Exam 2 Review Flashcards
Treatments for bipolar
1-lithium
2-Antiepileptics
3-antipsychotics
Lithium MOA
-not understood
-possibly stimulates inhibitory neurotransmission and dampens excitatory neurotransmission
-may uncouple G proteins from receptors
may inhibit enzymes
-may modulate NTs
-May reduce arachidonic acid turnover in brain
Lithium effects on INOSITOL
-depletes free inositol and membrane PIP2 in CNS
-impact PKC activity affecting neurolasticity
Lithium effects on GSK-3
-inhibitory effects on GSK-3
-modulate metabolism
-promote neuroprotection
-increase neuroplasticity
Lithium characteristics
-slow onset
-use has declined
-Narrow therapeutic index
Lithium clearence
-reduced during pregnancy
-reverts immediately after delivery
Lithium side effects
-tremor
-nausea
-diarrhea
-Leukocytosis
-cognitive impairment
-sexual dysfunction
-exaberate psoriasis
Lithium toxicity
-N/V, diarrhea, neurologic symptoms
-Dehydration, sodium depletion, kidney impairments, medications that decrease clearance can also contribute
Lithium considerations in pregnancy
-crosses placenta
-teratogenic
-excreted in breast milk
Antiepileptic drugs in Bipolar disorder
-Valproic acid
-carbamazepine
-lamotrigine
Valproic acid
-inositol depletion
-indirectly reduce GSK-3 activity
-inhibits histone deacetylase
Carbamazepine
-inositol depletion
-may be a CYP3A4 inducer
-blood dyscrasias less of an issue
Lamotrigine
-not effective in acute mania
-maintenance med and can be used in bipolar depression
-may have GSK-3 inhibitory effects
Antipsychotics in bipolar
-mostly second gen./atypical used
-D2 agonists
-can be used in combination with lithium or valproate
Second gen antipsychotics MOA
-5-HT2A blockade
-higher affinity for 5HT than D2
-lower risk of side effects
Effects of D2 antagonism
-positive symptoms become normal
-negative symptoms become worse
D2 blockade effects
-acute dystonia
-parkinsonism
-perioral tremor
-akathisia
-tardive dyskinesia
-hyperprolactinemia
Deutetrabenazine
-VMAT2 inhibitor: depletes vesicular monoamines
TD prevention/management
Deutetrabenazine side effects
-prolong QT interval
-fatigue
-somnolence
-HA
Clozapine
-M4 Agonist
-D2 antagonist
-Schizophrenia
Haloperidol
-FGA: high potency
-Schizophrenia
Chlorpromazine
-FGA: low potency
-Schizophrenia
Clozapine side effects
-Sialorrhea
-highest metabolic offender
-high risk of anticholinergic
Olanzapine and Risperidone
-SGA (D2 antagonist)
-Schizophrenia
Olanzapine side effect
DRESS
Paliperidone side effect
QT prolongation
Ziprasidone side effect
DRESS
Aripiprazole, Cariprazine,
Brexpiprazole
-D2 partial agonist
-Schizophrenia
-insomnia
Caffiene MOA
1) Blockade of adenosine receptors
-Block A1: prevents inhibition of wake promoting neurons
-Block A2A: prevents activation of sleep promoting neurons
What is the primary effect of caffeine on adenosine receptors?
Antogonist
Which subtype of adenosine receptor is responsible for sedative effects of Adenosine?
A1 (but bot A1 and A2A have effects)
What is the primary mechanism by which caffeine promotes wakefulness?
-block both A1 and A2A adenosine receptors
-prevents inhibition of wake promoting neurons
-prevents activation of sleep promoting neurons
What is involved in action of caffeine?
-blockade of adenosine receptors
-inhibition of PDE: increase cAMP and cGMP levels
-elevate intracellular calcium
amphetamine MOA release of NTs
-increase release of NTs (DA and NE)
-reverse transport of vesicles: interferes with VMAT
-inhibits DA transport: increases concentration
-further increases extracellular DA concentrations
Amphetamine MOA: inhibition of reutake
-clock reuptake of DA and NE
-inhibit transporters
Amphetamine MOA: increase DA synthesis
1) increase activity of TH: synthesize tyrosine to L-DOPA
2)decrease activity of MAO: stops break down of DA
Name 3 MOA for amphetamines
-release of NTs
-Inhibit reuptake
-increase intracellular DA synthesis
What is true about amphetamines?
-initially increase cytoplasmic DA, which further increases DA concentrations in synaptic cleft
What is the primary effect of increased NT levels induced by amphetamines in the synaptic cleft?
prolonged activation of postsynaptic receptors
What is the primary MOA of cocaine as a CNS stimulant?
-inhibition of dopamine reuptake by DAT
-increases extracellular DA concentration
How does phentermine act on the CNS to suppress appetite?
-Activates release of norepinephrine
What is the primary MOA of phentermine?
-increases release of NE and DA, activating POMC neurons to suppress appetite
Role of bupropion in appetite regulation?
-blocks NE and DA reuptake
-activates POMC neurons
-negative feedback loop
What is the primary MOA of Liraglutide?
Acts on GLP-1 receptors to suppress appetite
GLP-1 (as incretin)
enhances both insulin secretion and inhibits glucagon release
How does Orlistat contribute to weight loss?
-inhibits fat absorption in GI tract
What types of fat does Orlistat affect?
-Monoglycerides
-triglycerides
-free fatty acids
Clozapine
-agranulocytosis
-seizure rist
-myocarditis
-Orthostasis
-Sialorrhea(M4 agonism)
-Affected by CYP1A2
Olanzapine
-Sedation
-anticholinegic
-Orthostasis
-1A2
Quetiapine
-hyperlipidemia
-QT prolongation
Risperidone and Paliperidone
-similiar clinical profiles
-higher risk for EPS/TD/prolactin`
Ziprasidone
-lowest risk for weight gain
-Greatest risk for QT prolongation
Lumateperone
-good side effect profile
-sedation is most common
Lurasidone
-cariac arrthymia
-no weight gain
Ariprazole
-no weight gain
-INSOMNIA
-akathisia
No action at D2
