Psychiatric disease drugs 12.1 and 12.2 Flashcards
Give the 2 main ways CNS drugs work
1) Agonists or Antagonists of NT receptors ➞ compete with NT for binding site, mimic NT or block NT
2) Inhibitors of regulatory enzymes
Give an example for each catagory
Give 3 core symptoms of depression
Show 2 of 3:
- Low mood
- Anhedonia
- Decreased energy
Give 2 secondary symptoms of depression
- decreased appetite
- sleep disturbance
- reduced concentration
- Irritability
- reduced libido
- self harm or suicidal ideas or acts
Brifly explain the Monoamine Hypothesis of depression + a drug treatment and why
Depression due to deficiency of monoamine NTs ➞ NA and serotonin
Certain drugs that depleted these could induce depression e.g. Reserpine
Treatment: MAOIs, block enzyme monoamine oxidase from destroying NTs
Brifly explain the Neurotransmitter Receptor Hypothesis of depression
Abnormality in the receptors for monoamine transmission leads to depletion of NT ➞ causes compensatory up regulation of post synaptic receptors leading to depression
Brifly explain the Monoamine Hypothesis of Gene Expression
Deficiency in molecular functioning ➞ hypothesised problem within the molecular events distal to the receptor
What severity of depression are SSRIs used to treat?
Give 2 examples
Moderate - severe depression (with CBT) ➞ first line medication
- paroxetine most potent reuptake inhibitor
- citalopram most selective
Give 3 pharmacokinetics of SSRIs
- almost completely absorbed from gut
- long elimination half lives (once daily dosage)
- metabolised in liver
Give 3 common side effects of SSRIs + 2 rare
Common:
- anorexia
- nausea
- diarrhoea
Rare: precipitation of mania and increased suicidal ideation
Give 2 examples of Tricyclic antidepressants (TCAs)
Are these first line?
TCAs are first generation antidepressants
They are still used but less often and not first line
Eg. Amitryptiline, imipramine, clomipramine, lofepramine
Give 3 actions of TCAs
1) Inhibition of NA uptake ➞ sympathomimetic effect
2) Blocks Muscarinic cholinoceptors ➞ anticholinergic effect
3) Blocks α1-adrenoceptors ➞ sympatholytic effect
Give the pharmacokinetics of TCAs
- lipid soluble
- absorbed from gut
- long half lives
- metabolised in liver
Give 4 side effects/toxicity problems with TCAs
CNS: sedation + impaired psychomotor performance, lowering of seizure threshold
Autonomic: reduction in glandular secretions, block of eye accommodation
CVS: tachycardia, postural hypotension, impaired myocardial contractility
GI: constipation
What are Serotonin-noradrenalin reuptake inhibitors (SNRIs) + 2 examples
What “line” drugs are these?
‘Pure’ non-selective monoamine uptake inhibitors ➞ SSRIs with property of NA uptake inhibition
Eg. Duloxetine and Venlafaxine
Second/third line drugs
SNRIs are dose dependant, compare effect of lower vs higher doses?
Lower doses serotonin action
Higher doses noradrenaline action
Give 4 side effects/toxicity problems with SNRIs
SAME as SSRIs + sleep disturbance, increased BP, dry mouth, hyponatraemia
What is the implication of the half life and stopping treatment of SNRIs
Relatively short half-life therefore may be a withdrawal syndrome on discontinuation
Schizophrenia is an examples of a mental illness with ______ symptoms
Give 2 other conditons that also display these symtpoms
psychotic
Other examples: mania, severe depression, delusional disorder
What is psychosis?
Psychosis causes people to perceive or interpret things differently from those around them, they will have a different perspective on reality
Give 2 KEY symptoms of schizophrenia and explain each
1) Hallucination- a perception in the absence of an external stimulus (auditory, olfactory, visual, gustatory, tactile)
2) Delusion- a fixed false belief, not shaken by reasoning to the contrary, that is out of keeping with someone’s culture or religious beliefs
How is Schizophrenia diagnosed?
Give 2 environment interactions that are a/w Schizophrenia
Cannabis and Trauma
Give the 4 main dopamine pathways and the function of each
Mesolimbic- emotional response and behaviour
Mesocortical- important in arousal and mood
Nigrostriatal- key pathway damaged in Parkinson’s disease
Tuberoinfundibular - in hypothalamus and pituitary gland
Explain the dopamine theory of Schizophrenia + treatment and examples
Excessive dopamine transmission in the mesolimbic pathway
Theoried because amphetamine increases dopamine release and causes symptoms very similar to positive symptoms of schizophrenia
Could treat with dopamine antagonists BUT these do not treat negative symptoms
First generation antipsychotic drugs block ______ transmission but cause ______ side effects
dopamine, extrapyramidal
Is schizophrenia associated with increased 5-HT function
+ examples
5-HT has been implicated in a number of behaviours which are disturbed in schizophrenia (e.g. perception, attention, mood, aggression, sexual drive, appetite, motor behaviour, sleep)
Many effective antipsychotic drugs = antagonists at 5-HT-2A receptors eg Clozapine
Precursors of 5-HT (e.g. tryptophan) exacerbate schizophrenia
Is schizophrenia associated with decreased cortical glutamate function?
Glutamate is the predominant excitatory NT
Post-mortem studies have shown increased cortical glutamate receptors and increased binding of glutamate receptor ligands in cortex, basal ganglia and hippocampal formation.
BUT no current treatment
How is Schizophrenia diagnosed
Give 4 actions ALL antipsychotics will show + 2 long term s/e
- Sedation within hours
- Tranquilisation within hours
- Antipsychotic several days or weeks
- Extrapyramidal side effects hours or days
Longer term side effects ➞ tardive dyskinesia and metabolic syndrome
Give an example of a typical antipsychotics + 4 facts about these
Typical ➞ eg Haloperidol
- safe in emergencies
- more sedating
- well known side effects
- wide range of action: blocks dopamine and α adrenergic receptors + anticholinergic and antihistamine effects
Give 4 side effects/toxicity problem a/w typical antipsychotics
- Extrapyramidal side-effects
- Neuroleptic malignant syndrome
- Postural hypotension
- Weight gain
- Endocrine changes e.g. prolactinaemia
- Pigmentation
Give an example of 2 extrapyramidal side-effects
Parkinsonism, acute dystonia, akathasia, tardive dyskinesia
What is Neuroleptic malignant syndrome?
Severe rigidity, hyperthermia, increased CPK, autonomic lability
Give 4 advantges of Atypical antipsychotics
- Less EPSE
- different preparations e.g. dissolvable
- some once daily dosage
- differing side effect profiles can be matched to patient characteristics
What is the first line treatment in schizophrenia recommended by NICE
Atypical antipsychotics
Give 4 side effects of atypical antipsychotics
- extrapyramidal side effects at HIGH doses
- weight gain- e.g. olanzapine
- increased prolactin e.g. risperidone
- sedation
Vary between drugs
Which antipsychotic is used for treatment-resistant schizophrenia and the only one proven to reduce negative symptoms and aggression?
Give 2 disadvantges of this drug
Clozapine
1) Effective but many side effects ➞ CNS depression, cardiac toxicity, risk of sudden death with high dose
2) Requires regular blood tests due to risk of agranulocytosis
What are Anxiety disorders + examples
Fear out of proportion to situation resulting in avoidance
- Eg. Fear of dying, going crazy
Can also present with physical symptoms
- Eg. light headedness, SoB, hot/cold flushes, nausea, palpitations, numbness, pins and needles
How do we treat anxiety?
Non pharmacological approaches first line - CBT
Treat any co-morbid disorder
Drugs- antidepressants and anxiolytics
Give 3 principle neurotransmitter systems involved in anxiety
GABA, serotonin (5-HT), Noradrenaline
Give 2 examples of Benzodiazepines
+ the 2 main BDZ receptors and how they differ
Diazepam and lorazepam
Exerts effects through structure known as GABABDZ receptor complex ➞ 2 main groups high and low affinity (high responsible for anticonvulsant effects of BDZs)
BDZ act as full agonists at these receptor sites which lead to enhancement of GABA
Give 4 pharmacokinetics of Benzodiazapines
- Good oral bioavailability
- Highly lipid soluble + rapid CNS diffusion
- Renal excretion
- Long half life
What is a risk of long term OR stopping of bezodiazapine treatment?
Tolerance and Dependence
Tolerance ➞ need to increase the dose to achieve the same effect.
Dependence on discontinuation of treatment ➞ withdrawal effects such as insomnia, agitation, anxiety
Give 3 common side effects of benzodiazepines
+ one occasional and one rare side effecr
- drowsiness
- dizziness
- psychomotor impairment
Occasional ➞ dry mouth, blurred vision, GI upset, ataxia, headache, reduced blood pressure
Rare ➞ amnesia, restlessness, rash
Give 2 things which may occur if benzodiazepines are taken during pregnancy
Foetal cleft lip and palate
Respiratory depression + feeding difficulties in baby If taken late in pregnancy
How do we treat a benzodiazepines overdose?
Flumazenil ➞ antagonist/partial inverse agonist at BDZ receptors may be useful in reversing effects
What is Bipolar Disorder + what is the main treatment
Episodes of Depression and hypomania/mania
Treatment ➞ Lithium
Give 4 features of Mania
Give 4 examples of Mood stabilisers
- Lithium
- Sodium valproate
- Carbamazepine
- Lamotrigine
- Antipsychotics
What is the Lithium theory
1) Electrolytes and channels may compete with Mg and Ca2+ ions
2) NT-Li increases 5-HT ➞ chronic Li may reduce 5-HT receptor sites
3) Second messenger systems ➞ lithium attenuates the effects of certain NTs on their receptors without altering receptor density
Give 3 pharamcokinetics of Litheium + the clinical implication of these
1) renal excretion ➞ check renal function before starting + every 6 months (and thyroid b/c risk of hypothyroidism)
2) slow release preparations can be given once daily
3) narrow therapeutic window ➞ must be taken within 12 hours of last oral dose and requires monitoring (at least 3/month)
Give 4 common side effects of lithium + 4 other effects
- Memory problems
- Thirst
- Polyuria
- Tremor
- Drowsiness
- Weight gain
Other effects ➞ effect on kidneys, endocrine changes, hair loss and ashes
Give 4 toxic effects of Lithium
- vomiting
- diarrhoea
- coarse tremor
- dysarthria
- cognitive impairment
- restlessness
- agitation
How doe we treat Lithium toxicity
- supportive measures
- anticonvulsants
- increase fluid intake / IV Fluids etc
- haemodialysis may be necessary
Give 2 classes + drug examples for dementia medication
What severity of dementia is each recommended for?
ACh Inhibitors (mild-moderate) ➞ donepezil, galantamine, rivastigmine
NMDA antagonist (severe)➞ Memantine
Give 4 Important side effects of ACh Inhibitors
- nausea, vomiting, anorexia, diarrhoea
- fatigue insomnia, headache
- bradycardia
- worsening of COPD
- gastric/duodenal ulcers
Give 4 common side effects of Memantine
- Hypertension
- dyspnoea
- headache
- dizziness
- drowsiness
Why is Memantine useful in Alzheimer’s Disease
Blocks the NMDA receptor (glutamate receptor)
It is thought that excess glutamate leads to neuronal excitability and excessive stimulation in Alzheimer’s Disease
