Psychiatry: Antipsychotics, Anxiolytics, Antidepressants Flashcards
What are anxiolytics?
A drug used to relieve anxiety
What is the first line Tx for anxiety disorders
SSRIs
SSRI full form?
Selective serotonin reuptake inhibitors
Examples of SSRIs
setraline
fluoxetine
What are other effect Tx for GAD
SNRIs (Serotonin and norepinephrine reuptake inhibitors )
pregabaline
Examples of anxiolytic agents
- Benzodiazepines
- Antidepressants
- Buspirone
- (Azapirones)
- Pregabalin
- Beta blockers
Examples of Benzodiazepine
lorazepam, temazepam
oxazepam
diazepam
Pharmocology of Benzodiazepines
GABAa receptors agonist.
No enzyme induction.
Phase 1 metabolism to form active
metabolites
Clinical effects of Benzodiazepines
Anxiolytic
Hypnotic
Anticonvulsant (seizures)
Sedation
Adverse effects of Benzodiazepines
- Drowsiness and dizziness.
- Confusion (elderly).
- Cleft lip / palate and respiratory depression (avoid in pregnancy).
- Cognitive and psychomotor impairment.
- Tolerance and cross-tolerance with alcohol.
- Withdrawal and discontinuation symptoms.
Pharmocology of Antidepressants
5-HT reuptake blockage
Examples of antidepressants
setraline
steraline, fluoxetine
Clinical effects of antidepressants
SSRIs: 1st line
pharmacological
treatment for anxiety
disorders.
Clomipramine: OCD
Buspirone Pharmocology
5-HT1A-
receptor partial
agonist.
Short
elimination
half-life so the body clears it quickly
Clinical effects of Buspirone
(Azapirones)
Effective in GAD
Less effective in treating acute anxiety or social phobia.
Not a good augmenting agent with SSRI in anxiety disorders
Adverse effects of Buspirone
(Azapirones)
Nausea, dizziness and akathisia
Pharmacology of pregabalin
- Has affinity for voltage-gated Ca2+
- channels.
- Eliminated unchanged via kidneys
pregabalin Clinical effects
- Effective in treating GAD
- and social phobia.
- Useful as an augmentation
- strategy for
- antidepressant-treated
- anxiety disorders
Adverse effects of pregabalin
- Well tolerated.
- Discontinuation syndrome.
- Drug of abuse.
- Deranged liver function.
- Vertigo, dizziness and weight
- gain.
Pharmacology of beta blockers
bloackage of beta adrenoceptors
Clinical effects of beta blockers
- Reduction in the physical
- symptoms of anxiety.
- Akathisia and lithium-
- induced fine tremor.
Adverse effects of beta blockers
Bradycardia and hypotension.
Bronchospasm (in asthma
patients)
WHat are the different types of Benzodiazepine agents? Give examples
- **Short-acting agents **- e.g. lorazepam and temazepam: have greater
potential for abuse and dependence, but may be safer in acute
situations.
* Long-acting agents - e.g. diazepamLong acting and short acting
- Benzodiazepines can be used for ______ ______ management of severe
anxiety
- Benzodiazepines can be used for short-term management of severe
anxiety
Longer-term anxiety is better managed by ________________,
changing the environmental situation or by other medications (e.g. ______).
Longer-term anxiety is better managed by psychotherapy,
changing the environmental situation or by other medications (e.g. SSRIs).
Can Buspironebe used longer-term for anxiety disorders?
- Buspirone can be used in the longer-term, but may be less efficacious
than alternative strategies and is rarely used in clinical practice.
What happens if you are addicted to benzodiazepine?
- For those addicted to benzodiazepines, conversion is required to a longacting drug (i.e. diazepam) before starting a very slow reducing regimen
What benzidiazepine is not used as anxiolytics?
The non-benzodiazepine “Z drugs” **(zopiclone, zaleplon and zolpidem) **are
not used as anxiolytics though they act on the benzodiazepine receptor.
They are commonly prescribed as hypnotics and have little to offer over
benzodiazepines
Benzodiazepine metabolism
- Most benzodiazepines undergo phase I metabolism (oxidation,
reduction, hydrolysis and demethylation by CYP450). - Phase II metabolism (conjugation) - lorazepam, oxazepam and
temazepam.
what are antipsychotics
Drugs that treat psychosis
Antipsychotics have affects on what types of neurotransmitters
Dopamine
Acetylcholine
histamine and sertonin pathways
Classification of antipsychotics
Broadly classified into two major groups - first generation antipsychotics
(FGAs) and second generation antipsychotics (SGAs).
* Currently, there is an increasing shift towards “neuroscience-based
nomenclature” classification. This classification system is based on
contemporary pharmacological knowledge rather than clinical indications,
i.e. antidepressants, antipsychotics, etc.
What are the four major dopamine pathways?
Mesolimbic pathway:
Mesocortical pathway:
Nigrostriatal pathway:
Tuberoinfundibular pathway:
Which dopamine pathway controls prolactin secretion
Tuberoinfundibular pathway:
Which dopamine pathway is linked to postive symptoms - delusions,
hallucinations, disorganized speech / thinking and disorganised or
catatonic behaviour in psychosis and schizophrenia
Mesolimbic pathway:
Which dopamine pathway is linked to negative symptoms - alogia,
affective flattening, avolition etc in psychosis and schizophrenia
Mesocortical pathway:
Which dopamine pathway is controls motor movements
Nigrostriatal pathway:
Name some Characteristics of first generation antipsychotics
- Antipsychotic effects predominantly on D2 receptors (antagonism) -
requires about 70% D2 receptor occupancy for efficacy. - Extrapyramidal side effects (EPSEs): dystonia, drug-induced parkinsonism,
akathisia, tardive dyskinesia (up to 78 % D2 receptor occupancy). - Prolactin elevation.
- Muscarinic (cholinergic)-blocking properties.
- Limited efficacy on negative symptoms of schizophrenia.
Examples of first geberation antipsychotics?
chlorpromazine, haloperidol, trifluoperazine, fluphenazine,
zuclopenthixol and flupenthixol.
Characteristics of second generation antipsychotics
- Lower D2 receptor affinity.
- High serotonin / dopamine-binding ratio.
- Have greater efficacy for both positive and negative symptoms.
- Reduced risk for the development of extrapyramidal symptoms.
- Linked to the development of metabolic abnormalities more than
conventional agents. These abnormalities include: obesity (truncal),
hypercholesterolaemia / dyslipidaemia, elevated B.P and diabetes /
impaired glucose tolerance.
Examples of second generation antipsychotics?
clozapine, amisulpride, risperidone, olanzapine, quetiapine, and
aripiprazole (aripiprazole exhibits unique dopamine modulatory effects).
Name some Antipsychotic agent?
Amisulpride
Aripiprazole
Lurasidone
Olanzapine
Paliperidone
Risperidone
What is Amisulpride used for
Acute and chronic schizophrenia.
Negative symptoms at low doses.
What is Aripiprazole used for?
Acute and chronic schizophrenia.
Mood stabilisation.
Control of agitation and behavioural
disturbance in schizophrenia (short- acting
injectable).
Available in long-acting injectable form
(LAI)
What are Lurasidone used for?
Lowest ranked efficacious antipsychotic
agent in schizophrenia treatment.
Treatment of bipolar depression
What is Olanzapine is used for
Treatment of positive, negative and mood
symptoms of schizophrenia.
Short-acting injection (SAI) effective in
control of agitation and behavioural
disturbance.
Long-acting injection (LAI) - post injection
monitoring necessary due to a possible
post-injection syndrome.
What is Paliperidone used for
Treatment of schizophrenia
What is Risperidone used for?
Schizophrenia.
Acute treatment of mania
MoA of Amisulpride
D2 and D3 receptors selective antagonism.
5-HT7 receptor antagonism.
Limbic selective.
MoA of Aripiprazole
- D2 receptor partial agonism/antagonism.
- 5HT1A receptor partial agonism.
- 5HT2A and 5HT2C receptors antagonism.
- No anticholinergic effect.
MoA of Lurasidone
- Adrenergic, dopaminergic and serotonergic receptors
- antagonist.
- 5HT1A partial agonist
MoA of Olanzapine
- Multi-receptor antagonism (histaminergic, muscarinic,
- serotonergic, adrenergic and dopaminergic.
- D2 limbic receptor selectivity
MoA of Paliperidone
- Metabolite of risperidone but with lesser bioavailability.
- Less affinity for D4 receptor than risperidone.
- 5HT2A, 5HT2C, D2, H1 and adrenergic receptor antagonism.
- Oral and LAI forms
MoA of Risperidone
- 5HT2A, 5HT2C, D2, and adrenergic receptor antagonism.
- Low - moderate H1 affinity.
- Oral and LAI forms
Side effects associated with the use of antipsychotics
- Extrapyramidal side effects (EPSEs).
- Neuroleptic malignant syndrome (NMS).
- Prolonged QTc interval (a risk factor for occasionally fatal ventricular
arrhythmia). If QTc interval > 500 ms, refer the patient for cardiological
assessment. - Hyperprolactinaemia (with osteoporosis) and sexual dysfunction.
- Metabolic syndrome - weight gain, diabetes, dyslipidaemia (elevated
triglyceride and low HDL cholesterol level) and hypertension.
Decreased seizure threshold. - Anticholinergic effects - constipation etc.
- Hyponatraemia (syndrome of inappropriate secretion of antidiuretic
hormone - SIADH). - Photosensitivity.
- Agranulocytosis and myocarditis (clozapine).
What drug is used for treatment-resistant schizophrenia?
Clozapine
What should patient have if they are prescribed clozapine
All patients MUST be registered with a clozapine monitoring service.
* Patients on clozapine should have an FBC done weekly for the first 18
weeks from dose commencement (risk of neutropenia / agranulocytosis
greater), fortnightly until 52 weeks of treatment, and then four-weekly
thereafter
Side effects of clozapine
- Increased appetite, leading to significant weight gain.
- Constipation.
- Hypersalivation.
- Tachycardia.
- Seizures.
-
Neutropenia / agranulocytosis - concomitant use of lithium can increase
the white cell count. - Myocarditis and cardiomyopathy
What are the four general side effects of antipsychotic drugs
- Dystonic reactions
- Drug-induced parkinsonism
- Akathisia
- Tardive dyskinesia (TD)
What is Dystonic reaction and how do you treat it?
Oculogyric spasm and torticollis.
- Higher risks in the early stages of treatment or after increase in dose.
- It may also occur on drug withdrawal.
- Use oral or IM anticholinergics, e.g. procyclidine 5 - 10 mg.
What is Drug-induced parkinsonism?
- Tremor, bradykinesia and rigidity.
- Most patients will cope with the symptoms without active treatments
What is Akathisia?
- Subjective unpleasant state of motor restlessness. Linked to
violence and suicide. - Responds poorly to anticholinergics but can be treated by
changing to a drug with lower liability for akathisia - usually an
atypical.
.
What is Tardive dyskinesia (TD)
- Involves a wide variety of movements - lip-smacking,chewing,
tongue protrusion, choreiform hand movements, pelvic thrusting
and severe orofacial movements. - Caused by super-sensitivity of dopamine receptors due to
prolonged therapy with dopamine-blocking drugs.
What disease is Commonly associated with the use of haloperidol, risperidone,
quetiapine, olanzapine and clozapine.
Syndrome of inappropriate ADH (SIADH) secretion
What are the diseases associated with antipsychotic drugs?
(SIADH)
Hyperprolactinaemia
Reduced seizure threshold
Postural hypotension
Metabolic syndrome
Anticholinergic side effects
Neuroleptic Malignant Syndrome (NMS)
Which drugs have no affect to prolactin
Quetiapine, aripiprazole and clozapine
____________ is the antipsychotic that confers the highest risk of reducing
seizure threshold
** Clozapine** is the antipsychotic that confers the highest risk of reducing
seizure threshold
Postural hypotension is a particular risk when ____________ is prescribed for the elderly or
when high doses of antipsychotics are used.
is a particular risk when phenothiazine is prescribed for the elderly or
when high doses of antipsychotics are used.
What is Metabolic syndrome?
Which drugs cause this?
Consists of: truncal obesity, diabetes / impaired glucose tolerance,
hyperlipidaemia and elevated B.P.
* Clozapine tends to have the highest risk of weight gain, followed by
olanzapine, quetiapine and risperidone
What is neurpleptic malignant syndrome?
Neuroleptic malignant syndrome (NMS) is a life-threatening idiosyncratic reaction to antipsychotic drugs characterized by four group of symptoms fever, altered mental status, muscle rigidity, and autonomic dysfunction.
-medical emergency
-Occurs in ~0.5% of patients newly
treated with antipsychotics
Clinical features of NMS
which evolve rapidly over 24 - 72 hours,
* Laboratory findings include: elevated creatine kinase (CK) level,
leucocytosis, abnormal LFTs and myoglobinuria.
RF for NMS
Rapid antipsychotic dose increase
* Intramuscular (IM) medication
* Medical illness
* Male gender
* Dehydration
Treatment of NMS
- Antipsychotic agent discontinuation.
- Supportive treatment (hydration, antipyretics etc.).
- Dopamine agonists (bromocriptine, dantrolene) may help with reduction
in muscle spasm and to reverse anti-dopaminergic effects. - Transfer to the nearest medical facility for management - ICU may be
required. - Investigations: serum CK (raised in NMS), whilst temperature, pulse,
and B.P should be closely monitored.
What are antidepressants
type of medicine used to treat clinical depression or prevent it recurring.
What are the classes of Antidepressants?
- Selective serotonin reuptake inhibitors (SSRI)
- Noradrenaline reuptake inhibitors (SNRI)
- Noradrenaline and serotonin (non selective
monoamine) reuptake inhibitors (NSRI) - Monoamine oxidase inhibitors (MAOI)
- Tricyclic antidepressants (TCA)
- Atypical antidepressants
Examples of SSRIs
- Fluoxetine (Prozac)
- Sertraline (Zoloft)
- Paroxetine (Paxil)
- Citalopram (Celexa)
- Escitalopram (Lexapro)
- Fluvoxamine (Luvox)
- Full therapeutic effect
may not appear for 3-8
weeks after treatment
initiation
SSRI: Pharmacokinetics
- Absorbed in the gastrointestinal (GI) tract ->
bind to proteins and cross the brain-blood
barrier - Peak plasma levels: 1-8 hours
- Metobolise in the liver
- Half-life ~1 day (fluoxetine is 1-3 days) -> OD
- Inhibit P450 enzymes causing many drug-drug
interactions except citalopram and
escitalopram (used in elderly)
SSRI: uses & efficacy
- First-line antidepressants because of their efficacy, tolerability and general safety in overdose
- Anxiety, panic disorder, obsessive-compulsive disorder, posttraumatic stress, eating disorder, premenstrual syndrome
- A substantial proportion of patients fail to respond to SSRI therapy
(28–55%) and many continue to experience residual symptoms - The magnitude of SSRI efficacy compared with placebo increases
with severity of depression and may be minimal or nonexistent in
patients with mild or moderate symptoms - CYP26 and CYP2C19 polymorphisms affect SSRI efficacy and safety
SSRI: Side effects
- GI symptoms, dizziness, headache, sexual dysfunction,
drowsiness, weight gain (or loss), insomnia, syndrome of
inappropriate antidiuretic hormone (SIADH),
hyponatraemia, movement disorders - QT prolongation (dose-depended and mainly citalopram)
- Observational studies suggest increased risk of diabetes,
bleeding and bone loss - Suicidal and self-harm behaviour may be increased in
children and young adults - Discontinuation syndrome (within 5 days of abrupt
stopping): dysphoria, dizziness, GI distress, fatigue, myalgia - Pregnancy: use if benefits > risks, fluoxetine appears to be
safe
What is the most common NRI
Reboxetine -> major depressive disorder (MDD)
SE of NRI
Selective NRIs are generally well tolerated but the most common side effects reported are headache, dry mouth, abdominal pain, loss of appetite, nausea, vomiting and drowsiness. An increase in heart rate and blood pressure have been reported but are usually not clinically important.
Examples of Serotonin and norepinephrine
reuptake inhibitors (SNRI)
- Duloxetine and venlafaxine
SE of SNRI
: hypertension (not with duloxetine),
loss of appetite, hepatic failure
What is the function of Monoamine oxidase inhibitors
revent the catabolism of NE, DA
and 5-HT neurotransmitters by
blocking monoamine oxidase
irreversibly
What are the Serious and potentially lethal
adverse events MOAi
hypertensive crises and the
requirement for strict dietary
restrictions
Which MAOi is used for parkinson?
Selegiline (selective MAOb at low
doses -> Parkinson) transdermal
patch
SE of MOAi
ide effects: hypotension, dry
mouth, headache, GI upset,
myoclonic jerks
What should you never perscribe Monoamine oxidase inhibitors in combination with? What would it lead to?
Never co-prescribe with SSRI or
NSRI -> Serotonin syndrome
What is serotonin syndrome
Tx?
- Usually the result of interaction between multiple
medications that increase serotonergic
neurotransmission (e.g. SSRIs started earlier than
2 weeks after a MAOI has been stopped) - Presentation within 6 (up to 24) hours from
initiating or increasing the dose of a drug - Agitation, tachycardia, hypertension, tremor,
rigidity and clonus, hyperthermia, dilated pupils - Supportive treatment, benzodiazepines,
cyproheptadine (serotonin antagonist)
Examples of Tricyclic antidepressants (TCA)
Amitriptyline and itsmetabolite nortriptyline,
imipramine and its metabolite desipramine,
clomipramine
Function of TCA
Uses of TCA
depression, anxiety,
bulimia nervosa,
neuropathic pain,
smoking cessation
TCA: side effects
- Anti-histaminic effect: sedation, weight gain, confusion
- Anticholinergic actions: dry mouth, blurred vision (dilated pupils),
urinary retention and constipation - Antiadrenergic actions: orthostatic hypotension and dizziness
- Voltage-sensitive sodium channels (VSSCs) in heart and brain
blockade in overdose -> coma, seizures, cardiac arrhythmias and
cardiac arrest - All are potentially cardiotoxic (heart block and ventricular
arrhythmias), lower seizure threshold, bone marrow and liver
toxicity (rare) - However, not all TCA have the same affinity for all receptors:
– Nortriptyline well-tolerated
– Amitriptyline: potent antihistaminic action
Example of Atypical antidepressant
Bupropion (dopamine and norepinephrine reuptake inhibitor):
Mirtazapine (presynaptic α-2 adrenergic and postsynaptic serotonin
blockade)
Vilazodone and vortioxetine (block serotonin reuptake in addition to
various effects on 5-hydroxytryptamine (5-HT) receptor subtypes)
When do you review desired response to
SSRI?
A. Next day
B. 2-5 days
C. 4 weeks
D. 6 months
E. 1 year
F. No need to review because SSRIs are always
effective
C
SSRI is reviewed in a week cos there maybe side effects!
Which of the following can be added
to sertraline?
A. Any MAOI
B. Reboxetine
C. Nortriptyline
D. Citalopram
E. A and C
F. B and C
C
Usually you combine drugs from different classes
Which of the following are symptoms
of the serotonin syndrome?
A. Agitation
B. Hypertension
C. Tachycardia
D. Dilated pupils
E. A, B and C
F. All of the above
F
Clinical case No 1
* John is a 25 y.o. biomedical sciences student and
presents with low mood:
– Lost interest in playing football which has been his passion
since 5 years old
– Feels fatigued and prefers to stay at home. His friends are
concerned because they have not seen him for a month
and he is not replying to their messages
– His sleeping pattern has changed as he cannot sleep at
night
– His appetite has increased and put on weight
– Lacks concentration and struggles with his studies
– Duration of symptoms is at least 6 months
His doctor diagnoses depression and Px sertraline
50mg.His doctor diagnoses depression and Px sertraline
50mg. His doctor diagnoses depression and Px sertraline
50mg.
– Counselling
– Follow-up in 1 week
– Delayed effect of sertraline should be expected
– Upon further questioning, John reveals that his life
has no meaning and he would rather end it –> suicidal
ideation requires urgent attention by mental health
specialists!
Clinical case No 2
* Anna is 85 y.o. and has been referred to the
hospital with hyponatraemia (118) on routine
bloods
* On review of her medications polypharmacy
(>5) is identified and she is also on citalopram
10mg
* She has been taking it for many years and is
not sure why she has been on it.
What is the cause of hypoNa and how is it treated?
Anna is diagnosed with drug-induced SIADH and
citalopram is stopped
* She is warned of probable symptoms of
discontinuation (changes in mood, sleep,
appetite), which may last about a week and to
seek medical advice if more severe.
* Follow-up with GP is arranged to assess Na and
mood.
What is Actue Dystonic Reaction
They are characterised by uncontrolled muscle spasm, leading to abnormal
face and body movements such as oculogyric crisis and torticollis. The patient
may be unable to speak clearly or swallow. In severe cases the jaw can
dislocate.
* Acute dystonia can occur within the first few days of treatment and usually
within hours of starting antipsychotics (or more quickly than this if the IM or I.V
route is used for administration).
Which drug is considered to be high risk of causing acute dystonia
Haloperidol
Management options for patients experiencing parkinsonian symptoms
Onset is usually within days or weeks and management options include reducing
the dose, prescribing an anti-muscarinic such as procyclidine or switching to an
alternative
Use of anti-muscarinics should be reviewed every three months and they shouldn’t
be prescribed at night as the symptoms are usually absent during sleep.
How do you reduce akathisia symptom?
A reduction in symptoms may be seen with propranolol or low dose Clonazepam.
Serotonin antagonists such as Mirtazapine, Cyproheptadine and Misanserin may
also help. All are unlicensed treatments for this indication
Treatment for Tardive dyskinesia (TD)
- Treatment should include stopping the antipsychotic drug and substituting with
another. If this is not effective additional agents may be used - Tetrabenazine is
the only licensed treatment for TD in the U.K. Benzodiazepines have been used
