Psychopharmacology Flashcards
What are the five antidepressant drug class types?
Selective Serotonin Reuptake Inhibitors (SSRIs)
Serotonin Noradrenaline Reuptake Inhibitors (SNRIs)
Monoamine Oxidase Inhibitors (MAOIs)
Tricyclics Antidepressants (TCAs)
Alpha2-Adrenoreceptor Antagonists
When do antidepressant drugs start to work?
2 - 4 weeks
What do we do when there are no improvements seen with an antidepressant after two months?
We switch to another antidepressant
How long do we prescribe antidepressants for after the first depressive episode?
6 months to a year
How long do we prescribe antidepressants for after the second depressive episode?
2 years
How long do we prescribe antidepressants for after the third depressive episode?
Life-long
When are SSRIs prescribed?
They are the first line drug class used to manage several psychiatric conditions, including depression and anxiety disorders
List five SSRI examples
Sertraline
Fluoxetine
Paroxetine
Citalopram
Escitalopram
What are the two SSRIs initially administered?
Sertraline
Fluoxetine
What SSRI is administered in individuals who have chronic illnesses? Why?
Sertraline
It doesn’t produce that many drug interactions
How do SSRIs work?
They work by blocking the presynaptic serotonin reuptake, thus increasing its levels within the brain
What syndrome can occur when SSRIs are initially administered?
Activation syndrome
What is activation syndrome? What are the four clinical features associated?
It is caused by increased serotonin levels, in which a state of agitation, anxiety and restlessness occurs
In some cases, suicidal ideation can occur
How long does it usually take for activation syndrome to self-resolve?
2 – 10 days
What syndrome can occur when SSRIs are initially stopped?
Discontinuation syndrome
What is discontinuation syndrome? What are the three clinical features associated?
It is caused by decreased serotonin levels
Dizziness
Paraesthesia
Anxiety
How long does it take for discontinuation to present after SSRIs are stopped?
A few days
How long does it usually take for discontinuation syndrome to self-resolve?
Three weeks
How can we prevent discontinuation syndrome?
We usually wean the drug dose gradually over a period of four weeks.
However, this period is prolonged in individuals who have been taking antidepressants for longer
We can also consider switching patients to one 20mg fluoxetine per day
What are the four contraindications of SSRIs?
Poorly Controlled Epilepsy
Manic Phase of Bipolar
Hepatic Impairment
Congenital Long QT Syndrome
What are the two unique side effects of SSRIs - apart from GI upset?
Sexual Dysfunction
Hyponatraemia
What are the two main side effects associated with paroxetine?
Sedation
Weight gain
Due to the increased risk of GI bleeding, which patients do we reconsider administrating SSRIs to?
Those taking NSAIDs, aspirin or warfarin
Due to the increased risk of hyponatraemia, which patients do we reconsider administrating SSRIs to?
Those taking diuretics and PPIs
Which three drugs increases the risk of serotonin syndrome?
Tramadol
St John’s Wort
Triptans
When are SNRIs prescribed?
They are the second line drug class used to manage several psychiatric conditions, including depression and anxiety disorders
List two SNRIs examples
Duloxetine
Venlafaxine
Which SNRI is prescribed in individuals who have chronic illnesses? Why
Venlafaxine
it doesn’t produce many drug interactions
Which SNRI is associated with a greater risk of mortality from overdose?
Venlafaxine
In which circumstances do we prescribe duloxetine over venlafaxine?
When the patient suffers from hypertension and cardiac arrhythmia
How do SNRIs work?
They work by blocking the presynaptic serotonin and noradrenaline reuptake, thus increasing their levels within the brain
What syndrome can occur when SNRIs are initially administered?
Activation syndrome
What syndrome can occur when SNRIs are initially stopped?
Discontinuation syndrome
What are the five contraindications of SNRIs?
Cardiac Arrythmias
Uncontrolled Hypertension
Hepatic Impairment
Renal Impairment
Congenital Long QT Syndrome
Monoamine Oxidase Inhibitors
Why should SSRIs not be combiend with MAOIs?
There is a risk of serotonin syndrome
What are the eight clinical features of serotonin syndrome?
Fever
Confusion
Seizures
Renal impairment
Hepatic impairment
Arrhythmia
Increased muscle tone
Hypersecretion of sweat
How do we prevent serotonin syndrome?
There should be a 14 day washout period between SSRIs and MAOIs
What are the two unique side effects of SNRIs - apart from GI upset?
Hypertension
Sexual Dysfunction
When are MAOIs prescribed?
They are the second/third line drug class used to manage several psychiatric conditions, including depression and anxiety disorders
Who usually prescribes MAOIs?
Psychiatrists
GPs tend to continue this prescription, however it tends to be initiated in secondary care
List four MAOIs examples
Isocarboxazid
Phenelzine
Selegiline
Tranylcypromine
What should phenelzine not be prescribed with? Why?
Fluoxetine
An increased risk of central serotonin syndrome
How do MAOIs work?
They work by binding irreversibly to monoamine oxidase on the presynaptic membrane thereby preventing the inactivation of amines, such as serotonin, dopamine and noradrenaline
What are the four contraindications of MAOIs?
Cerebrovascular Disease
Manic Phase of Bipolar
Phaeochromocytoma
Severe Cardiovascular Disease
What are the three unique side effects of MAOIs - apart from GI upset?
Weight Gain
Postural Hypotension
Hypertensive Crisis
How do MAOIs lead to a hypertensive crisis?
When they are administered with tyramine-rich foods, such as cheese
When are TCAs prescribed?
They are the second/third line drug class used to manage several psychiatric conditions, including depression and anxiety disorders
Who usually prescribes TCAs?
Psychiatrists
GPs tend to continue this prescription, however it tends to be initiated in secondary care
What do all TCAs end in?
“ine”
List seven TCAs examples
Amitriptyline
Clomipramine
Doxepin
Desipramine
Imipramine
Nortriptyline
Trimipramine
Which TCA is used to manage anxiety?
Clompiramine
How do TCAs work?
They work by blocking the re-uptake of serotonin, noradrenaline and dopamine, thus increasing their levels within the brain
What are the two subtype classifications of TCAs?
Tertiary TCAs
Secondary TCAs
What are tertiary TCAs?
They are molecules composed of a three-ring structure, with two methyl groups on the nitrogen atom of the side chain
This means that they have tertiary amine side chains
What TCA subtype is associated with more side effects? Why?
Tertiary TCAs
The side chains are prone to cross react with other types of receptors
Tertiary TCAs have tertiary amine side chain
List four tertiary TCAs examples
Imipramine
Amitriptyline
Doxepin
Clomipramine
What are the two active metabolites of tertiary TCAs?
Desipramine
Nortriptyline
What are secondary TCAs?
They result from the metabolism of tertiary TCAs, during which there is loss of one methyl group on the nitrogen side chain
This means that they have secondary amine side chains
List two secondary TCAs examples
Desipramine
Nortriptyline
What is the main difference between tertiary and secondary TCAs?
Tertiary TCAs - They are more potent in blocking reuptake of serotonin
Secondary TCAs - They are more potent in blocking the reuptake of noradrenaline
What are the six contraindications of TCAs?
Arrythmias
Heart Block
Severe Hepatic Impairment
Severe Renal Impairment
Manic Phase of Bipolar
Congenital Long QT Syndrome
What are the two unique side effects of TCAs - apart from GI upset?
Weight Gain
Eye Accommodation
Which antidepressant has the greatest risk of mortality related to overdose? What does this mean?
TCAs
They should be carefully prescribed to individuals who experience suicidal ideation
When are alpha2-adrenoreceptor antagonists prescribed?
They are the second/third line drug class used to manage several psychiatric conditions
What condition do alpha2-adrenoreceptor antagonists treat?
Depression
List an alpha2-adrenoreceptor antagonist
Mirtazapine
How do alpha2-adrenoreceptor antagonists work?
They work by antagonising the adrenergic alpha2-autoreceptors and alpha2-heteroreceptors as well as blocking 5-HT2 and 5-HT3 receptors
This blocks reuptake of serotonin and noradrenaline, thus increasing their levels within the brain
What are the five contraindications of mirtazapine?
Cardiac Disorders
Diabetes Mellitus
Manic Phase of Bipolar
Hypotension
Psychosis
What are the two unique side effects of mirtazapine - apart from GI upset?
Weight Gain
Postural Hypotension
What are two mood stabiliser drug class types?
Lithium salts
Anticonvulsants
When are lithium salts prescribed?
They are the first line drug class used to manage psychiatric conditions, including bipolar disorder and schizophrenia
They can be used for the treatment of acute episodes of mania associated with bipolar disorder or the long-term management of bipolar disorder to prevent recurrence of acute episodes
List two lithium salt examples
Lithium carbonate
Lithium citrate
How do lithium salts work?
They work by increasing GABA levels, which is an inhibitory transmitter that also plays a role in modulating glutamate and dopamine
In bipolar disorder, individua’s have diminished GABA neurotransmission. Thus, low GABA levels can result in excitatory toxicity
What two investigations should be conducted prior to the administration of lithium?
Baseline bloods (U&Es, TSH)
Pregnancy test
How long post-dose should we measure lithium blood levels?
12 hours
Why do we conduct a pregnancy test prior to the administration of lithium?
This is due to the associated teratogenic risk of Ebstein’s anomaly
How do we administer lithium?
An initial dose of lithium (400mg, twice daily) is administered, which after 5-7 days is reviewed
The dose is gradually titrated up until a stable therapeutic level of 0.6 – 1.2 is achieved
What investigations should be conducted when administrating lithium? Why?
LFTs every 3 months
TFTs and U&Es every six months
To monitor for lithium toxicity
At what serum lithium concentration does lithium toxicity occur?
> 1.5mmol/L
What are the eight clinical features of lithium toxicity?
Diarrhoea
Vomiting
Dizziness
Coarse tremor
Blurred vision
Ataxia
Clonic limb movements
Convulsions
Which endocrine disorder is most commonly associated with chronic lithium toxicity?
Hypothyroidism
In which patients is lithium toxicity risk the greatest?
Those with chronic illnesses
How do we manage patients with suspected lithium toxicity?
It is recommended that an urgent lithium level is conducted immediately, and specialist advice is obtained
What are the eight contraindications of lithium?
Cardiac Arrythmias
Severe Renal Impairment
Hypothyroidism
Brugada Syndrome
Addison’s Disease
Diabetes Insipidus
Breastfeeding
Pregnancy
What are the five unique side effects of lithium?
Urinary Frequency
Weight Gain
Fine Tremor
Altered Taste Sensation
Thyroid Abnormalities
Which drugs are avoided when prescribing lithium?
Nephrotoxic drugs, such as ACEI, NSAIDs and diuretics
When are anticonvulsants prescribed?
They are the second line drug class used to manage psychiatric conditions, including bipolar disorder and schizophrenia
It can be used in individuals in which lithium is contraindicated or not tolerated
They can be used for the treatment of acute episodes of mania associated with bipolar disorder or the long-term management of bipolar disorder to prevent recurrence of acute episodes
List three anticonvulsant examples
Sodium valproate
Carbamazepine
Lamotrigine
How do anticonvulsants work?
They work by increasing GABA levels, which is an inhibitory transmitter that also plays a role in modulating glutamate and dopamine
In bipolar disorder, individua’s have diminished GABA neurotransmission. Thus, low GABA levels can result in excitatory toxicity
When do we prescribe sodium valproate?
It is recommended in individuals who suffer from several manic/depressive episodes a year
It is recommended in individuals who suffer from comorbid alcohol/substance use
How do we administer and monitor sodium valporate?
An initial dose of sodium valproate (500mg daily) is administered, which after 4-5 days is reviewed
The dose is gradually titrated up until a stable therapeutic level of 50– 125 is achieved, after which annual blood checks are conducted
What are the four contraindications of sodium valproate?
Acute Porphyria
Severe Hepatic Impairment
Urea Abnormalities
Mitochondrial Disorders
What are the three unique side effects of sodium valproate - apart from GI upset?
Weight Gain
Tremors
Hair Loss
How do we administer and monitor carbamazepine?
An initial dose of carbamazepine (100mg-200mg, 1-2 times daily) is administered, which after 5 days is reviewed
The dose is gradually titrated up until a stable therapeutic level of 4– 12 is achieved, after which monthly blood checks are conducted
What are the three contraindications of carbamazepine?
Acute Porphyria
AV Conduction Abnormalities
Bone Marrow Depression
What are the three unique side effects of carbamazepine - apart from GI upset?
Weight Gain
Rash
Fluid Imbalance
How do we administer and monitor lamotrigine?
An initial dose of lamotrigine (25mg daily on alternate days) is administered. The dose is gradually titrated up to 50mg daily after two weeks, and then 100mg daily after a further two weeks
In cases where patients experience compliance issues and stop administrating lamotrigine for 5 days, it is recommended that they start back at the initial dose
What are the three contraindications of lamotrigine?
Myoclonic Seizures
Parkinson’s Disease
Brugada Syndrome
What are the two unique side effects of lamotrigine - apart from GI upset?
Rash
Irritability
It is normal for individuals on anticonvulsants to experience deranged LFTS. When should we raise concerns?
If LFTs are increased three times greater than the baseline
When are anti-psychotics prescribed?
They are indicated in the management of psychotic disorders, including schizophrenia, bipolar disorder and psychotic depression
What two medications are antipsychotics commonly administered in conjunction with?
Lithium
Sodium valproate
How do antipsychotics work?
They work by inhibiting dopaminergic neurotransmission via four dopaminergic pathways
What are the four dopaminergic pathways?
Mesocortical Pathway
Mesolimbic Pathway
Nigrostriatal Pathway
Tuberoinfundibular Pathway
Where does the mesocortical pathway extend?
It connects the ventral tegmentum to the prefrontal cortex
What is the function of the mesocortical pathway?
It is thought to be involved in cognitive control, motivation and emotional response
What abnormalities in the mesocortical pathway results in psychotic disorders?
There are reduced levels of dopamine
What psychotic clinical features arise as a result of mesocortical pathway abnormalities?
Negative clinical features, such as anergia, anhedonia, lack of motivation, etc
Where does the mesolimbic pathway extend?
It connects the ventral tegmentum to the ventral striatum in the forebrain
What is the function of the mesolimbic pathway?
It is involved in reinforcement and reward-related motor function learning
What is another term of mesolimbic pathway?
Reward pathway
What abnormalities in the mesolimbic pathway results in psychotic disorders?
There are increased levels of dopamine
What psychotic clinical features arise as a result of mesolimbic pathway abnormalities?
Positive clinical features, such as hallucinations, delusions and thought disorders
Where does the nigrostriatal pathway extend?
It connects the substantia nigra in the midbrain to the basal ganglia in the forebrain
What is the function of the nigrostriatal pathway?
It is thought to be involved in movement regulation, by suppressing acetylcholine activity
What abnormalities in the nigrostriatal pathway results in psychotic disorders?
There are reduced levels of dopamine
What psychotic clinical features arise as a result of nigrostriatal pathway abnormalities?
Sympathetic motor deficits, such as bradykinesia, dyskinesia, tremors, rigidity, akathisia and dystonia
Where does the tuberoinfundibular pathway extend?
It connects the infundibular nucleus in the hypothalamus to the anterior pituitary gland
What is the function of the tuberoinfundibular pathway?
It is thought to be inhibit the secretion of prolactin from the anterior pituitary lactotrophs by binding to D2 receptors
What is a common complication when administering antipsychotics that bock the tuberoinfundibular pathway?
Hyperprolactinemia
What are the four main clinical features of hyperprolactinaemia?
Gynaecomastia
Galactorrhoea
Decreased libido
Menstrual dysfunction
What are the two classifications of antipsychotics?
Typical Antipsychotics
Atypical Antipsychotics
What is the mechanism of typical antipsychotics?
D2 dopamine receptor antagonists
When do we prescribe typical antipsychotics? Why?
They are used to manage severe psychotic conditions, which are resistant to newer medications
Due to the high risk of extrapyramidal and cardiotoxic/anticholinergic side effects
What type of typical antipsychotics are associated with extrapyramidal side effects?
High potency
List three high potency typical antipsychotics
Fluphenazine
Haloperidol
Pimozide
What are five extra-pyramidal features?
Parkinsonism
Acute dystonia
Sustained muscle contraction
Akathisia
Tardive dyskinesia
What are the two types of extra-pyramidal sustained muscle contractions?
Oculogyric crisis
Torticollis
What is oculogyric crisis?
It is a dystonic reaction that occurs shortly after initiation of anti-psychotics, resulting in an upward deviation of both eyes.
What are the two management options for oculogyric crisis?
Drug cessation
Anti-muscarinic administration - procyclidine
What are the three features of an acute dystonic reaction?
Oculogyric crisis
Tongue protrusion
Jaw spasm
These all occur suddenly
What is akasthesia?
Restlessness
What is tardive dyskinesia?
It is late onset of choreoathetoid movements, abnormal, involuntary - chewing and pouting of jaw
What is the cause of tardive dyskinesia?
The blockade of the dopamine receptor promotes hypersensitivity of the D2 receptor in the nigrostriatal pathway, thus giving rise to excessive movements.
What increases the risk of tardive dyskinesia?
Long-term use of antipsychotic drugs
How do we treat extra-pyramidal side effects?
We administer anti-cholinergics and beta-blockers
What three anticholinergics are used to treat extra-pyramidal features?
Benxtropine
Trihexyphenidly
Diphenhydramine
What beta-blocker is used to treat extra-pyramidal side effects?
Propanolol
What should we be cautious about when treating extra-pyramidal side effects?
If the patient is taking other meds with anticholinergic activity, such as TCAs
What type of typical antipsychotics are associated with cardiotoxic, anticholinergic side effects?
Low potency
List two low potency typical antidepressants
Chlorpromazine
Thioridazine
Why do the low potency typical antipsychotics cause cardiotoxic and anticholinergic adverse effects?
They have a lower affinity for the D2 receptors and tent to interact with nondopaminergic receptors
What are the four common side effects associated with typical antipsychotics?
Extrapyramidal features
Neuroleptic malignant syndrome
Hyperprolactinaemia
Prolonged QT interval
Metabolic syndrome
What is neuroleptic malignant syndrome?
It is a life threatening condition which can occur in individuals taking antipsychotic and dopaminergic medications
How soon after starting an antipsychotic can neuroleptic malignant syndrome occur?
Hours to days
What are the six clinical features of neuroleptic malignant syndrome?
Fever
Muscle rigidity
Hypertension
Tachycardia
Tachypnoea
Delirium
What are the two blood test results indicative of neuroleptic malignant syndrome?
Increased creatinine kinase levels
Increased leucocyte levels
What are the five management options of neuroleptic malignant syndrome?
Stop antipsychotic
IV fluids
Dantrolene
Bromcriptine
Dopamine agonist
What is the advantage of typical antipsychotics?
There is no weight gain
What is a contraindication of typical antipsychotics? What is administered instead?
Parkinson’s disease
IM Lorazepam
What is the mechanism of atypical antipsychotics?
Serotonin-dopamine 2 antagonists (SDAs)
Why are atypical antipsychotics considered atypical?
They affect dopamine and serotonin neurotransmission in the four dopaminergic pathways of the brain
When do we prescribe atypical antipsychotics? Why?
They are the first line antipsychotics administered
They are associated with fewer side effects
List five atypical antidepressants
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Clozapine
What is the first line antipsychotic prescribed?
Risperidone
What is the maximum dose of risperidone? Why?
6mg
A greater dose can result in adverse side effects
What are the five side effects commonly associated with risperidone?
Weight gain
Sedation
Hyperprolactinaemia
Extra-pyramidal features
Sexual dysfunction***
When is risperidone prescribed?
It is the first line antipsychotic used to treat manic and mixed bipolar episodes
It is also used in terms of long term maintenance of bipolar disorder
When is olanzapine prescribed?
It is used to treat manic, depressive and mixed bipolar episodes
What are the four side effects associated with olanzapine?
Weight gain***
Sedation
Hyperlipidaemia
Deranged LFTs
When is quetiapine prescribed?
It is used to treat manic and depressive bipolar episodes
It is also used in terms of long term maintenance of bipolar disorder
What are the four side effects associated with quetiapine?
Weight gain
Hyperlipidaemia
Deranged LFTs
Hypotension
When is aripiprazole prescribed?
It is used to treat manic and mixed bipolar episodes
It is also used in term of long term maintenance of bipolar disorder
What are the two side effects associated with aripiprazole?
Akathisia
Activation
However, there are generally fewer side effects compared to the other atypical antipsychotics
Which antipsychotic has the fewest side effects compared to to other typical antipsychotics?
Aripiprazole
It is particularly good for managing prolactin elevation
When is clozapine prescribed?
It is used to treat resistant psychotic disorders, in which two antipsychotics have been ineffectively trialled for a period of eight weeks respectively
What are the six side effects associated with clozapine?
Agranulocytosis**
Seizures
Sedation
Weight gain
Hyperlipidaemia
Deranged LFTs
Which blood test is used to work out if olanzapine has caused agranulocytosis?
FBC
What are the six contraindications of antipsychotics?
Cardiovascular Disease
Diabetes
Epilepsy
Myasthenia Gravis
Parkinson’s Disease
Prostatic Hypertrophy
What are the two administration methods for antipsychotics?
Oral route
Intramuscular route
What administration route is opted for after the third episode of schizophrenia? Why?
Intramuscular
This is due to reduced functioning and lower IQ symptoms resulting in compliance issues
What four blood tests are conducted prior to antipsychotic administration?
Fasting lipid profiles
Fasting blood sugars
LFTs
FBC
What ongoing monitoring is conducted when patients are administered antipsychotics? Why?
ECG
Due to the risk of QT prolongation
How long do we prescribe antipsychotics for? Why?
Life-long
This is due to the inevitable relapse of psychotic disorders
What four drugs are used to treat insomnia?
Melatonin
Benzodiazepines
Zopiclone
Temazepam
What is the main side effect of benzodiazepines?
Respiratory depression
What is the mechanism of action of zopiclone?
It is a non-benzodiazepine hypnotic acting on the α2-subunit of the GABA receptor
What are the two indications for melatonin administration in insomnia patients?
Patient - > 55 years old
Short term use - < 13 weeks use
How long does it take for insomnia patients to fall asleep after pharmacological intervention?
22 minutes
It doesn’t maintain sleep!!!
What two drugs are used to manage ADHD?
Atomoxetine
Methylphenidate
What is the mechanism of atomoxetine?
It is a norepinephrine reuptake inhibitor
What is the mechanism of action of methylphenidate?
It is a dopamine/norepinephrine reuptake inhibitor
Which high potency typical antidepressant?
x
