Antipsychotics

Question 1

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?

Answer 1

Nucleus accumbens

Question 2

What is the result of normal stimulation of mesolimbic D2 receptors?

Answer 2

Experience of pleasure

Question 3

What is the result of excessive stimulation of mesolimbic D2 receptors?

Answer 3

Positive symptoms of psychosis

Question 4

What is the result of D2 receptor antagonism/partial agonism in the mesolimbic pathway?

Answer 4

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

Question 5

What is the result of blocking mesolimbic/mesostriatal dopamine D2 receptors?

Answer 5

Secondary (medication-induced) negative symptoms

Question 6

What is the result of targeting tuberoinfundibular dopamine D2 receptors with D2 antagonists/partial agonists?

Answer 6

Hyperprolactinemia

Question 7

What is the result of targeting nigrostriatal dopamine D2 receptors with D2 antagonists/partial agonists?

Answer 7

Drug-induced Parkinsonism: Motor side effects such as tremor, muscular rigidity, bradykinesia, and akinesia

Question 8

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

Answer 8

Tardive Dyskinesia

Question 9

Symptoms:
Intermittent spasmodic or sustained involuntary contraction of the muscles in the face, neck, trunk, pelvis, extremities, or eyes

Answer 9

Dystonia

Question 10

What is the treatment for acute dystonia?

Answer 10

IM anticholinergic

Question 11

What is the term for a syndrome of motor restlessness commonly seen after treatment with D2 blockers?

Answer 11

Akathisia

Question 12

What are the subjective symptoms of akathisia?

Answer 12

1. Sense of inner restlessness
2. Mental unease
3. Dysphoria

Question 13

What are the objective symptoms of akathisia?

Answer 13

1. Restless movements, most typical being lower-limb movements such as rocking from foot to foot
2. Walking or marching in place when standing
3. Pacing

Question 14

What is the most effective treatment for akathisia?

Answer 14

Beta-adrenergic blockers or benzodiazepines

Question 15

What is the treatment for neuroleptic malignant syndrome (NMS)?

Answer 15

1. Abrupt stop of D2 blocker
2. Muscle-relaxing agents such as dantrolene
3. Dopamine agonists

Question 16

Other pharmacological properties of D2 antagonists

Answer 16

1. Muscarinic cholinergic antagonism
2. Antihistiminic actions (H1 receptor blockade)
3. a1-adrenergic antagonism

Question 17

What symptoms/SEs are associated with muscarinic cholinergic receptor blockade?

Answer 17

1. Dry mouth
2. Blurred vision
3. Constipation 2/2 paralytic ileus
4. Drowsiness
5. Cognitive dysfunction

Question 18

What symptoms/SEs are associated with H1 histamine receptor blockade?

Answer 18

1. Weight gain
2. Drowsiness

Question 19

What symptoms/SEs are associated with a1-adrenergic receptor blockade?

Answer 19

1. Drowsiness
2. CV effects such as orthostatic hypotension
3. Dizziness

Question 20

Three separate populations of coritcal glutamatergic pyramidal neurons which are stimulated by serotonin action at 5HT-2A receptors regulate what three key dopamine pathways?

Answer 20

1. Mesolimbic/mesostriatal pathway
2. Nigrostriatal pathway
3. Mesocortical pathway in VTA

Question 21

How does 5HT-2A receptor antagonism effect downstream dopamine release in the mesolimbic/mesostriatal pathway and what is the end result on dopamine levels?

Answer 21

On postsynaptic glutamate neurons which directly innervate this dopamine pathway;
DECREASES levels of excessive dopamine which decreases positive symptoms of psychosis

Question 22

How does 5HT-2A receptor antagonism effect downstream dopamine release in the nigrostriatal pathway and what is the end result on dopamine levels?

Answer 22

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

Question 23

How does 5HT-2A receptor antagonism effect downstream dopamine release in the mesocortical pathway and what is the end result on dopamine levels?

Answer 23

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