660 exam 1 Flashcards
Where does the Nigrostriatal Pathway start and end?
Substantia Nigra to the striatum
What is the issue with dopamine in the Nigrostriatal Pathway?
Too low → CSTC loops messed up→ we make it worse with D2 blockers → EPS
What causes Tardive Dyskinesia?
Chronic blockade of the nigrostriatal dopamine receptors.
How does dopamine regulate the indirect CSTC loop?
Dopamine inhibits the “stop” signal → produces movement
How long does it take for Dystonia to occur after the offending medication is given?
4 hours
How long does it take for Akinesia to occur after the offending medication is given? (Drug-induced parkinsonian symptoms)
4 days
How long does it take for Akathisia to occur after the offending medication is given?
4 weeks
How long does it take for Tardive Dyskinesia to occur after the offending medication is given?
months to years
What does dystonia look like?
- eyes roll up and out
- forced extension of neck
- forced lateral rotation of neck
- tongue protrudes and feels swollen but it isn’t
- sustained facial muscle spasms
- laryngospasms and spasticity
What is the treatment of Dystonia?
Benztropine or benadryl
What does drug induced Parkinsons look like? (Akinesia)
Rigidity, tremors, slowing of movements, loss of movements
What is the treatment for drug-induced Parkinsons look like? (Akinesia)
Benztropine, benadryl
Why do anticholinergics help drug induced Parkinsons? (Akinesia)
Dopamine typically decreases acetylcholine → if D2 inhibitor blocks, then more acetylcholine is released → Excitation of postsynaptic M1 receptors
Anticholinergics will block the acetylcholine
What does Akathisia look like?
Feelings of restlessness, jittery, dysphoria, mental unease, marching, pacing stomping
What is the treatment for Akathisia?
Betablocker and Benzos
What does Tardive Dyskinesia look like?
Constant movements – lip smacking, blinking, jaw clenching, twitchy/jerky limb movements
What causes TD?
Upregulation of dopamine receptors in the indirect pathway
What is the treatment for TD?
VMAT2 inhibitors
What are two VMAT2 inhibitors?
Deutetrabenzine and valbenzine
TAKE WITH FOOD
Where does the tuberoinfundibular pathway start and stop?
Hypothalamus to anterior pituitary
How does dopamine typically regulate prolactin?
inhibits the release
When should a prolactin lab be drawn?
- within 2 hrs of waking
- fasting
- Not within 30 min of exercise
- Stress/anxiety raises – fear of needles?
Which antipsychotic could you switch to if the patient is suffering from hyperprolactinemia?
Aripiprazole, brexpiprazole, cariprazine, or clozapine
Example of a dopamine agonist
Bromocriptine
Aripiprizole indications
Schizo, Bipolar
Brexipiprazole indications
Schizo
Chlorpromazine indications
Schizo, bipolar
Chlorpromazine key points
- Wide range of SE
- decreases seizure threshold
- Photosensitivity
- Very potent EPS
- QT interval prolongation
Clozapine indications
Treatment resistant schizo
Clozapine key points
- Only use after two other failed antipsychotic attempts
- Decreases seizure threshold
- Check ANC prior and cont to monitor
- ANC needs to be >1500 unless you have BEN then it needs to be >1,000
Clozapine SE
- Anticholinergic
- Wt gain
- Myocarditis
- Drooling
What to monitor with all atypical antipsychotics
Wt, fasting glucose/ lipids, BP,
What labs to monitor for clozapine
ANC and ECG
Clozapine CYP issues
- Smoking is an inhibitor
- Luvox is an inhibitor
Which medications have the highest risk for wt gain?
olanzapine
quetiapine
When should be not give IM olanzapine?
When the patient is on benzos
Clozapines risk of EPS is
not likely
Haloperidol ADR
HIGH risk for EPS
Prolonged QT with IV admin
Which first generation antipsychotics are high potency?
Haloperidol
Loxapine
Pimozide
Thiothixene
Trifluoperazine
Lurasidone (Latuda) key points
- Take with 350 calories
- grapefruit inhibits
- tegretol and st johns wort induces
Which antipsychotics are good to use for an overweight patient?
Lurasidone (Latuda) and Lumateperone (Caplyta) - does not cause metabolic disorder
Lumateperone (Caplyta) SE and keypoint
- Sedating
- Take with food
Ziprasidone (Geodon)
- Decreased Wt gain
- Take with 500 calories of food twice daily
Risperidone and Paliperidone key SEs
Hyper-prolactinemia and sedation
Olanzapine SE
- Wt gain
- Rash/Photosensitivity
- Sedation
Which antipsychotic is first choice for parkinson’s?
Quetiapine
Which antipsychotic can cause cataracts?
Quetiapine
Zisprasidone (Geodone) key points
- Ask if family hx of heart issues, sudden death etc –QT PROLONGATION
Perphenazine SE
- catatonia
- bluish gray skin
- photosensitivity
Which medication is sublingal?
Saphris (Asenapine)
What are the negative s/s of Schizo?
- Anhedonia (decreased pleasure)
- Asocial
- Alogia (few words)
- Blunted affect (decreased affect)
- Avolition (decreased desire/motivation)
- Apathetic (Doesn’t care)
- Abstract thinking is difficult
Which pathway is resposible for the negative s/s of schizo?
Mesolimbic
Which pathway is responsible for EPS and TD?
Nigrostriatal
Which dopamine receptor is more sensitive to dopamine, 2 or 3?
D3
Which area of the brain do not have DAT or D2/3 autoreceptors?
PFC
Which area of the brain DOES have D2/D3 autoreceptors?
Striatum
Dopamine (DA) receptors can be categorized as D1-like (D1 and D5 receptors) and D2-like (D2, D3, and D4 receptors). What differentiates the two groups of receptors?
D1-like receptors are excitatory and D2-like receptors are inhibitory.
Symptoms of schizophrenia are hypothetically attributable to malfunctioning in the:
Mesocortical and mesolimbic pathways
For which set of disorders is psychosis considered an associated feature rather than a defining feature for diagnosis?
Bipolar mania, Parkinson’s disease, Mania
Where does the mesolimbic pathway start and stop?
Brainstem to Nucleus accumbens in the ventral striatum
Where does the mesocortical pathway start and stop?
VTA of brainstem to PFC (DL and VM)
Hypofunctioning NMDA receptors lead to what
excessive glutamate release in the VTA – downstream excessive DA release in the nucleus accumbens and reduced DA release in the PFC
The neurodevelopmental hypothesis of schizophrenia centers heavily around the idea that aberrant competitive elimination occurs. Competitive elimination is a stage of neurodevelopment in which
Rarely used synapses are pruned, while frequently used synapses are preserved
How does glutamate regulate dopamine?
Glutamate in cortical brainstem regulates the mesocortical dopamine in the VTA INDIRECTLY
How does glutamate regulate dopamine?
Glutamate in cortical brainstem regulates the mesocortical dopamine in the VTA INDIRECTLY
Too much glutamate - L2 lots of GABA – too little dopamine
What three neurotransmitter systems are implicated in the neuropathology of psychosis?
Serotonin, glutamate, dopamine
Which receptor subtypes act as presynaptic autoreceptors to inhibit serotonin release?
5HT1A and 5HT1B/D receptors
Stimulation of 5HT3 receptors on GABA interneurons leads to inhibited release of:
Acetylcholine and norepinephrine
Psychosis in Parkinson’s disease or dementia may occur due to upregulation of which postsynaptic serotonin receptor on glutamate neurons in the prefrontal cortex?
5HT2A
Serotonin hypothesis of psychosis
Hyperactivity of the 5HT2A receptors in the cortex causes psychosis
Presynaptic serotonin receptors
1A
- Binding shuts down 5HT release
2B
- Binding increases 5HT release
1B/D
- Binding shuts down 5HT release
Which presynaptic serotonin receptors are inhibitory?
1A and 1B/D
5HT1A is always…
inhibitory
5HT1A / GABA /Dopamine relationship
If it inhibits a GABA neuron → you’re inhibiting the inhibitor so downstream there is a lack of inhibition → increased dopamine in the striatum and PFC
5HT2A receptors are always
excitatory and post synaptic
How does 5HT2A regulate dopamine?
Mesolimbic - directly
Nigrostriatal and Mesocortical- indirectly
5HT2A receptors on cortical glutamate pyramidal neurons are stimulated and release glutamate downstream – makes the dopamine pathway worse
Blockers would help decrease the symptoms
How does 5HT2A regulate prolactin?
Increases it
5HT2C
Generally excitatory
– Located primarily on GABA interneurons → generally inhibit the downstream release of neurotransmitters
5HT3
Excitatory
N/V
— Located in the chemoreceptor trigger zone of the brainstem — Mediate n/v
— Located in the GI tract — Mediate n/v/d (bowel motility)
— Blocking these may protect against serotonin-induced GI SE that often occur with 5HT release
In the PFC
— Located on GABA interneurons → net inhibitory
— Inhibit NE and Ach
Glutamate and 5HT regulate each other via 5HT3
5HT2A blockers help …
- Decrease hallucinations
- In Parkinson’s → decreased s/s bc they occupy some of the extra 5HT2A receptors that are causing too much excitatory effects
- In dementia → decreased behavior SE that are caused by too much excitatory effects from decreased GABA activity L2 too much serotonin
Low Potency 1st gen Antipyschotic SE and Affinity
COMMON:
EPS
TD
Sedation
Orthostatic Hypotension
Anticholinergic symptoms
D2: moderate affinity
Acetylcholine: strong
H1: strong
Alpha adrenergic: moderate
High Potency 1st gen Antipyschotic SE and Affinity
COMMON:
EPS
TD
UNCOMMON:
Sedation
Orthostatic Hypotension
Anticholinergic symptoms
D2: Strong affinity
Acetylholine, muscarinic, H1, alpha adrenergic: Weak
Tx for Neuroleptic Malignant Syndrome
Bromocriptine
Reduce fever, correct dehydration, correct electrolytes
Stop med
IV benzo, IV Dantrolene (muscle relax),
Bromocriptine – dopamine agonist
Amantadine - dopamine agonist with antichol effects
Differentiate Neuroleptic Malignant Syndrome from Serotonin Sydrome
NMS - Hyperreflexia, myoclonus, ocular clonus
NMS - S/S are within 24 hrs of starting/changing therapy
