Psychopharmacology Flashcards
Pathogenesis of schizophrenia
Dopamine dysregulation
* D1 receptor inhibition elicits -ve symptoms
* D2 receptor over activation elicits +ve symptoms
Glutamate underactivity
NMDA receptor hyperfunction
Typical antipsychotics
- first gen
- Haloperidol, Chlropromazine
- Blocks D2 receptors
- around 72% blockade for best effects
side effects of typical anti-psychotics
Dystonia
Akathisia= psychomotor restlessness
Tardive dyskinesia
Atypical antipsychotics
Second generation
* E.g. Clozapine, Resperidone
* Act on a range of receptors
* Improves positive and negative symptoms
* Cause fewer extrapyramidal side effects
Pharmacological targets for atypical antipsychotics
Adrenergic system –> hypostimulation
Dopamine system –> (overstimulation)
Histamine system
Serotonin (overstimulation)
Muscarinic system –> Hypo-stimulation
Glutamate system –> Hypostimulationm
role of serotonin
Sleep and mood
Motor neuron function
Sensory transmission and autonomic and endocrine function
Different serotonin receptors that anti psychotics target
5-HT inhibits dopaminergic function.
5-HT2A receptor antagonists (e.g. Olanzapine, risperidone)
5-HT receptor modulation of dopamine release
Effects of glutamate release
Effects of GABA stimulation
Common atypical antipsychotic receptor interactions
Amisulpiride (D2 and D3)
Paliperidone (D2, 5HT and alpha antagonist)
Asenapine (D2, 5HT)
Aripiprazole= (D2, 5HT 1a and 2a)
Atypical anti-psychotic metabolic side effects
Serotonin 5-HT 2C antagonism- Weight gain, diabetes mellitus
Serotonin 5HT 1A- Weight gain
Histamine H1 antagonism-Weight gain diabetes, sedation
Dopamine D2 antagonism- EPS, weigth gain, endocrine effects
Muscarinic M1 antagonism-Anticholinergic (dry mouth, blurred vision, constipation)
Muscarinic M3 antagonism- Diabetes
treatment considerations
- Clozapine given to patients that are resistant to other antipsychotic drugs.
- Atypical antipsychotics may be more suitable to treat negative symptoms of schizophrenia.
- Choice of medication influenced by patient and HCPs.
-medical history (diabetes, CVD etc.)
-medication history
-level of sedation needed
Clozapine
- Atypical Antipsychotic
- Inhibits 5HT (2A) receptors but also binds to dopamine and GABA receptors. It induces glutamate release.
- Important adverse effects
- Agranulocytosis (low WBC count)
- Hypogastric motility leading to severe constipation in upto 80% of patients necessitating the concomitant use of laxatives.
Anxiolytics
diazepam, alprazolam, chlordiazepoxide hydrochloride, clobazam, lorazepam, and oxazepam
Anxiety: state of emotional uneasiness that occurs in an anticipatory
manner.
* Threat may not be immediate or identifiable.
* Examples of anxiety disorders:
- Generalised anxiety disorder
- OCD
- Phobias
- Social anxiety disorder
- PTSD
* Traditional treatments include benzodiazepines and
barbiturates.
- Antidepressants and antipsychotics
GABA
(Gama Amino Butyric Acid)
The GABA system is the main inhibitory neurotransmitter in the brain
E.g. Benzodiazepin
Influencing factors 0f GABA
rug administration
Age
Drug interactions
Asians more susceptible to general effects of Benzodiazepines (Ajir et al., 1997).
Alcohol consumption
Cardio-respiratory side effects of GABA meds
Decrease in systemic vascular resistance
Hypertensive or emotionally stressed pt
Effect enhanced in hypovaleamic pt
Arrhythmia
bigeminy
ventricular ectopic
vasovagal
Bradycardia/Tachycardia
