Drugs Flashcards
Benzodiazepines
Benzodiazepines enhance the effect of the INHIBITORY neurotransmitter gamma-aminobutyric acid (GABA) by increasing the frequency of chloride channels. They therefore are used for a variety of purposes:
- sedation
- hypnotic
- anxiolytic
- anticonvulsant
- muscle relaxant
Patients commonly develop a tolerance and dependence to benzodiazepines and care should therefore be exercised on prescribing these drugs. The Committee on Safety of Medicines advises that benzodiazepines are only prescribed for a short period of time (2-4 weeks).
The BNF gives advice on how to withdraw a benzodiazepine. The dose should be withdrawn in steps of about 1/8 (range 1/10 to 1/4) of the daily dose every fortnight.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
If patients withdraw too quickly from benzodiazepines they may experience benzodiazepine withdrawal syndrome, a condition very similar to alcohol withdrawal syndrome. This may occur up to 3 weeks after stopping a long-acting drug. Features include: insomnia irritability anxiety tremor loss of appetite tinnitus perspiration perceptual disturbances seizures
Antipsychotics - mechanism
Act as D2 receptor antagonists, blocking dopaminergic transmission in the MESOLIMBIC pathways.
Antipsychotics - side effects
Typical antipsychotics are associated with Extrapyramidal side -effects (EPSEs):
- Parkinsonism
- acute dystonia: sustained muscle contraction (e.g.torticollis. oculogyric crisis),
- akathisia
- tardive dyskinsea (late onset of choreoathetoid movements, abnormal, involuntary, may occur in 40% of patients, may be irreversible, most common is chewing and pouting of jaw)
- EPSEs may be managed with PROCYCLINE
Specific warnings when antipsychotics are used in elderly patients:
- increased risk of STROKE
increased risk of venous thromboembolism -VTE
Other side-effects:
- antimuscarinic: dry mouth, blurred vision, urinary retention, constipation
- sedation, weight gain
- raised prolactin
- may result in galactorrhoea
- due to inhibition of the dopaminergic tuberoinfundibular pathway
- impaired glucose tolerance
- neuroleptic malignant syndrome: pyrexia, muscle stiffness
- reduced seizure threshold (greater with atypicals)
- prolonged QT interval (particularly haloperidol)
Zopiclone and the risk to elderly
Increases the risk of FALLS
Depression: switching antidepressants
Switching from citalopram, escitalopram, sertraline, or paroxetine to another SSRI:
- the first SSRI should be withdrawn (this means gradually reduce the dose then stop) before the alternative SSRI is started
Switching from fluoxetine to another SSRI:
- withdraw then leave a gap of 4-7 days (as it has a long half-life) before starting a low-dose of the alternative SSRI
Switching from a SSRI to a tricyclic antidepressant (TCA):
- cross-tapering is recommend (the current drug dose is reduced slowly, whilst the dose of the new drug is increased slowly)
- an exceptions is fluoxetine which should be withdrawn prior to TCAs being started
Switching from citalopram, escitalopram, sertraline, or paroxetine TO VENLAFAXINE
- cross-taper cautiously. Start venlafaxine 37.5 mg daily and increase very slowly
Switching from fluoxetine to venlafaxine
- withdraw and then start venlafaxine at 37.5 mg each day and increase very slowly
Side effects of Mirtazapine
- large increase in APPETITE (and subsequent weight gain)
- DROWNISNESS.
SSRIs and pregnancy?
- 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
What is Venlafaxine?
An antidepressant
Used in the treatment of major depression, anxiety and panic disorder
Mechanism of action of Venlafaxine
Serotonin and noradrenaline reuptake inhibitor (SNRI)
SNRI mode of action, examples and uses
Serotonin and noradrenaline reuptake inhibitor (SNRI’s) are a class of relatively new antidepressants. Inhibiting the reuptake increases the concentrations of serotonin and noradrenaline in the synaptic cleft leading to the effects.
Examples include venlafaxine and duloxetine.
They are used to treat major depressive disorders, generalised anxiety disorder, social anxiety disorder and panic disorder and menopausal symptoms.
What is clomipramine?
TCA
Common side effect of clozapine
Constipation/intestinal obstruction
Adverse effects of atypical antipsychotics?
- Weight gain
- Clozapine is associated with agranulocytosis
- hyperprolactinaemia
Examples of atypical antipsychotics
- clozapine
- olanzapine: higher risk of dyslipidemia and obesity
- risperidone
- quetiapine
- amisulpride
- aripiprazole: generally good side-effect profile, particularly for prolactin elevation
Adverse effects of clozapine
- agranulocytosis (1%), neutropaenia (3%)
- REDUCED SEIZURE THRESHOLD - can induce seizures in up to 3% of patients
- constipation
- myocarditis: a baseline ECG should be taken before starting treatment
- hypersalivation
SSRI adverse effects?
- GI symptoms - increased risk of GI bleeding. therefore PPI should be prescribed
- HYPOnatraemia
- patients should be counselled to be vigilant for increased anxiety and agitation after starting a SSRI
- Fluoxetine and paroxetine have a tiger propensity for drug interactions
SSRIs and interactions?
- NSAIDs: NICE guidelines advise ‘do not normally offer SSRIs’, but if given co-prescribe a proton pump inhibitor
- warfarin / heparin: NICE guidelines recommend avoiding SSRIs and considering mirtazapine
- aspirin
- triptans: avoid SSRIs as increased risk of serotonin syndrome
- monoamine oxidase inhibitors (MAOIs) - increased risk of serotonin syndrome
What is agranulocytosis a side effect of?
Clozapine
Agranulocytosis is the lowering of the white blood cell count, primarily neutrophils, as a consequence the abnormality found in the blood test results will be decreased leukocytes.
What is clozapine used in the treatment of?
Resistant schizophrenia
ECT therapy?
Short-term side-effects: - headache - nausea - short term memory impairment memory loss of events prior to ECT - cardiac arrhythmia
Long-term side-effects:
- some patients report impaired memory
Guidance on using hypnotics
- The hypnotics recommended for treating insomnia are short-acting BENZODIAZEPINES or NON-BENZODIAZEPINES (zopiclone, zolpidem and zaleplon).
- Diazepam is not recommended but can be useful if the insomnia is linked to daytime anxiety.
- Use the lowest effective dose for the shortest period possible.
- If there has been no response to the first hypnotic, doNOT prescribe another. You should make the patient aware that repeat prescriptions are not usually given.
- It is important to review after 2 weeks and consider referral for cognitive behavioural therapy (CBT).
What drugs can cause hyperprolactinaemia?
Risperidone
Amisulpride
What are the effects of hyperprolactinaemia?
Can involve:
- breast tenderness
- breast enlargement
- lactation
If risperidone is causing side effects - what could you change to?
Aripiprazole
its known for its having fewer side effects especially with respect to prolactin elevation
Which drug can be affected by smoking?
Clozapine - the dose may need to be changed if starting or stopping smoking
Mechanism of antipsychotics?
Dopamine antagonists
- so would cause hyPERprolacrinaemia as dopamine is a prolactin agonist
What is more likely to cause weight gain?
Atypical or typical antipsychotics?
Atypical
TCAs common side effects
- drowsiness
- dry mouth
- blurred vision
- constipation
- urinary retention
- lengthening of QT interval
Choice of tricyclic
- low-dose amitriptyline is commonly used in the management of neuropathic pain and the prophylaxis of headache (both tension and migraine)
- lofepramine has a lower incidence of toxicity in overdose
- amitriptyline and dosulepin (dothiepin) are considered the most dangerous in overdose
What are the more sedative TCAs
Amitriptyline
Clomipramine
Dosulepin
Trazodone*
What are the less sedative TCAs
Imipramine
Lofepramine
Nortriptyline
What can be used to treat moderate/severe tar dive dyskinesia?
Tetrabenazine
What class of drugs does amitriptyline fall into?
TCAs
What type of incontinence occurs in TCAs?
OVERFLOW incontinence
- TCAs have anticholinergic effects which may lead to urinary retention, leading to frequent leaking.
Serious side effects of clozapine
- Weight gain
- excessive salivation
- agranulocytosis
- neutropenia
- myocarditis
- arrhythmias
What do you do if clozapine doses are missed for 48 hours?
And why?
- RE-TITRATE the clozapine doses again slowly (will need to be restarted again slowly) - like when they first started on it
- you do this because when you start Clozapine after a break of >48 hours, it can make side effects worse, such as BP changes, drowsiness and dizziness.
If there is a gap in treatment of 3 days (72 hours) then you may also rewire more frequent blood tests for a short period
What is the choice of SSRI post MI?
Sertraline
What is the SSRI of choice in children and adolescents?
Fluoxetine
What is the mechanism of action of lithium
Its not fully understood
2 theories:
- interferes with inositol triphosphate formation
- interferes with cAMP formation
What are the adverse effects of lithium?
- nausea/vomiting, diarrhoea
- fine tremor
- nephrotoxicity: polyuria, secondary to nephrogenic diabetes insipidus
- thyroid enlargement, may lead to hypOthyroidism
- ECG: T wave flattening/inversion
- weight gain
- idiopathic intracranial hypertension
- leucocytosis
hyperparathyroidism and resultant hypercalcaemia
Monitoring of patients on lithium therapy
- inadequate monitoring of patients taking lithium is common - NICE and the National Patient Safety Agency (NPSA) have issued guidance to try and address this.
- after starting lithium levels should be performed WEEKLY and after each dose change until concentrations are STABLE
- once established, lithium blood level should ‘normally’ be checked every 3 months
- after a change in dose, lithium levels should be taken a week later and 12 hours after the last dose
- thyroid and renal function should be checked every 6 months
- patients should be issued with an information booklet, alert card and record book
Why would someone prescribe Mirtazapine? and what is this drug?
How does it work?
Antidepressant
- preserved due to its useful side effects
- its known to stimulate APPETITE
works by blocking alpa 2 adrenergic receptors
Mirtazapine has FEWER SIDE EFFECTS and interactions than many other antidepressants and so is useful in OLDER PEOPLE who may be affected more or be taking other medications. Two side effects of mirtazapine, SEDATION and an INCREASED APPETITE, can be beneficial in older people that are suffering from insomnia and poor appetite.
It is generally taken in the evening as it can be sedative.
Monoamine oxidase inhibitors - overview, examples of non -selective monoamine oxidase inhibitors, adverse effects
Overview
- serotonin and noradrenaline are metabolised by monoamine oxidase in the presynaptic cell
Non-selective monoamine oxidase inhibitors
- e.g. tranylcypromine, phenelzine
- used in the treatment of atypical depression (e.g. hyperphagia) and other psychiatric disorder
- not used frequently due to side-effects
Adverse effects of non-selective monoamine oxidase inhibitors
- hypertensive reactions with tyramine containing foods e.g. cheese, pickled herring, Bovril, Oxo, Marmite, broad beans
- anticholinergic effects (DRY)
What class of drugs is Amitriptyline? And effects from it ?
Tricyclic antidepressants
anticholinergic effects
- therefore associated with tachycardia, dry mouth, mydriasis and urinary retention.
What are the effect of SSRI on GI?
Increased incidence of GI bleeding
therefore give a PPI
How long do you have to gradually withdraw SSRI? And which one is not the same and why?
over a 4 week period
This not necessary with fluoxetine due to its longer half-life.
What is the risk of using SSRIs in the first trimester and third?
small increased chance 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
What is the use of SSRIs in the third trimester?
Risk of PULMONARY HYPERTENSION of the newborn
What is the first line treatment for delirium tremens?
Oral chlordiazepoxide
What class of drugs is Mirtazapine? How does it work?
- a noradrenergic and specific serotonergic antidepressant
- blocks alspha2 adrenergic receptors
