Pharmacology Flashcards
What are the clinical uses of antidepressant drugs
Moderate to severe depression
Dysthymia
Generalised anxiety disorder
Panic disorder, OCD, PTSD
Premenstrual dysphoric disorder
Bulimia nervosa
Neuropathic pain
What are the main classes of antidepressant
Monoamine oxidase inhibitors
Monoamine reuptake inhibitors which includes:
- tricyclics
- SSRI
- noradrenaline reuptake inhibitors
Atypicals
What are the monoamine neurotransmitters
Noradrenlaine
5-HT (serotonin)
Dopamine
How do most anti-depressants work
Altering the monoamine neurotransmission in some way
Most enhance their activity at the synapses
How might monoamines be affected in those with depression
There is a deficit in monoamine transmitters which causes depression - particularly serotonin and noradrenaline
Drugs that deplete stores of monoamines can induce low mood
CSF from depressed patients have reduced levels of monoamines or metabolites
Name some MAO inhibitors
Phenelzine - irreversible
Moclobemide - reversible
How do MAO inhibitors work
Irreversible (Phenelzine) or reversible (Moclobemide) inhibitors of monoamine oxidase A and B (enzymes)
MOA A and B are responsible for the metabolism of the monoamine neurotransmitters such as serotonin and noradrenaline
Therefore the inhibitors facilitate their release and storage
What are the side effects of MAO inhibitors
Prevents breakdown of dietary tyramine - cheese
Anticholinergic effects
Hypertensive crisis
Insomnia
Postural hypotension
Peripheral oedema
Name common tricyclic antidepressants
Imipramine
Amitriptyline - used for pain now and more sedating
How do the tricyclic antidepressants work
Block the reuptake of monoamines (mainly noradrenaline and 5-HT) into presynaptic terminals
Named for the 3 rings in their chemical structure
What are the side effects of tricyclic anti-depressants
Anticholinergic - blurred vision, dry mouth, constipation, urinary retention
Sedation
Weight gain
Cardiovascular - Postural hypotension, dizziness tachycardia, arrhythmias
Cardiotoxic in overdose - arrhtymia and arrest
Also seizure and coma
Name common SSRIs
Fluoxetine
Citalopram / Escitalopram
Sertraline
Paroxetine
How do SSRIs work
Selectively inhibit reuptake of serotonin (5-HT) from the synaptic cleft.
List come common side effects of SSRIs
Nausea, V and diarrhoea
Increased risk of GI bleeding
Headache and dizziness
Insomnia
Worsened anxiety/agitation
Transient increase in self-harm / suicidal ideation in <25 years
Sweating / vivid dreams
Sexual dysfunction
Hyponatraemia (in elderly)
Discontinuation effects
How do SNRIs work
Dual monoamine reuptake inhibitors
They block the reuptake of noradrenaline and 5-HT (seratonin) into presynaptic terminals.
Therefore similar side effects to SSRIs
Name common SNRIs
Venlafaxine
Duloxetine
Name common atypical antidepressants
Mirtazapine - blocks alpha 2 adreno- and serotonin receptors
Bupropion - dopamine uptake inhibitor
What are the side effects of mirtazapine
Weight gain
Increased appetite
Sedation - best to take in the evening
Can be good if patient is complaining of lack of appetite and loss of sleep
Also presents with some SSRI side effects like nausea and sexual dysfunction due to serotonin blockage. Though generally less than other SSRIs
Do anti-depressants start working immediately
No
Most have a delayed onset of action of several weeks
Why do you need to be cautious when prescribing anti-depressants to young adults/ teenagers
There can be a transient increase in suicidal ideation, self harm and aggressive ideas in this age group when they take the medications
What is the aim of bipolar treatment
Acutely it is to treat the symptoms = reduce mood in mania and raise mood in depression
Long term it is to stabilise mood - prevent recurrence of mania or depression
How is lithium used
As first-line maintenance in bipolar - mood stabiliser
It reduces both the number and severity of relapses
Offers some protection against antidepressant-induced hypomania if on dual treatment
Can be used in acute mania as well
May be used in recurrent depressive disorder, or schizoaffective disorder
Do you need to monitor lithium doses
YES
Very narrow therapeutic index and can lead to toxicity
Also has a very long half life
Monitor blood levels - 12 hours post-dose
Check weekly when starting or changing dose
Levels are checked every 3-6 months once stable
Also need to check thyroid and renal function every 6 months
What are the common side effects of lithium treatment
Dry mouth / strange taste
Nausea/vomiting and diarrhoea
Polydipsia and polyuria
Tremor - fine
Hypothyroidism - due to thyroid enlargement
Hyperparathyroidism
Long term reduced renal function
Nephrogenic diabetes insipidus
Weight gain
idiopathic intracranial hypertension
leucocytosis
hyperparathyroidism and resultant hypercalcaemia
What are the symptoms of lithium toxicity
Vomiting
Diarrhoea
Ataxia / coarse tremor
Drowsiness / altered conscious level
Convulsions
Coma
Which anti-convulsant drugs can be used as mood stabilisers
Valproic acid/ sodium valproate
Lamotrigine
Carbamazepine
What are the side effects of valproic acid
Drowsiness
Ataxia
CV effects
Induces liver enzymes
Hepatotoxicity
Teratogenicity - causes neural tube defects
Blood dyscrasia: Thrombocytopenia, leucopoenia, red cell hypoplasia.
Weight gain
Nausea, vomiting and diarrhoea.
Loss of hair
Headache, confusion and lethargy.
Pancreatitis
What are the side effects of carbamazepine
Drowsiness
Headache and diplopia
Ataxia
CV effects
Leucopenia
Hepatoxicity, liver failure and cholestatic jaundice.
Induces liver enzymes - interacts with other drugs
Teratogenicity: Spina bifida
Risk of SJS and TEN
What are the side effects of lamotrigine
Small risk of Stevens-Johnson syndrome
Flu-like symptoms
Aseptic meningitis
Ataxia and blurred vision
Which anti-psychotics can be used as mood stabilisers
Quetiapine
Aripiprazole
Olanzapine
Lurasidone
What are the side effects of the anti-psychotics used as mood stabilisers
Sedation
Weight gain
Metabolic syndrome
Extra-pyramidal side-effects (Aripiprazole)
Which herbal/complementary medicine can cause serotonin syndrome
St John’s Wort
Functions similarly to an MAOI
Higher risk if a conventional antidepressant is prescribed alongside it
Which anti-psychotic is most likely to cause extra pyramidal side effects
Chlorpromazine
First generation drugs acting on the D2 receptors will cause these symptoms
Women of child bearing age should not be prescribed sodium valproate - true or false
True
Unless other options are unavailable, AND adequate contraception (ideally depot or IUD) is in place.
Which anti-psychotic is most likely to cause weight gain
Clozapine
Olanzapine
How does acamprosate work to treat alcohol dependence
It acts on the neurotransmitter systems in the brain to reduce the reliance on and craving for alcohol
It helps to normalise the brain chemistry that has been disrupted by alcohol
Good for those who wish to control their drinking, but is not prepared to commit to abstinence from alcohol
List side effects of clozapine
Sialorrhoea - excessive salivation
Constipation - severe
Nausea and vomiting
Seizure
Weight gain
Hypotension - dose related
Neutropenia/agranulocytosis
Myocarditis and cardiomyopathy
How is dopamine involved in the treatment of psychotic disorders
Some evidence that an increase in dopamine level in the mesolimbic system contributes to psychotic disorders like schizophrenia
Many antipsychotics act on dopamine receptors - all act on D2
The more the dopamine receptor binding affinity, the better the therapeutic effect and clinical potency of the antipsychotic agent
What symptoms are associated with the mesolimbic pathway
Linked to positive symptoms – delusions, hallucinations, disorganized speech/thinking and disorganized or catatonic behaviour
What symptoms are associated with the mesocortical pathway
Linked to negative symptoms – Alogia, affective flattening, avolition
List examples of first generation antipsychotics
Chlorpromazine
Haloperidol
Trifluoperazine
Also called typical antipsychotics
List examples of extra-pyramidal side effects that may be caused by anti-psychotics
Acute dystonia
Drug-induced parkinsonism
Akathisia - unpleasant state of motor restlessness
Tardive dyskinesia - most common is chewing and pouting of jaw
List examples of second generation anti-psychotics
Clozapine
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Also known as atypicals
Which receptors do second generation anti-psychotics act on
Lower D2 receptor affinity.
Work on a variety such as D2,3,4 and 5-HT
High serotonin/dopamine binding ratio.
List side effects of olanzipine
Sedation
Weight gain
Metabolic syndrome - dyslipidaemia
Dry mouth and constipation (anti-muscarinic)-
What is risperidone used to treat
Schizophrenia
Acute treatment of mania
Which ECG changes can be caused by antipsychotics
QT prolongation
Particularly haloperidol
Anti-psychotics are used for which conditions
Schizophrenia
Mania
Other psychoses including psychotic depression and schizoaffective disorder
As augmenting agents in the treatment of obsessive-compulsive disorder and in the control of severely disturbed behaviour
Clozapine is used in which conditions
It is licensed for treatment-resistant schizophrenia - used 3rd line if others have not worked
Can improve manic symptoms in treatment resistant bipolar disorder
Those on clozapine must be monitored - true or false
True
Severe side effect profile so must be checked
e.g. FBC weekly for first 18 weeks due to neutropenia/agranulocytosis risk
Which antipsychotics can cause SIADH
Haloperidol, risperidone, quetiapine, olanzapine and clozapine
Presents with mild hyponatreamia - confusion, cramps, nausea etc
Which antipsychotics can cause an increase in prolactin
Risperidone and paliperidone are the worst
Olanzapine has a transient minimal effect
May present with galactorrhoea
List common anti-cholinergic side effects
Dry mouth, blurred vision, urinary retention and constipation
Seen with chlorpromazine and clozapine
What is Neuroleptic Malignant Syndrome
Life-threatening condition seen in some patients started on anti-psychotics - typically with sudden dose increases
Presents with hyperthermia, muscular rigidity, decreased conscious level and labile blood pressure
Acute onset
Which drugs are used first line in the treatment of depression
SSRIs
What are the contraindications for tricyclic antidepressant use
Arrhythmias
Recent MI
Heart block
Avoided in elderly due to cardiotixc events
Mania and hypomania - can causes manic switch
Acute porphyria
In which types of depression are MAOIs mainly used
severe depression, treatment resistant depression and atypical depression
Which antidepressant is the only one recommended for use in children and young people
Fluoxetine is the only one with the evidence that shows that benefits outweigh risks in the treatment of moderate to severe depression
What is the risk of prescribing an antidepressant to a child or young person
Associated with an increase in suicidal behaviour, self‑harm or hostility, particularly at the beginning of treatment.
Must be closely monitored and is only used in extreme circumstances
How does ECT work
It involves induction of seizure by applying an electrical stimulus to the brain
The exact mechanism of action is still under investigation - may induce changes in neurotransmitters, neuroplasticity and functional connectivity
How is ECT carried out
The patient is given general anaesthesia and a muscle relaxant
Monitoring is performed throughout - ECG, EEG etc.
Electrodes are placed on the head - bilateral or unilateral
A short electrical impulse is passed through the head to induce a seizure
Patient is taken to recovery and are usually fine within an hour
Usually delivered 2 to 3 treatments per week
There are no absolute contraindications for ECT - true or false
True
What is ECT used for
Acute treatment of moderate to severe depression, mania or catatonia in patients who have failed in responding to other treatments
It is the most effective treatment for major depression
List some of the potential side effects of ECT
Adverse effects relating to use of general anaesthesia.
Confusion, headache and nausea.
Cognitive impairment - usually short term and resolves but has been permanent in some patients
Memory loss of events prior to ECT
Cardiac arrhythmia
Which drugs are used first line in treatment of anxiety disorders
SSRIs
Clomipramine for OCD
How are benzodiazpeines used in anxiety
Used in the short term only for severe anxiety
Which benzos are short and long acting
Short - lorazepam
Long - diazepam
List side effects of benzodiazepines
Drowsiness and dizziness
Confusion (elderly)
Respiratory depression
Cognitive and psychomotor impairment.
Tolerance and cross-tolerance with alcohol.
Withdrawal and discontinuation symptoms
Addiction
List some common anxiolytic drugs
Benzodiazepines - short-term
SSRIs - 1st line
Buspirone - rare
Pregabalin - GAD and social phobia
Beta Blockers - reduces physical symptoms
In which form is lithium usually given
Normally as lithium carbonate
Can lithium be used in pregnancy and breastfeeding
Not safe in first trimester due to risk of Ebstein’s heart anomaly
Not advisable in breastfeeding mums either - can affect the baby
The adverse effects of lithium are dependent on the serum concentration - ture or false
True
Which tests must be done before starting lithium treatment
Serum electrolyte, urea and creatinine, thyroid function and ECG
UandE and TFTs are rechecked every 6 months
Valproate is used in the treatment of which conditions
As a mood stabiliser in mania, rapid cycling bipolar and as maintenance in bipolar
Carbamazepine is used in the treatment of which conditions
Prophylaxis of bipolar disorder which has been unresponsive to lithium
Acts as a mood stabiliser
Which drugs does carbamazepine increase the metabolism of
Psychotropic medications – antidepressants, antipsychotics, valproate etc.
Oral contraceptive agents leading to failure.
Anticoagulants
Lamotrigine is used in the treatment of which conditions
Has a modest antidepressant activity
Used as a adjunct in bipolar - can prevent depressive relapse
How do you treat acute mania
STOP antidepressant medication.
Atypical Antipsychotics: Risperidone, quetiapine, olanzapine etc.
Mood Stabilisers: Lithium and Valproate
How do you treat alcohol withdrawal
Use benzodiazepines - typically chlordiazepoxide on a reducing schedule (dose dependent on severity of withdrawal)
Can also use diazepam
Carbemazepine can be effective
Also give Pabrinex to avoid development of Wernicke’s encephalopathy
How does disulfiram work to reduce alcohol dependence
It inhibits aldehyde dehydrogenase resulting in the accumulation of acetaldehyde in the body
Therefore when you drink on top of it it makes you sick - flushing, hypotension, palpitation and nausea and vomiting
How is methadone used
It is a long acting opioid that aims to wean people off IV opioid use to reduce harm
How is naltrexone used
It is an opiate antagonist, effective in the treatment of alcohol and opiate
dependence
Reduces craving and relapses in alcohol dependent people
Which drugs can be used for symptom relief in dementia
Donepezil
Galantamine
Memantine
How does memantine work in symptom control in dementia
It is an NMDA receptor antagonist
It stops excitatory cell death in Alzheimer’s and vascular dementia
How do donepezil/galantamine work in symptom control in dementia
The are acetylcholinesterase inhibitors
Prevent metabolisation of ACh so increase the duration of action
Cholinergic neurons are lost in Alzheimers so there is a decrease in ACh
How can you treat acute dystonia caused by antipsychotic drugs
Procyclidine
Anti-psychotic drugs can increase the risk of stroke in the elderly - true or false
True
Increased risk of stroke and VTE
Which atypical anti-psychotic has the best side-effect profile
Aripiprazole
Particularly good for those who have experienced raised prolactin on other drugs
List the major side effects of clozapine
Agranulocytosis and neutropenias - need regular FBC
Reduced seizure threshold
Constipation
Myocarditis - need a baseline ECG
Hypersalivation
How does smoking affect the action of clozapine
Smoking can reduce the amount of clozapine in the body
If someone suddenly stops smoking their levels can go up risking side effects
If they start smoking or smoke more, levels may go down
Dose adjustments may be needed
List symptoms of benzodiazepine withdrawal
Insomnia
irritability
anxiety
tremor
loss of appetite
tinnitus
perspiration
perceptual disturbances
seizures
Describe the action of benzodiazepines
They enhance the action of GABA - main inhibitory neurotransmitter - buy increasing the frequency of chloride channels
What is the SSRI of choice post-MI
Sertraline
What is the SSRI of choice in children and adolescents
Fluoxetine
Which SSRI is at higher risk of QT prolongation
Citalopram
List the symptoms that may be experienced on discontinuation of SSRIs
increased mood change
restlessness
difficulty sleeping
unsteadiness
sweating
gastrointestinal symptoms: pain, cramping, diarrhoea, vomiting
paraesthesia
What are the risks of using SSRIs in pregnancy
Use during the first trimester gives a small increased risk of congenital heart defects
Paroxetine has an increased risk of congenital malformations, particularly in the first trimester
Use during the third trimester can result in persistent pulmonary hypertension of the newborn
