Chapter 4 - Central Nervous System Flashcards
What are the three main classes of antidepressants?
- Tricyclic antidepressants (TCAs)
- Monoamine oxidase inhibitors (MAOIs)
- Selective serotonin re-uptake inhibitors (SSRIs)
How long is it thought to take for an antidepressant to exert its therapeutic effect?
2 weeks
Which two criteria are used in the diagnosis of depression?
ICD-10 (international classification of diseases)
DSM-4 (Diagnostic and statistical manual of mental disorders) NICE guidelines uses this diagnostic criteria
Depression can be caused by psychological, genetic and biological factors. What are the likely ‘biological candidates’ which have shown to play a part in depression?
Cortisol and Monoamines
monoamine hypothesis proposes a functional deficit of monoamine transmission in
the central nervous system, involving deficits of the neurotransmitters noradrenaline, serotonin (5-HT) and dopamine in the synaptic cleft.
Depression is thought to cause higher cortisol levels
Which drugs may contribute to ‘drug induced depression’?
Isotretinoin
Montelukast
Systemic corticosteroids
Levodopa
What important counselling point should you give to patients starting mirtazepine?
Mirtazepine may cause blood disorders - patients are advised to report any sore throat, fever or other signs of infections
What role do benzodiazepines have in the treatment of mania?
Useful in the initial stages of treatment for behavioural disturbance or agitation. Long periods aren’t used because of the risk of dependence
What treatment options are available for the long term treatment of bipolar disease?
Antipsychotics (e.g olanzapine)
Lithium
Valproate or Lamotrigine
Which antipsychotic drugs are generally used in the treatment of acute episodes of mania?
Olazanpine, quetiapine and risperidone
How long does it generally take for the full prophylactic effect of lithium to occur for the treatment of bipolar disease?
6-12 months
What major side effects are associated with lithium use?
- Hypo or hyperthyroidism- lithium increases intrathyroidal iodine content, inhibits the coupling of iodotyrosine residues to form iodothyronines (thyroxine [T4] and triiodothyronine [T3]), and inhibits release of T4 and T3
- renal dysfunction
- lithium toxicity
When should samples be taken to check lithium levels?
12 hours after the dose, 7 days after initiation
What should optimum serum lithium levels be?
0.4-1mmol/L
What specific advice should patients/carers be given for someone initiated on lithium?
Report signs/symptoms of:
- lithium toxicity
- hypothyroidism
- renal dysfunction (polyuria, polydipsia (excessive thirst))
- benign intercranial hypertension (persistent headache, visual disturbances)
Attend all routine blood tests
Can different preparations of lithium be used interchangeably?
No, preparations vary in bioavailability. Changing preparations requires the same precautions as initiation of treatment
Which antidepressant is safe to be used in a patient who has unstable angina or had a recent myocardial infarction?
Sertraline
Which class is the most ‘efficacious’ antidepressant?
None, all have similar efficacy to each other. The side-effect profile and patient factors determines choice.
Which electrolyte imbalance is commonly associated with antidepressant use?
Hyponatraemia - particularly with SSRIs
What is the MOA of TCAs?
Block the re-uptake of serotonin and noadrenaline by blocking the re-uptake channels. They als adversely block muscarinc and histamine receptors which accounts for their increased side effect profile in comparison to SSRIs.
TCAs can be roughly dicided into sedating and less sedating properties. Which TCAs have sedative properties?
Amitriptyline Clomipramine Dosulepin Doxepin Mianserin Trimipramine
Which TCAs are less sedative?
Imipramine
Lofepramine
Nortriptyline
Which two TCAs are NOT recommended for the treatment of depression?
Amitriptyline and dosulepin - particularly dangerous in overdose
Which TCA has more marked antimuscarinic effects?
Imipramine
Which TCA is less dangerous in overdose and has a lower incidence of side effects?
Lofepramine
True or False: TCAs have a long half-life
True - which is why it allows for once daily administration usually given at night
Are tricyclics effective in treating depression in children?
Studies have shown that they aren’t effective in treating depression in children
Why are MAOIs not generally used unless started under a specialist for the treatment of depression?
Have dangerous drug and food interactions
What is the MOA of MAOIs?
Block the monoamine oxidase enzyme which functions to breakdown serotonin and noradrenaline when they have been re-uptaken back into the Pre-synaptic neurones to be repackaged.
There are two subtypes of Monoamine oxidases
Which drugs belong to the MAOIs?
Phenelzine
Tranylcypromine
Isocarboxazid
Moclobemide
Citalopram and Escitalopram are contra-indicated in patients with what?
QT-interval prolongation - both can cause QT-prolongation as a side-effect
What are the first generation antipsychotics?
Phenothiazines: ‘azine’s’
Chlorpromazine, levopromazine, promazine, pericyazine, fluphenazine, perphenazine, prochlorperazine and trifluoperazine
Butyrophenones: ‘peridol’s’
Haloperidol
Benperidol
Thioxanthenes: ‘thixol’s’
Flupentixol
Zuclopenthixol
Others:
Supiride
Pimozide
What is the MOA of first gen antipsychotics?
D2 receptor antagonists
What side-effects are most associated with first gen antipsychotics?
Extrapyramidal side-effects
Antimuscarinic side-effects
elevated prolactin
What are the second generation antipsychotics?
Amisulpride Aripiprazole Clozapine Olanzapine Lurasidone Paliperidone Quetiapine Risperidone
What do EPSE consist of?
Parkinsonism symptoms
Dystonia (abnormal face and body movements)
Dyskinesia
Akathesia (restlessness)
Tardive dyskinesia (rhythmic involuntary movements of tongue, face and jaw - may be irreversible)
How may Parkinsonism symptoms be suppressed?
Administration of an antimuscarinic drug
Which antipsychotics are most likely to cause symptomatic hyperprolactinaemia?
First gen +
of the 2nd gen:
Risperidone (RISE-PAIRidone - give RISE to a PAIR of breasts)
Amisulpride
Which antipsychotic is the only one which reduces prolactin?
Aripiprazole - because it’s a partial dopamine-receptor agonist
Which two antipsychotics are most commonly associated with sexual dysfunction?
Haloperidol and risperidone
Which two antipsychotics have a particular concern with QT-interval prolongation?
Pimozide and haloperidol
Which antipsychotics have been associated with hyperglycaemia the most?
2nd gen: Clozapine Olanzapine Quetiapine Risperidone
Which two antipsychotics commonly cause weight gain?
Clozapine and olanzapine
Which potentially life-threatening side-effect as a result of antipsychotic use, is reason for the immediate discontinuation of the drug?
Neuroleptic malignant syndrome (NMS)
Which antipsychotics are better at treating the negative symptoms of schizophrenia?
2nd generation are thought to be better
Which antipsychotic has neglible effect on QT-interval?
Aripiprazole
When is clozapine initiated?
Failure with two or more antispsychotic drugs (one of which should be a 2nd gen) each tried for at least 6-8 weeks
What serious side-effects are associated with clozapine use?
Agranulocytosis
Myocarditis and cardiomyopathy
Intestinal obstruction
Non-opioid drugs are suitable for what types of pain?
Musculoskeletal pain
e.g paracetamol, aspirin, NSAIDs
Opioid drugs are useful for what types of pain?
Moderate to severe pain or visceral (relating to the nervous system) origin
What types of pain relief is effective in dental pain?
Non-opioid pain relief e.g paracetamol, NSAIDs are effective for temporary relief (usually for 1-7 days) until causative factor has become under control
Opioid pain relief is generally ineffective in dental causes
oral muscosal related pain may be relieved by the use of benzydamine hydrocholoride mouthwash or spray
What is the MOA of benzydamine?
Anti-inflammatory, non-opioid analagesic.
mostly exerts its effects through inhibition of the synthesis of proinflammatory cytokines including tumour necrosis factor-alpha (TNF-α) and Interleukin-1β (IL-1β) without significantly affecting other pro-inflammatory (IL-6 and 8) or anti-inflammatory cytokines (IL-10, IL-1 receptor antagonist).
What kind of pain is nefopam indicated for?
Moderate pain
What types of people is nefopam contra-indicated in?
patients with convulsive disorders (may lower seizure threshold); patients who have had an MI
Is nefopam an opioid or non-opioid analagesic?
Non-opioid, centrally acting analgesic
Potent analgesic - has not been found to cause respiratory depression unlike the opioid analgesics
What kinds of pain are NSAIDs useful in?
Chronic disease pain associated with inflammation ; dysmenorrhoea; treat pain caused by secondary bone tumours, many of which produce lysis of bone and release prostaglandins.
Which strong opioid is the standard against which all other opioids are measured?
Morphine
In addition to relief of pain, how else does morphine exert CNS effects?
- Nausea and vomiting
- euphoria
- mental detachment
Which opioid is the choice of treatment of severe pain in palliative care?
Morphine
Does buprenorphine have a longer or shorter duration of action than morphine?
Longer: 6-8 hours
Effects of morphine can be reversed in overdose with the use of which drug?
Naloxone
Is dipipanone more or less sedating than morphine?
Less sedating, but the only preparation available contains an antiemetic, therefore not suitable for regular pain regimens in palliative care
Why is diamorphine the preferred option in palliative care?
Greater solubility allows for effective doses to be given at smaller volumes. This is especially useful in emaciated patients (those who are very frail and thin)
Oxycodone is used primarily for?
Control of pain in palliative care. Preferred option in patients with impaired renal function as it is safer than morphine in these patients
What is the MOA of tramadol?
produces analgesia by two mechanisms: an opioid effect and an enhancement of serotonergic and adrenergic pathways.
Weak opioids such as codeine or dihydrocodeine are useful in treating what type of pain?
Mild to moderate pain where the use of paracetamol/NSAIDs have not been effective
Meptazinol is an opioid or non-opioid analagesic?
Weak opioid analgesic
Why should opioid analgesics be avoided in patients with head injuries or raised intracranial pressure?
Opioids due to their CNS effects, interfere with pupillary reponse which is essential for neurological assessment
What common side-effects are associated with opioids?
constipation nausea pruritis drowsiness euphoria hallucinations hypotension (with large doses)
What side-effects of opioids with long term use/higher doses are of more concern?
Hypogonadism and adrenal insufficiency - long term use; can affect both males and females.
Hyperalgesia - state where prolonged use has resulted in sensitisation. aTx involves reducing the opioid dose and switching therapy
Respiratory depression - major concern. Tx with naloxone and artificial ventiliation should be commenced
Codeine should not be used in children under what age and why?
< 12yo
Associated with a risk of respiratory side-effects
Who is codeine contra-indicated in?
- children < 12yo
- breastfeeding mothers
- ultra metabolisers of CYP2D6 enzyme
What does codeine get metabolised to?
Morphine - degree to which codeine can be metabolised to codeine varies considerably
True or False: People of African descent in comparison to Caucasian decent have more prevalence of ultra-rapid metabolisers of the CYP2D6 enzyme
True - hence more care should be taken when prescribing codeine in patients of African descent.
How is neuropathic pain managed?
Tricyclic antidepressants or with certain antiepileptic drugs
Is amitriptyline licensed for the treatment of neuropathic pain?
No, unlicensed use
Which anti-epileptics are commonly used for the treatment of neuropathic pain?
pregabalin and gabapentin
What drug is licensed and is effective for the treatment of trigeminal neuralgia?
Carbamazepine
