Psychopharmacology - drugs Flashcards
Antipsychotics - both generations
Mechanism of action
Dopamine (D2) antagonists at post synaptic receptors
There are three main loops affected in the CNS:
1) mesolimbic/mesocortical (midbrain to limbic system/frontal cortex
Blocking this probably causes most antipsychotic effect
2) nigrostriatal pathway (substantia nigra to striatum (basal ganglia))
3) hypothalamus - pituitary gland (tuberohypophyseal) pathway
X) there are also D2 receptors in the chemoreceptor trigger zone
Antipsychotics - first generation - typical
Side effects (1/2)
from blocking the nigrostriatal pathway
(neurological)
movement abnormalities:
- acute dystonic reactions - parkinsonian symptoms/muscle spasms
- akathisia (a state of inner restlessness)
- neuroleptic malignant syndrome (rare)
All occur early after treatment
tardive dyskinesia - months/years later
- pointless, involuntary repetitive movements (lip smacking) - may be permanent
Antipsychotics - first generation - typical
Side effects (2/2)
from blocking the nigrostriatal pathway
(others)
Drowsiness
Hypotension
QT prolongation ( => arrhythmias)
Erectile dysfunction
Tuberohypophyseal blockage can cause hyperprolactinaemia
Danger of using Antipsychotics - first generation - typical in a dementia patient?
increased risk of stroke and death
Name some Antipsychotics - first generation - typical
haloperidol
chlorpromazine
prochlorperazine
Haloperidol is what type of drug is it?
Antipsychotics - first generation - typical
Chlorpromazine is what type of drug is it?
Antipsychotics - first generation - typical
Prochlorperazine is what type of drug is it?
Antipsychotics - first generation - typical
Antipsychotics - first generation - typical
Uses
= Psychomotor agitation
= Schizophrenia - if metabolic side effects of atypical antipsychotics is going to be a problem
= Bipolar disorder - acute
= nausea and vomiting control - especially in palliative setting
Atypical antipsychotics - second generation
Mechanisms (how they differ from first generation
Still block D2 receptors
But also affect other receptors too.
‘Looser D2 binding’
Better for treatment resistant forms of schizophrenia
Atypical antipsychotics - second generation
Side effect profile
Degree of sedation Parkinsonian symptoms can happen but less than with first generation typical antipsychotics Metabolic disturbances: Weight gain, diabetes, lipid changes Long QTc - arrhythmias Hyperprolactinaemia (risperidone esp)
How is prolactin release usually controlled?
Prolactin is produced in the lactotroph cells of the anterior pituitary gland, under inhibitory control by dopamine (less dopamine = more prolactin)
Hyperprolactinaemia
In women, hyperprolactinaemia inhibits gonadotrophin secretion (follicle-stimulating hormone (FSH) and luteinising hormone (LH)), leading to menstrual dysfunction. It also may cause galactorrhoea.
In men, hyperprolactinaemia has a direct, reversible effect on the hypothalamus, causing secondary hypogonadism which results in reduced libido and erectile dysfunction.
Name some Atypical antipsychotics - second generation
Risperidone, olanzapine, clozapine, quetiapine
What is Risperidone
Atypical antipsychotics - second generation
First line
What is Olanzapine
Atypical antipsychotics - second generation
First line
What is Clozapine
Atypical antipsychotics - second generation
Second line
What is Quetiapine
Atypical antipsychotics - second generation
What is Modecate
Fluphenazine decanoate
Long acting ‘depot’ injection
Anti psychotic given every 2-5 weeks
What is aripiprazole
Atypical antipsychotic
Best for not affecting the QTc
Doesn’t have loads of side effects relatively
What is Dopamine’s effect on blood pressure
Dopamine (dopamine hydrochloride) is a catecholamine drug that acts by inotropic effect on the heart muscle (causes more intense contractions) that, in turn, can raise blood pressure
Selective serotonin reuptake inhibitors
Mechanism of action
Inhibit neuronal reuptake of serotonin (5-HT) so that there’s more for neurotransmission
Metabolised by the liver
Selective serotonin reuptake inhibitors
Side effects
GI upset, appetite and weight can go up/down Skin rash (hypersensitivity reactions) Hyponatraemia - confusion May increase suicidal thoughts Bleeding
Sudden withdrawal - GI upset, neuro/flu symptoms, sleep disturbance
Name some selective serotonin reuptake inhibitors
citalopram
fluoxetine
sertraline
escitalopram
What is Citalopram
Selective serotonin reuptake inhibitor
(fewer interactions with other drugs)
Prolong QTc
PO
What is Fluoxetine
Selective serotonin reuptake inhibitor
PO
What is Sertraline
Selective serotonin reuptake inhibitor
PO
What is Escitalopram
Selective serotonin reuptake inhibitor
PO
(fewer interactions with other drugs)
How long should SSRIs be continued after symptoms stop?
6 months
First line treatment for moderate to severe depression
- or in mild if psychological treatments fail
SSRIs
Tricyclic anti depressants
Mechanism of action
Inhibit neuronal reuptake of serotonin and noradrenaline
Also block muscarinic, histamine (H1), a1, a2 and dopamine receptors
Work from the first week
Tricyclic anti depressants
Side effects
Anti muscarinic - dry mouth, constipation, urinary retention
H1/a1 blockage - sedation, hypotension
Dopamine block - prolactin up etc, and parkinsonian symptoms
More toxic than SSRIs so dont use if suicide risk
Name some tricyclic anti depressants
Amitripyline, lofepramine
What is Amitriptyline
Tricyclic anti depressant
Also good for neuropathic pain
What is Lofepramine
Tricyclic anti depressant
What is Amisulpride
selective dopamine receptor antagonist with high affinity for mesolimbic D2 and D3 receptors.
atypical antipsychotic
What is Valproate
- First choice for generalised seizures
- mood stabiliser - for manic episodes and for prophylaxis
Weakly inhibits neuronal Na channels and increases brain GABA
Teratogenic is first 1/3 of pregnancy (but 90% chance baby will be okay)
What is Lithium
Mood stabliser
First line in bipolar disorder
monitoring required. aim for 0.5-1mmol/l
Serotonin noradrenaline receptor inhibitors (SNRI)
Name 3
venlafaxine
desvenlafaxine
duloxetine
(mirtazapine isnt an SNRI but works on a2 adrenoceptors and 5HT2c’s so does increase NAd+5-HT)
What is Venlafaxine
SNRI
5-HT uptake inhibitor, but less selective for 5-HT versus noradrenaline than SSRIs. It is metabolised to desvenlafaxine, which is also antidepressant.
What is Duloxetine
SNRI
inhibits NA and 5-HT uptake.
Bupropion is a
noradrenaline and dopamine uptake inhibitor.
What is Mirtazapine
blocks α2 adrenoceptors and 5-HT2C receptors, enhancing noradrenaline and 5-HT release.
causes sedation - so take at night
Symptoms of lithium toxicity
when above 1.5mmol/l
Nausea, vomiting, diarrhoea, confusion,
excessive sleeping, seizures, myoclonic jerks and coarse tremor
What may happen if you suddenly stop SSRIs?
Sudden withdrawal of SSRIs can cause gastrointestinal upset, neurological and influenza-like symptoms and sleep disturbance.
Low mood and peptic ulcer. Prescribe SSRI? Why?
SSRIs increase bleeding risk If patient (without peptic ulcers) is taking aspirin/NSAIDs and needs SSRI - gastro-protection should be prescribed too
Side effects of SNRIs
GI upset (dry mouth, nausea, weight changes, diarrhoea/constipation) CNS - (headache, weird dreams, insomnia, confusion, seizures)
Benzodiazepines - what do they do and how?
Facilitate GABA binding to receptors (main inhibitory neurotransmitter)
- depressant effect on synapses
- reduced anxiety, sleepiness/sedation, anti-convulsive effect
Uses of benzodiazepines
First line for Seizures/status epilepticus (lorazepam) as well as alcohol withdrawal reactions (chlordiazepoxide)
Short term treatment of insomnia/anxiety (if distressing)
Name some long acting benzodiazepines
Diazepam, lorazepam, chlordiazepoxide
Long acting for seizures, alcohol withdrawal etc
Name some short/intermediate acting benzodiazepines
Midazolam (sedation for procedure) Short
Temazepam - intermediate
Carbamazepine - uses in psych etc
For focal seizures, trigeminal neuralgia, and bipolar prophylaxis if the other drugs arent working
teratogenic tho
Gabapentin
Binds to calcium channels - stopping neurotransmission
(Closely related to GABA in structure. This is irrelevant to its action though)
Migrane prophylaxis
Neuropathic pain
Add on for focal seizures
CAn cause drowsiness/dizziness
Can make urine dipsticks look like there is protein in urine #FalsePositive
Pregabalin
Binds to calcium channels - stopping neurotransmission
Generalised anxiety disorder
Focal epilepsy add on
neuropathic pain
SE: drowsy/dizzy
Z drugs - action & effect
Like benzo’s - open the GABA channels causing sedation - they are hypnotic drugs, generally with a shorter duration than benzo’s
only use short term - dependence can occur. good for specific, acute situations (night before surgery etc)
name 2 Z drugs
zopiclone
zolpidem
Define hypnotic
A drug which will sedate when given during the day - provokes drowsiness facilitating sleep
Anxiolytics
‘sedatives’ will induce sleep when given at night
but mainly kinda to treat anxiety - reduces anxiety, causing calm and quietness in patient
