Drugs Flashcards
Describe antidepressants and name one of each type
- Most work on serotonin activity and aim to increase activity at post synaptic receptors
- Most have most of their effect in two to three weeks.
- To maximise impact of these (and analgesics) you need to be warm and emphatic.
- Most commonly used antidepressants are SSRI’s
- Other types include:
- SNRIs (Setatonin and Noradrenaline reuptake inhibitors) Venlafaxine
- NASSA (Noradrenaline-seratonin specific antidepressents): Mirtazapine
- Tricyclics - Amitriptyline
- NARIs (noradrenaline reuptake inhibitors) - Reboxitine
- MAOIs
- SARIs (Seratonin antaonist and reuptake inhibitors) - Trazodone
NICE guidance is that these can be given in mild to moderate depression if no response to initial low-intensity therapy (then also offering high intensity) as well as severe depression as an adjunctive to therapy
Describe SSRI’s
- Increase serotonin activity by reducing the presynaptic reuptake of serotonin after release
- Therefore more serotonin sits in the nerve junction
- Leads to a down regulation of post-synaptic receptors
- Used for depression and anxiety
- Sertraline (50 to 200mgs) — safest in cardiac disease
- Citaloprem (20 to 40mgs}/Escitaloprarn (10- 2Orngs) - watch out for QTc prolongation but does not usually cause death
- Fluoxeline (20 to 60 mgs)- watch out for seratonin syndrome when switching as very high half life
- Paroxetine (20 to 60mgs) — very potent but short half life: watch out for discontinuation syndrome
Common side effects include:
• Sense of restlessness, agitation on initiation (countered by judicious use of benzodiarepines)
• Nausea, GI disturbance
• Headache
Long term
• Weight changes (usually weight loss)
• Sexual dysfunction (arousal and orgasm)
• Less common — bleeding need a PPI if on an NSAID too.
Suicidal ideation — Time when starting when less depressed in terms of lethargy but still low mood. If happens numbers are very small and in young men
Describe NSRIs (Noradrenaline and Serotonin Reuptake Inhibitors)
- Act in the same way as SSRI’s but bind to noradrenaline reuptake receptors as well.
- Have an evidence base for neuropathic pain
- Side effects similar to SSRIs but greater potential for sedation, nausea and sexual dysfunction
- Two NSRls: • Duloxetine (60 to 120mgs}: low dose range
- Venlafaxine (75 to 375mgs): more efficacious and can go to a higher dose. Caution with higher doses in heart disease — hypertensive risk at doses above 225mgs.
What is special about mitrazapine and vortioxine
mitrazapine
- Used to be called a NaSSA (Noradrenergic and Specific Serotonergic Antidepressant)
- Unique class. Acts as a 5HT-2 and 51-1T-3 antagonist
- Strong H1 (histamine) activity— hence sedation
- Major side-effects are sedation and weight gain
- “Side-effects” can be used to therapeutic advantage
Vortioxitine - serotonin modulator and stimulator
- New drug with all sorts of serotonergic activity (differs according to receptor)
- Effective
- Well tolerated - most common side effect is nausea but only at high doses
- Evidence for improvement in difficult to treat cognitive symptoms
Describe the tricyclic antidepressants
- Out of favour because SSRIs tolerated better but reasonably effective and useful for those who do not respond to SSRI’s
- Newer tricyclics (such as lofepramine and and nortriptyline) tolerated better than older tricyclics (amitriptyline)
- All tricyclics have the potential to cause muscarinic and histaminic side effects
- Can be fatal in overdose — TCAs can behave like class 1A antiarrhythmics cause QTc prolongation and arrhythmias
- Are used at low doses for neuropathic pain
- New concern of a link to dementia with long-term use
Describe MAOIs
- Monoamine oxidase inhibitors — A work more on serotonin and B work more on dopamine. Last resort.
- Possibly more effective for atypical depression
- Irreversible— more dangerous: Phenelzine; Isocarboxazid
- Reversible — less dangerous: Moclobamide; Tranylcypromine
What you need to know:
• Potential for significant and dangerous interaction with other drugs
• Potential for tyramine reaction (tyramine binds onto adrenergic receptors and cause crisis) leading to hypertensive crisis — avoid cheese, pickled meats, wine and other tyramine products
• If changing to another antidepressant need a washout period (up to 6 weeks)
How do you decide which antidepressant to use?
What do you do if it doesn’t work?
Which antidepressant to use
- What has been used before?
- Was it effective and/or tolerated?
- Are there particular symptoms or comorbidities you may want to address: • Weight loss • Insomnia • Neuropathic pain
- In new cases with no previous treatment start with an SSRI unless there is major weight loss or major sleep difficulty— in which case consider Mirtazapine
Increasing the Dose or Switching
- You don’t need to wait 4 weeks to have an idea about effectiveness.
- For depression: if an antidepressant has absolutely no benefit at a typical dose it’s not worth increasing the dose — switch. If partial benefit increase the dose.
- For anxiety: consider increasing dose if no initial benefit.
- If an antidepressant has significant side-effects these may get better in a couple of weeks but if they cause a big problem for the patient —switch.
Describe discontinuation and setotonin syndrome
Antidepressants are not addictive (Craving, increased dose required) but they can be difficult to stop
Syndrome is characterised by:
Flu like symptoms: Sweating, shakes. Problems Sleeping: insonia, irritability, agitation. Sensory and movement symptoms: headaches, N&V, paraesthesia, clonus
- This is influenced by half-life
- The shorter the half-life the bigger the problem
- It is very unpleasant but not life-threatening
- Paroxitine and Venafaxine are trickest to stop.
- Go slow - alternate days
- Sometimes worth switching to Fluoxetine and then reducing that
Serotonin Syndrome
• Very vague presentation - occurs in sensitive, overdose
- Cognitive - headaches, agitation, hypomania, confusions, coma
- Autonomic - shivering, sweating, hyperthermia is marked, tachycardia, nausea and diarrhoea
- Somatic - myoclonus, hyper-reflexia and tremor
Diagnosis
must have taken a serotonergic agent and meet ONE of the following conditions
- Spontaneous clonus
- Inducible clonus PLUS agitation or diaphoresis
- Ocular clonus PLUS agitation or diaphoresis
- Tremor PLUS hyperreflexia
- Hypertonia PLUS temperature > 38°C PLUS ocular or inducible clonus
• Treatment usually supportive: stop treatment, fluids and monitoring.
Describe the wanted and unwanted pathways for antipsychotics
What are the important side effects?
- Also called neuroleptics
- All current antipsychotics reduce level of dopamine activity at D2 receptors.
- Target pathways are mesocortical and mesolimbic
- Unwanted pathways are nigrostriatal (movement - causing extrapyrimidal ADRs) and tuberoinfundibular (hypothalamic-pituitary-adrenal axis)
- All antipsychotics have potential for sedation, extrapyramidal side-effects, QTc prolongation and weight gain (but note the variation between typical and atypical)
• All antipsychotics can cause acute dystonia, including oculogyric crisis (where eyes point upwards with hyperextended neck
Drug Monitoring required
What are the indications for antipsychotics?
- Patients suffering from psychotic symptoms i.e. delusions and hallucinations. They are the mainstay of treatment for schizophrenia
- They can also be used in other conditions that present with positive psychotic symptoms such as depression, mania, delusional disorders, acute and transient psychotic disorders, delirium and dementia, as well as those with violent or dangerously impulsive behaviours and psychomotor agitation
- Clozapine is the only one this is more effective but should only be used in treatment resistant schizophrenia (after two other drugs)
Differentiate typical and atypical antipsychotics and give examples
Typical
Are older and more likely to case extra-pyrimidal side effects
Tend to bind more to muscarinic and histaminic receptors
More likely to cause - EPSE’s including bradykinesia, muscle stiffness and termor, tardive dyskinesia, akathisia (feeling of inner restlessness and need to be in motion)
Haloperidol
Flupenthixol
Zuclopenthixol
Chlorpromazine - avoid in elderly as increases stroke risk
Atypical
Tend to have more serotonergic activity
More likely to cause - Weight gain, dyslipidaemia and diabetes. May also impair temperature control due to 5HT2 receptor.
Clozapine
Olanzapine
Risperidone
Quetiapine
Amiulprinde
Aripiprazole - not a D2 partial agonist - fewer side effects so good to start
What are the common side affects of anti-psychotics?
Though their main function is to block D2 receptiors (extra-pyrimidal SE in typical), Anti-psychotics have an affinity for muscarinic, 5HT, histaminergic, and adrenergic receptors
Adrenergic
- Sweating
- Tremor
- Headaches
- Nausea
- Dissiness
Muscarinic (Ach) (can’t see, can’t wee, can’t spit, can’t shit)
- Dry mouth difficulty swallowing, thirst
- Blurred vision
- Difficulty urinating, urinary retention, constipitation
- Hot and flushed skin. Dry skin
Histimine
- Dry mouth
- Weight gain
- Drowsiness
- Nausea and Vomiting
Describe clozapine
Most effective ever. Improvements can continue over several months.
D2 antagonist; 5HT-2 antagonist
- Should be used in schizophrenia after two other antipsychotics have not worked
- Significant potential for agranulocytosis (severe leukopenia): therefore close monitoring of FBC: weekly for first 18 weeks then fortnightly then monthly.
- Significant potential for gastrointestinal hypomobility: constipation, potentially fatal bowel obstruction.
- Other side-effects include hypersalivation and urinary incontinence.
- Dose titrated slowly upward over two weeks and vital signs monitored due to potential for autonomic dysregulation
What is neuroleptic (antipsychotic) malignant syndrome
• Rare, life-threatening reaction to antipsychotics
The Cause is unknown
While symptoms usually develop during the first two weeks of antipsychotic therapy, the association of the syndrome with drug use is idiosyncratic
NMS is also seen in patients treated for parkinsonism in the setting of withdrawal of L-Dopa or dopamine agonist therapy
• Risk factors include:
High potency dopamine antagonists (typical antipsychotics) in antipsychotic naive, high doses, young men. Use of other psych meds inc. lithium
Tetrad of Symptoms
• Fever; confusion, muscle rigidity, sweating, autonomic instability
●Mental status change is the initial symptom in 82%, mostly agitated delirium with confusion rather than psychosis. Catatonic signs and mutism can be prominent. Evolution to profound encephalopathy with stupor and eventual coma is typical
●Muscular rigidity is generalized and is often extreme “lead-pipe rigidity” Superimposed tremor may lead to a ratcheting quality.
●Hyperthermia is a defining symptom > 38°C are typical (87 percent), but even higher temperatures, greater than 40°C, are common (40 percent)
●Autonomic instability typically takes the form of tachycardia (in 88 percent), labile or high blood pressure (in 61 to 77 percent), and tachypnea (in 73 percent)
Ix
CK is increased
leukocytosis and left shift
DDx
Seratonin Syndrome: shivering, hyperreflexia, myoclonus, and ataxia with prodrome of Nausea, vomiting, and diarrhea
Malignant catatonia: usually a behavioral prodrome of some weeks that is characterized by psychosis, agitation, and catatonic excitement.
• Death usually due to:
Rhabdomyolysis, renal failure, seizures, torsades de pointes and cardiac arrest
Treatment:
- Emergency referral to A&E;
- stop antipsychotics
- fluid resuscitation
- reduce temperature
- Consider dantroline
What are extrapyrimidal side effects?
What can be used to treat them?
Antipsychotic medications try to reduce dopamine which cause psychotic symptoms.
However the pyrimidal system also uses dopamine to cause muscular relaxation and therefore the drugs commonly produce extrapyramidal symptoms as side effects.
- Acute dystonic reactions can occur in days (acute painful spasms of muscles)
- tardive dyskinesia (after years) abnormal, involuntary movement e.g. chewing
- Parkinsonism occurs in weeks/months (tremor, bradykinesia, rigidity, masked facies, shuffling gait)
- Akinesia (finding it hard to start a movement)
- akathisia occurs in weeks/months (finding it hard to keep still)
- neuroleptic malignant syndrome.
Extrapyramidal symptoms are caused by dopamine blockade or depletion in the basal ganglia; this lack of dopamine often mimics idiopathic pathologies of the extrapyramidal system.
Associated with some antidepressants, lithium, various anticonvulsants, antiemetics and, rarely, oral-contraceptive agents.
Treamtments
- Change antipsychotic
- Take an anticholinergic such as procyclidine or orphenadrine which will cause muscle relaxation
- Propanolol for akathisia
What is rapid tranquillisation and what are the dangers of it?
Rapid tranquillisation is when medicines are given to a person who is very agitated or displaying aggressive behaviour to help quickly calm them. This is to reduce any risk to themselves or others, and allow them to receive the medical care that they need.
It is preferable to use lorazepam alone for rapid tranquillisation when behavioural disturbance occurs in a non-psychotic context.
Lorazepam in combination with an antipsychotic should be considered in the context of psychosis.
Can cause excessive sedation and loss of consciousness, loss of airway, and respiratory and cardiovascular collapse.
Vital signs should be monitored regularly, until the person becomes active again.
