Psychopharmacology Flashcards
Is acetylcholine excitatory or inhibitory?
Excitatory
Is glutamate excitatory or inhibitory?
Excitatory
Is dopamine excitatory or inhibitory?
Excitatory
Is GABA excitatory or inhibitory?
Inhibitory
Is serotonin excitatory or inhibitory?
Inhibitory
Is noradrenaline excitatory or inhibitory?
Both, depending on the receptor
What is the mechanism of action for SSRIs?
Bind to the SERT (serotonin transporter) on the presynaptic neuron to inhibit the reuptake of serotonin, and increase the amount of serotonin in the synaptic cleft. This increases stimulation of post-synaptic neurons
What are the side effects of SSRIs?
Feeling agitated, shaky or anxious, feeling or being sick.
indigestion, diarrhoea or constipation, sexual dysfunction (loss of libido, difficulty getting and maintaining an erection, difficulty orgasming)
What are some examples of SSRIs?
Fluoxetine, paroxetine, citalopram, sertraline
What is the mechanism of action of SNRIs?
Bind to the SERT and NAT (noradrenaline transporter) on the presynaptic membrane to inhibit their uptake, and increase the amount of neurotransmitter in the synaptic cleft
What are the side effects of SNRIs?
Feeling agitated, shaky or anxious.
feeling or being sick.
indigestion, diarrhoea or constipation
What are some examples of SNRIs?
Venlafaxine, duloxetine
What are the side effects of TCA antidepressants?
Blocks muscarinic receptors too - dry mouth,
slight blurring of vision, constipation, problems passing urine, drowsiness, dizziness, weight gain
What is the mechanism of action of TCA anti-depressants?
Bind to the SERT and NAT (noradrenaline transporter) on the presynaptic membrane to inhibit their uptake, and increase the amount of neurotransmitter in the synaptic cleft
What are some examples of TCA antidepressants?
Lofepramine, amitriptyline
What is the mechanism of action of monoamine oxidase inhibitor anti-depressants?
Inhibit the action of mono-amine oxidase enzymes (MAO-A and MAO-B), to reduce the breakdown of mono-amine neurotransmitters and increase their availability for post synaptic transmission
MOA-A breaks down serotonin, dopamine, melatonin, adrenaline and noradrenaline, so these are increased
Remeber - similar to PD, these drugs inhibit the breakdown of dopamine
What are some examples of MAOI anti-depressants?
Phenelzine
What is the mechanism of action of NaSSA antidepressants? (noradrenergic and specific serotonergic)
Antagonises the adrenergic alpha2-autoreceptors in the presynaptic neuron membrane – these receptors inhibit exocytosis of adrenaline or noradrenaline, so antagonising them increases exocytosis of the NTs.
What are some examples of NaSSA antidepressants?
Mirtazapine
What is the mechanism of action for serotonin antagonists and reuptake inhibitors (SARIs)
Inhibits the reuptake of serotonin by blocking the serotonin transport protein, antagonises 5-HT-2A receptors, H1 receptors, and alpha-1-adrenergic receptors, and redirects the serotonin to areas that help regulate mood
I think 5HT2a has a wider role in things outside of mood stabilisation, so by blocking it you redirect more to mood?
What is an example of a SARI antidepressant?
Trazodone
What is the mechanism of action of anti-convulsants for anxiety?
Inhibits release of excess excitatory neurotransmitters like glutamate by binding to the widely distributed voltage-dependent sodium/calcium channels in the overexcited neurons of the brain and spinal cord
What are the side effects of carbamazepine?
Carbamazepine - CARBA MEAN - confusion, ataxia, blurred vision, aplastic anaemia, bone marrow suppression, eosinophilia, agranulocytosis, neutropenia. Also an enzyme inducer.
What is an example of an anti-convulsant used for anxiety?
Pregabalin
What is the mechanism of action of benzodiazepines used for anxiety?
Benzos enhance the activity of the inhibitory neurotransmitter GABA by facilitating it’s binding to GABA receptors, producing a sedative effect
What are the side effects of benzodiazepines for anxiety?
Drowsiness, difficulty, concentrating, headaches, vertigo, an uncontrollable shake or tremble in part of the body (tremor) , low sex drive
What are some examples of benzodiazepines used for anxiety?
Usually diazepam
What is the function of the mesolimbic dopaminergic pathway and where does it travel from and to?
Reward pathway, transmitting dopmaine from the ventral tegmental area to the ventral striatum
What is the function of the mesocortical dopaminergic pathway and where does it travel from and to?
Cognition and emotion, transmitting dopamine from the VTA to the prefrontal cortex
What is the function of the nigrostriatal dopaminergic pathway and where does it travel from and to?
Movement regulation, transmitting from the substantia nigra in the midbrain to the caudate nucleus and putamen in the dorsal striatum
What is the function of the tuberoinfundibular dopaminergic pathway and where does it travel from and to?
Regulates secretion of pituitary hormones, transmitting from the infundibular nucleus of the hypothalamus
What causes positive symptoms in schizophrenia?
Hyperactivity of dopamine D2 receptorsin the mesolimbic pathway
What causes negative symptoms in schizophrenia?
Negative symptoms, such as flattened affect, are attributed to thehypoactivity of the dopamine D2 receptorsin the mesocortical pathway
What are the extrapyramidal side effects of antipsychotics and which type are they most common with
Acute Dystonia
Akathisia
Parkinsonism
Tardive dyskinesia
(ADAPT)
What are the common signs of neuroleptic malignant syndrome?
Triad of fever, muscle rigidity and altered mental status (drowsiness, agitation, confusion, delirium, coma), as well as autonomic dysfunction (labile BP, tachypnoea, tachycardia, sweating and flushing)
What are the signs of anticholinergic toxicity?
Flushing and feeling hot (from vasodilation), anhidrosis (dry mucous membranes, not sweating), mydriasis, fever, urinary retention, tachycardia, arrhythmias
Progresses to altered mental status (delirium, hallucinations, agitation, restlessness, confusion),
ACh controls the parasympathetic NS, gland secretion (tears, saliva, digestive juices, milk), urine release, cognitive functions such as memory etc
What is the mechanism of action of first generation antipsychotics?
Inhibition of D2 dopaminergic receptors in the mesolimbic pathway of the brain, leading to a decrease in the incidence of positive symptoms. They also have noradrenergic, cholinergic and histaminergic blocking properties.
What are some examples of common anticholinergic side effects of typical antipsychotics?
Dry skin, blurred vision, tachycardia, constipation, vomiting, sedation (due to antihistamine effects),
What are some examples of first generation antipsychotics?
Haloperidol, droperidol, fluphenazine, chlorpromazine, prochlorperazine, loxopine
What is the mechanism of action of second generation antipsychotics?
Inhibition of D2 dopamine receptors in the mesolimbic pathway of the brain, leading to a decrease in the incidence of positive and negative symptoms. This is as well as serotonin receptor (5-HT2A) antagonist action
Is QTc prolongation more of a concern with first or second generation antipsychotics?
Second generation
Are extrapyramidal side effects more common in first or second generation antipsychotics?
First generation
What are some common or dangerous side effects of clozapine?
Common: hypersalivation, tachycardia, hypotension, constipation
Serious: agranulocytosis and leukopenia, bowel ileus/obstruction, lower seizure threshold, myocarditis/cariomyopathy
What are some examples of second generation antipsychotics?
Olanzapine, quetiapine, clozapine, risperidone, Iloperidone, aripiprazole
What are the signs of lithium toxicity?
- Nausea, vomiting, tremor, fatigue (mild)
- Confusion, agitation, delirium, tachycardia, hypertension (moderate)
- Coma, seizures, hyperthermia, hypotension (severe)
What are the theorised mechanisms of action of lithium?
It’s not well understood, but it’s thought that it either interferes with inositol triphosphate formation or cAMP formation
What are the types of lithium?
Lithium carbonate, lithium citrate
What anticonvulsants are used as mood stabilisers?
Carbamazepine, lamotrigine, valproate
What antipsychotics are used as mood stabilisers in an acute manic episode?
Haloperidol, olanzapine, quetiapine, risperidone
For how long should antidepressants be continued before stopping, to reduce the risk of relapse?
Antidepressants should be continued for at least 6 months after remission of symptoms to decrease risk of relapse
How long do antidepressants take to work?
between 3-6 weeks, but may be as quick as 1 week or as long as 3 months
What foods should patients on MOAIs (phenelzine) avoid and why?
Cheese - it can cause a hypertensive crisis. Remember, MAOuses like cheese!
Which atypical antipsychotic has the most favourable side effect profile?
Aripiprazole - especially for prolactin related symptoms like gynaecomastia
What is the most common side effect of atypical antipsychotics like olanzapine?
Weight gain
What is the potential risk of an SSRI+NSAID?
GI bleed - prevented with a PPI
When should lithium levels be checked?
7 days after initiation/change, the sample should be taken 12 hours post-dose
How is alcohol withdrawal managed in people with liver cirrhosis/hepatic impairment?
Lorazepam - chlordiazepoxide is metabolised extensively by the liver and has a longer half-life than lorazepam
How do ACh inhibitors like donezapil and rivastigmine help in dementia?
Acetylcholinesterase inhibitors inhibit breakdown of ACh in synapses to boost ACh in the synpase, which stabilises deterioration for a year or 18 months (but doesn’t slow progression)
What is a side effect of TCAs?
Urinary retention, dry mouth, blurred vision, drowsiness, constipation etc. due to antimuscarinic effects
What are the metabolic side effects of antipsychotics?
Metabolic side effects of antipsychotics include dysglycaemia, dyslipidaemia, and diabetes mellitus
What medications should be avoided in patients taking an SSRI?
Triptans (or anything that increases serotonin)
Which psychiatric drug causes hyperparathyroidism?
Long-term lithium use can result in hyperparathyroidism and resultant hypercalcaemia
Which SSRI is most likely to lead to QT prolongation
Citalopram
What is the mechanism of action of methadone and buprenorphine in supporting opioid addicts?
Binds and agonises opioid receptors to reduce side effects and prevent cravings
What is the mechanism of action of naltrexone in supporting opioid addicts?
It binds and antagonises opioid receptors, blocking the effect of opioids and preventing intoxication in former opioid addicts
How is acute dystonia managed?
Procyclidine
What medication should SSRIs not be prescribed with, and why?
Triptans, increases risk of serotonin syndrome
When should patients <25 be reviewed after starting an SSRI and why?
Patients ≤ 25 years who have been started on an SSRI should be reviewed after 1 week
What are some side effects of NaSSA antidepressants?
Sedation, increased appetite (this is why mirtazapine is good for people who can’t sleep or who are losing weight)
Which SSRI is preferred in children and adolescents?
Fluoxetine is the SSRI of choice in children and adolescents
Which SSRI is most likely to lead to QT prolongation and Torsades de pointes?
Citalopram
Which antipsychotic has the most tolerable side effect profile?
Aripiprazole (especially for prolactin elevation-related side effects)
How is tardive dyskinesia managed?
Tetrabenazine
Which 2 antidepressants should never be prescribed together, and why?
SSRIs and MAOIs should never be combined as there is a risk of serotonin syndrome
What are the side effects of TCAs?
Dry mouth, constipation, blurred vision (anticholinergic) and weight gain and drowsiness (antihistaminic) are side effects of TCAs
What is the MOA of TCAs?
Serotonin (5-HT): This neurotransmitter has a pivotal role in mood regulation. Inhibition of its reuptake leads to increased concentrations in the synaptic cleft, enhancing serotonergic neurotransmission.
Noradrenaline (NA): Similar to 5-HT, blocking the reuptake of NA increases its synaptic cleft concentration, intensifying noradrenergic neurotransmission.
What monitoring do SNRIs need?
BP - NICE recommend that all patients have their blood pressure monitored at initiation and each dose titration of venlafaxine.
What monitoring does citalopram need?
ECG as it can cause QT prolongation
What are the side effects of lithium?
Leucocytosis
Increased urine output
Tremor (fine)
Hypothyroid
Increased weight gain
Upset stomach (diarrhoea)
Mum’s beware (Ebstein anomaly)
Nephrogenic diabetes insipidus (AVP resistance)
What are the symptoms of neuroleptic malignant syndrome?
Fever
Autonomic dysfunction
Rigidity (lead pipe rigidity)
Mental status altered
What is the acronym to remember the symptoms of serotonin syndrome?
MAN
Mental status changes
Autonomic hyperactivity (hyperthermia, hypertension, tachy)
Neuromuscular abnormalities (clonus, spasticity)
GI symptoms (diarrhoea, N/V, abdominal pain)
What blood results are seen in neuroleptic malignant syndrome
Elevated CK, elevated WCC
How is NMS managed?
Stop the offending antipsychotic, correct electrolyte imbalances and volume deficits, give dopamine agonists (bromocriptine), dantrolene to relax the muscles, cooling methods don’t work. If rhabdomyolysis and acute kidney injury occur then alkalinisation of urine and dialysis are often required.
do a dance
What are some important side effects of atypical antipsychotics?
QT prolongaiton
Hyperprolactinaemia => menstrual abnormalities and sexual dysfunction (normally typical, but risperidone is a notable cause)
Dyslipidaemia and impaired glucose metabolism
Weight gain
What condition is memantine contraindicated in?
Uncontrolled hypertension (Can cause a hypertensive crisis)
What condition is donepezil contraindicated in?
Bradycardia is a contraindication as these medications can exacerbate or cause bradycardia by increasing vagal tone, potentially leading to heart block or syncope
What is the mechanism of action of procyclidine?
Anticholinergic
What monitoring should be done before starting lithium?
U&Es, TFTs, ECG, FBC
What should be monitored during lithium treatment? How often?
TFTs, U&Es, eGFR, every 6 months
How often are lithium levels checked?
One week after starting treatment, one week after every dose change, then weekly until stable. Following this, every 3 months.
How often are clozapine levels measured?
Clozapine requires differential white blood cell monitoring weekly for 18 weeks, then fortnightly for up to one year, and then monthly as part of the clozapine patient monitoring service
What is the mechanism of action of opioids? What are some examples?
Stimulates opioid receptors
Heroin
What is the mechanism of stimulants?
Cocaine blocks the reuptake of dopamine (D and C are next to each other in the alphabet)
MDMA (ecstacy) increases dopamine release and blocks it’s reuptake
Meth stimulates serotonin release and blocks it’s reuptake
What is the mechanism of depressants? What are some examples?
Alcohol, benzos - stimulates GABA receptors
What is the mechanism of action of hallucinogens? What are some examples?
LSD, psilocybin (magic mushrooms) - stimulates serotonin receptors (5-HT2A)
What is the mechanism of action of nicotine?
Stimulates nicotinic ACh receptors
What is the mechanism of action of anticonvulstants like pregabalin and gabapentin?
Blocks voltage gated calcium ion channels, reducing the release of excitatory NTs
What is the mechanism of action of cannabinoids?
Stimulates cannabinoid receptors (CB1/2)
What should you check before starting a patient on anticholinesterase inhibitors such as donepazil?
ECG - due to the bradycardic effect
Contraindicated in QT prolongation, second or third degree heart block, bradycardia <50
What are the side effects of valproate?
Vomiting, alopecia, liver toxicity, pancreatitis/pancytopenia, retained fats, oedema, appetite increase, tremor/teratogenic
How long should you wait to restart antipsychotics after NMS has occurred?
2 weeks
How is serotonin syndrome managed?
Cessation of drug, observe for 6 hours to ensure it doesn’t develop if moderate to mild. Benzos can help with anxiety, cyproheptadine (anti serotonin) can help with neuromuscular excitation.
If severe, sedate, intubate etc
What are some signs of SSRI discontinuation syndrome?
Diarrhoea, abdominal cramping, vomiting, dizziness, electric shock sensations
What are some side effects of donezapil?
These drugs cause cholinergic side effects such as diarrhoea, nausea and vomiting, bradycardia, increased salivary production and urinary incontinence (think about excess ACh, or the opposite of anticholinergic side effects - can’t see can’t pee can’s spit can’t shit)
What monitoring should be done for patients on second generation antipsychotic drugs?
Weight, BMI, ECG, blood pressure, lipid levels, prolactin levels, fasting blood sugars/HbA1c
What are the signs of heroin withdrawal?
Shaky, anxiety, agitation, irritability, sweating, running eyes and nose, diarrhoea, goose pimples, piloerection, tachycardia
List some acute physical effects of dependent drug use.
Overdose - respiratory depression
SE of opiate: “rush”, drowsy, relaxed, reduced mental function, reduced RR, bradycardia, constipation, low salivary flow, heavy feeling extremities
SE of cocaine: euphoric, high energy, anxious, confident, risk taking behaviour, tachycardic, hyperthermic, vasoconstriction, local anaesthesia
List some chronic physical effects of dependent drug use.
Injecting: blood-borne virus transmission e.g. Hep C, HIV, abscesses at site of infection
Snorting: deviated nasal septum, loss of sense of smell
Smoking: worsening of chronic lung diseases like asthma, COPD
General: weight loss
Increased risk of: CVD, liver failure, seizures, stroke, cancer
Effects of poverty on health
List some social effects of dependent drug use:
Effects on families / relationships
Social exclusion
Unemployment
Homelessness
Driven to criminality –> imprisonment
List some psychological effects of dependent drug use:
Increased risk of anxiety, depression, psychosis
Symptoms of dependence such as fear of withdrawal, narrowing of the repetoire, tolerance, guilt - all are temporarily alleviated by drug use.
How does heroin act? How is it used?
Acts at opiate receptors; used 8 hourly
Routes of administration:
> smoking / snorting
> oral / rectal
> sub cut / IV / IM
What are the “beneficial” effects of heroin?
Euphoria
Intense relaxation
Miosis (excessive pupil constriction)
Drowsiness
What are the “negative” effects of heroin?
Acute: reduced HH, HR, drowsiness, reduced concentration/mental function
Chronic:
Dependence
Withdrawal symptoms
Abscess, cellulitis and infection at sites of injection
Opportunistic infections from being immunocompromised
DVT from injection of insoluble debris (drugs might be cut badly)
Scarred and collapsed peripheral veins
Blood borne viruses
Over dose :(
How does cocaine / crack act?
Blocks re-uptake of mood-enhancing neurotransmitters at the synapse (dopamine)
Intense, pleasurable sensation
Reinforcement leads to further use
What are the “beneficial” effects of cocaine / crack?
Confidence, well-being, euphoria, impulsivity, increased energy, alertness
impaired judgement, decreased need for sleep
What are the “negative” effects of cocaine / crack?
Acute effects: may produce anxiety, psychosis, hypertension, arrhythmias, tachycardia or bradycardia, coronary artery vasospasm, subarachnoid haemorrhage, seizures, hypertonia, hyperreflexia
subsequent ‘crash’ leading to dysphoria
Chronic effects: depression, panic, paranoia, psychosis, damaged nasal septum
How is lithium toxicity managed?
In secondary care the treatment is supportive and lithium levels are normally rechecked every 6–12 hours. Osmotic or forced alkaline diuresis may be required, however peritoneal or haemodialysis may be used if levels are above 3 mmol/L.
What do antipsychotics increase risk of in the elderly?
Stroke
How long is hypomania? How long is mania?
Hypomania is >4 days
Mania is >7 days
What do you do if clozapine doses are missed for 48 hours?
Start low and re-titrate up again
Can SSRIs be used in pregnancy?
Risks outweigh the benefits, as they can cause congenital malformations
What are the different assessments for diagnosing autism?
ADOS - autism diagnostic observation schedule
ADI-R - autism diagnostic interview - revised
Done in an autism assessment with a psychiatrist or paediatrician
What are the different assessments for diagnosing ADHD?
Young DIVA 5
What is the most common cause of a painful third nerve palsy?
Posterior communicating artery aneurysm, found in the circle of Willis
What are sympathomimetic drugs?
Cocaine, amphetamines - stimulants that mimic the effects of the sympathetic NS