Lecture 5: Drug Effects On Cognition - Pete

Front 1

Psychotropic medications affect what three domains of human funcitoning?

Back 1

Perception, behaviour and mood.

Front 2

Antidepressants are all __________ _______.

Back 2

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.

Front 3

Most antidepressants block ______________ reuptake (i.e. E, NE, 5HT and DA)

Back 3

Most antidepressants block MONOAMINE reuptake (i.e. E, NE, 5HT and DA)

Front 4

Fewer than __% of all patients with
depression show full remission with
optimised treatment, including trials on
numerous medications with and without
concurrent psychotherapy

Back 4

Fewer than 50% of all patients with
depression show full remission with
optimised treatment, including trials on
numerous medications with and without
concurrent psychotherapy

Front 5

Antidepressants ___ ____elevate mood in
healthy humans.

Back 5

Antidepressants do not elevate mood in
healthy humans.

Front 6

WHAT % of patients will have treatment failure with their first tried antidepressant?

Back 6

40%

Front 7

What are the 3 “generations” of drugs to treat
depression and related affective disorders
(anti-depressants)?

Back 7

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

Front 8

Tricyclic antidepressants (TCAs):

Main mode of action?

Back 8

Block the re-uptake of both norepinephrine and
serotonin and thus elevate neurotransmitter levels
in the synapse

Front 9

In TCAs

Blocking of muscarinic cholinergic receptors will produce what side effects?

Back 9

Dry mouth
Blurred vision
Urinary retention
Constipation,
Confusion,
Memory problems

Front 10

In TCAs

Blocking of H1 histamine receptors causes

Back 10

Sedation and weight gain

Front 11

In TCAs

Blocking of alpha1 adrenergic receptors causes

Back 11

Postural hypotension and dizziness

Front 12

How much medication is required for a lethal TCA overdose?

Back 12

A 8-10 day supply can be a lethal dose; hence shift to SSRIs

Front 13

Venlafaxine =

What generation anti-depressant is it?

Therefore?

Back 13

Effexor

3rd

Both a TCA and an SSRI therefore both the
effects and the attenuated side effects of both

Front 14

What are the three advantages of venlafaxine?

Back 14

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

Front 15

What are the disadvantages of venlafaxine relative to SSRIs? (2)

Back 15

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. Dose needs to be titrated

Front 16

Four most common side effects of Effexor (venlafaxine)? (4)

Back 16

1. slightly anticholinergic
2. nausea
3. dizziness
4. sedation

Front 17

Two uncommon side effects of Effexor?

Back 17

1. SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)
2. Serotonin syndrome

Front 18

In effexor:

At higher doses (i.e. TCA), dose-dependent
increases in what three things?

Back 18

1. blood pressure (rarely observed below 225 mg/day)
2. sweating
3. tremors

Front 19

What are some of the common side effects of Zyban (bupropion). (10)
Less if taken?

Back 19

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.

Front 20

Bupropion (Zyban) and sexual side effects relative to other SSRI's?

Back 20

Sexual side effects normally accompanying SSRI's do not accompany bupropion. Interestingly, patients commonly report increased libido, perhaps evidence of its dopaminergic properties.

Front 21

What are some of the contraindications of Bupropion (Zyban)? (5)

Back 21

1. Seizure disorder
2. current use of other form;
3. bulimia/anorexia;
4. MAOI in last 14 days;
5. heavy alcohol use

Front 22

Bupropion is what class of antidepressant ?

Back 22

Norepinephrine-dopamine reuptake inhibitor

Front 23

Citalopram
Fluoxetine
Paroxetine

Class of drugs?

Back 23

SSRI

Front 24

Amitriptyline
Maprotiline

Back 24

TCAs

Amitriptyline = tricyclic
Maprotiline = tetracyclic

Front 25

which is the most studied drug with regard to antidepressant action and cognitive effect?

Back 25

Amitriptyline

Front 26

Which antidepressant has the greatest sedative and anticholinergic property?

Back 26

Amitriptyline

Front 27

Performance impairment is always significant with regard to which antidepressant?

Back 27

Amitriptyline

Front 28

Describe the effect of a single dose of Amitriptyline?

Back 28

The effect starts 30 minutes following a single
administration and is maximal by 2 to 4 hours

Front 29

Which drug should be carefully applied in individuals with recent memory problems or in Alzheimer’s disease?

Back 29

Amitriptyline

Front 30

Patients with depression are subject to neuropsychological deficits in (5)

Back 30

1. attention
2. memory
3. psychomotor speed
4. processing speed
5. executive function.

Front 31

When depressed patients are treated, what happens to their cognitive function relative to controls?

Back 31

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.”

Front 32

How well will depressed patients on bupropion perform on a battery of cognitive tests relative to controls?

Back 32

Depressed patients on bupropion perform AS WELL as
normals do on a battery of neurocognitive tests.

Front 33

How well will depressed patients on venlafaxine and SSRIs perform on a battery of cognitive tests relative to controls?

Back 33

They will not perform as well.

Front 34

The cognitive benefit of some antidepressants may occur relative to an antidepressant's _________________ activity.

A lack of benefit may relate to its ___________ activity.

Back 34

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.

Front 35

In single-dose studies, the main impairment in
cognitive function occurs in the agents with strong
____________ or ____________ effects.

Back 35

In single-dose studies, the main impairment in
cognitive function occurs in the agents with strong
anticholinergic or sedative effects

Front 36

Sedative qualities of the TCAs have their
greatest effect of ________________ functioning while
both the sedative and the anticholinergic effect
contribute to _____________compromise.

Back 36

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

Front 37

What potentiates the effect of the sedative
antidepressants?

Back 37

alcohol

Front 38

1st line treatments for GAD, Panic, SAD, OCD & PTSD?

Back 38

SSRIs

Front 39

What replaced barbiturates?

Back 39

BZD

Front 40

What was originally touted as the cure for living in our highly pressured, technological society?

Back 40

BZD.

Front 41

Fives uses for BZD?

Back 41

Anxiolytic
Sedative and hypnotic
Anticonvulsant
Muscle relaxant
Alcohol withdrawal

Front 42

Risks of BZD (8)

Back 42

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

Front 43

BZDs are one of the _______ _________ ______ drugs (4% of all prescriptions from General Practitioners)

Back 43

BZDs are one of the most prescribed drugs (4% of all
prescriptions from General Practitioners)

Front 44

Long term benzodiazepine users are significantly impaired in comparison to controls in which areas of cognition?

Back 44

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.

Front 45

In BZD use, which cognitive domains seem to be more severely affected than are others? (4)

Back 45

1. Sensory processing
2. Psychomotor speed
3. non-verbal memory
4. Visuospatial processing

Front 46

The results of the three meta-analyses support __________ __________in the use of long-term benzodiazepine therapy.

Back 46

The results of the three meta-analyses support EXTRENE CAUTION in the use of long-term benzodiazepine therapy.

Front 47

The effect of long term benzodiazepine use is comparable to the deficits noted in what?

Back 47

The effect of long term benzodiazepine use is comparable to the levels of deficits noted with moderate to severe closed head injury.

Front 48

Is there a justifiable clinical application for the
benzodiazepines for any presentation on a long-term basis?

Back 48

No.

Front 49

Where do z-class drugs bind?

Back 49

Bind to a subset of GABAA receptors with alpha 1
subunits

Front 50

What effects do z-class drugs have?

Back 50

They produce pure sedation (without anxiolytic,
anticonvulsant or muscle relaxing effects)

Front 51

What is the effect of Z-class drugs on REM sleep?

Back 51

Minimal.

Front 52

What is the indication of Z-class drugs?

Back 52

Insomnia

Front 53

What is the main advantage of z-class drugs relative to BZD and barbituates?

Back 53

Less daytime impairment compared to the benzodiazepines and the barbiturates.

Front 54

What appears to be better preserved in people by non-benzodiazepine agents than by benzodiazepines. (2)

Back 54

Psychomotor tasks and memory capacities

Front 55

On-the-road studies involving benzodiazepine hypnotics reveal what?

Back 55

On-the-road studies revealed that benzodiazepine hypnotics significantly impaired driving ability the morning following bedtime administration.

Front 56

On-the-road studies involving benzodiazepine hypnotics reveal what regarding afternoon performance the following day?

Back 56

Impairment was sometimes also significant in the afternoon (16–17 h after administration).

Front 57

Long-term efficacy of BZD use?

Back 57

limited.

Front 58

Which benzodiazepines exhibit negative effects on psychomotor and memory function

Back 58

All.

Front 59

In terms of recent BZD use, the neuropsychologist should be aware of.....

Back 59

Thus the neuropsychologist should be aware of all
benzodiazepine use in the last month but particularly
within the last week.

Front 60

BZD:

It is clear that the long-term residual effects persist
for at least ___ ________ post cessation.

Back 60

Also it is clear that the long-term residual effects persist for at least 6 mths post cessation.

Front 61

In terms of neuropsychological assessment, Z drugs only really a problem in ____ _____ _____after use.

Back 61

Z drugs only really a problem in first few hours after use

Front 62

There are 3 “generations” of drugs which are used to treat schizophrenia and related psychotic disorders (anti-psychotics).

What are they?

Back 62

1st generation: neuroleptics or typical antipsychotics
2nd generation: atypical anti-psychotics
3rd generation: Aripiprazole (Abilify)

Front 63

Typical anti-psychotics are _______ _____ ______ antagonists.

Back 63

Typical anti-psychotics are dopamine D2
receptor antagonists

Front 64

The ___________ of a typical anti-psychotic for the
D2 receptor is positively associated with
treatment outcome

Back 64

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.

Front 65

1st generation anti-psychotics are effective at treatment what symptoms?

Back 65

Only effective at treating positive symptoms

Front 66

What are the side effects of 1st generation anti-psychotics and what?

Back 66

Parkinson-like syndrome (because you’re blocking dopamine in the basal ganglia too)

Front 67

What is tardive dyskinesia and why does it occur?

Back 67

Abnormal facial and limb movements due to sensitization of D2 receptors.

Front 68

Most anti-psychotics affect other
neurotransmitter systems including (4)

What does this explain?

Back 68

1. Histamine,
2. Acetylcholine,
3. Adrenaline
4. Serotonin

Additional side effects

Front 69

Why were atypical anti-psychotics developed?

Back 69

Atypical anti-psychotics have been developed because of their more selective action on the dopamine system and/or action on other neurotransmitter systems.

Front 70

What do all effective antipsychotic drugs block?

Back 70

D2 receptors.

Front 71

Which receptors does Haloperidol mainly act on?

Back 71

D2 receptors.

Front 72

Haloperidol has some effect on which other two receptors?

Back 72

Serotonin 5-HT2 and a 1 receptors

Front 73

Clozapine binds more to ___, ____, ___, and ________ H1 receptors than to either D2 or D1 receptors.

Back 73

Clozapine binds more to D4, 5-HT2, 61, and histamine H1 receptors than to either D2 or D1 receptors.

Front 74

Risperidone is about equally potent in blocking ___ and _________ receptors

Back 74

Risperidone about equally potent in blocking D2 and 5-HT2 receptors.

Front 75

Side effects of anti-psychotic medication:

Dopaminergic effects on the striatum (EPSE)? (4)

Back 75

Dystonia/oculogyric crisis
Parkinsonism
Akathisia
Tardive dyskinesia and BLMs

Front 76

Side effects of anti-psychotic medication:

Anti-cholinergic (muscarinic)? (3)

Back 76

Dry mouth
Blurred vision
Constipation and difficulty in passing urine

Front 77

Side effects of anti-psychotic medication:

Anti-adrenergic (adrenaline): (5)

Back 77

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

Front 78

Side effects of anti-psychotic medication:

Anti-histaminergic: (1)

Back 78

sedation

Front 79

Phenothiazenes and halperidol, which
have little anticholinergic activity, do not
seem to impair __________ ________.

Back 79

Phenothiazenes and halperidol, which
have little anticholinergic activity, do not
seem to impair MOTOR SPEED.

Front 80

However, Phenothiazenes and halperido are more likely to produce _______ and may thereby cause
decreases in motor speed and coordination.

Back 80

However, these agents are more likely to
produce extrapyramidal symptoms (EPS) and may thereby cause decreases in motor speed and
coordination.

Front 81

In terms of anti-epileptic drugs, ___________produced the worst performance in terms of cognitive function.

Back 81

In terms of anti-epileptic drugs, phenobarbital produced the worst performance in terms of cognitive function.

Front 82

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.

Back 82

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.

Front 83

Carbamazepine and valproate are both agents are considered to be ____ __________ and therefore less neuropsychologically _____ ;

Back 83

Carbamazepine and valproate are both agents are considered to be LESS SEDATING sedating and
therefore less neuropsychologically TOXIC ;

Front 84

Which AED productes the greatest negative neuropsychological effects?

Back 84

Phenobarbital.

Front 85

Mechanism of action in lithium?

Back 85

Mechanism of action not fully understood.

Front 86

Early dose related adverse effects of lithium?

Back 86

1. GI distress
2. Sedation, weight gain
3. Muscle weakness
4. Polyuria, polydipsia
5. Impaired cognitive function
6. Tremor

Tolerance may develop

Front 87

Adverse effects of L Dopa? (2)

Back 87

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)

Front 88

What occurs in 20 - 25% of the population on L Dopa?

Back 88

Behavioral disturbances.

Front 89

L Dopa can induce: (5)

Back 89

Psychosis
Confusion
Hallucination
Anxiety
Delusion

Front 90

What are the 7 red flags in clinical situations?

Back 90

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.

Front 91

What are the five Factors that should be integrated more fully into the typical neuropsychological
assessment of patients taking psychotropic medications?

Back 91

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

Front 92

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....

Back 92

TCAs are of most concern (particularly
amitriptyline) within the antidepressant class
with acute psychomotor and concentration
effects and persisting anti-cholinergic associated
memory impairment.

Front 93

Which two classes of antidepressant drugs are in need of more definitive study but are largely safe?

Back 93

SSRIs and MAOIs.

Front 94

Among the anxiolytics, benzodiazepines all
produce compromise in which four cognitive domains?

Back 94

1. Sedative
2. Psychomotor
3. Concentration
4. memory compromise

Front 95

Atypical vs typical antipsychotics: Which is better in terms of cognitive benefit?

Back 95

Now seems clear that there is no substantive
cognitive benefit of atypical versus typical
antipsychotics

Front 96

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.

Back 96

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.

Front 97

Which AEDS produce mild effects on cognition?

Back 97

Carbamazepine, valproic acid and, to a lesser
extent, phenytoin, produce more mild effects.

Front 98

Generally you are unlikely to make a false
positive diagnosis with the principal exception of
the effects of which two psychotropic classes?

Back 98

Benzodiazepines and TCAs