Antipsychotics Flashcards
What is considered to be the “pleasure center” of the brain and is a major target of mesolimbic/mesostriatal dopamine neurons in the ventral emotional striatum?
Nucleus accumbens
What is the result of normal stimulation of mesolimbic D2 receptors?
Experience of pleasure
What is the result of excessive stimulation of mesolimbic D2 receptors?
Positive symptoms of psychosis
What is the result of D2 receptor antagonism/partial agonism in the mesolimbic pathway?
Reduction of positive symptoms of schizophrenia AND blockade of reward system, which leads to feelings of apathy, anhedonia, avolition, disinterest, and a lack of joy from social interactions
What is the result of blocking mesolimbic/mesostriatal dopamine D2 receptors?
Secondary (medication-induced) negative symptoms
What is the result of targeting tuberoinfundibular dopamine D2 receptors with D2 antagonists/partial agonists?
Hyperprolactinemia
What is the result of targeting nigrostriatal dopamine D2 receptors with D2 antagonists/partial agonists?
Drug-induced Parkinsonism: Motor side effects such as tremor, muscular rigidity, bradykinesia, and akinesia
Symptoms:
1. Involuntary continuous movements, often about the face and tongue (e.g. lip smacking, constant chewing motion, tongue protrusions, facial grimacing)
2. Quick, jerky, or dancing motions of limbs
Tardive Dyskinesia
Symptoms:
Intermittent spasmodic or sustained involuntary contraction of the muscles in the face, neck, trunk, pelvis, extremities, or eyes
Dystonia
What is the treatment for acute dystonia?
IM anticholinergic
What is the term for a syndrome of motor restlessness commonly seen after treatment with D2 blockers?
Akathisia
What are the subjective symptoms of akathisia?
- Sense of inner restlessness
- Mental unease
- Dysphoria
What are the objective symptoms of akathisia?
- Restless movements, most typical being lower-limb movements such as rocking from foot to foot
- Walking or marching in place when standing
- Pacing
What is the most effective treatment for akathisia?
Beta-adrenergic blockers or benzodiazepines
What is the treatment for neuroleptic malignant syndrome (NMS)?
- Abrupt stop of D2 blocker
- Muscle-relaxing agents such as dantrolene
- Dopamine agonists
Other pharmacological properties of D2 antagonists
- Muscarinic cholinergic antagonism
- Antihistiminic actions (H1 receptor blockade)
- a1-adrenergic antagonism
What symptoms/SEs are associated with muscarinic cholinergic receptor blockade?
- Dry mouth
- Blurred vision
- Constipation 2/2 paralytic ileus
- Drowsiness
- Cognitive dysfunction
What symptoms/SEs are associated with H1 histamine receptor blockade?
- Weight gain
- Drowsiness
What symptoms/SEs are associated with a1-adrenergic receptor blockade?
- Drowsiness
- CV effects such as orthostatic hypotension
- Dizziness
Three separate populations of coritcal glutamatergic pyramidal neurons which are stimulated by serotonin action at 5HT-2A receptors regulate what three key dopamine pathways?
- Mesolimbic/mesostriatal pathway
- Nigrostriatal pathway
- Mesocortical pathway in VTA
How does 5HT-2A receptor antagonism effect downstream dopamine release in the mesolimbic/mesostriatal pathway and what is the end result on dopamine levels?
On postsynaptic glutamate neurons which directly innervate this dopamine pathway;
DECREASES levels of excessive dopamine which decreases positive symptoms of psychosis
How does 5HT-2A receptor antagonism effect downstream dopamine release in the nigrostriatal pathway and what is the end result on dopamine levels?
On postsynaptic glutamate neurons that indirectly innervate nigrostriatal dopamine neurons via a GABAergic interneuron in the substantia nigra;
INCREASES levels of insufficient dopamine which reduces drug-induced Parkinsonism SEs
How does 5HT-2A receptor antagonism effect downstream dopamine release in the mesocortical pathway and what is the end result on dopamine levels?
On postsynaptic glutamate neurons that indirectly innervate mesocortical dopamin neurons via a GABAergic interneuron in the ventral tegmental area;
INCREASES levels of insufficient dopamine which improves negative symptoms of psychosis and cognitive dulling
