308 Drugs of psychiatric disorders Flashcards
Name some SSRI’s
Fluoxetine
Paroxetine
Sertraline
Citalopram
Escitalopram
What are the indications for SSRI’s?
-Depression
-Anxiety disorders
-Panic disorders
-OCD
-PTSD
Which SSRI has the shortest half life?
Paroxetine (20 hours)
Which SSRI has the longest half life?
Fluoxetine (2-4 days)
But active metabolite has 14 day half life
How do SSRI’s work?
They prevent the reuptake of serotonin so it stays in the synaptic cleft longer and has more of a chance of acting
What are the main side effects of SSRI’s?
-Agitation and anxiety
-Dizziness, balance problems
-Nausea, diarrhoea
-Flu-like symptoms
Occur on abrupt cessation of the SSRI
How does Mirtazapine work?
It’s a noradrenergic and specific serotonergic antidepressant (NaSSA)
It works on alpha-2 receptors to cause continuous release of serotonin and noradrenaline without breaks
What are the side effects of Mirtazapine?
-Helps people to fall asleep
-Causes hunger and therefore weight gain
Name some tricyclic antidepressants
-Amitrptyline
-Imipramine
-Lofepramine
-Dothiepin
Why are tricyclic antidepressants not commonly used?
- Worse side effects
- Dangerous with overdose
Dothiepin: most cardio toxic
How do tricyclic antidepressants work?
They bind to reuptake inhibitors which increase the levels of neurotransmitters in the synaptic cleft
What are some side-effects of tricyclic antidepressants?
-‘They’re dry’: cause dry mouthy, constipation, urinary retention, cognitive effects (confusion)
-Psychotropic effects (agitation, nightmares)
-Sexual dysfunction
-Akathisia (restlessness)
-Muscle twitches
-Cardiac arrhythmias (QT interval)
How does Venlaflaxine work?
It’s a serotonin and noradrenaline reuptake inhibitor (SNRI)
Often combines with Mirtazapine in treatment resistant depression (Referred to as California rocket fuel)
What are some side effects of Venlafaxine?
-Headaches
-Nausea
-Hypertension
-Discontinuation syndrome
What alternative uses of Duloxetine are there?
An SNRI that doesn’t come with the risk of hypertension
Used for diabetic neuropathy and urinary stress incontinence at different doses and depression
How do MAOI’s work?
They prevent the action of monoamine oxidase which stops noradrenaline and serotonin being broken down
What are the food interactions of MAOI’s?
Most cheese
Red wine
Yeast production liver
Broad bean pods
Fermented sausages Eg. salami
These cause the tyramine reaction which is normally prevented by monoamine oxidase
What does an accumulation of tyramine cause?
A hypertensive crisis
Why are MAOI’s not commonly used?
-Lots of food interactions
-Increased risk of serotonin syndrome (so can’t be combined with SSRI’s. If medication is being switched, time is given for the medication to wash out of the system before the new medication is started)
Name some SNRI’s
Venlafaxine
Duloxetine
Name some tricyclic antidepressants
Amitriptyline
Dothiepin
How do tricyclic antidepressants work?
They block the serotonin and noradrenaline reuptake pump
Name some MAOI’s
Phenelzine
Monclebamide
Name some tetracyclic antidepressants
Mirtazapine
Which neurotransmitter do antipsychotic medications work?
Dopamine
Which receptors does dopamine work on?
Metabotropic G-protein coupled receptors
What is the precursor to dopamine?
Tyrosine
What does dopamine do?
Executive functions
Motor control
Motivations
Reward
Lactations
Nausea
Name some dopamine pathways in the brain
Mesocortical
- from VTA to prefrontal cortex
Mesolimbic
- from VTA to nucleus accumbens
Tuberoinfundibular
- from hypothalamus to pituitary gland
Nigrostriatal
- from substantia nigra to caudate nucleus and putamen
What is the VTA?
The ventral tegmental striatum
What is the mesocortical pathway for?
Motivation
Emotion
Executive functions
What is the Mesolimbic pathway for?
Pleasure and reward
What is the Tuberoinfundibular pathway for?
Regulates prolactin secretion to the pituitary gland
What is the Nigrostriatal pathway for?
Voluntary movement through basal ganglia motor loops. It can influence cognition, reward, and addiction
Decreased function in which brain pathway causes negative symptoms of schizophrenia?
The mesocortical pathway
Increased function in which brain pathway causes positive symptoms of schizophrenia?
The mesolimbic pathway
Why are antipsychotics most effective at treating positive symptoms?
Because they block the effect of dopamine
Positive symptoms are caused by too much dopamine
How do antipsychotics cause hyperprolactinaemia?
Dopamine has an inhibitory effect on prolactin release and antipsychotics block dopamine
What are extrapyramidal side effects?
Symptoms like:
inability to sit still
involuntary muscle contraction
tremors
stiff muscles
involuntary facial movements
Parkinsonism
Dystonias
Tardive dyskinesia
Hyperprolactinaemia
How do antipsychotics cause extrapyramidal side effects?
Dopamine is needed in the nigrostriatal pathway. Decreased dopamine causes the symptoms
What are the symptoms of raised prolactin?
Lactation
Amenorrhoea
Sexual dysfunction
Osteoporesis
What is the serotonin hypothesis of depression?
It’s a theory as to the cause of depression
Some hallucinogenic drugs like LSD have structural resemblance to serotonin, some newer antipsychotics act on serotonin receptors eg, clozapine
What is the glutamate hypothesis?
Theory that there is abnormal glutamate activity in schizophrenia
Phenocyclidine (PCP) is a glutamate agonist that produces schizophrenia-like symptoms
What are neuroleptic drugs?
Another name for typical antipsychotics
What is the difference between typical and atypical antipsychotics?
Typical antipsychotic drugs act on the dopaminergic system, blocking the dopamine type 2 (D2) receptors
Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors, and a high degree of occupancy of the serotoninergic receptors 5-HT2A
What are the main symptoms of typical antipsychotics?
Parkinsonism
Akathisia
Dystonia
Tardive dyskinesia
Give examples of typical antipsychotics
Butyrophenones:
Haloperidol
Phenothiazines:
Chlorpromazine
Trifluoperazine
Fluphenazine
Thioxanthines:
Flupenthixol
Name some atypical antipsychotics
Risperidone
Olanzapine
Quetiapine
Aripiprazole
Which are newer, atypical or typical antipsychotics?
Atypical antipsychotics
What is tardive dyskinesia?
A condition where your face, body or both make sudden, irregular movements which you cannot control
Typical symptoms include facial grimacing, sticking out the tongue, sucking or fish-like movements of the mouth
What are some muscarinic (cholinergic) receptor side effects of antipsychotics?
Blurred vision
Dry eyes
Dry mouth
Tachycardia
Dyspepsia
Constipations
Dizziness
Impaired memory and congition
What are muscarinic receptors?
They’re activated by acetylcholine
Associated mainly with parasympathetic functions
What are some alpha adrenergic receptor side effects of antipsychotics?
Orthostatic hypotension
Vertigo
Palpitations
Sexual dysfunction
How do antipsychotics cause vertigo?
Because they can lower blood pressure
What is the difference between alpha and beta adrenergic receptors?
Alpha adrenoceptors mediate smooth muscle contraction and vasoconstriction
Beta (β) receptors mediate vasodilation, smooth muscle relaxation, bronchodilation, and excitatory cardiac function
What is vertigo?
Dizziness
What is the most effective antipsychotic?
Clozapine
It’s used for treatment resistant cases because it has a lot of side effects
What are some side effects of clozapine?
Hypersalivation
Hypotension
Haematological problems
Constipations
Blurred vision
Fast, pounding, or irregular heartbeat
Drowsiness
Trembling hands and legs
Which antipsychotics can be given for rapid tranquillisation?
Haloperidol
Olanzapine
Lorazepam
Midazolam
Name some mood stabiliser medications
Lithium
Sodium valproate
Lamotrigine (Carbamazepine)
Rarely used: gabapentin
What are the advantages of using lithium?
It reduces suicidality
Reduced signals that contribute to mania
Which medication inhibits inositol?
Lithium
What is Inositol?
Also called myo-inositol, D-chiro-inositol, or hexaphosphate (IP6)
It plays a critical function in the body’s cellular growth. Though it used to be referred to as Vitamin B8, inositol is not actually a vitamin. It’s a type of sugar that helps your body process insulin
How does Lithium act in the body?
At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission
What are the side effects of Inositol deficiency?
Hair loss (alopecia)
Skin problems such as eczema (extremely dry, itchy skin)
Mental health symptoms such as troubles with sleep, mood, anxiety.
Constipation.
Hyperlipidemia (too many fats such as cholesterol or triglycerides in the blood).
Muscle weakness
What are the short term side effects of lithium?
Polydipsia and polyuria
Nausea
Fine hair
Loose stools
How does lithium cause alopecia?
Because it causes a hypoactive thyroid
What are the long term side effects of lithium?
Renal impairment
Hypothyroidism
Weight gain
Acne
How does lithium cause acne?
When lithium is taken, many neutrophils move from the bloodstream to the skin, where they can cause inflammation and increase the likelihood of pimples
How does lithium cause hypothyroidism?
It inhibits iodine uptake
How does lithium cause polyuria and polydypsia?
The most common renal side effect of lithium is of concentrating urine despite normal or elevated concentrations of the antidiuretic hormone vasopressin
The concentrating defect leads to decreased urine osmolality and increased urine volume (polyuria)
What is the therapeutic index of lithium?
0.4 - 1.0 mmol/L
What are the symptoms of lithium toxicity?
Coarse tremor
Nausea
Vomiting
Ataxia
Cerebellar signs
Confusion
What is a coarse tremor?
It has more of a displacement than a fine tremor (More shaking)
What can cause lithium toxicity?
Dehydration
Drug interactions Eg, NSAID’s
Deteriorating renal function
What effects does lithium have on protein kinase C and gene regulation?
Lithium decreases the phosphorylation of CREB
It decreases protein kinase C translocation
What effects does valproate have in the body?
Inhibition of Ca2+ and Na+ channels
Enhances inhibitory GABA
reduces excitatory glutamate
How does Valproate produce a calming effect?
It enhances GAMA so blocks transmission across neurones and this has a calming effect
What are the uses of valproate?
Mood stabiliser
migraine prophylaxis
What are the side effects of valproate?
VALPROATE
Vomiting
Alopecia
Liver dysfunction
Pancreatitis
Retention of fat
Oedema
Appetite increase
Tremor
Enzyme inducer
Teratogenic and causes developmental disorders (contraindicated in women of child baring age)
What are the side effects of Carbamazepine?
CABSANT
CYP450 inducer
Ataxia, diplopia
Bone marrow suppressor (thrombocytopaenia, neutropoenia)
Steven Johnson and other rashes
Aplastic anaemia
Na - Hyponatraemia (SIADH)
Teratogenic
What is a Steven Johnson rash?
Starts off as flu-like symptoms
It’s made up of circular patches that are darker in the middle and lighter around the outside
What are anxiolytic drugs?
Medications that prevent anxiety
Name some commonly-used bendodiazapines
Diazepam
Lorazepam
Clonazepam
Temazepam
Clobazam
Name a short-acting benzodiazepine
Lorazepam
Name a long-acting benzodiazepine
Clonazepam
What are the uses of benzodiazepines in psychiatry?
Hypnotics
Anxiolytics
Minor tranquillisers
Management of alcohol withdrawal
Anticonvulsant (clobazam) and muscle relaxant
How do benzodiazepines produce their effect in the body?
They bind to BZP site of GABA-A receptors (the main inhibitory neurotransmitter in the CNS)
What are the disadvantages of using benzodiazepines?
They create tolerance
- But there are people where long-term treatment is still indicated
Abrupt withdrawal can precipitate acute delirium, rarely psychosis, convulsions
Withdrawal causes nausea, hyperacusis, dizziness and imbalance, tinnitus, depersonalisation
What are hypnotic drugs?
Medications used to induce, extend, or improve the quality of sleep, and to reduce wakefulness during sleep
What is tinnitus?
Experience of ringing or other noises in the ear
What is depersonalisation?
Where you have the feeling of being outside yourself and observing your actions, feelings or thoughts from a distance
How is alcohol withdrawal managed?
Vitamin supplementation
Medications:
Acamprostate - reduces cravings
Naltrexone - reduces cravings/enjoyment via opioid receptors
Disulfiram (antabuse) - induces severe reaction if alcohol is consumed. It blocks the breakdown of alcohol
Benzodiazepines
What is Chlodiazepoxide used for?
It’s an anxiolytic
Can be used instead of diazepam
Which medications are given instead of diazepam or Chlordiazepoxide in hepatic compromise?
Oxazepam or lorazepam
What is the difference between diazepam and chlordiazepoxide?
Chlordiazepoxide has a lower abuse potential
Chlordiazepoxide is used short-term for severe anxiety, muscle spasm and alcohol withdrawal
What does pregabalin do in the body?
It binds to and modulates voltage-gated calcium channels in the CNS
Originally developed for neuropathic pain but now has a role in anxiety, panic disorders, and partial seizures
There are concerns with misuse because it gives a euphoria
What is Buspirone used for?
It’s a partial agonist ay 5HT_1a receptors
Licenced for generalised anxiety disorder but there are doubts over efficacy
