical antipsychotics
    • often used as adjunctive therapy when bipolar pts manfest psychotic sx
    • either during manic or depressive episodes
    • have been used as monotherapy for episodes of mania or bipolar dep.
    • useful for prevention and maintenance tx
  87. names of atypical antipsychotics
    • Clozaril (Clozapine)
    • Zyprexa (olanzapine)
    • Seroquel (quetiapine)
    • Risperdal (risperidone)
    • Geodon (ziprasidone)
    • Abilify (aripiprazole)
  88. Symbax-mechanism of action
    • unknown
    • may be due to...
    • 3 monoaminergic neural systems (serotonin, norepinephrine, and DA) is responsible for its enhance antidepressant effect
    • Olaznapine/fluoxetine=synergistic icnreases in NE and DA release in prefrontal cortex compared w/ either component alone, as well as increases in serotonin
  89. BD-med compliance
    • people like being "high" on mania
    • serious side effects
    • difficulty w/ polypharmacy
    • often see many changes in meds
  90. BC-components for psychoeducational protocols
    • education about BD
    • relapse prevention
    • medication compliance
    • communication skills training
  91. BD-research on family based interventions
    • lower rates of family separataions
    • greater improvements in levels of family functioning
    • higher rates of full recovery
    • lower rates of rehospitalization for 2 years post Rx
  92. Cyclothymia
    • somewhere b/w BD and normal
    • hypomanic episodes
    • some dep but not full depth
    • must have d/o for at least 2 years before it is diagnosed
    • must be chronic
  93. cyclothymia tx
    • no evidence for effectiveness of meds
    • have tried lithium and valproic acid
    • psychotherapy is indicated for characterological probs
  94. Use of stabilizers and other d/os
    • Borderline PD
    • no evidence for effectiveness of meds
    • based on idea that BPD is a subtype of BD (Bipolar V)
    • schizoaffective
    • lithium
    • migraine prophylaxis
    • lithium and valproic acid
  95. Depression facts
    • 12-20% of adults-lifetime
    • 11 M Americans each year
    • 2:1 F:M ratio
    • peaks at ages 35-45
  96. MDD
    • can never have had a manic or mixed episode to be diagnosed with MDD
    • one or more major dep episodes for at least 2 wks
  97. depression bio-beh probs
    • sleep distrubance
    • hypersomnia and hyposomnia
    • appetite disturbance
    • weight loss or gain
    • psychomotor disturbance
    • agitation or retardation
    • fatigue
  98. hypersomnia-dep.
    • excessive sleeping
    • not related to a lack of sleep
  99. hyposomnia-dep
    terminal or initial insomnia
  100. dep.-psychological probs
    • incredible sad and depressed mood
    • anhedonia
    • concentration probs
    • guilt
    • suicidality
  101. DIGES CAPS
    • D-dep mood most of the day nearly every day
    • I-loss of interest
    • G-guilty feelings, worthlessness, hopelessness
    • E-energy-loss of energy, fatigue
    • S-sleep-insomnia or hypersomnia
    • C-concentration-diminished ability to think, concentrate, decide
    • A-appetite change, weight gain/loss
    • P-psychomotor agitation or retardation
    • S-sucidality-recurrent thoughts of death or suicide w/ or w/out specific plan
  102. disorders that can manifest as MDD
    • medical d/os
    • drugs and substances
    • primary psychiatric clinical dep d/os
  103. medical d/os that can cause dep.
    • endocrine
    • infectious
    • metabolic
    • rheumatic and inflammatory
    • neurological
    • other GMCs
  104. endocrine d/os-dep
    • hyppthyroidism/myxdema
    • hyperthyroidism/thyrotoxicosis/Grave's disease
    • hormonal changes
    • Addison's disease
  105. dep-hypothyroidism/mxedema
    • too little thyroid horomone
    • most common med d/os result in dep illness
  106. dep.-hyperthyroidism/thyrotoxicosis/Grave's disease
    exzcessive thyroid horomone
  107. dep-horonomal changes
    • menopause
    • post partum
    • premenstrual
  108. dep-Addison's disease
    reduced production of adreno-corticosteroid horomones
  109. dep-Infectious d'os
    • AIDS/HIV
    • infectious hepatitis
    • influenza
    • syphilis
    • chronic infections such as...
    • mononucleosis
    • tuberculosis
  110. dep-metabolic d'os
    • diabetes
    • malnutrition
    • porphyria
    • defects in production of red blood cells
    • anemia
    • uremia
    • build up of toxins in the blood secondary to kidney failure
  111. dep-GMCs
    • sleep apnea
    • asthma
    • congestive heart failure
    • chronic pain
    • cancer
  112. dep. neurological d/os
    • Parkinson's
    • MS
  113. dep-rheumatic and inflammatory d/os
    • chronic fatigue syndrome
    • rheumatoid arthritis
  114. drugs that can CAUSE dep.
    • Alcohol
    • Antianxiety drugs
    • anti-hypertensive meds
    • anti-parkinsonian drugs
    • horomones
  115. dep-alcohol
    CNS depressant and when used regularly can cause or exacerbate dep sx
  116. dep-antianxiety meds
    • can cause or exacerbate sx
    • especially benzos
  117. dep-horomones
    • female contraceptives
    • horomone replacement therapy for menopausal women
    • steroids-cortisone
  118. d/os w/ features of MDD
    • mood
    • MDD, dysthymia, BD I and II
    • anxiety
    • PTSD, PD, OCD
    • Borderline PD, Dep. PD
  119. dep-Monoamine (MA) Hypothesis
    • decrease in monoamines at critical synapses
    • NE
    • 5HPT
    • DA
    • less in epinephrine
  120. causes of MA (monoamine) prob
    • excessive reuptake by presynaptic neurons
    • decreased release of NT by pre synaptic neurons
    • MAO excess
    • abnormalities in psotsynpatic neuron receptors related to second messenger systems
  121. dep. MA-excessive reuptake by presynaptic neurons
    • isntead of neurotransmitter remaining in synapse and interacting again with postsynaptic receptors
    • too much is reabsorbed into presynaptic neurons
  122. dep. MA-decreased relaease of NT by pre synaptic neurons
    • reduction in synthesis of NT
    • impaired ability to store NT
    • abnormalities in vessicle migration and fusion w/ cell membrane
  123. dep. MA-MAO excess
    • enzyme in pre synaptic neurons
    • breaks fown NTs into amino acids
    • if MAO enzyme is too active and breaks down excessive amounts of NTs --> insufficient amounts of NTs for release into synapse
  124. dep. MA-abnormalities in post synaptic neuron receptors related to second messenger systems
    • these receptor abnormalities include..
    • changes in # of receptors (reregulation down or up)
    • altered (increased or decreased) receptor sensitivity
  125. dep-Biogenic Amine Hypothesis
    • indirect evidence
    • lowered amines
    • reserpine
    • effective tx for hypertension by reducing peripheral adrenergic activity
    • induced depression in sig. # of pts
    • found to inhibit vesicular storage of monoamines, allowing metabolism by MAO
    • other early drugs
    • reduce biogenic amine levels and precipitated dep.
    • early effective antidepressants
    • found to acutely increase intracellular monoamine levels
    • also reversed reserpine-induced dep
  126. Monoamine Model of Dep
    not enough activity of monoamine neurons, especially NE and 5 HT neurons cause dep
  127. Problem w/ MA theory of dep
    • time lag issue
    • takes 2-3 HOURS for drugs to exert effect on synapse
    • takes 3-5 (or more) WEEKS for drugs to exert their antidepressant effect
  128. MA theory of dep-effects of blocking reuptake
    • increase 5HT at terminal ending (desired therapeutic effect)
    • increase inhibition at dendritic autoreceptors
  129. pharmacotherapy-TCAs
    • therapeutic effects
    • mediated through down regulation of autoreceptors over time
    • reduction in side effects
    • mediated by eventual down regulation of post synaptic 5 HT receptors
  130. pharmacotherapy-blockade of MA reuptake
    • dep caused by low levels of MA (NE & 5HT)
    • high levels of post synapic receptors
    • drug tx
    • TCAs or SSRIs administered
    • blockade of NE and 5 HT reuptake pumps
    • increase in NE and 5HT levels primarily detected initially at autoreceptors
  131. dep-autoreceptors
    • after presynaptic neuron releases NT across synaptic cleft several events occur
    • detected by receptors on postsynaptic neuron
    • detected by receptors on presynaptic neuron
    • autoreceptors on presynaptic membrane
    • provide feedback to presynaptic neuron about rate of NT synthesis and release
    • function to control internal cell processes including synthesis and release of NT
    • diff than transporter molecules or proteins
  132. transporter proteins
    • transporters exist in membrance of neurons and glia
    • serve to carry NT across membranes and transport them to specific locations
    • transporters in synaptic membrane serve to remove NT from synaptic cleft and prevent their action or bring it to an end
    • MA transporters are NT transporters that transfer MA NT in or out of cells
  133. depression caused by...
    • low levels of NE and 5 HT
    • high levels of post synaptic receptors
  134. drug tx for dep
    • TCA or SRRI administration
    • selective blockade of NE and 5 HT reuptake pumps
    • increase in NE and 5 HT levels primarily detected initially at autoreceptors
  135. blockade of MA reputake for dep-intermediate effects
    • autoreceptors down regulate due to high levels fof available NE and 5 HT (no longer brought back up)
    • -->more NE and 5HT is released at synapse
  136. blockade of MA reputake for dep-long term effects
    post synaptic receptors down regulate to more "normal" levels
  137. alternatives to MA hypothesis for dep
    • supersensivity
    • habituation
    • multiple communication systems
  138. Supersensitivity theory
    • supersensiviity of MA system not low levels of MA transmitters
    • antidepressants exert effects by causing post synaptic cells to down regulate
    • reduce receptor sensitivity/density
    • process would involve changes in protein synthesis over several weeks
  139. Habituation theory of dep
    • habituation to increased 5 HT is gradual
    • 5HT synapses increases immediately after antidepressants
    • autoreceptors on presynaptic cells detect increased 5HT and thus prevent further 5HT release
    • period of adjustment (increase in Serotonin conduction) takes weeks
  140. depressive disorders and antidepressants most likely involve...
    • other NTs
    • 2nd messengers and hormones
    • interact in complex ways-MA sys involved in but necessarily the ultimate cause or solution of dep
  141. Biogenic Amine Hypothesis of Dep
    • early antidepressants were not selective for certain monoamines
    • historically, US favored catecholmines (DA and NE)
    • Europe favored Serotonin
    • Now, no isolated systems are nvolved, it is a complex interaction
  142. biology of dep
    • no single brain area stands alone
    • no such thing as localization
    • no single drug affects only one system
    • dep cannot be attributed to any single NT
    • dep cannot be attributed to any single brain area
  143. Biogenic Amine Hypothesis for Dep (2)
    • evidence that amine hypothesis is too simple
    • affective disorders are complex
    • disconnect bw pharmacology and therapeutic benefit
    • lack of correlation bw druh potency and effective therapeutic dose
    • no evidence for amine depletion in dep ppl
  144. Broader view of cause of dep
    • environment
    • history
    • genes
    • NTs (monoamine hypothesis)
    • 2nd messenger system (alter normal gene function)
    • receptors (#, affinity)
  145. overview of diff drugs for dep
    • monoamine oxidase inhibitors (MAOIs)
    • Tricyclics (TCAs)
    • SSRIs
  146. Newer pharmacotherapies for dep
    • norepinephrine (noradrenergic) reuptake inhibitor (NaRI)
    • Reversible inhibitor of Monoamine Oxidase A (RIMA)
    • Serotonin and NE reuptake inhibitor (SNaRI)
    • DA reuptake inhibitor (RaMI)
    • herbal remedy
  147. slide 42
  148. Monoamine Oxidase (MAOIs)
    • found mainly on outer mitochondrial membrane in cells throughout central nervous system
    • there are two diff isozyme forms of MAO
    • MAO-A and MAO-B
  149. MAO-A
    • red wine and cheese effect
    • preferentially metabolizes serotonin but also will metabolize DA, epi, NE and others
  150. MAO-B
    preferentially metabolizes DA but also many other amines
  151. the first MAOIs
    • iproniazid-given to pts in hopes of treating their turberculosis
    • some pts reported "enlightening" effect
    • research soon attributed effect to a raise in NT levels due to MAO inhibition
  152. MAOIs 1957-1970
    • both non selective and irreversible
    • single dose of MAOIs increase
    • NE, Epi, DA and sero
    • this increase is seen all over the body
    • brain, heart, intestines and blood
  153. MAOIs-pharmacodynamics
    block metabloism (inactivation) of monoamines by MAO
  154. MAOIs=1970-present
    • more selective MAOIs have been developed w/ identification of MAO subtypes
    • MAO-A and MAO-B inhibitors
  155. MAO-A inhibitors
    • moclobemide selectively and REVERSIBLY inhibit MAO-A
    • inhibition results in a rise of NE, DA and Sero in synaptic cleft
  156. MAO-B inhibitors
    • L-deprenyl and IRREVERSIBLY inhibits MAO-B
    • results in rise in DA primarily
    • used in combo with levodopa to treat Parkinson's
  157. MAOIs pharmacokinetics
    • oral admin
    • rapid absorption from GI tract (2-4 hrs)
    • hepatitic (liver) metabolism
    • half life=2-3 hrs for iproniazid
    • protein (depot) binding is variable (50-80%)
    • excretion is mainly via urine
  158. common MAOIs
    • Nardil (phenelzine)
    • Parnate (tranylcypromine)
    • Marplan (isocarboxazid)
    • Deprenyl (seleginine)
    • EMSAM-selegiline transdermal patch
    • 2006 FDA tx for MDD
    • continuous delviery system, better than oral admin
  159. MAOIs-side effects
    • hypertensive crisis
    • orthostatic hypotension
    • weight gain
    • anorgasmia, impotence
    • urinary hesitancy, constipation
    • seizures
    • sometimes insomnia (parnate)
    • need to consider other drug interactions
  160. MAOIs-anticholinergic effects
    • ataxia (loss of coordination)
    • blurred vision
    • confusion
    • dry nouth
    • dry skin
    • constipation
    • delayed urination
    • weight gain
    • sexual dysfunction
  161. dysthymic d/o-SSRIs
    • used freq
    • 62% response rate
    • up to 44% response rate to placebo
    • tx response increases if pt thinks dysthymia is a biological d/o
  162. dysthymia-anxiolytics
    • no effect over placebo
    • have been noted to worsen depression
  163. Hypericum/St, Johns Wart
    • natural herb
    • increases 5 HT levels in brain (up to 4 wks)
    • may mimic SSRIs or MAOIs
    • German study showed equal effective to TCAs for mild to mod dep
    • US study showed no more effective than placebo
    • some side effects
  164. Organic alternatives for dep meds
    • St. Johns Wart/hypericum
    • DHEA
    • SAM-e
  165. DHEA (dehydroepiandrosterone)
    • super horomones
    • can have interactions with other drugs
    • unsupported-FDA says be careful
  166. SAM-e (s-adenosylmethionine)
    • compound found in all living cells
    • can induce mania
    • can have interactions with other drugs
    • unsupported-FDA says be careful
  167. psychostimulants used for...
    • increase
    • alertness
    • concentration and focus
    • mood
    • reduce
    • fatigue
    • weight (anorectics)
  168. illegal psychostimulants
    • cocaine
    • methamphetamines (street created)
    • illicitly used prescribed stimulants
  169. legal psychostimulants
    • prescribed amphetamines (ritalin)
    • nicotine
    • caffeine (most common)
  170. stimulants are drugs (sympathomimetics) that...
    • increase alertness
    • heighten arousal
    • cause beh excitement
  171. cocaine
    • shrub like tree from mountains of Peru, Bolivia, Colombia
    • coca leaves containe between 0.6% and 1.8% alkaloid cocaine
    • chewing leaves produces mild psychoactive effects
  172. history of cocaine
    • s. americans chewed coca leaves for 5000 years
    • banned by Spanish in 1500-lifted when they saw how hard ppl worked when could chew
    • isloated from leaves in 1859
    • used by soldiers recreationally in 1900
    • currently used as local anesthetic (novocaine)
    • 1990, 11% of US pop reported having used cocaine at least once
  173. cocaine-routes of admin
    • snorting/insufflation
    • drawn into nasal cavity and blood stream-3 min
    • injecting
    • cocaine hydrochloride is water soluble-15 sec
    • smoking
    • crack cocaine absorbed isntantly in lunchs-5 sec
  174. cocaine-mechanism of action
    • opp of amphetamine
    • little or no effect on catechholamine release
    • cocaine blocks DA, NE, and 5HT reuptake
    • may alter the DA transporter in open configuration, allowing release of DA into cleft
    • cocaine also blocks axonal voltage-gated sodium channels
    • (local anethetic property)
    • temporary depletion in DA/cocaine
    • want cravings of coke-->dysphoria
  175. mechanism of cocaine action (2)
  176. chronic cocaine use
    • cocaine psychosis
    • cocaine toxicity
  177. cocaine psychosis
    • chronic use-->transient paranoid psychosis w/ delusions and hallucinations
    • has not been well documented like amphetamine
  178. cocaine toxicity
    • does not appear to directly damage neurons except at very high doses
    • death may result from seuizures, stroke, heart attack and intracerebral hemorrhage
  179. amphetamine
    • naturally occuring compounds
    • cathinone
    • ephdrine
  180. cathinone
    found in khat-an evergreen shrub native to East Africa and the Arabian peninsula
  181. ephedrine
    • found in herb Ephedra vulgaris (Chinese herb Ma Huang)
    • bronchodilator (asthma use)
  182. amphetamines cause increase in...
    • alertness
    • focus
    • sustained attention tasks
    • low doses will do this-even if not fatigued, can benefit you
    • high doses-interferes w/ performance and concentration
  183. amphetamines-routes of admin
    • orally
    • nasally
    • inhalation (smoked)-rapid and intense high
    • IV-rapid and intense high
  184. amphetamine is a weak base
    • absoption following oral consumption is slow
    • almost all the drug is ionized in the stomach
    • effects take 30 min after a 5-15 mg oral dose
  185. amphetamine-mechanism of action
    • increases release of catecholamines (DA, NE, 5HT)
  186. amphetamine-Exchange Diffusion Model
    • blocks reuptake
    • taken into pre synaptic cells via DA transporter
    • transporter reverses and ejects DA into synapse
    • displaces DA from vessicles
    • inhibits MAO
  187. amphetamine-neuronanatomy and physiology
    • increased: blood pressure
    • respiration rate (tachypnea)
    • heart rate (tachycardia)
    • matabolic rate
    • oxygen consumption
    • may result from increased release or reuptake blockade of NE in SNS
  188. amphetamine-side effects at higher doses
    • rebound dysphoria
    • hypersomnia (2-3 dys)
    • sterotypy (teeth grinding)
    • restlessness
    • paranoia
    • inflated self importance
    • tangential speech, pressured speech
    • these can look like other mental d/os
  189. clinical use of amphetamines
    • ADHD
    • conduct d/o
    • Bipolar affective d/o-cyclic, emotional
    • narcolepsy
    • prevent sleep attacks
    • obesity
  190. types of amphetamines-ADHD
    • Dexedrine (dextroamphetamine)
    • Aderall (amphetamine/dextroamphetamine)
    • Methedrine (methamphetamine)
    • Metadate (methylphenidate)
    • Methylin (methylphenidate)
    • Ritalin (methylphenidate)
    • Concerta (methylphenidate)
    • Focalin (dexmethylphenidate)
    • Cylert (pemoline)-Removed from market for liver toxicity
  191. methylphenidate
    • derivate of amphetamine
    • similar pharmacodynamics
    • available in several diff forms
    • some are short acting (3-5 hrs)
    • otehrs have extended effects (8-12 hrs)
  192. types of methylphenidate
    • Ritalin
    • Metadate
    • Concerta
    • Methylin
    • Daytrana (trasndermal patch)
  193. Multimodal tx of ADHD (MTA)
    • beh vs. meds. vs. combined
    • all conditions improved
    • beh-medication for many measures
    • combined tx was the best on most measures
    • meds alone were better than beh alone for core ADHD sx
    • meds alone were sufficient tx at 14 mo
  194. MTA-long term effects
    • reduction in growth-20% but catch up occurs in most
    • 2 yrs-meds are better
    • 3 yrs-loss of meds benefit
    • 8 yrs-loss of benefit of meds
    • 30% still met criteria for ADHD
    • 61% stopped taking meds at year 8
    • kids who stopped taking meds were as good as those still on it
    • physicological and height probs absent at 8 years
    • med group had sig, more substance abuse
  195. MTA (2)
    • 8 year follow up
    • no diffs in sx or functioing among diff groups
    • suggests type of ADHD tx at year 1 does not predict future functioning
    • youths w/ ADHD still had more academic, social and conduct probs than peers
    • more dep and psychiatric hospitalization too
  196. MTA overall data
    • drugs alone-best at 2 yrs
    • at 3 yrs-dop off med benefit
    • at 8 yrs-unclear if drugs helped at all
  197. amphetamines-ADHD-increase focus
    • not an effective tx for ADHD by itself for most children
    • based on MTA follow up data
    • need to consider importance of skills training
    • may need to assess parenting or school situation
  198. clinical tx of ADHD
    • antidepressants
    • TCAs-effective but risky
    • wellbutrin (bupropion)-stimulating
    • off label for AHDH
    • SSRIs not as effective
    • Straterra (atomoxetine)
    • on label for ADHD
    • new NaRI with clinical effectiveness
  199. Narcolepsy
    • sleep d/o-irresistible attacks of sleep in daytime
    • can be dangerous-while driving, etc
    • attacks must occur daily over a period of at least 3 mo and must be accompanied by either:
    • cataplexy
    • REM intrusions
  200. cataplexy
    • brief sudden episoeds of loss of bilateral muscle tone usually realted to experience of intense emotions
    • person loses voluntary control over skeletal muscles
  201. REM intrusions
    • recurrent intrusions of elements of REM sleep into the transition b/w sleep and wakefulness
    • hypnagogic imagery
    • hypnapompic imagery
    • sleep paralysis
  202. hypnagogic imagery
    • when falling asleep
    • REM intrusions-narcolepsy
  203. hypnapompic imagery
    • when awakening
    • REM intrusions-narcolepsy
  204. amphetamines-narcolepsy
    • any stimulants
    • dextroamphetamine-most common
    • Provigil (modafinil)
    • new atypical stimulant available and recommended
  205. commonly used amphetamines for narcolepsy
    • Cylert (pemoline)
    • Metadate (methylphenidate)
    • Methedrine (methamphetamine)
    • Methylin (methylphenidate)
    • Ritalin (methylphenidate)
    • Dexedrine (dextroamphetamine)
  206. weight loss/appetite suppressors
    • anorectics
    • common stimulants
    • Dexedrine (dextroamphetamine)
    • Adipex (phentermine)
    • Meridia (sibutramine)
    • Tenuate (diethylpropion)
    • Have seen in the past
    • Desoxyn (methamphetamine)
    • same probs as amphetamines
  207. Fenfluarmine-illegal
    • creation of heart valve problems
    • Fen/Phen (OTC)-combo of fenfluramine and phentermine
  208. Fenfluarmine
    • appetite supressants
    • reverses 5HT transporter and prevent vessicular storage
    • Redux (dexfenfluamine HCL)
    • Pondamin (fenfluramine)
  209. Fenfluarmine-side effects
    • drowsiness
    • diarrhea
    • dry mouth
    • hypertension
  210. appetite suppresants with phentermine-like drugs
    • increases release of catecholamines (NE and DA, possibly NE and 5HT)
    • phenazine, plegine (phendimetrazine)
    • tenuate (diethylpropion)
    • FDA approved-may be addictive
    • Preludin (phenmetrazine)
    • removed from market
  211. Meridia (sibutramine)
    • SNaRI
    • no antidepressant effect
    • similiar to ampheta,ine in effect (not dynamically)
    • FDA laveled as anorectic only-DFA approved
    • large European trials helped obses ppl lose wt for 2 yrs
  212. Meridia-side effects
    • may be addictive
    • headache
    • constipation
    • dry mouth
    • insomnia
  213. OTC diet aids and weight loss products
    • Ephedra or ma huang
    • now illegal in US
    • boosted metabolism
    • FDA wanrings-related to cardiac probs and death
  214. OTC diet aids-side effects
    • cardivascular probs
    • manic like psychosis
    • anxiety
    • insomnia
    • dizziness
    • numbness
  215. clinical issues with obesity
    • addictive potential of drugs
    • broader life sytle choices
    • look at other health probs
    • heart diease
    • diabetes
    • chronic hypertension
    • interventions focus on broad issue not just weight
    • need to teach diet mgmt not just weight loss
  216. stimulants-gastrointestinal and metabolic side effects
    • upset stomach
    • decreased appetite
    • nausea
    • vomiting
    • weight loss
    • diarrhea/constipation
    • problem for children bc not getting enough calories/nutrition
    • growth usually catch up when off meds
  217. stimulants-cardiovascular side effects
    • activate SNS...
    • increased HR and pulse rate (tachycardia)
    • cardiac arrhythmias
    • chest pain
    • increased sweating
  218. stimulants-cardiovascular side effects-elderly
    • high risk
    • may have cardiovascular disease and comprimised cardio system
  219. stimulants-neurological side effects
    • nervousness
    • tension
    • restlessness
    • irritability
    • anxiety
    • agitation
    • insomnia
  220. stimulants-tics and tremors
    • high comorbidity of ADHD and tic disorders (Tourettes)
    • child already has a tic, stimulant will make tic worse
  221. chronic amphetamine use
    • psychomotoe effects become sensitized
    • stereotyped beh
    • amphetamine psychosis
  222. chronic amphetamine use-sensitized
    repeated intermittent use leads to a decrease i nthe dose required to activate these psychomotor beh
  223. chronic amphetamine use-stereotyped beh
    bizarre limb mvmts, continuous chewing or licking, nail biting, aimless walking
  224. amphetamine psychosis
    long term users can develop PERMANENT condition that resembles paranoid schizo
  225. amphetamine toxicity
    • larges doses-->cell death in DA and 5HT systems
    • nigrostriatal DA sys partially susceptible to amphetamine toxicity
  226. sx of amphetamine overdose
    • initial
    • tachycardia
    • hypertension
    • seizures
    • later
    • hypotension
    • coma
  227. amphetamine-abuse and dependence
    • very high
    • very euphoric effects
    • good fit for this culture
  228. amphetamine-dangers
    • higher dosees-bad effects
    • illegal forms-very dangerous concoctions
  229. Nicotone-pharmacology
    • 5% of the dried tobacco leaf
    • 9 mg of Nicotine in one cig, 1 mg absorbed by smoker
    • 25% nicotine binds to acetylcholine receptors in brain within 7 sec of inhalation
    • 2x faster with IV
  230. Nicotine-mechanism of action
    • nicotine readily crosses blood brain barrier and enters brain
    • stimulates Nicotinic Acetylcholine receptors (nAChRs)
  231. nicotinic cholinergic receptors
    • major acetylcholine receptors subtypes
    • widespread throughout brain
    • especially concentrated in...
    • midbrain tegmentum
    • striatum (basal ganglia)
    • nucleus accumbens
    • sub. nigra
    • VTA
  232. nicotine-mechanism of action (2)
    • many nicotinic receptors located at pre synaptic terminals:
    • cholinergic
    • dopaminergic
    • glutamatergic
    • stimulation of receptors-->increase release of NT at terminals
    • effective in raising neuronal activation through release of excitatory NT
  233. nicotine-dose dependent response-low doses
    • nausea and vomiting
    • gain tolerance with exposure
    • calming effect
    • may be beh distraction
    • anti-diuretic effect
    • prevents formation of urine
    • can have laxative effects
  234. nicotine-dose dep. response-high doses
    • agiation
    • nausea
    • vommiting
    • mental confusion
    • muscle weakness
    • can get this effect with low doses
  235. nicotine-chronic user, higher doses
    • induces liver enzymes
    • inactivates drug rapidly
    • key issue for clin. pops
    • smokers may require higher doses of some meds
  236. nicotine toxicity
    • fatal dose-60 mg
    • not common-most nicotine is destroyed as it burns
    • if swallowed, vomiting usually occurs before ingestion
  237. symptoms of nicotine toxicity
    • nausea, salivation, abdominal oain, vomiting, diarrhea, headache, dizziness, distrubances of vision and hearing, mental confusion, muscle weakness
    • eventually collapse and terminal convulsions-death from respiratory failure
  238. nicotine withdrawal
    • nausea
    • headache
    • GI distrubance (constipation)
    • increased appetite
    • fatigue
    • irritability
  239. nicotine dependence
    • high dependence
    • used for pleasure
    • work to eliminate withdrawal symptoms
    • nicotine addiction-similar to that od coke and heroin
    • appx. 70% of users want to quit
  240. nicotine-quitting
    • average smoker tries to quit 6-9 times
    • fewer than 7% of smokers who try to quit remain smoke free after 1 year
  241. tx of nicotine dependence
    • not very effective
    • smoking cessation therapies more likely to succeed for smokers...
    • who are ready to quit AND
    • receive additional advice and support
  242. Zyban (bupropion)
    • more effective than placebo
    • high relapse rates
  243. nicotine replacement systems
    • nicotine patches/gum
    • similar effectiveness for relapse
  244. behavioral smoking cessation programs
    • skills training, relapse prevention
    • similar effectiveness for relapse
  245. nicotine replacement
    • diff associated with smoking cessation is sig related to nicotine withdrawal sx
    • blocking these sx by maintaining certain circulating level of nicotine can assist in terminating smoking
    • gum chewing is safer than smoking
  246. Chantix (varenicline)
    • more effective than placebo
    • more effective than bupropion
    • more comprehensive tx approach than medicine or replacement alone
    • targets specific acetylcholine nicotinic receptor
  247. chantix-mechanism of action
    • binding to subtype of nicotinic receptor-agonist acitivity
    • prevents binding of nicotine
    • stimulates receptor mediated actitvity but at lower level than nicotine
    • blocks ability of nicotine to acitivate a4b2 receptors/ stimulate CN DA sys believed to by neuronal mechanism underlying reinforcement and reward experienced upon smoking
  248. chantix-agonist
    • binds to nicotine receptor site
    • stimulates receptors
    • not as much as nicotine
  249. chantix-competitive antagonist
    prevents mediated pathway to drug reinforcement
  250. chantix-side effects
    • nausea and vomiting
    • changes in dreaming
    • constipation
    • gas
    • % highest for insomnia
  251. chantix outcome data
    • 12 wks-44%
    • 52 wks-22%
    • still higher than placebo (15% diff)
  252. chantix-beh intervention w/ meds
    • pts received materials and 10 min of smoking cessation counseling each week
  253. chantix-warnings
    • changes in beh
    • agitation
    • dep mood
    • suicidal ideation
    • attempted and completed suicide
  254. caffeine
    • most widely used stimulant
    • 1. coffee (caffeine)
    • 2. tea (theophylline and caffeine)
    • 3. soda (caffeine)
    • 4. chocolate (theobromine)
    • various responses acorss diff ppl
  255. caffeine-mechanism of action
    • does not directly influence catecholamine systems in same way as amphetamine and cocaine
    • hypothesis=blockade of adenosine receptors
  256. caffeine-adenosine hypothesis
    • inhibits firing of neurons by activating K+ channels
    • inhibits release of NT
    • caffeine is competitive antagonist for certain adenosine receptors
  257. caffeine-toxic effects
    • 700-1000mg
    • sensory distrubances
    • insomnia
    • muscle tension
    • anxiety
    • restlessness
    • irritability
  258. caffeine-tolerance
    • tolerance to stimulating functions
    • tolerance to psychomotor effects
  259. caffeine withdrawal
    • headaches
    • increased fatigue
    • sleepiness
  260. caffeine-sedative hypnotics
    • may counteract effects of sed/hyp
    • will not improve psychomotor and coordination deficits
  261. caffeine-diuretic
    • major issues for taking any med
    • drugs processed in kidneys
    • eliminated in urine
    • balance of drugs not excreted by require more body fluid or NA levels
  262. caffeine and tobacco
    • tobacco increases metabolism of caffeine
    • person quits smoking-->elevated caffeine levels
    • feel jittery when quit smoking
    • may get to toxic effects of caffeine
  263. MAOIs considerations
    • largely moved away from bc of side effects and lethality
    • now used for non responders (treatment refractory)
    • may be considered for those who present with anx and dep
  264. MAOIs-warnings
    • irriversible MAOIs cause rise in amine levels and hypertensive crisis
    • strong interactions with SSRIs, OC cold meds
    • red wine and cheese effect
    • hazardous interactions with food with thyramine
  265. red wine and cheest effect
    • aged cheese, red wine and some beer caused pts on MAOIs when eating these foods to have a stroke
    • rise in BP
  266. MAOIs and tyramine
    • dangerous food interactions
    • cheese, yogurt, meats, soy sauce, coffee, chocoalte, wine, etc
  267. Irreversible/nonselective MAOIs
    • phenelzine
    • tranylcypromine
    • isocarboxaid
  268. reversible MAOI-A
    • moclobemide
    • not available in US
  269. selective inhibitors of MAO-B
    deprynyl
  270. MAOIs and alcohol
    sedation and CNS depression
  271. MAOIs and hypertension
    • amphetamine, ephedrine
    • dextromethorphan
    • fluoxetine
    • TCAs
  272. MAOIs-interactions
    • opiates
    • antihistamines and decongestants
    • other MAOIs
    • SSRIs
  273. MAOIs and opiates
    • hypotension
    • CNS depression
  274. MAOIs and antihistamines/anticongestants
    • OTC and Rx
    • hypertensive crisis
  275. MAOIs and other MAOIs
    need 14 day washout
  276. MAOIs and SSRIs
    • serotonin syndrome
    • 14 day washout
    • Prozac needs 5 wk washout
  277. herbs that resemble MAOIs
    • St. John's Wort
    • Ginseng
    • 5HTP
    • bitter orange
    • brewers yeast
    • ephedrine
    • Vitamin b6
    • L-tyrosine
    • Yohimbe
  278. ER if taking MAOIs...
    • severe headache
    • excessive sweating
    • lightheadedness
    • vomiting
    • increased HR witout exertion
  279. Cyclic antidpressants
    • discovered as tx for psychosis
    • share similar three ring structure with many anyipsychotics
    • greatly improved on side effects of MAOIs
  280. multiple generations of TCAs
    • first generation
    • second generation-modified TCAs
    • SSRIs
    • third generation-atypical antidepressants
  281. first generation TCAs
    imipramine (tofranil, anafranil)
  282. second gen TCAs
    • modified TCAs
    • less adverse effects than 1st gen
    • nortriptyline (Pamelor, Aventyl)
    • Desipramine (Norpramin)
    • Protriptyline (vivactil)
  283. SSRI's-TCAs
    • selective reuptake antagonists
    • Prozac (fluoxetine)
    • Zoloft (sertraline)
    • Paxil (paroxetine)
  284. 3rd gen TCAs
    • atypical antidpressants
    • wellbutrin (bupropion)
    • Desyrl (trazodone)
    • Serzone (nefazodone)
  285. TCAs-inhibition of neuronal uptake mechanisms
    • normally terminate actions of NT
    • by inhibiting reuptake, duration of NT action at synapse is prolonged
    • enhanced synaptic activity is thought to alleviate dep
    • there is no apparent relationship b/w potency for uptake inhibition and potency for clinical effectiveness
  286. TCAs-specificity of action
    • 1st gen-little specificty for uptake inhibition
    • will affect most monoamine synapses
    • SSRIs=more specific for serotonin reuptake
    • selectively enhance serotonin synapse activity
    • 3rd gen=specific but just for 5HT
    • ex. may block DA reuptake or may selectively block combos
    • All of these drugs exhibit some affinity for post synaptic receptors
  287. TCAs-mechanism of action
    • allosteric modulators of monoamine reuptake transporters
    • bind to allosteric sites near receptor location for monoamine
    • when allosterically bound, the receptor loses its affinity for NT
  288. steps for how TCAs work
    • 1. low levels of NE and 5HT and high levels of post synaptic receptors (ex. dep)
    • 2. ADM (TCA or SSRI) administered
    • selective blockade of NE and 5HT reuptake pumps
    • increase in NE and 5 HT levels primarily at somatodendritic autoreceptors
    • 3. somatodendritic autoreceptors eventually down-regulate
    • after down regulation, more NE and 5 HT released at synapse
    • 4. post synaptic receptors down regulate to more normal levels
  289. tertiary amine tricyclics
    • sedating
    • tofranil (imipramine)
    • elvail (amitripyline)
    • anafranl (clomipramine)
    • adapin and sinequan (doxepin)
  290. secondary amine tricyclics
    • stimulating
    • norpramin (desipramine)
    • pamelor (nortiptyline)
    • vivactil (protriptyline)
  291. tetracyclics
    • mixed stimulating and sedation
    • asendin (amoxapine)=low sedation, anti psychotic properties
    • ludiomil (maprotiline)=highly sedating
  292. TCAs-side effects
    • strong anticholinergic effects
    • hpotension probs
    • manic "switch over"
  293. TCAs-anticholinergic effects
    • blurred vision
    • dry mouth, dry eyes
    • rapid heart rate (tachycardia)
    • urinary hesitation
  294. TCAs-hypotension probs
    • fuzzy headed feeling
    • dizzy
    • nauseous
    • sedation
  295. TCAs-lethality
    • cardiotoxicity
    • unreoverable delayed conduction and arrythmia
    • OD will stop heart
    • Elavil is eso. lethal
  296. cyclics-Rx
    • dr, usually prescribes weeks rx
    • still enough to OD on
    • long and irreversible

    many drug interactions
  297. types of SSRIs
    • Prozac; Sarafem (fluoxetine)*
    • Luvox (fluvoxamine)*
    • Paxil (paroxetine)*
    • Zoloft (sertraline)*
    • Celexa (citalopram)
    • Lexapro (escitalopram) –isomer of Celexa
  298. cyclics timeline
    takes 3-5 weeks to work
  299. SSRIs timeline
    • effects are seen faster
    • within 3 wks
  300. why SSRIs?
    dont have same side effects as other TCAs
  301. fluoxetine (Prozac, serafem, prozac SR)
    • SSRI
    • longer half life (72 hr active)
    • 4 dys after multiple dosing
    • Pro: compliance issues
    • con: reactions; can cause manic switch over
  302. SSRIs-side effects
    • sexual dysfunction
    • induction of mania
    • weight loss
    • teratogenicity
    • apathy syndrome
    • serotonin syndrome
    • SSRI discontinuation syndrome
  303. SSRIs-sexual dysfunction
    • up tp 80%
    • 60% on average
    • can be augmented with other meds
    • some discussion of permanent sexual dysfunction following SSRI discontinuation
  304. SSRIs-induction of mania
    clinical trials 1%
  305. SSRIs-teratogenicity
    Paxil has effects in first trimester
  306. SSRIs=Apathy Syndrome
    • After months of tx and sx reduction, pt experiences ex superficially similar to reemergence of MDE but pt denies sad mood
    • best treated by reducing SSRI dose
    • may see addition of augmenting meds such as stimulant or bupropion
  307. Apathy Syndrome-sx
    • Decreased enjoyment of activities, mild anhedonia
    • Decreased sense of emotional aliveness, flat mood
    • Deceased spontaneity
    • Loss of motivation
    • Passivity
    • Lethargy and low energy
    • Decreased libido
  308. SSRIs=Serotonin Syndrome
    • serious and can become life threatening-ppl have died
    • caused by excessive activation of serotonin system
    • usually seen in ppl taking 2 or more serotonergic meds
    • STOP taking SSRIs immediately
  309. Serotonin Syndrome-MAOI interaction
    • has occured most often in ppl who were on SSRIs and then prescribed MAOIs
    • SSRIs and MAOIs should NEVER be taken together
    • need at least 2 wks eashout period between drugs
  310. Serotonin Syndrome-sx
    • euphoria, drowsiness, feeling drunk and dizzy, intoxication
    • sustained rapid eye mvmt
    • overreaction of reflexes
    • muscle contraction and relaxation in jaw, restlessness, muscle twitching
    • clumsiness
    • sweating, hody body temp, shivering
    • diarrhea
    • MSE changes (confusion, hypomania)
    • loss of consciousness
  311. SSRIs and dependence
    • NO dependence
    • do not give psychological effect of stimulation or sedation
    • do not give immediate effect
    • not habit forming
  312. SSRIs and withdrawal
    may see maintained use to avoid withdrawal sx
  313. SSRI=Discontinuation Syndrome
    • stopping SSRIs can cause probs
    • somatic and psych probs
    • sx occus on 1/3 of those on SSRIs
    • onset is 24-72 hrs
    • may last for 14 days
    • do not mistake SSRI withdrawal and dep sx
  314. Discontinuation Syn=neurologic sx
    • dizziness
    • headache
    • paresthesia
  315. Disc. Syn=types of sx
    • neurologic
    • gastrointestinal
    • motor
    • somatic
    • psychaitric
  316. Disc Syn=motor sx
    • dystonia
    • tremor
  317. disc syn=gastrointestinal sx
    • nausea
    • vomiting
  318. disc syn=somatic sx
    • chills
    • fatigue
    • lethargy
    • myalgias
    • rhinorrhea
  319. disc. syn=psychiatric sx
    • anx
    • crying spells
    • insomnia
    • irritability
    • mood lability
    • vivid dreams
  320. % of pts who exp SSRI disc syn
  321. mechanisms of disc. syn.
    • re-regulation of somatodentritic autoreceptors and post synaptic receptors
    • pharmacodyanmic properties of SSRI
    • half life of drug and active metabolites
  322. half lives and active metabolites-SSRIs
    • Paroxetine-21 hrs; None
    • Fluvoxamine-15 hrs, none
    • sertraline-26 hrs, desmethyl sertraline
    • fluoxeine-84 hrs, nor fluoxetine
  323. SSRI-long half life and active metabolite
    • Fluoxetine
    • Sertraline
  324. SSRI-short half life and no active metabolite
    • fluvoxamine
    • paroxetine
  325. managing SSRI discontinuation
    • gradually taper off all SSRIs except fluoxetine
    • for acute sx, reinstitute dosage and slow rate of taper
    • treat with agent with an extended half life (ex. fluoxetine)
    • reassure pt that sx are short lived and mild
    • augment with CBT
  326. SSRIs interaction with CNS depressants
    • ETOH, opiates, antipsychotic meds
    • potentiate sedative effects
    • CNS depression
    • psychomotor impairment
    • Paxil and dextromethorphan given together prevents metabolism of dextromethorphan-->lethal levels
    • with each addition of CNS depressant, the SSRI decreases its effectiveness
  327. SSRI interaction with MAOIs
    risk of serotonin syndrome
  328. SSRI interaction with TCAs
    paroxetine or fluoxetine with TCAs can raise blood levels of cyclics to fatal levels
  329. SSRI interaction with Clozapine
    fluxomamine prescribed with haloperidol or clozapine can raise blood levels to fatal levels
  330. SSRI interaction with Lithium
    may increase lithium levels to fatal levels
  331. new atypical antidepressants
    • at least 14 5HT receptor subtypes
    • many diff meds-pros and cons
  332. atypical antidepressants
    • act diff than classic cyclics or SSRIs
    • New:
    • NaRI
    • SNaRI
    • DaNaRIs
    • SNaDaRIs
    • all have similar effects on dep
    • all have side effects
    • introduction of seizures
  333. Na R Blocker/Da R blocker (DaNaRIs)
    • Wellbutrin (buproprion)
    • stimulating effects seuizures (esp with ETOH)
    • weight loss
    • no sex probs
  334. DaNaRIs interactions
    • SSRIs=increases SSRI levels
    • serontonin syndrome
    • TCAs=increases TCA levels
    • decreased liver metabolism (inhibted with TCAs)
    • seizures
  335. SNaRIs
    • Serzone (nefazodone)
    • blockade of 5HT type 2A receptors
    • inhibiting pre synaptic serotinin and noradrenergic reuptake
    • antocholinergic effects
    • extreme probs with liver toxicity (hepatotoxicity)
    • pulled from market
  336. SNaRIs interactions
    benzos=increases potencyof trizolam and alprazolam
  337. NaSSAs (noradrenergic specific serotonergic antidepressants)
    • Remeron (mirtzapine)
    • SSRI gains
    • less sexual side effects
    • weight gain/increased appetite
    • can be quite pronounced
    • sedation
    • abnormal thinking/dreams
  338. Effexor (venlafaxine)
    • SNaRI-serotonin norepinephrine reuptake inhibitor
    • atypical antidepressant
    • fair effectiveness
    • seizures
    • dizziness
    • headache, nausea, sleepiness
    • high sexual side effects
    • High SSRI discontinuation syndrome
  339. Vestra (reboxetine)
    • atypical antidepressant
    • NRI (norepinephrine reuptake inhibitor)
    • side effects
    • insomnia
    • loss of appetite
    • excessive sweating
    • dizziness, vertigo, hypotension
    • loss of libido, impotence and urological probs
    • urinary retention in men, pain on ejaculation, increased orgasm intensity, premature ejaculation
    • anxiety
  340. Strattera (atomoxetine)
    • NRI on label for ADHD
    • no clinical effect for MDD
  341. Cymbalta (duloxetine)
    • SSNaRI-atpical antidepressant
    • given for diabetic neuropathic pain AND dep
    • unknown mechanism of action
    • believed to act on Sero and Noradrenergic activity in CNS
    • duloxetine is potent inhibitor of neuronal serotonin and NE reuptake and a less potent inhibitor of DA reuptake
  342. Pristiq (desvenlafaxine)
    • SNaRI-atypical antidepressant
    • synthetic form of major active metabolite venlafaxine
    • lower response rate than other drugs
    • higher relapse rates
    • high side effects
    • nausea most frequent
    • higher suidical ideation rate
    • High SSRI discontinutation syndrome
  343. Deseryl (trazodone)
    • not very good antidepressant
    • typically used for sleep aid
    • has some serious side effects
    • heart probs
    • tachycardia
    • priapism-1/3 requires surgery
  344. considerations for drug Rx
    • not everyone wants to be on meds
    • they are expensive
    • not all pts are accurately diagnosed
    • much individual variability in reponses
  345. types of drug outcomes
    • responders=at least 50% reduction in sx
    • non responders=less than 50% reduction in sx
    • remission=full reduction in sx
    • relapse=return to dep state
  346. SSRIs vs. placebo
    • very little of the positive effects are from the SSRI, most is from placebo
    • drug effect vs placebo...
    • placebo effect /drug effect=ratio
  347. Cohens effect size
    • difference bw two means divided by pooled SD for those means
    • 0.2 small
    • 0.5 medium
    • 0.8 large
  348. active placebo
    • compare antidepressants with active placebo
    • placebos with side effects
    • give drug but with main tx effects (just side effects)
    • reduces clinical effectiveness of active drug
    • see essentially no diff w active placebo and real drug
  349. placebo effects
    • history
    • cyclic nature of disease
    • maturation
    • known as expectancy effects
  350. Zoloft and children
    • 10 wk SSRI trial
    • 69% saw improvement vs. 59% with placebo
    • placebo/drug ratio=85% (59/69)
  351. Prozac and children
    • 41% complete remission of dep vs. 20% placebo
    • placebo/drug ratio=49%
    • ONLY DRUG approved by FDA for children and dep
  352. Paxil and children
    • 63% showed improvement vs. 46% placebo
    • placebo/drug ratio=73%
    • drug was ineffective in two otehr studies
    • potential increased suicidal thoughts
  353. SSRIs and suicidality
    • FDA caution with SSRIs and Efexor, Wellburtin, remeron, and serzone
    • close observation of SI
    • esp when starting, swithing or ending a drug
    • anxity, agitation, panic, insomnia, irritability, mania, restlessness (akathesia)
  354. Efexor and suicidality
    • atpical antidepressant SNaRI
    • 8.8 times increase in SI
    • next highest is Paxil at 2.65
    • NO ACTUAL suicide, just higher SI
  355. psychotherapy for dep
    • clinical efficacy trials
    • 16 wks SSRIS and visit to therapy 57% response rate
    • placebo and therapy
    • CBT alone=57% response rate
    • 16 wk follow up relapse rate
    • CT=25%
    • meds=40%
    • placebo=81%
  356. antidepresant drug/therapy costs
    • 16 wks drugs=$2500+
    • therapy=$2200+

    but therapy more expensive bc combines meds
  357. antidepressant relapse rate at 1 year follow up for
    • meds alone=50-60%
    • CBT and CBT + meds=only 10% relapse
    • higher relapse for PTSD
    • stop meds=76%
    • stay on meds=47%
  358. choice of ADM based on pt hx
    • buproprion=no if hx of seizures
    • TCAs or duloxetine=no if hx of chronic pain or diabetic neuropathic pain
    • use ADM ONLY with mood stablizier for BD
  359. recommendations for starting Rx tx
    • start at low dose and gradually increase dose over 10-14 days until within therapeutic range
    • most ADM take 2-4 wks before reduction of vegetative sx
    • pts need encouragement
    • side effects within first week
    • do not stop meds suddenly-should be tapered over 4-6 wks
    • reduce alcohol and benzo use-ETOH and benzos can make dep sx worse
    • SSRI-->DNRI or NRI
  360. acute phase-dep
    begins with first med dose and lasts until patient is asymptomatic (usually 6-8 wks)
  361. continuation phase-dep
    to avoid acute relapse into dep, patients should continue drug tx for a minimum of 6 mo after acute phase/asymptomatic
  362. maintenance phase-1st dep episode
    • to prevent relapse
    • at end of continuation phase, taper meds over 4-6 wks
    • if sx return, ADMdosage should be returned to effective tx levels
  363. maintenance phase-2nd dep episode
    • lifelong med tx suggested if any of the following:
    • family hx of mood d/o
    • first dep episode before 18
    • most recent episode is one of severe dep
    • pt never becomes fully asymptomatic with current tx
    • if none of these factors are present, taper over 4-6 wks
  364. maintenance phase-3rd dep episode or more
    lifelong med tx recommended

What would you like to do?

Home > Flashcards > Print Preview