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219 Cards in this Set
- Front
- Back
Psychotropic medications affect what three domains of human funcitoning?
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Perception, behaviour and mood.
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Antidepressants are all __________ _______.
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Antidepressants are all EQUALLY EFFECTIVE (50-60%
improvement as compared to 30-40% on placebo) and have similar drop-out rates. As a result, drug choice should be tailored to the individual patient, based on patient choice, side effect profile, previous response, co-morbidity, suicide risk and cost. |
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Patients seem to have better outcomes if given _______ __________ about anti-depressants.
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Patients seem to have better outcomes if given clear
information about anti-depressants. |
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Important determinants of efficacy: read
Prior treatment history in patient/family members Patient preferences Expertise of prescribing provider Side effect profile (sedating or activating) Safety in overdose (8-10 days of a TCA can be a lethal overdose) Drug-drug interactions |
Important determinants of efficacy
Prior treatment history in patient/family members Patient preferences Expertise of prescribing provider Side effect profile (sedating or activating) Safety in overdose (8-10 days of a TCA can be a lethal overdose) Drug-drug interactions |
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There are at least _______ separate pharmacological
actions of antidepressants. |
There are at least EIGHT separate pharmacological
actions of antidepressants |
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Most antidepressants block ______________ reuptake (i.e. E, NE, 5HT and DA)
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Most antidepressants block MONOAMINE reuptake (i.e. E, NE, 5HT and DA)
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Some block ___ receptors and can therefore increase
the release of NE by blocking this pre-synaptic auto receptor |
Some block 62 receptors and can therefore increase
the release of NE by blocking this pre-synaptic auto receptor. |
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Some antidepressants act by blocking the enzyme _________ __________.
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Others act by blocking the enzyme MONOAMINE OXIDASE.
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Some have their action on only one __________ _________ ____________, and some on more than one.
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Some have their action on only one monoamine
neurotransmitter system, and some on more than one. |
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Fewer than __% of all patients with
depression show full remission with optimised treatment, including trials on numerous medications with and without concurrent psychotherapy |
Fewer than 50% of all patients with
depression show full remission with optimised treatment, including trials on numerous medications with and without concurrent psychotherapy |
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Antidepressants ___ ____elevate mood in
healthy humans. |
Antidepressants do not elevate mood in
healthy humans. |
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WHAT % of patients will have treatment failure with their first tried antidepressant?
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40%
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What are the 3 “generations” of drugs to treat
depression and related affective disorders (anti-depressants)? |
1st generation: monoamine oxidase inhibitors
(MAOI’s) and tricyclic anti-depressants 2nd generation: selective serotonin reuptake inhibitors (SSRI’s) 3rd generation: tricyclic anti-depressants with a twist |
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Tricyclic antidepressants (TCAs):
Main mode of action? How many other mechanisms of action do they have? |
Block the re-uptake of both norepinephrine and
serotonin and thus elevate neurotransmitter levels in the synapse Have at least THREE other mechanisms of action. |
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What gives rise to the side effects in TCAs
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Blockade of OTHER receptors gives rise to the
side-effect profile seen with the TCAs |
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In TCAs
Blocking of muscarinic cholinergic receptors will produce what side effects? |
Dry mouth
Blurred vision Urinary retention Constipation, Confusion, Memory problems |
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In TCAs
Blocking of H1 histamine receptors causes |
Sedation and weight gain
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In TCAs
Blocking of 61 adrenergic receptors causes |
Postural hypotension and dizziness
|
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Other side effects of TCAs
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1. Increased frequency of epileptic seizures
2. Sedation 3. Cardiotoxicity ( irregularity of heart rate may be a factor in sudden death in elderly patients with heart disease dangerous in over-dosage; |
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How much medication is required for a lethal TCA overdose?
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A 8-10 day supply can be a lethal dose; hence shift to SSRIs
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Mania; convulsions; movement disorders: tremor, akathisia, dystonia or dyskinesia ECG, BP or heart rate changes (arrhythmias)
Common, uncommon, or rare side effects of SSRis? |
Rare
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Sedation; dry mouth; sweating; sexual dysfunction including decreased libido, anorgasmia, delayed ejaculation syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH); low sodium, leading to confusion and delirium
Common, uncommon, or rare side effects of SSRis? |
Uncommon
|
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Stimulant effects such as ‘nervousness’, insomnia
Other CNS effects: dizziness, headache, tremor GI effects: nausea, vomiting, diarrhoea, abdominal discomfort. Weight loss/gain Common, uncommon, or rare side effects of SSRis? |
Common
|
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Venlafaxine =
What generation anti-depressant is it? It is classified as what type of drug? |
Effexor
3rd Both a TCA and an SSRI therefore both the effects and the attenuated side effects of both |
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What are the three advantages of venlafaxine?
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1 Clinically meaningful more rapid onset of action (within 1 week)
2 Safety in over dosage is high 3 Probably less interactions with other drugs |
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What are the disadvantages of venlafaxine relative to SSRIs?
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1. Potential for blood pressure elevation at higher doses - requires BP to be monitored closely during first 2 months of being stabilised on any dose above 225 mg/day
2. Original need for twice a day dosing schedule now overcome with extended release formulation 3. Dose needs to be titrated |
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Four most common side effects of Effexor (venlafaxine)?
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1. slightly anticholinergic
2. nausea 3. dizziness 4. sedation |
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Two uncommon side effects of Effexor?
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1. SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)
2. Serotonin syndrome |
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In effexor:
At higher doses (i.e. TCA), dose-dependent increases in what three things? |
1. blood pressure (rarely observed below 225 mg/day)
2. sweating 3. tremors |
|
Bupropion =
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Zyban
|
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What are some of the common side effects of Zyban (bupropion).
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Dry mouth, tremors, anxiety, loss of appetite,
agitation, dizziness, headache, excessive sweating, increased risk of seizure, and insomnia. Bupropion causes less insomnia if it is taken just before going to bed. |
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Bupropion (Zyban) and sexual side effects relative to other SSRI's?
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Sexual side effects normally accompanying SSRI's do not accompany bupropion. Interestingly, patients commonly report increased libido, perhaps evidence of its dopaminergic properties.
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What are some of the contraindications of Bupropion (Zyban)?
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1. Seizure disorder
2. current use of other form; 3. bulimia/anorexia; 4. MAOI in last 14 days; 5. heavy alcohol use |
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Bupropion is what class of antidepressant ?Norepinephrine-dopamine reuptake inhibitor
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Norepinephrine-dopamine reuptake inhibitor
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Citalopram
Fluoxetine Paroxetine Class of drugs? |
SSRI
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Venlafaxine
Class of drug? |
SNRI
|
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Amitriptyline
Maprotiline |
TCAs
Amitriptyline = tricyclic Maprotiline = tetracyclic |
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Tests commonly used to assess effects of drugs on CNS functioning?
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Critical Flicker Fusion (CFF)
Choice Reaction Time (CRT) Compensatory Tracking Task (CTT) Digit Symbol Substitution (DSST) Sternberg Test Shopping List Task Driving Test Sustained Attention Test |
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With normal controls, a single administration can
have one of three effects (on tests of attention; learning and motor and psychomotor functioning) Single dose of amitriptyline, imipramine, mianserin and other tricyclics? |
Cognitive impairment
|
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With normal controls, a single administration can
have one of three effects (on tests of attention; learning and motor and psychomotor functioning) A single dose of Paroxetine, sertraline? |
Cognitive enhancement
|
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With normal controls, a single administration can
have one of three effects (on tests of attention; learning and motor and psychomotor functioning) Single dose of Fluvoxamine, bupropion, fluoxetine, meclobomide? |
No cognitive impairment
|
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which is the most studied drug with regard to antidepressant action and cognitive effect?
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Amitriptyline
|
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Which antidepressant has the greatest sedative and anticholinergic property?
|
Amitriptyline
|
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Performance impairment is always significant with regard to which antidepressant?
|
Amitriptyline
|
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Describe the effect of a single dose of Amitriptyline?
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The effect starts 30 minutes following a single
administration and is maximal by 2 to 4 hours |
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Middle and long-term administration with
healthy volunteers. Describe the normalization of cognitive function over time. |
Normalisation on cognitive tests occurred between
days seven and 14 for most sedative compounds but from daily 14 to day 21 for amitriptyline |
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Which drug should be carefully applied in individuals with recent memory problems or in Alzheimer’s disease?
|
Amitriptyline
|
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A combination of alcohol plus amitriptyline in normal participants caused more cognitive impairment than alcohol with desipramine or zimeldine (Linnoila et al., 1983). What does this indicate?
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Alcohol potentiates the negative effects of sedative antidepressants
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Patients with depression are subject to neuropsychological deficits in (5)
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1. attention
2. memory 3. psychomotor speed 4. processing speed 5. executive function. |
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When depressed patients are treated, what happens to their cognitive function relative to controls?
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They perform better, but they do not perform as well as normal controls.
As such, they improve, at least to a degree, but do not “normalize.” |
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In depressed patients, Neurocognitive testing may be a function of the ______________ with which they are treated.
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Neurocognitive testing may be a function of the
ANTIDEPRESSANT with which they are treated. |
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How well will depressed patients on bupropion perform on a battery of cognitive tests relative to controls?
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Depressed patients on bupropion perform AS WELL as
normals do on a battery of neurocognitive tests. |
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How well will depressed patients on venlafaxine and SSRIs perform on a battery of cognitive tests relative to controls?
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They will not perform as well.
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The cognitive benefit of some antidepressants may occur relative to an antidepressant's _________________ activity.
A lack of benefit may relate to its ___________ activity. |
The cognitive benefit of some antidepressants may occur relative to an antidepressant's norepinephrine activity.
A lack of benefit may relate to its serontenergic activity. |
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In single-dose studies, the main impairment in
cognitive function occurs in the agents with strong ____________ or ____________ effects. |
In single-dose studies, the main impairment in
cognitive function occurs in the agents with strong anticholinergic or sedative effects |
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Sedative qualities of the TCAs have their
greatest effect of ________________ functioning while both the sedative and the anticholinergic effect contribute to _____________compromise. |
Sedative qualities of the TCAs have their
greatest effect of PSYCHO-MOTOR functioning while both the sedative and the anticholinergic effect contribute to MEMORY compromise |
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Normalisation of cognitive function in clinical
groups parallels ______ ____________. |
Normalisation of cognitive function in clinical
groups parallels mood improvement |
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Agents with ______________ or ________________properties
should be carefully prescribed in the elderly |
Agents with sedative or anticholinergic properties
should be carefully prescribed in the elderly. |
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Agents with ____________ or _________________ properties
should be carefully prescribed in the elderly |
Agents with sedative or anticholinergic properties
should be carefully prescribed in the elderly |
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What potentiates the effect of the sedative
antidepressants? |
alcohol
|
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Three types of phobia?
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Agoraphobia
Social phobia Specific phobia |
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Three types of anxiety states
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Panic disorder
Generalized anxiety disorder Obsessive compulsive disorder |
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Three types of trauma-related anxiety?
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Post-traumatic stress disorder
Anxiety from medical condition Substance induced anxiety |
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1st line treatments for GAD?
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SSRIs
Venlafaxine 2nd = Imipramine, Buspiron 3rd = unclear |
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1st line treatments for Panic Disorder?
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SSRI
(TCA) 2nd = BZD, Phenelzine 3rd = Moclobemide, nefazodone, valproate, ondansetron |
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1st line treatments for Social Anxiety Disorder?
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SSRI
2nd = phenalzine, BZD, mocloblernide 3rd = venlafaxine, gabapentin, pregabalin, nefazodone |
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1st line treatments for OCD?
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SSRI
2nd line clomipramine 3rd = augment with haloperidol, respiridone, or lithium |
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1st line treatments for PTSD?
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SSRi
2nd = Amitryptaline, Imipramine, phenelzine 3rd = unclear |
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What replaced barbiturates?
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BZD
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When BZD come into use and for what reason?
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Used since 1960’s as anxiety reduction agents
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What was originally touted as the cure for living in our highly pressured, technological society?
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BZD.
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What are the four uses of BZD
|
1 Generalised anxiety disorder - short term
2 Sleep disturbance - short term 3 Acute alcohol withdrawal 4 Adjunctive treatment in schizophre |
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Medical indications of BZD
Anxiolytic – |
chronic/phobic anxiety and panic attacks
|
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Medical indications of BZD
Sedative and hypnotic - |
sleep disturbance and anaesthesia/premedication
|
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Medical indications for BZD use
Anticonvulsant - |
status epilepticus,
myoclonic and photic epilepsy |
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Medical indications for BZD use
Muscle relaxant |
muscle
spasm/spasticity |
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Medical indications for BZD use
Alcohol withdrawal |
Alcohol withdrawal
|
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Fives uses for BZD?
|
Anxiolytic
Sedative and hypnotic Anticonvulsant Muscle relaxant Alcohol withdrawal |
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Risks of BZD (8)
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1. Cognitive impairment, decreased motor skills,
2. daytime sedation; often used as “date rape” drugs 3. Additive CNS depression (ethanol,antihistamines, opioids) 4. Dependence 5. Behavioural disinhibition (paradoxical) 6. Anterograde amnesia 7. Abrupt withdrawal can result in panic attacks, 8. rebound anxiety Risk of foetal deformation (1st trimester) “Doctor shopping |
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BZDs are one of the _______ _________ ______ drugs (4% of all prescriptions from General Practitioners)
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BZDs are one of the most prescribed drugs (4% of all
prescriptions from General Practitioners) |
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What percentage of the Australian population are daily and long-term users of BZDs?
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Up to 2% of the Australian adult population may be daily and long-term users of BZDs.
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Enough BZD is prescribed to enable ___% of the population to use every day (Cape et al., 2002, p.224)
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Enough BZD is prescribed to enable 3% of the population to use every day (Cape et al., 2002, p.224)
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What are the predictors of BZD use? (4)
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1. being female
2. being elderly 3. being an established patient 4. attending a busy doctor, or a doctor in inner urban area |
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What percentage of prescriptions are given to people >70 years.
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Over 40% of prescriptions given to people >70 years
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_______ ______ _____tends to increase with age.
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Night time use tends to increase with age
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58% of current users report _________ ______ for >6 months.
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58% of current users report _________ ______ for >6 months.
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In the United States and some Western European nations, which have historically led trends in drug use, rates of use of _____________ have declined in recent years, whereas use of _____________ has remained stable or increased.
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In the United States and some Western European nations, which have historically led trends in drug use, rates of use of anxiolytics have declined in recent years, whereas use of hypnotics has remained stable or increased.
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Long term benzodiazepine users are significantly impaired in comparison to controls in which areas of cognition?
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Moderate to large effect sizes were found for all cognitive domains, indicating that long term benzodiazepine users were significantly impaired in comparison to controls in all the areas assessed.
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This indicates that the effects of BZD are _______ and not specific to any ____________ _________.
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This indicates that the effects are global and not specific to any cognitive domain,
but some domains (e.g. sensory processing, psychomotor speed, non-verbal memory and visuospatial processing) seem to be more severely affected than are the others |
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In BZD use, which cognitive domains seem to be more severely affected than are others?
|
1. Sensory processing
2. Psychomotor speed 3. non-verbal memory 4. Visuospatial processing |
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When compared to their initial assessment, previous longterm benzodiazepine users improved across which cognitive domains examined at the follow-up assessment?
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ALL.
When compared to their initial assessment, previous longterm benzodiazepine users improved across all of the cognitive domains examined at the follow-up assessment. |
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Does the cognitive function of long-term benzodiazepine users improve following withdrawal?
Visuospatial, attention/concentration, general intelligence, psychomotor speed and non-verbal memory) indicating that these categories of cognitive functioning ___________ __________for the benzodiazepine users when they discontinued. |
Visuospatial, attention/concentration, general
intelligence, psychomotor speed and non-verbal memory) indicating that these categories of cognitive functioning SIGNIFICANTLY IMPROVED for the benzodiazepine users when they discontinued. |
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Are previous long-term benzodiazepine users still impaired at follow-up compared to controls or
normative data? When compared to controls or norms, previous long-term benzodiazepine users performed more poorly on which cognitive domains when examined at follow-up. |
All domains except sensory processing.
When compared to controls or norms, previous long-term benzodiazepine users performed more poorly across all cognitive categories, except sensory processing, when examined at follow-up assessment. |
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The results of Crowe's meta-analysis indicate that, compared to controls or norms, previous long-term benzodiazepine users performed more poorly across all cognitive categories, except ________ _______when examined at follow-up assessment.
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The results of Crowe's meta-analysis indicate that, compared to controls or norms, previous long-term benzodiazepine users performed more poorly across all cognitive categories, except sensory processing, when examined at follow-up assessment.
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The results of the three meta-analyses support __________ __________in the use of long-term benzodiazepine therapy.
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The results of the three meta-analyses support EXTRENE CAUTION in the use of long-term benzodiazepine therapy.
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Although these findings suggest that previous long-term benzodiazepine use may lead to impairments in cognition, __________ ________ of improvement in cognitive function after withdrawal is observed.
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Although these findings suggest that previous long-term benzodiazepine use may lead to impairments in cognition, _________ _________ of improvement in cognitive function after withdrawal is observed.
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However, the data do not support a full recovery, at least in the first three months following cessation and suggest that there may be some __________ __________ or deficits that take periods longer than three months to recover.
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However, the data do not support a full recovery, at least in the first three months following cessation and suggest that there may be some PERMANENT DEFICITS or deficits that take periods longer than three months to recover.
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Previous long term benzodiazepine users assessed after at least 6 months of abstinence ___________ ___ ________ __________ ______ in a number of areas as compared to matched normal and anxious
controls. |
Previous long term benzodiazepine users assessed after at least 6 months of abstinence continue to display cognitive deficits in a number of areas as compared to matched normal and anxious controls.
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Previous long term benzodiazepine users assessed after at least 6 months of abstinence:
Significant moderate to large effects sizes were noted for which three cognitive domains? |
1. Verbal memory
2. Motor control/performance 3. Non-verbal memory No effect for visuospatial skill, but strong trends |
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In Crowe's study comparing BZD vs Anxious vs controls, there was a significant difference on between normal and anxious controls on what one test?
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Milner (austin) Maze.
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_______ and ___________ differences exist between the
performance of long-term benzodiazepine users and those who do not use the drugs independent of their status with regard to anxiety. |
CLEAR and CONSISTENT differences exist between the
performance of long-term benzodiazepine users and those who do not use the drugs independent of their status with regard to anxiety |
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In Crowe's series of studies on BZD use, two largest effects noted in each of these studies were in which domains?
|
1. Verbal memory
2. Motor control/performance |
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In Crowe's series of studies on BZD use, two largest effects noted in each of these studies were in verbal memory and motor control/performance.
Which two areas of the brain sub-serve these cognitive functions? |
These functions are largely subserved by the hippocampal formation and the reticular formation amongst other regions.
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The effect of long term benzodiazepine use is comparable to the deficits noted in what?
|
The effect of long term benzodiazepine use is comparable to the levels of deficits noted with moderate to severe closed head injury.
|
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Is there a justifiable clinical application for the
benzodiazepines for any presentation on a long-term basis? |
No.
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Benzodiazepines with the longest half lives (e.g.
chlordiazepoxide (10 hours), diazepam (24 hours), and flurazepam (80 hours) metabolise to the active agent __________ (60 hours) |
Benzodiazepines with the longest half lives (e.g.
chlordiazepoxide (10 hours), diazepam (24 hours), and flurazepam (80 hours) metabolise to the active agent NORDIAZEPAM (60 hours). |
|
Short-acting BZD agents include?
Do they have active metabolites? |
Alprazolam (12 hours)
Oxazepam (8 hours) Triazolam (2.5 hours) They do do not have active metabolites |
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With recent onset of use, steady-state concentrations occur after about ________ half lives.
This can take how long in healthy subjects using long acting agents? |
With recent onset of use, steady-state concentrations occur after about FOUR half lives (which can be as long as several weeks for healthy subjects using long acting agents).
|
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After discontinuation of of BZD, elimination takes about how many half lives?
|
6
|
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What are the benzo-like drugs?
|
Zaleplon (Sonata), Zopiclone (Imovane) and
Zolpidem (Stilnox) |
|
Where do z-class drugs bind?
|
Bind to a subset of GABAA receptors with alpha 1
subunits |
|
What effects do z-class drugs have?
|
They produce pure sedation (without anxiolytic,
anticonvulsant or muscle relaxing effects) |
|
What is the effect of Z-class drugs on REM sleep?
|
Minimal.
|
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What is the indication of Z-class drugs?
|
Insomnia
|
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What is the main advantage of z-class drugs relative to BZD and barbituates?
|
Less daytime impairment compared to the benzodiazepines and the barbiturates.
|
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What is the is the ultra short half-life of Zaleplon?
|
Approximately 1 hour.
|
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Zolpidem and zopiclone have longer half-lives, what are they?
(approximately 2.4 and 5 hours, respectively). |
Zolpidem = 2.4
Zopiclone = 5 hours |
|
The low risk of residual effect, in addition to the _____________ may explain the limited negative influences of these agents on daytime performance.
|
Short half-life
|
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What appears to be better preserved in people by non-benzodiazepine agents than by benzodiazepines.
|
Psychomotor tasks and memory capacities
|
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With Z-class drugs, cognitive deficits almost exclusively coincide with the ______ __________ __________.
|
With Z-class drugs, cognitive deficits almost exclusively coincide with the PEAK PLASMA CONCENTRATION.
|
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With Z class drugs, impairment can emerge in the first hours after drug administration, whereas psychomotor and memory tests carried out 7-8 hours later (i.e. in the morning) generally show __ ________ __________.
|
In particular, impairment can emerge in the first hours after drug administration, whereas psychomotor and memory tests carried out 7-8 hours later (i.e. in the morning) generally show no relevant alterations.
|
|
On-the-road studies involving benzodiazepine hypnotics reveal what?
|
On-the-road studies revealed that benzodiazepine hypnotics significantly impaired driving ability the morning following bedtime administration.
|
|
On-the-road studies involving benzodiazepine hypnotics reveal what regarding afternoon performance the following day?
|
Impairment was sometimes also significant in the afternoon (16–17 h after administration).
|
|
Similar driving impairment was observed with ____________ . However, the magnitude of impairment depends on various factors including the
half-life and dosage of the drug, and the time after administration. |
Similar driving impairment was observed with ZOPICLONE. However, the magnitude of impairment depends on various factors including the
half-life and dosage of the drug, and the time after administration. |
|
Patients receiving what drugs should be cautioned when driving a car?
|
Patients treated with benzodiazepine hypnotics or zopiclone should be cautioned when driving a car.
|
|
Which two z-class drugs do not signficant affect driving performance the morning following bedtime administration?
|
Both zolpidem and zaleplon do not significantly affect driving performance the morning following bedtime administration
|
|
Middle-of-the-night administration of _____________ significantly impairs driving ability in a dose-dependent manner. In contrast, ____________ did
not affect driving ability 4 h after middle-of-the-night administration. |
Middle-of-the-night administration of zolpidem significantly impairs driving ability in a dose-dependent manner. In contrast, zaleplon did
not affect driving ability 4 h after middle-of-the-night administration. |
|
Benzodiazepines and longterm use: 6 negative consequences?
|
1 altered use patterns (from night time to
daytime use) 2. excessive sedation 3. cognitive impairment 4. increased risk of accidents 5. Adverse sleep effects 6. Dependence and withdrawal (even at therapeutic doses) |
|
BZDs have an additive effect with alcohol/other
CNS depressants, increasing ______ ______ _______ _____. |
BZDs have an additive effect with alcohol/other
CNS depressants, increasing the risk of harm |
|
Long-term efficacy of BZD use?
|
limited.
|
|
Which benzodiazepines exhibit negative effects on psychomotor and memory function
|
All.
|
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While the __________ effects resolve with tolerance to
sedation, however, the ___________ effects mostly persist. |
While the psychomotor effects resolve with tolerance to sedation, the amnesic effects mostly persist.
|
|
Ruled out explanations for the impairment in vigilance in BZD use?
|
Impairment of vigilance does not appear to be explained by sedation and repeated dosing does not substantially diminish the effect.
|
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In terms of recent BZD use, the neuropsychologist should be aware of.....
|
Thus the neuropsychologist should be aware of all
benzodiazepine use in the last month but particularly within the last week. |
|
BZD:
It is clear that the long-term residual effects persist for at least ___ ________ post cessation. |
Also it is clear that the long-term residual effects persist for at least 6 mths post cessation.
|
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In terms of neuropsychological assessment, Z drugs only really a problem in ____ _____ _____after use.
|
Z drugs only really a problem in first few hours after use
|
|
There are 3 “generations” of drugs which are used to treat schizophrenia and related psychotic disorders (anti-psychotics).
What are they? |
1st generation: neuroleptics or typical antipsychotics
2nd generation: atypical anti-psychotics 3rd generation: Aripiprazole (Abilify) |
|
Each generation of antipsychotics differs in pharmacology: resulting in different (3)?
|
Different neurotransmitter systems
Different effects on symptoms Different side-effects |
|
Typical anti-psychotics are _______ _____ ______ antagonists.
|
Typical anti-psychotics are dopamine D2
receptor antagonists |
|
The ___________ of a typical anti-psychotic for the
D2 receptor is positively associated with treatment outcome |
The affinity of a typical anti-psychotic for the D2 receptor is positively associated with treatment outcome (higher affinity better treatment outcome.
Higher affinity better treatment outcome. |
|
1st generation anti-psychotics are effective at treatment what symptoms?
|
Only effective at treating positive symptoms
|
|
What are the side effects of 1st generation anti-psychotics and what?
|
Parkinson-like syndrome (because you’re blocking dopamine in the basal ganglia too)
|
|
What is tardive dyskinesia and why does it occur?
|
Abnormal facial and limb movements due to sensitization of D2 receptors.
|
|
Most anti-psychotics affect other
neurotransmitter systems including (4) What does this explain? |
1. Histamine,
2. Acetylcholine, 3. Adrenaline 4. Serotonin Additional side effects |
|
Why were atypical anti-psychotics developed?
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Atypical anti-psychotics have been developed because of their more selective action on the dopamine system and/or action on other neurotransmitter systems.
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What do all effective antipsychotic drugs block?
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D2 receptors.
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Chlorpromazine and thioridazine block ___ _________ more potently than D2 receptors.
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Chlorpromazine and thioridazine block a1 adrenoceptors more potently than D2 receptors.
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Chlorpromazine and thioridazine block __________ 5-HT2 receptors relatively strongly.
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Chlorpromazine and thioridazine block SEROTONIN 5-HT2 receptors relatively strongly.
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In Chlorpromazine and thioridazine, affinity for D1 receptors is relatively _______.
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In Chlorpromazine and thioridazine, affinity for D1 receptors is relatively weak.
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Which receptors does Haloperidol mainly act on?
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D2 receptors.
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Haloperidol has some effect on which other two receptors?
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Serotonin 5-HT2 and a 1 receptors
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Haloperidol has negligible effects on on which receptors?
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D1 receptors.
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Pimozide and amisulpride act almost exclusively on which receptors?
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D2 receptors
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Clozapine binds more to ___, ____, ___, and ________ H1 receptors than to either D2 or D1 receptors.
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Clozapine binds more to D4, 5-HT2, 61, and histamine H1 receptors than to either D2 or D1 receptors.
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Risperidone is about equally potent in blocking ___ and _________ receptors
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Risperidone about equally potent in blocking D2 and 5-HT2 receptors.
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Olanzapine is more potent as an antagonist of ________
receptors. and has less potency at which three receptors? |
Olanzapine is more potent as an antagonist of 5-HT2
receptors. lesser potency at D1, D2, and 61 receptors |
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Quetiapine is a lower-potency compound with relatively similar antagonism of which receptors? (4)
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5-HT2, D2, 61, and 62 receptors
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Clozapine, olanzapine and quetiapine are
potent inhibitors of __ _________ receptors consistent with their __________ properties. |
Clozapine, olanzapine and quetiapine are potent inhibitors of H1 histamine receptors consistent with their sedative properties.
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Aripiprazole has partial agonist effects at ___ and 5-HT1A receptors.
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Aripiprazole has partial agonist effects at D2 and 5-HT1A receptors
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61 = 5-HT2 > D2 > D1 =
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Chlorpromazine
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D2 > D1 = D4 > 61 > 5-HT2
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Haloperidol
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D4 = 61 > 5-HT2 > D2 = D1
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Clozapine:
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Clozapine =
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D4 = 61 > 5-HT2 > D2 = D1
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Side effects of anti-psychotic medication:
Dopaminergic effects on the striatum (EPSE)? (4) |
Dystonia/oculogyric crisis
Parkinsonism Akathisia Tardive dyskinesia and BLMs |
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Side effects of anti-psychotic medication:
Anti-cholinergic (muscarinic)? (3) |
Dry mouth
Blurred vision Constipation and difficulty in passing urine |
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Side effects of anti-psychotic medication:
Anti-adrenergic (adrenaline): (5) |
1. Drop in blood pressure on standing (postural hypertension)
2. Sedation 3. Failure of ejaculation (especially Thioridazine) 4. Skin rashes, e.g., photosensitivity 5. Weight gain (possibly due to blockade of H1 and 5HT2 |
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Side effects of anti-psychotic medication:
Anti-histaminergic: (1) |
sedation
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Side effects of clozapine:
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Weight gain
Seizures Nocturnal salivation agranulocytosis myocarditis lens opacities Other: Diabetes Hypercholerestemia sedation moderate movement disorder hypotension |
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Effects on normals; typicals
Drugs with significant anti-cholinergic properties e.g., TDZ or CPZ in higher doses impair performance on a variety of ________ and __________ tasks. |
Effects on normals; typicals
Drugs with significant anti-cholinergic properties e.g., TDZ or CPZ in higher doses impair performance on a variety of MOTOR and COGNITIVE tasks. |
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Phenothiazenes and halperidol, which
have little anticholinergic activity, do not seem to impair __________ ________. |
Phenothiazenes and halperidol, which
have little anticholinergic activity, do not seem to impair MOTOR SPEED. |
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However, Phenothiazenes and halperido are more likely to produce _______ and may thereby cause
decreases in motor speed and coordination. |
However, these agents are more likely to
produce extrapyramidal symptoms (EPS) and may thereby cause decreases in motor speed and coordination. |
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Effects on patients; typicals
Patients with schizophrenia improved significantly on _________ ___________, indicating that modest improvement in neuropsychological functioning can be observed in treated patients with schizophrenia (Daston, 1959). |
Patients with schizophrenia improved
significantly on associative learning, indicating that modest improvement in neuropsychological functioning can be observed in treated patients with schizophrenia (Daston, 1959). |
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Continuing administration of antipsychotics to
patients with schizophrenia results in few significant changes in neuropsychological test performance, with the possible exception of the tendency to see improvement in _____________ and _______________ after medication. |
Continuing administration of antipsychotics to
patients with schizophrenia results in few significant changes in neuropsychological test performance, with the possible exception of the tendency to see improvement in ATTENTION and CONCENTRATION after medication. |
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Change in cognition with treatment
in schizophrenia: Participants with schizophrenia showed a significant improvement in ________ ________ _________ |
Participants with schizophrenia showed a significant improvement in most cognitive tasks.
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In assessing the effects of treatment on cog functioning in schizophrenia.
Which tests may be the best candidate for a cognitive endophenotype? |
Semantic verbal fluency
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The cognitive improvements observed in the
schizophrenia treatment trial were consistent with what? |
Practice effects.
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What are the dose related Side Effects of Phenytoin? (6)
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Ataxia
– Diplopia – Dizziness – Drowsiness – Encephalopathy – Involuntary movements |
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What are the Non-Dose-Related Phenytoin Side Effects? (3)
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– Gingival hyperplasia
– Peripheral neuropathy – Vitamin deficiencies |
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Carbamazepine Side Effects (6)
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1. Weight gain
2. Neurotoxicity ( Diplopia, drowsiness, blurred vision, vertigo which are transient and reversible with dose reduction) 3. Mild elevation of liver enzymes 4. Hypersensitivity rash (uncommon) 5. Hematologic effects ( Rare: agranulocytosis, blood dyscrasia) -Discontinue when fever, sore throat, rash, mouth ulcers, bruising or bleeding 6. Syndrome of inappropriate antidiuretic hormine (SIADH) - Cardiac conduction abnormalities (sometimes arrhythmia) |
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Valproate Side Effects (7)
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1. GI: anorexia, indigestion, nausea, vomiting, heartburn, diarrhoea (decrease dose, antacid or H2-antagonist)
2. Irreversible but rare hepatotoxicity 3. Weight gain, increased appetite (Decrease dose, monitor weight) 4. Neutropenia and thrombocytopenia 5. Sedation, tremor (decrease dose Beta blocker for tremor) 6. Menstrual disturbances and polycystic ovaries is possible 7. Transient alopecia |
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Lamotrigine Side Effects (4)
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1. Skin rash (Stevens-Johnson’s Syndrome, toxic epidermal necrosis, hypersensitivity syndrome) -> risk of skin infections
2. GI (Abdominal pain, indigestion, nausea, vomiting) 3. Asthenia, pain 4. Ataxia, dizziness, headache, somnolence |
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In terms of anti-epileptic drugs, ___________produced the worst performance in terms of cognitive function.
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In terms of anti-epileptic drugs, phenobarbital produced the worst performance in terms of cognitive function.
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The cognitive effects of antiepileptic agents:
Seizure patients administered antiepileptics appear to _____________ from seizure control, but ______________ typically overcomes any potential benefit with heavy sedation and negative effects on a wide range of functioning. |
Seizure patients administered antiepileptics
appear to BENEFIT from seizure control, but PHENOBARBITAL typically overcomes any potential benefit with heavy sedation and negative effects on a wide range of functioning. |
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Phenytoin specifically effects _______ _________ speed and ________.
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Phenytoin specifically effects motor speed and
accuracy. |
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Carbamazepine’s effects may be more in slowing ___________ _____________.
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Carbamazepine’s effects may be more in slowing verbal responses.
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Phenobarbital:
Impaired cognition in which four domains (4) > |
1. intelligence
2. vigilance 3. memory 4. psychomotor functioning. Nonepileptic individuals experience greater adverse effects than do epileptic patients |
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Phenytoin:
Impaired cognition in which domains? |
1. vigilance
2. psychomotor functioning 3. memory 4. general intelligence 5. school and work performance in a dose dependent fashion. This may be due to the effect on motor speed and accuracy |
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Carbamazepine and valproate are both agents are considered to be ____ __________ and therefore less neuropsychologically _____ ;
Nonetheless while relatively safe, carbamazepine can adversely affect cognition most notably psychomotor speed |
Carbamazepine and valproate are both agents are considered to be LESS SEDATING sedating and
therefore less neuropsychologically TOXIC ; Nonetheless while relatively safe, carbamazepine can adversely affect cognition most notably psychomotor speed |
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Which AED productes the greatest negative neuropsychological effects?
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Phenobarbital.
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In terms of AEDs
Phenytoin has a __________ _________ but has a significant sedative effect and dose dependently compromises motor speed and accuracy as well and memory. |
Phenytoin has a SMALLER EFFECT but has a significant
sedative effect and dose dependently compromises motor speed and accuracy as well and memory. |
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Carbamazepine and valproate have lesser __________
properties but are worse in high-dose or with ______________. |
Carbamazepine and valproate have lesser sedative
properties but are worse in high-dose or with polypharmacy. |
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Mechanism of action in lithium?
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Mechanism of action not fully understood.
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Mood-stabilizing effect has been postulated to be due to reduction of ________________ neurotransmitter concentration
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Mood-stabilizing effect has been postulated to
be due to reduction of CATECHOLAMINE neurotransmitter concentration. Possibly related to Na-K-ATPase to improve membrane transport of Na ion. |
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Alternative postulate that lithium may decrease
_______ ______ ___________, which would decrease sensitivity of hormonal-sensitive adenylcyclase receptors. |
Alternative postulate that Li may decrease
cyclic AMP concentrations, which would decrease sensitivity of hormonal-sensitive adenylcyclase receptors |
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Early dose related adverse effects of lithium?
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1. GI distress
2. Sedation, weight gain 3. Muscle weakness 4. Polyuria, polydipsia 5. Impaired cognitive function 6. Tremor Tolerance may develop |
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Strategies to manage dose-related adverse effects of lithium? (2)
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1. Take with meal
2. Beta blocker for tremor |
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Late Adverse effects of lithium? (5)
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1. Psoriasis / acne exacerbation
2. Diabetes insipidus 3. Hypothyroidism 4. Cardiac issues 5. Leukocytosis (increased white blood cell count) |
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Adverse effects of L Dopa? (4)
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1. Cardiac arrhythmia from stimulation of adrenergic
receptors in heart. Dose needs to be adjusted for people with cardiac problems 2. Abnormal involuntary movements (50%) - i.e.. grimacing of face and tongue movements; slow writhing type of movements (not jerky movements) in arm and face) |
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Why does peak dose chorea occur?
How is it managed? |
1. This is due to high dose of L Dopa and occurs early
in therapy at 2 to 4 weeks i.e. “peak dose chorea” 2.Best way to handle is by reducing dose Long Term |
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What occurs in 20 - 25% of the population on L Dopa?
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Behavioral disturbances.
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Another consequence of L Dopa treatment is trouble in _________
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Trouble in thinking (cognitive effects).
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L Dopa can induce: (5)
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Psychosis
Confusion Hallucination Anxiety Delusion |
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Some individuals develop ___________ which can
include inappropriate sexual behavior; "dirty old man", "flashers" |
Some individuals develop HYPOMANIA which can
include inappropriate sexual behavior; "dirty old man", "flashers". |
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Dopaminergic and anticholinergic treatments both led to improvement in __________ __________ but their effects upon cognitive performance dissociated.
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Dopaminergic and anticholinergic treatments both led to improvement in MOTOR CONTROL but their effects upon cognitive performance dissociated.
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Anticholinergic drugs produced impairment in processes underlying the immediate _____________ of ______________.
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Anticholinergic drugs produced impairment in processes underlying the immediate registration of information
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Dopaminergic therapy produces improvement on a tasks dependent on working memory and _________ __________.
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Dopaminergic therapy produces improvement on a task dependent on working memory and cognitive sequencing.
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Cognitive impairment in Parkinson's disease is
____________ in origin: |
Cognitive impairment in Parkinson's disease is
multifactorial in origin: short-term memory processes are served by both dopaminergic and cholinergic subcorticofrontal systems but much of the cognitive impairment of Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex. |
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Short-term memory processes are served by both __________________ and ________________ ___________________systems.
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Short-term memory processes are served by both dopaminergic and cholinergic subcorticofrontal
systems. |
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Much of the cognitive impairment of Parkinson's disease is independent of subcortical
neurochemical pathology and may be due to early ___________ ___________ within the __________ cortex. |
Much of the cognitive impairment of
Parkinson's disease is independent of this subcortical neurochemical pathology and may be due to early neuronal dysfunction within the cerebral cortex. |
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What are the 7 red flags in clinical situations?
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1. Recent change in medical condition that has not been assessed by their Primary Care Physician (PCP)
2. Symptoms of withdrawal from drugs or alcohol (sweating, shaking, pale pasty skin, lethargy) 3. Acute change in mental status 4. Evidence of inability to care for self (malnourished, dehydrated, dirty, malodorous, risk of exposure to elements) 5. Evidence of recent sexual or physical abuse that has not been evaluated 6. Suggestions of serious side effects to medications 7. Acknowledged or observed suggestions of suicidality or homicidality factors. |
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What are the five Factors that should be integrated more fully into the typical neuropsychological
assessment of patients taking psychotropic medications? |
1. chronicity of drug administration
2. metabolic capacity 3. the positive neuropsychological effects of disease management 4. a direct comparison of speeded versus nonspeeded tasks within cognitive domains 5. the temporal onset of patient/significant other cognitive complaints with respect to drug initiation/cessation and increase/reduction |
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Summary and conclusions (1)
Within the antidepressant class, which drug is the most concern and for what three reasons? Acute (2) effects and persisting impairment in (1) due to.... |
TCAs are of most concern (particularly
amitriptyline) within the antidepressant class with acute psychomotor and concentration effects and persisting anti-cholinergic associated memory impairment. |
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Which two classes of antidepressant drugs are in need of more definitive study but are largely safe?
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SSRIs and MAOIs.
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Among the anxiolytics, benzodiazepines all
produce compromise in which four cognitive domains? How long do these impairments persist for? |
1. Sedative
2. Psychomotor 3. Concentration 4. memory compromise |
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Atypical vs typical antipsychotics: Which is better in terms of cognitive benefit?
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Now seems clear that there is no substantive
cognitive benefit of atypical versus typical antipsychotics |
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Seizure patients administered antiepileptics
appear to benefit from seizure control, but __________________ typically overcomes any potential benefit due to _________ __________ and negative effects on a wide range of functioning. |
Seizure patients administered antiepileptics
appear to benefit from seizure control, but phenobarbital typically overcomes any potential benefit with HEAVY SEDATION and negative effects on a wide range of functioning. |
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Which AEDS produce mild effects on cognition?
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Carbamazepine, valproic acid and, to a lesser
extent, phenytoin, produce more mild effects. |
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What does long term treatment with L Dopa produce?
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Denervation supersensitivity
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Generally you are unlikely to make a false
positive diagnosis with the principal exception of the effects of which two psychotropic classes? |
Benzodiazepines and the sedating and anticholinergic TCAs
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