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NPP 1.5 Flashcards

1
Q

What is the main concern regarding stroke risk in the elderly receiving antipsychotics?

A

There is evidence of a ‘class’ effect related to stroke risk

The major risks are age and co-incidental physical illness, not specifically dementia.

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2
Q

Does evidence support a particular risk with atypical antipsychotics?

A

No, evidence does not support a particular risk with ‘atypicals’

The mechanism for the observed risks remains unknown.

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3
Q

What types of issues should be avoided when prescribing antipsychotics to the elderly?

A

Avoid antipsychotics for non-specific purposes such as anxiety or insomnia

It is important to discuss issues with relatives, especially educated ones.

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4
Q

What should be tried before resorting to antipsychotics in elderly patients?

A

Try psychological and behavioral methods first

Documenting awareness of the issues is crucial.

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5
Q

What is the impact of prior psychotropic drug use on stroke patients compared to matched controls?

A

Higher all-cause mortality in patients with previous stroke vs controls

This includes various classes of psychotropic drugs like SSRIs, TCAs, and antipsychotics.

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6
Q

What are some common neurological adverse effects of low potency antipsychotics?

A

Paralysis of accommodation, dry eyes, impaired sweating

These effects can lead to complications like angle closure glaucoma and heat stroke.

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7
Q

What are the common extrapyramidal side effects associated with antipsychotic drugs?

A

Acute dystonias, akathisia, drug-induced parkinsonism, tardive dyskinesia

These side effects can vary by onset and duration.

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8
Q

Which antipsychotic side effect is characterized by involuntary movements typically occurring after long-term exposure?

A

Tardive dyskinesia

It often involves orofacial movements and can be permanent.

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9
Q

What is the typical onset time for acute dystonias after starting antipsychotic treatment?

A

90% have onset within 5 days of starting

Treatment typically involves anticholinergics.

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10
Q

What is the clinical significance of drug-induced parkinsonism (DIP)?

A

It presents with bradykinesia, rigidity, and tremor, similar to other forms of parkinsonism

The emphasis is on bradykinesia in DIP.

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11
Q

What should be considered when assessing negative symptoms in patients on antipsychotics?

A

All negative symptoms should be considered drug effects until proven otherwise

This includes addressing potency, dosage, and compound issues first.

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12
Q

What is clozapine known for in the context of antipsychotic medications?

A

Clozapine is known to be the most toxic drug used in modern psychiatric practice

Its benefits are considered slight compared to its risks.

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13
Q

What are the event rates for myocarditis and cardiomyopathy associated with clozapine?

A

Myocarditis event rate is 7/1000 exposures; cardiomyopathy event rate is 6/1000 exposures

Symptoms for both conditions are non-specific.

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14
Q

True or False: All antipsychotics have equal efficacy but vary greatly in tolerability.

A

True

Their receptor binding profiles guide tolerability.

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15
Q

Fill in the blank: The major brain dopamine pathways affected by antipsychotics include the _______ and _______.

A

substantia nigra, ventral tegmental area

These pathways are involved in motor control and reward processing.

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16
Q

What is the event rate for myocarditis following exposure?

A

7/1000 exposures

This statistic is relevant for understanding the risk associated with certain medications, particularly antipsychotics.

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17
Q

What is the event rate for cardiomyopathy following exposure?

A

6/1000 exposures

This statistic is comparable to myocarditis and highlights the potential cardiovascular risks of certain drugs.

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18
Q

What is the case fatality rate for myocarditis?

A

78/1000 (up to 25% reported)

Indicates the severity of myocarditis as a potential side effect.

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19
Q

What should be done if persistent tachycardia is observed in a patient on clozapine?

A

Stop clozapine and refer to cardiology

Persistent tachycardia (>120 bpm) requires immediate action to prevent further complications.

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20
Q

What type of hypersensitivity is associated with rashes from CPZ?

A

Delayed (Type 4) hypersensitivity

This type of allergic reaction can lead to skin rashes in some patients.

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21
Q

What is the prevalence of sensitivity to sunlight with CPZ?

A

~3%

This reflects the common occurrence of phototoxicity among patients taking this medication.

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22
Q

What are the potential consequences of hepatotoxicity from antipsychotic drugs?

A

Transient enzyme elevations and mixed allergic cholestasis

Hepatotoxicity can vary in severity and presentation among different patients.

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23
Q

What is the risk of biliary cirrhosis as a consequence of hepatitis?

A

Very rare

The outcome is generally more favorable than idiopathic disease.

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24
Q

What is the primary mechanism of action of lithium?

A

Multiple, complex actions at three levels: neurotransmitter modulation, signal transduction, gene transcription

This complexity contributes to the therapeutic effects of lithium.

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25
What is the recommended upper normal value for lithium levels according to expert consensus?
0.8mmols/L ## Footnote This reflects updated guidelines for managing lithium therapy.
26
What is the most important advice for patients taking lithium to avoid toxicity?
Maintain hydration (>2L/day) ## Footnote Adequate hydration is crucial due to lithium's renal excretion.
27
What adverse effect can occur at lithium levels below 1.0-1.2mmols/L?
Adverse effects include epigastric discomfort, nausea, and altered bowel frequency ## Footnote Monitoring is essential to prevent these effects.
28
What is the teratogenic reputation of lithium in psychotropic agents?
Branded as uniquely teratogenic, but this reputation is overstated ## Footnote Modern studies suggest low risks of cardiac malformations with first trimester exposure.
29
What is the main pharmacological action of carbamazepine?
Marrow suppression leading to agranulocytosis and aplastic anaemia ## Footnote These are serious side effects that necessitate careful monitoring.
30
Fill in the blank: The mode of action of lithium involves the _______ pathway.
phosphatidylinositol pathway ## Footnote This pathway is crucial for understanding lithium's effects on neurotransmission.
31
True or False: Antipsychotics as a class vary significantly in effectiveness.
False ## Footnote They have equivalent efficacy, with treatment choices based on tolerability.
32
What is the risk of developing hypothyroidism from lithium use?
Inhibits thyroid hormone synthesis and release ## Footnote Monitoring thyroid function is essential in patients on lithium.
33
What is the risk of teratogenicity associated with valproate?
10-11% risk of multi-organ dysgenesis ## Footnote Valproate is known to cause significant developmental disorders in offspring when used during pregnancy.
34
What are some non-target actions of carbamazepine?
* Sedation * Nausea/vomiting * Loose bowels * Tremors * Inappropriate ADH * Hyponatremia/oedema * Weight gain * Metabolic syndrome * Encephalopathy * Carnitine deficiency ## Footnote These effects are not the primary therapeutic targets of carbamazepine.
35
True or False: Lamotrigine is generally well tolerated but can cause skin rashes.
True ## Footnote Skin rashes can lead to serious conditions like Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).
36
What is the mortality rate associated with Stevens-Johnson syndrome (SJS)?
3-5% mortality ## Footnote SJS is a severe skin reaction that can lead to significant health complications.
37
What is the mortality rate associated with Toxic Epidermal Necrolysis (TEN)?
25-30% mortality ## Footnote TEN is a more severe form of skin reaction compared to SJS.
38
What genetic mutations are strongly associated with SJS and TEN reactions to medications?
* HLA-B*15.02 allele * HLA-B*15.11 * HLA-B*31.01 ## Footnote These mutations increase the risk of allergic reactions to certain medications, notably carbamazepine and lamotrigine.
39
What are some adverse actions associated with valproate use?
* Weight gain * Metabolic syndrome * Amenorrhea * Hyperandrogenism * Polycystic ovary syndrome (POS) * Hypothyroidism * Gynaecomastia * Reduction in male fertility ## Footnote Valproate has significant impacts on endocrine function and reproductive health.
40
Fill in the blank: The incidence of neural tube defects due to valproate exposure is approximately ______.
1-2% ## Footnote This is significantly higher than the general population risk, which is important for understanding the teratogenic effects of valproate.
41
What is the developmental impact of in utero valproate exposure?
* Delayed milestones * Cognitive disadvantage * Autism spectrum disorder (ASD) risk increase * Structural effects highly dose-dependent ## Footnote Children exposed to valproate in utero may face various developmental challenges.
42
What are the key features of fetal valproate spectrum disorder?
* Facial dysmorphism * Skeletal developmental disorders * Multi-system disorders * Cardiovascular abnormalities * Genito-urinary issues ## Footnote This disorder arises from teratogenic effects of valproate during pregnancy.
43
What are the changes introduced by the EMA regarding valproate?
* Smaller pack sizes * Pictograms on packs * Registration with PREVENT for women of childbearing potential * Introduction of Annual Risk Assessment Form (ARAF) ## Footnote These changes aim to enhance safety and awareness regarding the risks of valproate.
44
What is the prevalence of developmental disorders in offspring of fathers exposed to valproate?
~ 5% ## Footnote This statistic highlights the risks associated with paternal exposure to valproate prior to conception.
45
What is the teratogenic risk associated with carbamazepine?
x2.3 risk of fetal damage ## Footnote Carbamazepine is associated with a risk of organ dysgenesis similar to that seen with alcohol exposure.
46
What is the suggested risk of autism associated with lamotrigine use during pregnancy?
Neutral or only slightly raised risk ## Footnote More research is needed to confirm any potential association with autism.
47
What are the implications of valproate's complex pharmacology?
* Inhibits POLG gene action * Disrupts folate metabolism * Epigenetic effects on gene expression ## Footnote These mechanisms may contribute to the teratogenicity of valproate.
48
What is the role of histone deacetylase in valproate's pharmacological action?
Determines chromatin configuration affecting gene expression ## Footnote Valproate's inhibition of histone deacetylase leads to increased gene transcription.
49
What are safer alternatives to valproate for mood stabilization?
* Antipsychotics * Lithium * ECT ## Footnote These alternatives are recommended for use in psychiatry, especially for women of childbearing potential.
50
What should be avoided during the first trimester of pregnancy regarding psychotropic medication?
All psychotropics ## Footnote The risk of developmental disorders is highest during early fetal development.
51
What is the recommendation for lithium use during pregnancy?
Generally safe after the first trimester ## Footnote Data on risks during pregnancy is limited, but no critical periods have been established.
52
What is the commonest benzodiazepine configuration?
(α1)₂(β2)₂(γ2) ## Footnote This configuration is found in the GABAA receptor, which is a heteropentameric protein.
53
What are the five common actions of benzodiazepines?
* sedation/hypnosis * anxiolysis * anticonvulsant * peripheral muscle relaxation * anterograde amnesia
54
True or False: Benzodiazepines are primarily effective in the generation of seizures.
False ## Footnote Benzodiazepines are better at preventing the propagation of seizures than at preventing their generation.
55
What factors substantially differentiate benzodiazepines in terms of pharmacokinetics?
* metabolism (extent of active metabolites and their half-lives) * lipophilicity
56
Which benzodiazepine is known as the first BDZ introduced in 1960?
Chlordiazepoxide ## Footnote It has a short half-life but its metabolite can last up to 100 hours.
57
Fill in the blank: The clinical effect of benzodiazepines is attributable to limited distribution to _______.
[fat, lungs, liver, muscle, etc.]
58
What is the half-life range of clonazepam?
18 – 50 hours
59
What is the primary use of benzodiazepines in the context of alcohol withdrawal?
They are used mainly as sedative/hypnotics.
60
What are the three main ‘z’ drugs and their half-lives?
* zopiclone ~ 5 hours * zolpidem ~ 2 hours * zaleplon ~ 1 hour
61
Which benzodiazepine has the longest half-life of all?
Flurazepam's metabolite can last up to 250 hours.
62
True or False: Benzodiazepines are considered remarkably safe when used alone.
True
63
What are the clinically significant unwanted effects of benzodiazepines?
* impaired awareness/self-judgment * impaired attention * impaired reaction-time * impaired motor coordination (ataxia/dysarthria, etc.)
64
What is a paradoxical reaction associated with benzodiazepines?
Dyscontrol syndrome
65
What is the common metabolic pathway for diazepam?
N-demethylation (desmethyldiazepam) via CYP3A4/2C19
66
Fill in the blank: The role of _______ in determining clinical effect is significant in the context of benzodiazepines.
[lipophilicity]
67
What is the classification of benzodiazepines by half-life for short-acting?
Short-acting (~<12 hours)
68
What are the therapeutic uses of benzodiazepines?
* sedatives * anxiolytics * anticonvulsants * hypnotics
69
True or False: Benzodiazepines can be lethal when used in combination with other central respiratory depressants.
True
70
What are endogenous ligands for GABAA receptors referred to as?
Endozepines
71
What is the half-life range of lorazepam?
10 – 12 hours
72
What is the significance of clinical effects being classified as 'not everything'?
Half-life is not the sole determinant of clinical effects.
73
What are central respiratory depressants that can be lethal?
Examples include alcohol and opiates ## Footnote Benzodiazepines (BDPs) can also be lethal in combination with these substances.
74
Which combination of drugs causes more deaths under 25s in the US than road traffic accidents?
Combinations of benzodiazepines (especially alprazolam) and opiates (especially oxycodone)
75
What is a significant risk associated with all benzodiazepines?
Dependency, with approximately 40% risk after 6 months of regular use of short half-life compounds
76
What is the greatest risk factor for benzodiazepine dependency?
Short half-life drugs (e.g. lorazepam, temazepam)
77
When do withdrawal symptoms typically occur after stopping benzodiazepines?
5 to 7 days after sudden cessation
78
What are some typical withdrawal symptoms from benzodiazepines?
Nausea, vomiting, anorexia, agitation, tremulousness, insomnia, fits ## Footnote Withdrawal is also characterized by perceptual distortions.
79
What is the recommended duration for regular use of benzodiazepines?
Not more than 2 to 4 weeks
80
What is Flumazenil?
A specific benzodiazepine receptor antagonist that swiftly reverses the effects of benzodiazepines
81
What is the half-life of Flumazenil at the site of action?
Approximately 30 minutes
82
What is the terminal elimination phase half-life of Flumazenil?
Approximately 60 minutes
83
What are some of the oldest sedative/hypnotics used in modern medicine?
Chloral hydrate, paraldehyde, barbiturates, meprobamate, chlormethiazole, benzodiazepines
84
What are DORAs?
Dual orexin receptor antagonists
85
What are the two proteins related to orexins?
Orexin A and Orexin B
86
What is the role of orexins in the body?
They control energy expenditure and integration of metabolism with circadian rhythms
87
Name three licensed products internationally that are DORAs.
Suvorexant, lemborexant, daridorexant
88
What type of receptors are cholinergic receptors?
Muscarinic and nicotinic receptors
89
What is the importance of nicotinic sites in neuropharmacology?
They are increasingly studied and should not be conflated with muscarinic sites
90
What are the types of antimuscarinics?
Diphenhydramine-like, Trihexyphenidyl-like, Mixed ## Footnote Examples include diphenhydramine, trihexyphenidyl, and benzatropine.
91
What are the classifications of muscarinic receptors?
M1, M2, M3, M4, M5
92
What is a potential risk associated with long-term anticholinergic use?
Dementia
93
What types of studies have indicated a relationship between anticholinergic use and dementia?
Post-mortem studies, cross-sectional studies, retrospective studies, prospective community-based studies
94
What is the mechanism by which Gq effectors activate pathways?
They activate β-phospholipase C conversion of PIP2 to DAG and IP3
95
What are the major G-protein alpha subunits?
Gαs, Gαi, Gαq11, Gα12, Gα13
96
What effect do antimuscarinics have on mood and cognition?
They can elevate mood/excitement and impair cognition/memory/learning
97
What are antimuscarinics commonly used for?
Involuntary movement disorders
98
What is the biological plausibility of the amyloidogenic pathway related to antimuscarinics?
Activation of Gq-activated cascades may inhibit cleavage of amyloid precursor protein
99
What is biperiden?
An antimuscarinic drug used in the treatment of Parkinson's disease ## Footnote Biperiden is one of the antimuscarinic agents that can help alleviate symptoms of Parkinsonism.
100
What is the indication for tetrabenazine?
Involuntary movement disorders, including tardive dyskinesia ## Footnote Tetrabenazine is indicated for managing disorders associated with abnormal movements.
101
What is VMAT2?
Vesicular monoamine transporter 2, an anitporter involved in neurotransmitter uptake ## Footnote VMAT2 plays a crucial role in packaging neurotransmitters into vesicles.
102
What is the primary action of tetrabenazine?
Inhibiting VMAT2 ## Footnote Tetrabenazine binds to a specific site on VMAT2, which may overlap with the reserpine site.
103
What are common adverse effects of tetrabenazine?
* Drowsiness/fatigue * Parkinsonism * Depression * Insomnia * Akathisia * Nervousness/anxiety * Nausea/vomiting ## Footnote Adverse effects data is based on retrospective studies reviewed by Guay, 2010.
104
True or False: The anti-parkinsonian actions of antimuscarinic drugs correlate with actions at muscarinic GPCRs.
False ## Footnote The clinical action of these drugs may be due to mechanisms other than direct GPCR interactions.
105
What characterizes Attention Deficit-Hyperactivity Disorder (ADHD)?
Executive dysfunction, hyperactivity/restlessness, impulsivity ## Footnote ADHD is a neurodevelopmental disorder that can persist into adulthood.
106
What is the heritability estimate for ADHD?
Approximately 75% ## Footnote This indicates a strong genetic component to the disorder.
107
What are psychostimulants used in the treatment of ADHD?
* Methylphenidate * Dexamphetamine * Lisdexamphetamine ## Footnote These drugs are commonly prescribed to manage symptoms of ADHD.
108
What is the mechanism of action of methylphenidate?
Blocks both dopamine and noradrenaline transporters, especially DAT ## Footnote Methylphenidate's pharmacology is complex and not fully understood.
109
What are the adverse effects of psychostimulants?
* Nausea * Diarrhoea * Anorexia * Weight loss * Restlessness * Anxiety * Aggression * Psychosis * Tremor * Tics * Seizures * Insomnia * Impaired growth * Tachycardia * Palpitations * Hypertension * Cardiomyopathy ## Footnote These effects highlight the need for careful monitoring in patients receiving these medications.
110
What is the role of amphetamines in ADHD treatment?
Act as indirect dopamine agonists ## Footnote Amphetamines increase dopamine availability in the synapse, aiding in symptom control.
111
Fill in the blank: The pharmacology of amphetamines involves _______ transport.
Reverse ## Footnote This refers to the mechanism by which amphetamines promote the release of neurotransmitters.
112
What is the significance of TAAR1 in the pharmacology of amphetamines?
It mediates cAMP accumulation and influences neurotransmitter release ## Footnote TAAR1 is a trace amine-associated receptor that plays a role in the action of amphetamines.
113
What is the relationship between amphetamines and Parkinson's disease risk?
Regular use is associated with a two/three-fold increase in risk ## Footnote Epidemiological studies suggest a potential long-term risk for Parkinson's disease with amphetamine use.
114
What does TAAR1 stand for?
trace amine-associated receptor 1
115
What is the function of the DA transporter (DAT)?
transmitter uptake
116
What ion is involved in depolarizing impulses at the presynaptic membrane?
Ca²⁺
117
What is the role of VMAT2 in neurotransmitter function?
transmitter uptake
118
What is exocytosis?
process of neurotransmitter release
119
What is the pharmacological effect of amphetamines?
reverse transport of DA and probably NA
120
True or False: Regular use of amphetamines is associated with an increased risk of Parkinson's disease.
True
121
What does tetrabenazine inhibit?
VMAT2
122
What are acetylcholinesterase inhibitors (AChEIs) used for?
cognitive enhancers
123
Who discovered acetylcholine?
Sir Henry Dale, 1914
124
Fill in the blank: Acetylcholinesterase is abbreviated as ______.
AChEase
125
What is the catalytic triad in acetylcholinesterase composed of?
Ser-200, His-440, Glu-327
126
What is donepezil?
selective acetylcholinesterase inhibitor
127
What is the main outcome of new approaches to dementia therapeutics so far?
disappointing legacy
128
What is β-amyloid (Aβ) formed from?
cleavage of amyloid precursor protein (APP)
129
What is a significant problem with active immunization against Aβ protein?
severe immunological reaction
130
What type of receptors are CB1 and CB2?
GPCRs
131
What are the two known endogenous ligands for cannabinoid receptors?
* 2AG * anandamide
132
What is the role of cannabinoids like cannabidiol?
anticonvulsant effect
133
What do hallucinogens commonly agonize?
5HT2A receptors
134
What is the classification of opioid receptors based on?
subtypes: μ, κ, δ, nociception
135
What is the pharmacological effect of DMT?
modification of trace amine, tryptamine
136
What is the mechanism of action of donepezil?
inhibits acetylcholinesterase
137
What is the primary neurotransmitter involved in cholinergic transmission?
acetylcholine
138
What is the significance of NMDA antagonists like memantine in Alzheimer's treatment?
moderate-severe Alzheimer's disease
139
True or False: None of these drugs significantly modify the disease process of Alzheimer's.
True

core psychiatry (6 decks)

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