Psychopharmacology Flashcards
What are antidepressants generally used for?
- Unipolar and bipolar depression
- Organic mood disorders
- Schizoaffective disorder
- Anxiety disorders including OCD, panic, social phobia
- PTSD
- Premenstrual dysphoric disorder
- Impulsivity associated with personality disorders
What is the mechanism of action of Tricyclic antidepressants?
Monoamine (serotonin and noradrenaline) reuptake is blocked by the TCAs which antagonise the amine transporter, resulting in a greater monoamine concentration in the synapse
What are examples of TCAs?
- Amitriptyline
- Clomipramine
- Nortriptyline
When are TCA’s indicated for use?
- Depression
- Anxiety disorder
- Neuropathy
What are common side effects of TCA’s?
- Anti-cholinergic effects - dry mouth, blurred vision, constuipation, hypotension, urinary retention
- Arrhythmias/Heart block
- Hyponatraemia - due to SIADH
What is the mechanism of action of monoamine oxidase inhibitors?
Amine neurotransmitters (e.g. 5HT, catecholamines, dopamine) are broken down to inactive metabolites by the enzyme monoamine oxidase (MAO), of which two isoforms exist, in nerve terminals:
- MAOA - found principally in the gut and liver
- MAOB - found in the brain
MAO inhibitors prevent breakdown of amine neurotransmitters by irreversibly binding with the enzyme
When are monoamine oxidase inhibitors used?
- Resistant depression
- Parkinson’s Disease
What are side effects of MAOI’s?
- Orthostatic hypotension
- Weight gain
- Dry mouth
- 3 S’s - Sedation, Sexual dysfunction, Sleep disturbance
What is the mechanism of action of SSRI’s?
Serotonin is a monoamine neurotransmitter with a role in regulation of mood. SSRIs selectively inhibit the reuptake of the monoamine serotonin (5-HT) within the synapse. The prolongation of the presence of serotonin in the synapse causes an upregulation of its effects on the postsynaptic neuron.
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What are examples of SSRI’s?
- Citalopram
- Fluoxetine
- Paroxetine
- Sertraline
- Paroxetine
What is a specific adverse reaction that can occur with MAOI’s?
Tyramine (cheese) reaction - Tyramine in foodstuffs is not broken down by bound MAOA and enters circulation causing dangerous hypertension due to its sympathomimetic effect
When are SSRI’s indicated for use?
- Depressive illness
- Panic disorder
- Obsessive compulsive disorder
- Anxiety disorders
What problem can occur when MAOI’s are taken in combination with medications which increase serotonin?
Serotonin syndrome
What is serotonin syndrome?
A group of symptoms that may occur following use of certain serotonergic medications or drugs:
- Abdo pain/diarrhoea
- Sweats
- Tachycardia
- HTN
- Myoclonus
- Irritability
- Delerium
Can lead to hyperpyrexia, CVS shock and death
When starting someone on SSRI’s, what do you have to warn them about?
Activation and discontinuation syndromes
What symptoms occur in activation syndrome that is caused by SSRI’s?
- Nausea
- Increased anxiety, panic and agitation
How long does activation syndrome last in patients who have been started on SSRI’s?
2-10 days
What are the symptoms associated with discontinuation syndrome with SSRI use?
- Agitation
- Nausea
- Disequilibrium
- Dysphoria
More common with drugs with shorter half-life
What are the most common side effects associated with SSRI’s?
- GI upset
- Sexual dysfunction
- Anxiety
- Restlessness
- Nervousness
- Insomnia
- Fatigue
- Sedation
- Dizziness
What can occur when SSRI’s are used in combination with other drugs that increase seratonin levels?
Seratonin syndrome
What drugs of abuse can in increase the risk of serotonin syndrome developing if used with SSRI’s?
- Amphetamines
- Cocaine
- LSD
Why does fluoxetine have a lower risk of discontinuation syndrome than other SSRI’s?
Longer half-life
What is the mechanism of action of serotonin/noradrenaline reuptake inhibitors?
Inhibit both serotonin and noradrenergic reuptake like the TCAS but without the antihistamine, antiadrenergic or anticholinergic side effects
What are the indications for SNRI use?
- Depression
- Anxiety
- Sometimes neuropathic pain
What are the typical (first generation) antipsychotic medications?
- Haloperidol
- Chlorpromazine
What are the indications for Antipsychotic medications?
- Acute mania
- Acute psychosis
- Chronic schizophrenia
- Sedation in acute confusional states
- Premedication before general anaesthesia
How do antipsychotic medications act?
All are dopamine receptor type 2 antagonists. This is the most likely explanation for their sedative / tranquilizing effect. The antipsychotic effect is probably an adaptive response to the antidopaminergic actions.
The atypical antipsychotic drugs have greater effects on other receptors than the dopamine receptor (including 5HT2 receptor, histamine receptor).
Which class of antipsychotic medications are more at risk of causing extra-pyramidal side effects?
1st generation (typical) antipsychotics - due to their greater action on dopamine receptors
What is important to bear in mind about antipsychotics in terms of side effects?
The greater the sedative level of the drug, the less extrapyramidal or anticholinergic side effects there are
What are the main atypical (second generation) antipsychotic medications?
- Respiradone
- Olanzapine
- Quitiepine
- Aripiprazole
- Clozapine
What side effects are seen with antipsychotic use?
- Extra-pyramidal side effects
- Anti-cholinergic side effects
- Hyperprolactinaemia
- Hyperglycaemia
- Temp regulation interference
- Venous thromboembolism
- Prolonged QT interval
What are extra-pyramidal side effects?
Drug-induced movement disorders that include acute and tardive symptoms:
- Parkinsonian symptoms
- Dystonia (abnormal face and body movements) and dyskinesia
- Akasthisia (restlessness)
- Tardive dyskinesia
What are anti-cholinergic side effects?
- Dry mouth
- Blurred vision
- Difficulty passing urine/retention
- Constipation
- Hypotension
- Rare - Ileus, Glaucoma
What is dyskinesia?
https://www.youtube.com/watch?v=IR1K7HW6KZ0
The impairment of voluntary motor activity by superimposed involuntary motor activity
What is akasthisia?
https://www.youtube.com/watch?v=pSXzuCNlI6Q
A subjective sense of uncomfortable desire to move, relieved by movement of the affected part. Often a side effect of neuroleptic drugs
What is tardive dyskinesia?
A movement disorder associated with long-term treatment with neuroleptic drugs. Characterised by abnormal movements, especially of the mouth and tongue such as lip smacking, sucking and puckering. It can also involve other parts of the body with chore-athetoid movements of the finger, toes and writhing movements of the trunk. They tend to increase when the patient is aroused and are typically absent when they are asleep. In some cases it is irreversible.
What are the side effects associated with respiradone?
- Increased risk of EPSE
- Most likely to induce hyperprolactinaemia
- Weight gain
- Sedation
What side effects are associated with Olanzapine?
- Weight gain - can be as much as 30-50lbs
- Hypertriglyceridemia, hypercholesterolemia, hyperglycemia - even without weight gain
- Hyperprolactinemia - less than risperidone
- Abnormal LFT’s - 2% of all patients
What are the side effects of Quitiepine?
- Abnormal LFT’s - 6% of all patients
- Weight gain - though less than seen with olanzapine
- Hypertriglyceridemia, hypercholesterolemia, hyperglycemia - however less than olanzapine
- Orthostatic hypotension
Which antipsychotic is most likely to cause orthostatic hypotension?
Quitiepine
What are the side-effects of clozapine?
- Agranulocytosis
- Increased risk of seizures - especially if combined with lithium
- Sedation
- Weight gain
- Abnormal LFT’s
- Hypertriglyceridemia, hypercholesterolemia, hyperglycemia
- Nonketotic hyperosmolar coma and death
- Neutropenia
- Idiopathic hyperthermia
- Hypersalivation
Which atypical antipsychotic is the most sedative?
Clozapine
Which antipsychotics cause abnormal LFT’s?
- Quitiepine
- Olanzipine
- Clozapine
Which atypical antipsychotics cause weight gain?
All except Aripirazole
What is neuroleptic malignant syndrome?
A rare, but life-threatening, idiosyncratic reaction to neuroleptic/antipsychotic medications. Characterised by:
- Severe muscle rigidity
- Fever
- Altered mental status
- Autonomic instability
- Elevated WBC
What is the mechanism of action of benzodiazepines?
Potentiation of GABA neurotransmission
What are examples of benzodiazepines?
- Diazepam
- Lorazepam
- Midazolam
- Temazepam
When are benzodiazepines indicated for use?
- Seizure termination - particularly prolonged/status epilepticus - CHECK SIGN GUIDELINES
- Severe panic disorders if resistant to antidepressants*
- Anxiety disorders - short term use only
- Insomnia - short term use only
- Alcohol withdrawal
- Perioperative sedation
What are the side effects of benzodiazepines?
TOLERANCE/DEPENDENCE - long term use
- Drowsiness
- In-coordination
- Muscle weakness
- Dizziness
- Confusion
Why do extra-pyramidal side effects occur?
Occur as a result of D2 receptor blockade in the nigrostriatal pathway and are more likely to be associated with high potency antipsychotics (70-80% D2 occupation) which have little anticholinergic action, such as the piperazine phenothiazines and the butyrophenones
What can occur as a result of hyperprolactinaemia?
- Galactorrhea.
- Menstrual irregularities.
- Sexual dysfunction.
- Osteoporosis.
- Increased risk breast cancer.
What are the commonly used mood stabilisers?
- Lithium
-
Anticonvulsants
- Valproic acid
- Carbemazepine
- Lamotrigine
What is the mechanism of action of lithium?
The mechanism of action of lithium is unknown. It may include alterations in transmembrane ion flux and / or reduction in phosphatidylinositide turnover, which lead to mood stabilization.
What are the indications for use of lithium?
- Treatment and prophylaxis of mania
- Bipolar disorder
- Recurrent depression
- Aggressive or self-mutilating behaviour (rarely used)
What are the side effects of lithium?
- Gastro intestinal disturbance
- Fine tremor
- ADH antagonism + tubulointerstitial damage -> nephrogenic diabetes insipidus
- Weight gain and oedema
- Exacerbation of psoriasis
- Goitre and thyroid dysfunction
- Reduced seizure threshold
- Toxicity
What are signs of lithium intoxication?
- Vomiting, diarrhea
- Ataxia
- Dizziness
- Slurred speech
- Nystagmus
What signs/symptoms would indicate severe lithium toxicity?
- Hyper-reflexia
- Convulsions
- Psychosis
- Syncope
- Renal insufficiency
What is the blood level that is aimed for when using lithium?
0.6-1.2
When considering starting lithium, what should you do first?
- Baseline U+E and TSH
- Pregnancy test in woman
How long does it take for lithium to reach a steady state after first dose?
5 days
How often should lithium levels be checked once steady state is established?
3 months
When should you recheck U+E’s, creatinine and TSH?
6 months
What is the mechanism of action of sodium valproate/valproic acid?
Three separate methods:
- Increasing the amount of GABA in the brain
- Blocking Sodium Channels
- Blocking Calcium Channels
It increases the amount of GABA in the brain by inhibiting the enzyme GABA Transaminase, which normally breaks down GABA.
By blocking both sodium and calcium channels, Valproate prevents the depolarisation/firing of neurones
What are the side effects of sodium valproate/valrpoic acid?
- SEVERE - sudden onset of liver failure, acute pancreatitis and severe thrombocytopenia.
- Nausea and vomiting
- Diarrhoea
- Weight gain
- Oedema
- Hallucinations
When giving sodium valproate/valproic acid, what baseline tests should you do?
- LFTs
- Pregnancy test
- FBC
When is carbemazepine indicated for use?
- Acute mania
- Mania prophylaxis
What is the first line treatment for acute mania and mania prophylaxis?
Carbemazepine
What is the mechanism of action of carbemazepine?
Carbamazepine acts by binding to the sodium channels of neuronal membranes and prevents the influx of sodium into the cell which normally leads to an action potential. By preventing depolarisation of these neurones, there is not the repeated “firing” of action potentials that is responsible for epileptic seizures.
What are the side effects of carbemazepine use?
- Skin conditions
- SIADH
- Nausea and vomiting
- Dry mouth
- Peripheral Oedema, weight gain
- Dizziness
- Drowsiness and fatigue
- Headache
- Abnormal LFTs
- AV conduction delays
What serious skin conditions can occur with the use of carbemazepine and lamotrigine?
- SJS
- Toxic Epidermal Necrolysis
What baseline measurements should you take before starting someone on carbemazepine?
- FBC
- LFTs
- ECG
What is the mechanism of action of lamotrigine?
Acts as a sodium channel blocker, to reduce the influx of sodium ions into neurones, and therefore reduced action potentials. This effectively stops the neurones from repetitively “firing” and therefore prevents seizures.
What are the side effects of lamotrigine?
- Rashes
- Nausea, vomiting and diarrhoea
- Somnolence or insomnia
- Headache
- Dizziness
- Blurred vision or diplopia
- Ataxia
- Skin conditions
- Haematological abnormalities