Drugs

Question 1

Typical vs atypical antipsychotics and their effect on dopamine receptors

Answer 1

• D1-like are coupled to stimulatory G-protein Gs and have a stimulatory
effect on neurotransmission

• The D2-like are coupled to inhibitory Gi proteins, and have an inhibitory
effect on neurotransmission

Typical (1st generation)
• High affinity for D2 receptors
• Effective for +ve symptoms
• Do little for –ve symptoms
• Cause movement and motor side effects (as they block dopamine receptors)
• Haloperidol, Zuclopenthixol, Flupentixol, Chlorpromazine, Fluphenazine

Atypical (2nd generation)
• Higher affinity for 5HT-2 receptors than D2 receptors
• Richer pharmacology
• Effective for +ve symptoms
• Do more for –ve symptoms
• More significant metabolic ADRs
• Quetiapine, Risperidone, Olanzapine, Clozapine, Aripiprazole, Paliperidone
Lurasidone

Question 2

Risperidone

Answer 2

• Risperidone
– first ‘atypical’ on the market
– antagonist at 5HT2a, 5HT2c, alpha 1, D2
– hypothesis that the 5HT blockade mitigates against
EPSE – dose dependent
– also available as depot injection
– Oral is generic

Question 3

Quetiapine

Answer 3

• Quetiapine
– Alpha 1 blockade causes postural hypotension when starting (use low starting dose and titrate)
– very low incidence of hyperprolactinemia
– Available as a once daily MR product
– Both formulations generic

Question 4

Olanzapine

Answer 4

• Olanzapine
– antagonist at assorted DA and 5HT receptors
– also at H1 receptors: weight gain & drowsiness
– dyslipidaemia, diabetes
– also available as olanzapine pamoate depot – care
due to ‘post-injection syndrome’
– generic as orodispersible also

Question 5

Typical antipsychotic examples

Answer 5

Haloperidol,
Zuclopenthixol,
Flupentixol,
Chlorpromazine,
Fluphenazine

Question 6

Atypical antipsychotic examples

Answer 6

Quetiapine,
Risperidone,
Olanzapine,
Clozapine,
Aripiprazole,
Paliperidone,
Lurasidone

Question 7

Treatment resistance options for schizophrenia

Answer 7

Have to have tried 2 antipsychotics with compliance and length

• Around a third of people with schizophrenia are described as treatment
resistant

• What does this mean?
• Clozapine & Depots
• BNF Maximum Doses
• Psychology input

Question 8

Clozapine

Answer 8

Clozapine
– The ONLY drug licensed for treatment-
resistant schizophrenia

– 1% incidence of neutropenia/agranulocytosis (check FBC)
• mandatory registration of patient, prescriber and dispenser with appropriate monitoring service
• baseline FBC, then weekly for 18 weeks, fortnightly for 1 year, then every four weeks for the duration of treatment
• Avoid other agranulocytosis-causing drugs, e.g.
carbamazepine
• Dose titration & re-titration after 48hours

Question 9

Clozapine side effects

Answer 9

– Unpleasant side effect profile
• postural hypotension
• drowsiness
• weight gain
• ?diabetes
• hypersalivation
• constipation N.B. has caused fatalities
• seizures, esp above 600mg/day ?consider valproate

Smoking cigarettes increases metabolism so if patients come into hospital and stop smoking factor this in with dose

Question 10

Side effects of anti psychotics

Answer 10

Extra pyramidal:
Dystonia
Pseudo Parkinsonism
Akathisia (inability to remain still)
Tardive dyskinesia

Other side effects:
Cardio toxic
Lower seizure threshold
Weight gain
Sedation
High prolactin
Dry mouth
Metabolic syndrome
Postural hypotension
Constipation
NMS (neuroleptic malignant syndrome)

Question 11

Management of the side effect of antipsychotics - acute dystonia

Answer 11

– a slow, contained muscular
contraction involving
• neck
• jaw
• tongue
• eye muscles (oculogyric crisis)
• eyelids (blepharospasm)
• glossopharyngeal (speaking,
swallowing problems)

• Treatment: procyclidine 5mg p.o.
– Consider syrup if jaw is locked
– consider I.M. (10mg) if warranted

Question 12

Acute akathisia side effect management

Answer 12

• A subjective feeling of muscular discomfort and restlessness
– agitation, dysphoria,
– pacing
– standing and sitting in
rapid succession
• Symptoms are primarily motor, and difficult for the patient to control

• Treatment
– reduce antipsychotic dose/change drug
– antimuscarinics are not very effective
– ? Use of propranolol or benzodiazepine

Question 13

Neuroleptic induced parkinsonism side effect management

Answer 13

Neuroleptic induced parkinsonism

• Muscle stiffness
– ‘lead pipe’ or ‘cogwheel’
• shuffling gait
• stooped posture
• drooling
• ‘mask-like’ face, perioral tremor
• coarse tremor

Treatment
– Rx antimuscarinics at lowest effective dose
– withdraw after 4-6 weeks
• tolerance to this SE can develop
• 50% of patients might need ongoing antimuscarinic Rx
– Can persist for 2/52 to 3/12 after withdrawal of antipsychotics

Question 14

Neuroleptic Malignant Syndrome

Answer 14

• Rare but can be fatal (1 in 10 die) - rapid changes in dopamine blockade
• Watch out for rigidity, hyperthermia, tachycardia, sweating, fluctuating
consciousness, raised CK (creatinine kinase)
• STOP antipsychotic and initiate specialist treatment

Usually when dose titrated up too much
Dehydrated
Organic brain disease
Alcoholism
Hyperthyroidism

• Mood and behaviour
– muscular rigidity
– dystonia
– agitation
– akinesia
– mutism
– changes in level of
consciousness

• Autonomic effects
– hyperpyrexia (usually
over 38C)
– sweating
– pallor
– tachycardia, BP
fluctuations
– incontinence of urine

• Lab Results
– Raised white blood cell counts
– Raised serum creatinine phosphokinase
– Raised serum myoglobin

Question 15

Management of NMS

Answer 15

• Discontinue ALL antipsychotics
– Other drugs which might be implicated include
• Antidepressants
• Lithium
• Antiepileptics

– Benzodiazepines are not associated with NMS
• A suitable drug of this class may be used for seizure prophylaxis, management of agitation until the syndrome abates

• Refer to Physician
• medical support measures
– possible Rx of iv dantrolene (muscle relaxant) or oral bromocriptine (DA
agonist)
– treat for 5-10 days as appropriate

Question 16

Antipsychotic counselling

Answer 16

Antipsychotic Counselling
• Starting treatment what to expect
• How to take
• How long to start working?
• Don’t just stop – and why?
• Risk of relapse upon discontinuation
• Possible side effect and what to do if they occur
• Signposting – for information

Question 17

Which one of the following is not
an atypical antipsychotic?
• Quetiapine
• Risperidone
• Promethazine
• Amisulpride

Answer 17

Promethazine

Question 18

Which of the following is not a side effect of antipsychotics?
• Acute dystonia
• Parkinsonism
• Tardive dyskinesia
• Hypersalivation
• Hypertension

Answer 18

Hypertension

Question 19

Which of the following is NOT a side effect of
Clozapine?
• Constipation
• Bradycardia
• Agranulocytosis
• Weight gain
• Hypersalivation

Answer 19

Bradycardia

Question 20

An 84-year-old lady has become aggressive on the ward after being
admitted with a UTI . She has type 2 diabetes and angina. She is
becoming a danger to herself and other staff, so a decision is made
to start a drug to calm her down. She had a slight prolonged QT
interval on admission .
Which of the following drugs should be avoided
– Diazepam
– Haloperidol
– Lorazepam
– Propofol
– Zopiclone

Answer 20

Haloperidol

Question 21

What is rapid tranquillisation?

Answer 21

WHAT IS RAPID TRANQUILLISATION (RT)?
▪ The use of medication to control acutely disturbed or violent behaviour in in-patients in an emergency situation.
▪ NICE Guideline NG10 Violence and Aggression May 2015 defines IM medication as RT (treatment);
▪ Oral medication is part of de-escalation (prevention)

Question 22

What drugs are used in rapid tranquillisation?

Answer 22

WHAT DRUGS ARE USED?
lorazepam - benzodiazepine
midazolam - benzodiazepine
quetiapine - antipsychotic
olanzapine - antipsychotic
haloperidol - antipsychotic
promethazine - antihistamine

Question 23

What is used to reverse too much benzodiazepine when used in rapid tranquillisation?

Answer 23

flumazenil

Question 24

Antipsychotic rapid tranquillisation effects

Answer 24

ANTIPSYCHOTICS– RT EFFECTS
▪ Block postsynaptic D2 receptors
▪ Antipsychotic effect
▪ State of apathy and reduced arousal
▪ Slowed thinking and movement
▪ Reduce aggressive tendencies

Question 25

Antihistamine use in rapid tranquillisation

Answer 25

▪ Can be used in RT to produce sedation
▪ Don’t have as many of the side effects and risks associated with antipsychotics
▪ eg promethazine (oral or IM)
MONITOR LEVEL OF CONSCIOUSNESS

Question 26

Benzodiazepine use in rapid tranquillisation

Answer 26

BENZODIAZEPINES
▪ Reduction in anxiety and aggression
▪ Sedation and induction of sleep
▪ Reduction of muscle tone
▪ Few side effects
▪ Lorazepam most often used
Can be given IM or orally

Question 27

Flumazenil

Answer 27

FLUMAZENIL
▪ Binds competitively to GABA receptor
▪ Reverses effects of benzodiazepines
▪ Used in acute toxicity
▪ Must be given IV
▪ Duration only 2h

Question 28

NICE guidance for rapid tranquillisation

Answer 28

WHICH DRUG?
Evidence of cardiovascular disease, including a prolonged QT interval, or no electrocardiogram has been carried out use intramuscular lorazepam instead.

Partial response to intramuscular lorazepam or haloperidol /
promethazine , consider a further dose.

No response to intramuscular lorazepam, consider intramuscular
haloperidol combined with intramuscular promethazine and vice
versa

If frail/ elderly/ long qt or dementia use benzodiazepines

Question 29

Common SSRI’s.

Answer 29

fluoxetine, citalopram, sertraline, paroxetine, and escitalopram

Question 30

Types of SNRI’s

Answer 30

venlafaxine and duloxetine

Question 31

Side effects of SSRI’s

Answer 31

Side effects
Common side effects of SSRI’s include:
o Blurred vision
o Nausea, vomiting or diarrhoea
o Dizziness
o Agitation, shaking, anxiousness
o Sexual problems: loss of libido, difficulty
reaching orgasm or inability to maintain an erection
o Excessive sweating and dry mouth
o Loss of appetite and weight loss
o Insomnia
o Drowsiness
o Suicidal thoughts

Question 32

Uses of SSRI’s

Answer 32

Uses
Commonly prescribed antidepressant.
Mainly prescribed to treat depression often in combination with
cognitive behavioural therapy (CBT)

Also used to treat other mental health conditions such as:
o Generalised anxiety disorder (GAD)
o Obsessive compulsive disorder (OCD)
o Panic disorder
o Phobias (agoraphobia, social phobia)
o Bulimia
o Post traumatic stress disorder (PTSD)

Sometimes prescribed to treat other conditions such as
premenstrual syndrome (PMS), irritable bowel syndrome (IBS),
fibromyalgia and occasionally for pain.

Question 33

Mechanism of action of SSRI’s

Answer 33

Mechanism of action
Selective serotonin reuptake inhibitors selectively inhibit the presynaptic reuptake of the monoamine neurotransmitter serotonin (5- hydroxytryptamine).

This increases the concentration of serotonin remaining in the synaptic cleft, allowing prolonged stimulation of post synaptic
receptors.

Question 34

Serotonin syndrome

Answer 34

Serotonin syndrome
Uncommon but serious side effects associated with the use of SSRI’s when levels of serotonin in the brain become too high.

Symptoms include:
o Confusion
o Shivering
o Diarrhoea
o Muscle twitching
o Agitation
o Sweating

Question 35

SSRI’s used to treat depression in under 18’s

Answer 35

Fluoxetine

Question 36

Anxiety disorder
1st line
2nd line
3rd line

Answer 36

1st LINE:
SSRIs e.g. Sertraline, escitalopram, fluoxetine - work by increasing serotonin in the brain
Sertraline is used most commonly due to it being the most cost effective and is prescribed as follows:
- 25mg daily for 1week
- Increase to 50mg daily
- Increase by 50mg per week as required up to 200mg

If the first SSRI taken is not suitable/ no improvement after 12 weeks another SSRI may be commenced

2nd LINE:
SNRIs e.g. duloxetine, venlafaxine - work by increasing serotonin AND NORADRENALINE in the brain

Similar side effects to SSRIs except BP.
SNRIs can increase BP - regular monitoring required

Duloxetine prescribing for anxiety:
- 30mg daily for 1 week
- Can be increased to 60mg once a day if required

Venlafaxine prescribing for anxiety:
- 75mg daily initially
- May be gradually increased as required up to 375mg

Contraindications:
Last month of pregnancy, bleeding disorders, cardiac disease, elderly, history of mania, hypertension, seizures,

Alternatives:
Pregabalin - anticonvulsant mainly used to treat epilepsy. Especially useful for treating GAD-related sleep disturbances

Side effects:
- Drowsiness
- Dizziness
- Increased appetite and weight gain
- Blurred vision
- Headaches
- Dry mouth
- Vertigo

Contraindications:
Respiratory compromise, renal impairment, older than 65 years, taking other CNS depressants, history of substance abuse, severe congestive heart failure

Benzodiazepines - SHORT TERM ONLY (2-4 weeks max) for periods of increased anxiety.
Benzos are a type of sedative known to ease anxiety symptoms within 30-90 minutes of consumption. HIGHLY ADDICTIVE

Side effects:
- Drowsiness
- Decreased concentration
- Headache
- Vertigo
- Tremor
- Decreased sex drive

Question 37

Several months of episodes of not being able to breathe, accompanied by dizziness, palpitations and chest tightness.
What could potential diagnosis be?

Answer 37

Cognition/ Situational
• Anxiety disorder
• Substance abuse
• Drug / alcohol withdrawal
• Depression
• Specific phobia
• PTSD

Cardiorespiratory, Endocrine
• Arrhythmia
• Postural hypotension
• Asthma attack
• Hyperthyroidism
• Goitre /thyroid eye disease/ family history
• Phaeochromocytoma
• Headache
• Hypoglycaemia
• Low BMI / Eating disorder

Question 38

1) A14yearoldgirlisdiagnosedwithAnorexiaNervosa.Herparents presented due to noticing her restricting her dietary intake. She has lost 5kg in weight. What is the most appropriate first-line therapy?
1) Fluoxetine
2) Individual CBT
3) Family-based therapy
4) Sertraline
5) Group CBT

Answer 38

ANSWER – FAMILY-BASED THERAPY
For adults with anorexia nervosa, NICE recommend one of:
• Individual eating-disorder-focused cognitive behavioural therapy (CBT-ED)
• Maudsley Anorexia Nervosa Treatment for Adults (MANTRA)
• Specialist supportive clinical management (SSCM).

In children and young people, NICE recommend ‘anorexia focused family therapy’ as the first-line treatment. The second-line treatment is cognitive behavioural therapy.
The prognosis of patients with anorexia nervosa remains poor. Up to 10% of patients will eventually die because of the disorder.

Question 39

2) A 35 year old woman presents with tearfulness and low mood. Her 6 year old daughter died 1 month ago following a boating accident. She has been unable to sleep and reports seeing/speaking to her daughter despite knowing she is not there. Which of the following is she most likely to be suffering from?
1) Anxiety
2) Cyclothymia
3) Normal grief reaction
4) Severe depression
5) Psychosis

Answer 39

ANSWER – NORMAL GRIEF REACTION
• It can be difficult to distinguish between depression and a normal grief reaction.
• After a major loss, a normal grief reaction can last up to 6 months.
• Grief tends to be divided into 5 stages: 1 – Denial, 2 – Anger, 3 – Bargaining, 4 - Depression, 5 – Acceptance, but many people will not go through all 5 stages.

Question 40

3) A 23 year old woman is diagnosed with Generalised Anxiety Disorder. She was started on Sertraline 6 months ago and has not felt any significant improvement in her symptoms. She would like to try an alternative medication. Which of the below would be the best option for her?
1) Propranolol
2) Stay on Sertraline for another 6 months
3) Mirtazapine
4) Venlafaxine
5) Haloperidol

Answer 40

ANSWER - VENLAFAXINE
• The patient has tried a selective serotonin reuptake inhibitor (SSRI), sertraline, which is first-line treatment that has not been effective for her.
• Second-line options for generalised anxiety disorder (GAD) include a different SSRI, such as paroxetine or escitalopram or a selective serotonin-noradrenaline reuptake inhibitor (SNRI), such as duloxetine or venlafaxine.

Question 41

4) A 62-year-old man is involved in a road traffic collision. Ten days after the incident, he reports repeated flashbacks, difficulty sleeping and nightmares. What is the most likely diagnosis?
1) Panic disorder
2) Generalised anxiety disorder
3) Acute stress reaction
4) Depression
5) Post traumatic stress disorder (PTSD)

Answer 41

ANSWER – ACUTE STRESS REACTION
• Acute stress disorder is defined as an acute stress reaction that occurs in the 4 weeks after a traumatic event.
• PTSD is diagnosed after 4 weeks.

• Management
• Trauma-focused CBT is first-line
• Benzodiazepines
• Sometimes used for acute symptoms such as agitation, sleep disturbance
• Should only be used with caution due to potential addiction

Question 42

5) A 35 year old woman attends her GP with a 2 month history of low mood and lack of interest in her usual activities – this is happening most days. She also expresses feelings of worthlessness and poor sleep. She has tried adjusting lifestyle factors, but has not noticed any improvement. She tells you that she has had success with antidepressant medication in the past, and expresses a strong preference for this. What is the most appropriate treatment to offer?
1) Counselling
2) Individual CBT
3) Guided self-help
4) Antidepressant medication
5) Group CBT

Answer 42

ANSWER – ANTIDEPRESSANT MEDICATION
• Depression diagnosis and treatment is divided into ‘less severe’ and ‘more severe’, based on PHQ-9 score.
• PHQ-9 <16 = Less Severe, PHQ-9 >16 = More Severe
• Although NICE recommend guided self-help as the first line intervention for less severe depression, in this scenario, the patient’s preference should be taken into account.