Psychiatry

Question 1

What is Chlorpromazine and when is it used?

Answer 1

• It is a phenothiazine and a Typical antipsychotic used in Schizophrenia and other psychoses
• Short-term adjunctive management of severe anxiety
• Psychomotor agitation, excitement, and violent or dangerously impulsive behaviour
• Nausea and vomiting in palliative care (where other drugs have failed
• intractable hiccups

Question 2

What are Typical antipsychotics?

Answer 2

• Haloperidol
• Chlorpromazine

Question 3

What is the mechanism of Chlorpromazine Hydrochloride?

Answer 3

• antagonist (blocking agent) on different postsynaptic receptors
  
  • on dopaminergic receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties and anti-emetic properties
  • on serotonergic-receptors (5-HT1 and 5-HT2 on productive and unproductive symptoms)

Question 4

What are the different routes of Chlorpromazine Hydrochloride?

What are the dose equivalents?

Answer 4

• 100 mg chlorpromazine base given rectally as a suppository ≡
• 20–25 mg chlorpromazine hydrochloride by intramuscular injection ≡
• 40–50 mg of chlorpromazine base or hydrochloride given by mouth.

Question 5

What is important to note when prescribing antipsychotics in emergencies?

Answer 5

• An intramuscular dose should be lower than the corresponding oral dose → absence of first-pass effect
• This is more true in active patients as increased muscle blood flow → enhanced rate of absorption
• Prescriptions should specify the dose for each route and shout not imply that the same dose can be given by mouth or by IM
• doses of antipsychotic drugs for emergencies should be reviewed at least daily

Question 6

What are antipsychotic drugs used for?

Answer 6

• used in the sort term to calm disturbed patients whatever the underlying psychopathology (Scz, brian damage, mania, toxic delirium, agitated depression)
• can be used to alleviate severe anxiety in the short-term

Question 7

What are the effects of antipsychotics on Schizophrenia?

Answer 7

• relieve positive psychotic symptoms (thought disorder, hallucinations, and delusions), they prevent relapse
• they are less effective on negative psychotic symptoms e.g apathy and social withdrawal
  
  • may persist between episodes of treated positive symptoms
  • early treatment can protect against the development of negative symptoms over time
• Patients with acute Scz respond better than patients with chronic Scz

Question 8

How do First-generation antipsychotics work?

Answer 8

• They fall within three main deritivae groups of Phenothiazine
• They block Dopamine D2 receptors in the brain
• They are not selective of the four main dopamine pathways in the brain, therefore, are likely to cause a range of extra-pyramidal symptoms and elevated prolactin

Question 9

What are drugs in First-generation (Typical) Antipsychotics Phenothiazine Group 1 derivatives?

How are they characterized?

Answer 9

Chlorpromazine Hydrochloride, levomepromazine, and Promazine hydrochloride,

Generally characterised by pronounced sedative effects and moderate antimuscarinic and extrapyramidal side effects.

Question 10

What are drugs in First-generation (Typical) Antipsychotics Phenothiazine Group 3 derivatives?

How are they characterized?

Answer 10

Fluphenazine decanoate, perphenazine, prochlorperazine, and trifluoperazine

Generally characterised by fewer sedative and antimuscarinic effects but more pronounced extrapyramidal side effects than group 1 and 2.

(Haloperidol and Benperidol resemble this group in their clinical properties)

Question 11

What are drugs in First-generation (Typical) Antipsychotics Phenothiazine Group 2 derivatives?

How are they characterized?

Answer 11

Pericyazine

Generally characterised by moderate sedative effects and fewer extrapyramidal side effects than group 1 or 3

Question 12

What is Olanzapine and when is it used?

Answer 12

• A second generation (atypical) antipsychotic used to treat
  
  • Psychosis
  • Mania
  • and used as a Mood Stabiliser

Question 13

What is the mechanism of action of Olanzapine?

Answer 13

• antagonism of dopamine D1, D2, D3, D4, D5;
• serotonin 5HT2A/2C,
• 5HT3,
• 5HT6;
• cholinergic muscarinic receptors M1-M5;
• α1 adrenergic; and
• histamine H1 receptors.

Question 14

What are adverse drug reactions when taking antipsychotics?

Answer 14

• Extrapyramidal symptoms
• Parkinsonian Symptoms
• Dystonia
• Akathisia
• Tardive dyskinesia
• Hyperprolactinemia
• Sexual dysfunction
• Cardiovascular side effects
• Hyperglycaemia and weight gain
• Hypotension and interference with temperature regulation
• Neuroleptic malignant syndrome (most syndrome)
• Blood dyscrasias

Question 15

What is Neuroleptic Malignant Syndrome?

Answer 15

an adverse drug reaction that occurs when taking antipsychotics (dopamine antagonists). can occasionally occur in abrupt withdrawal of dopamine agonists (levodopa)

Question 16

What are the symptoms of Neuroleptic Malignant Syndrome?

Management?

Answer 16

• Hyperthermia
• Fluctuating levels of consciousness
• Muscle rigidity
• Autonomic dysfunction with → parlour, tachycardia, labile BP, sweating and urinary incontinence

→ discontinuation of antipsychotics medication, symptoms may persist at least 5 to 7 days after discounituation

Question 17

Explain the relation between antipsychotics and sexual dysfunction

Answer 17

• One of the main causes of non-adherence of anti-psychotic medication along with physical illness, psychiatric illnesses, and substance misuse
• Risperidone and Haloperidol commonly cause sexual dysfunction
• Caused by:
  
  • redecude DA transmission, hyperprolacteniam → decrease in libido
  • antimuscirnic effects → disorders in aurosal
  • alpha1-adrenorecptor antagonsits → erection and ejaculation problems in men

Question 18

What monitoring is required on Antipsychotic medication

Answer 18

• Full blood count, Urea and electrolytes, Liver function is needed at initiation and then annually.
• Blood lipid & Weight is measured at baseline, 3-months, then yearly.
• Fasting blood glucose should be measured at baseline, 4-6 monthly then yearly.
• Before initiating antipsychotics, an ECG may be required, especially if cardiovascular risk factors exist.
• Blood pressure monitoring is advised before initiating therapy and then frequently after.

Question 19

What are the risks of anti-psychotics in the elderly?

Answer 19

In elderly patients with dementia, antipsychotic drugs are associated with a small increased risk of mortality and an increased risk of stroke or transient ischaemic attack.

Furthermore, elderly patients are particularly susceptible to postural hypotension and to hyper- and hypothermia in hot or cold weather.

Question 20

What are three recommendations when prescribing anti-psychotics in elderly patients?

Answer 20

1. Antipsychotic drugs should not be used in elderly patients to treat mild to moderate psychotic symptoms.
2. Initial doses of antipsychotic drugs in elderly patients should be reduced (to half the adult dose or less), considering patient’s weight, co-morbidity, and concomitant medication.
3. Treatment should be reviewed regularly.

Question 21

What are recommendations when prescribing antipsychotics to patients with learning disabilities?

Answer 21

1. Dose reduction or discontinuation of long-term antipsychotic treatment;
2. Review of the patient’s condition after dose reduction or discontinuation of an antipsychotic drug;
3. Referral to a psychiatrist experienced in working with patients who have learning disabilities and mental health problems;
4. Annual documentation of the reasons for continuing a prescription if the antipsychotic is not reduced in dose or discontinued.

Question 22

Blockades of Dopamin D2 receptors leads to which main side effect?

Answer 22

Extrapyramidal symptoms

Question 23

Blockades of Dopamin D2 receptors leads to which main side effect?

Answer 23

Drowsiness

Question 24

Blockades of Seritiergic receptors leads to which main side effect?

Answer 24

Hypotension and interference with temperature regulation

Question 25

Blockades of Alpha-adrenergic receptors leads to which main side effect?

Answer 25

Nasal congestion, erection and ejaculation problems in men

Question 26

Blockades of Chloinergic receptors leads to which main side effect?

Answer 26

Antimuscuricin symptoms: *altered levels of consciousness, seizures, sinus tachycardia, hypertension, hyperthermia, urinary disorders, N&V*

Question 27

What are the pharmacological properties of Chlorpromazine Hydrochloride?

Answer 27

is readily absorbed in the gastro-intestinal tract, is subject to first pass metabolism, is extensively metabolised in the liver and excreted in the urine and faeces. The plasma half-life is only a few hours but it has a prolonged terminal elimination phase of up to about 3 weeks. Chlorpromazine is extensively bound to plasma proteins.

Question 28

What are the pharmacodynamic properties of Chlorpromorphine Hydrochlodride?

Answer 28

Chlorpromazine has depressant actions on the Central Nervous System, with **alpha-adrenergic blocking** and **anticholinergic** activities. It **inhibits Dopamine** and Prolactin release-inhibitory factor, thus stimulating the release of **Prolactin**. It increases the turnover of Dopamine in the brain. It has anti-emetic, anti-pruritic, serotonin-blocking and weak anti-histamine properties and slight ganglion blocking activity. It inhibits the heat regulating centre in the brain, and is analgesic and can relax skeletal muscle. Due to its action on the autonomic system it produces vasodilation, hypotension and tachycardia. Salivary and gastric secretions are reduced.

Question 29

What are Extrapytimadal symptoms?

Answer 29

Parkinisonian Symptoms Tardive Dyskinesia Dystonia Akathisia

Question 30

What are Parkinsonian Symptoms? how could it be managed?

Answer 30

* Tremor, Rigidity, Slowness of movement, Poor balance and coordination, Speech difficulty Managed by → withdrawing offending drug, suppressed by anticholinergic or antimuscarinics → anticholinergics not advised as they can worsen tardive dyskinesia

Question 31

What is Dystonia and when does it occur?

Answer 31

abnormal face and body movements - it appears after a few doses of antipsychotics

Question 32

What is Akathisia and when does it occur?

Answer 32

Restlessness - occurs after large initial doses of antipscyhotic and may resemble an exacerbation of the condition being treated; so easy to miss

Question 33

What is Tardive Dyskinesia and when does it occur?

Answer 33

* Rhythmic, involuntary movements of tongue, face, and jaw * It develops on **long-term** therapy or with **high** dosage, (but also on short-term treatment with low doses) * Short-lived tardive dyskinesia may occur after withdrawal of the drug. * Most serious as it may be irreversible once withdrawing therapy and treatment for Td is usually ineffective * In children TD is more likely to occur when therapy is withdrawn

Question 34

What is the effect of all antipsychotics on prolactin?

Answer 34

* Most antipsychotic drugs, (1^st & 2^nd gen), increase prolactin concentration because dopamine inhibits prolactin release. * Risperidone, amisulpride, and 1^stgen antipsychotics are most likely to cause symptomatic **hyperprolactinaemia**. * Aripiprazole (2^nd gen) a dopamine-receptor partial agonist reduces prolactin. * The **clinical symptoms** of hyperprolactinaemia include sexual dysfunction, reduced bone mineral density, menstrual disturbances, breast enlargement, and galactorrhoea.

Question 35

What foods should those on Monamine Oxidase inhibitors (tranylcypromine, phenelzine) be advised to avoid?

Answer 35

Chees and foods high in or containing tyramine → this can lead to a hypertensive crisis

Question 36

What are the guidelines of using SSRIs in pregnancy?

Answer 36

- BNF says to weigh up benefits and risk when deciding whether to use in pregnancy. - Use during the first trimester gives a small increased risk of congenital heart defects - Use during the third trimester can result in persistent pulmonary hypertension of the newborn - Paroxetine has an increased risk of congenital malformations, particularly in the first trimester

Question 37

What Medications should be avoided when taking SSRI's and why?

Answer 37

* Triptans: used in the treatment of sever migraines * Monoamine oxidase inhibitors: used to treat depression e.g *Rasagiline, Moclobemide, Phenelzine, Tranylcypromine* Both of these class of drugs cause Serotonin syndrome: _present with fever, confusion, seizures, renal and hepatic impairment, arrhythmia, increased muscle tone, and hypersecretion of sweat_

Question 38

What monitoring is required for Serotonin Noradrenaline reuptake inhibitors (SNRI's) and why?

Answer 38

* Blood pressure - due to risk of developing hypertension * blood pressure should be measured at baseline and at each dose titration e.g *veneflaxine*

Question 39

What is the BNF guidelines/ withdrawal protocol for benzodiazepines

Answer 39

The dose should be withdrawn in steps of about 1/8 (range 1/10 to 1/4) of the daily dose every fortnight. A suggested protocol for patients experiencing difficulty is given: * switch patients to the equivalent dose of diazepam * reduce dose of diazepam every 2-3 weeks in steps of 2 or 2.5 mg * time needed for withdrawal can vary from 4 weeks to a year or more