Psychopharmacology Flashcards
How long does it take after finding a therapeutic dose of an antidepressant for it to affect the symptoms?
3-6 weeks
Take two months before changing to another one if not working
Name antidepressants that cause lengthening of the QT interval?
TCAs
SSRIs
SNRIs
Name some TCAs and how they work?
Imipramine, amitriptyline, doxepin, clomipramine
Have active metabolites including desipramine and nortriptyline
Potentiate the action of the monoamines, noradrenaline and serotonin, by inhibiting their reuptake into nerve terminals
What are the side effects of TCAs?
Dry mouth Constipation Tremor Blurred vision Urinary retention Cardiovascular effects QT prolongation Arrhythmias Postural hypotension Convulsant activity Lowered seizure threshold Other effects Weight gain Sedation Mania (rarely) High risk of toxicity/overdose so don't give to suicidal patients
Name some monoamine oxidase inhibitors and how they work
Bind irreversibly to monoamine oxidase thereby preventing inactivation of amines such as norepinephrine, dopamine and serotonin leading to increased synaptic levels
Moclobemide, selegiline
What are some side effects of MAOIs?
orthostatic hypotension, weight gain, dry mouth, sedation, sexual dysfunction and sleep disturbance
Hypertensive crisis can occur if taken when a diet is high in tyramine-rich foods or sympathomimetics (Tyramine is present in cheese, pickled herrings, yeast extracts, certain red wines, and any food, such as game, that has undergone partial decomposition. Dopamine is present in broad beans)
Name some Selective Serotonin Reuptake Inhibitors and how they work
Selective serotonin reuptake inhibitors (SSRIs) selectively inhibit the reuptake of the monoamine serotonin (5-HT) within the synapse
Citalopram and its laevo-isomer, escitalopram, fluvoxamine, fluoxetine, paroxetine and sertraline
What are the side effects of SSRIs?
GI upset, sexual dysfunction, anxiety, restlessness, nervousness, insomnia, fatigue or sedation, dizziness
risk of bleeding
What is serotonin syndrome?
toxic hyper-serotonergic state, which can be caused by the ingestion of two or more drugs that increase serotonin levels, e.g. an SSRI combined with a monoamine oxidase inhibitor, a dopaminergic drug (e.g. selegiline) or a tricyclic antidepressant. Symptoms include agitation, confusion, tremor, diarrhoea, tachycardia and hypertension; hyperthermia is characteristic. This is a medical emergency and treatment may require admission to hospital
Name some Serotonin/Norepinephrine reuptake inhibitors and how they work
Blocker of both serotonin and noradrenaline (norepinephrine) reuptake. At higher doses, it also affects dopamine transmission
Venlafaxine, duloxetine
Name two novel antidepressants
Buproprion
Mertazepine
What are the side effects of mertazepine?
can be sedating in low dose and can cause weight gain. An uncommon adverse effect is agranulocytosis
How is treatment resistance in depression combatted?
Combination of antidepressants eg SSRI or SNRI with Mirtazepine
Adjunctive treatment with Lithium
Adjunctive treatment with atypical antipsychotic eg Quetipaine, Olanzapine or Aripiprazole
ECT
What are three classes of mood stablisers?
Lithium, anticonvulsants, antipsychotics
What tests must be done before the use of lithium?
Get baseline U&E and TSH. In women do a pregnancy test
As lithium causes hypothyroidism, renal damage and abnormalities in a foetus
What are the side effects of lithium?
Most common are GI distress including reduced appetite, nausea/vomiting, diarrhea
Thyroid abnormalities
Non Significant leukocytosis
Polyuria/polydipsia secondary to ADH antagonism. In a small number of patients can cause interstitial renal fibrosis.
Hair loss, acne
Reduces seizure threshold, cognitive slowing, intention tremor
What are the levels for lithium toxicity?
Mild- levels 1.5-2.0 see vomiting, diarrhea, ataxia, dizziness, slurred speech, nystagmus.
Moderate-2.0-2.5 nausea, vomiting, anorexia, blurred vision, clonic limb movements, convulsions, delirium, syncope
Severe- >2.5 generalized convulsions, oliguria and renal failure
What tests should be done before starting someone on valproic acid?
baseline liver function tests (lfts), pregnancy test and FBC
What are the side effects of valproic acid?
Thrombocytopenia and platelet dysfunction
Nausea, vomiting, weight gain
Sedation, tremor
Increased risk of neural tube defect secondary to reduction in folic acid
Hair loss
In what conditions is carbamazepine good for?
First line agent for acute mania and mania prophylaxis
Indicated for rapid cyclers and mixed patients
What are the side effects of carbamazepine?
Rash- most common SE seen
Nausea, vomiting, diarrhea
Sedation, dizziness, ataxia, confusion
AV conduction delays
Aplastic anemia and agranulocytosis (<0.002%)
Water retention due to vasopressin-like effect which can result in hyponatremia
How long should patients be left on antidepressants if they are working?
First episode-6 months
Second episode-2 years
Third episode-possible lifelong treatment
Need to keep on for less risk of relapse
What is the mesocortical pathway?
Projects from the ventral tegmentum (brain stem) to the cerebral cortex. This pathway is felt to be where the negative symptoms and cognitive disorders (lack of executive function) arise. Problem here for a psychotic patient, is too little dopamine
What is the mesolimbic pathway?
Projects from the dopaminergic cell bodies in the ventral tegmentum to the limbic system. This pathway is where the positive symptoms come from (hallucinations, delusions, and thought disorders). Problem here in a psychotic patient is there is too much dopamine.
What is the nigrostriatal pathway?
projects from the dopaminergic cell bodies in the substantia nigra to the basal ganglia. This pathway is involved in movement regulation. Remember that dopamine suppresses acetylcholine activity. Dopamine hypoactivity can cause Parkinsonian movements
What is the tuberoinfundibular pathway?
Projects from the hypothalamus to the anterior pituitary. Remember that dopamine release inhibits/regulates prolactin release. Blocking dopamine in this pathway will predispose your patient to hyperprolactinemia
What are the two groups of anti-psychotics?
Typicals
Atypicals
What receptors do typical anti-psychotics act on and what side effects does this give?
Are D2 dopamine receptor antagonists
As a result they have higher risk of extrapyramidal side effects
Examples include Fluphenazine, Haloperidol, Pimozide.
Low potency typical antipsychotics have less affinity for the D2 receptors but tend to interact with nondopaminergic receptors resulting in more cardiotoxic and anticholinergic adverse effects including sedation, hypotension.
Examples include chlorpromazine and Thioridazine.
What receptors do atypical anti-psychotics work on?
serotonin-dopamine 2 antagonists
What are the side effects of risperidone?
Increased extrapyramidal side effects (dose dependent)
Most likely atypical to induce hyperprolactinemia
Weight gain and sedation (dosage dependent)
What are the side effects of olanzapine?
Weight gain (can be as much as 30-50lbs with even short term use)
May cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain)
May cause hyperprolactinemia
May cause abnormal LFT’s
Works a few weeks quicker than the others
What are the side effects of Quetiapine?
May cause abnormal LFT’s
May be associated with weight gain, though less than seen with olanzapine
May cause hypertriglyceridemia, hypercholesterolemia, hyperglycemia (even without weight gain), however less than olanzapine
Most likely to cause orthostatic hypotension
What are the side effects of Aripiprazole?
Unique mechanism of action as a D2 partial agonist
Low EPS, no QT prolongation, low sedation
Could cause potential intolerability due to akathisia/activation.
Not associated with weight gain
When is clozapine used?
After two trials of different anti-psychotics that haven’t worked, need to have tried each for at least eight weeks
What are the side effects of clozapine?
Associated with agranulocytosis and therefore requires weekly blood draws x 6 months, then Q- 2weeks x 6 months)
Increased risk of seizures (especially if lithium is also on board)
Associated with the most sedation, weight gain and abnormal LFT’s
Increased risk of hypertriglyceridemia, hypercholesterolemia, hyperglycemia, including nonketotic hyperosmolar coma and death with and/or without weight gain
What is Neuroleptic Malignant Syndrome (NMS)?
Characterized by severe muscle rigidity, fever, altered mental status, autonomic instability, elevated WBC, CPK and lfts. Potentially fatal.
Usually occurs when using higher doses of drug
How can extra pyramidal symptoms be managed as a result of anti-psychotics?
Anticholinergics such as benztropine, trihexyphenidyl, diphenhydramine
Dopamine facilitators such as Amantadine
Beta-blockers such as propranolol
Need to watch for anticholinergic SE particularly if taken with other meds with anticholinergic activity ie TCAs
What is Buspirone (Buspar)?
Anxiolytic
Mechanism of action is 5HT1A agonist
No sedation
What is done if clozapine isn’t effective as a last resort?
Can add another anti-psychotic of lithium/anticonvulsant
ECT
Why is it important to treat akathisia and how is it treated?
Higher risk of suicide
Anticholinergic agent or propranolol
