Exam #2 Flashcards
Treatment for Bipolar disorder
Normal
Anti seizure drugs
Antipsychotics
Normal: lithium Anti seizure drugs: - valproic acid - carbazepime - Lamatrigine Antipsychotics: - Quetiapine
Lithium MOA
- activates GABA release
- inhibits glutamate and dopamine
- inhibits phosphoinositol cascade (IP3 and DAG pathway)
- Inhibition of glycogen synthase kinase-3 (GSK-3) leading to neuroprotection
Lithium therapeutic range
0.6-1.5 mEq/L
Lithium Pharmokinetics
Competes w Na+ for tubular reabsorption in the kidneys (Lithium can be in by Na+ loss often seen in diuretic use)
-diuretics can inc lithium concentration
Lithium Adverse Effects
Hypothryroidism (weight gain, dry skin, hair loss, and constipation)
Tremors
Ataxia (ESP WHEN PAIRED W ATYPICAL PSYCHOTICS)
Nephrogenic diabetes insipidus (dec response to ADH leading to polyuria)
Nausea, vomiting, diarrhea
PREGNANCY = Ebstein anomaly
Carbamazepine CYP
inducer
Monoamine Hypothesis
Depression resulting from pathological dec in serotonin, NE, and/or dopamine neurotransmission
Neurotropic Hypothesis
Loss of neurotrophic support leading to depression (Brain derived neurotrophic factor)
Hypothalamic-Pituitary-Adrenal Axis Dysregulation
Elevated levels of cortisol and CRH
Thyroid Dysregulation
Depression associated w hypothyroidism or hyperthyroidism
SSRIs names
Fluoxetine Paroxetine Sertraline Citalopram Escitalopram Vilazadone
SNRIs names
Duloxetine
Venlafaxine
Milnacipran
Levomilnacipran
initial inhibition of SERT induces
activation of 5-HT1A and 5-HT1D autoreceptors
TCS names
Imipramine
Amitriptyline
TCA nonselective effects
Antimuscarinic
Antihistaminic
Alpha-blockade
5-HT2 Antagonists
Trazodone
Nefazodone
5-HT2 Antagonists Nonselective effects
Antimuscarinic, antihistamine, alpha-blockade
MOA-A and MOA-B irreversible inhibitors
Phenelzine
Tranylcypromine
MOA-B irreversible inhibitor only
Selegiline
bupropion MOA
inhibits the norepinephrine transporter (NET) and the dopamine transporter (DAT)
Mirtazapine moa
alpha-2 inhibition increases presynaptic release of serotonin and norepinephrine
Trazodone moa
serotonin modulator (antagonizes 5-HT receptors and inhibits 5-HT reuptake)
increased risk of suicide between children, adolescents and young adults. SSRI SNRI TCA MOA inhibitor Atypical
SSRIs: -Escitalopram -Fluoxetine SNRIs: -Duloxetine TCAs: -Imipramine MOA inhibitor: -Phenelzine Atypical: -Bupropion
Schizophrenia pathology
- Inc dopaminergic activity (D2 receptor)
- Inc serotonergic activity (5-HT2A and 5-HT2C)
- Diminished GABA activity leading to hyperstimulation
Typical antipsychotics names
Chlorpromazine
Haloperidol
Atypical antipsychotics names
Chlorpromazine
Haloperidol
Typical antipsychotics MOA
D2 antagonist
Atypical antipsychotics MOA
Preferential antagonism of 5-HT2A receptors; some D2 antagonist action
Aripiprazole MOA
partial agonist at D2
5-HT2A
Transducer:
Effect:
Transducer: Gq
Effect: PKC mediated reduction of Ca2+ and Na+ conductance
5-HT2C
Transducer:
Effect:
Transducer: Gq
Effect: PKC mediated reduction of Ca2+ and Na+ conductance
Dopamine Inhibition
α-adrenergic Inhibition
Muscarinic Inhibition
Histamine (H1) Inhibition
Dopamine Inhibition: -extrapyramidal reaction -hyperprolactinemia α-adrenergic Inhibition: -orthostatic hypotension Muscarinic Inhibition -urinary retention -constipation -blurred vision -dry mouth Histamine (H1) Inhibition: -sedation
antipsychotics w highest Dopamine Inhibition
haldol
Neuroleptic Malignant Syndrome
Life threatening disorder most commonly associated w/ typical antipsychotics with high affinity for D2 receptors Symptoms: -Hyperthermia -extreme muscle rigidity -tachycardia
typical psychotics adverse effects
Weight gain
QT prolongation
Sedation
Diazepam MOA
GABAa agonist that hyperpolarizes the cell via opening of Cl- channels
Baclofen MOA
GABAb agonist which hyperpolarizes via:
- Closure of pre-synaptic Ca+2 channels
- Increased post-synaptic K+ channels
- Inhibits dendritic Ca+2 influx channels
Tizanidine MOA
alpha2 adrenergic agonist in spinal cord (pre and post synaptic inhibitor in spinal cord, inhibits nociceptive transmission in dorsal horn)
Tizanidine contraindication
Potent CYP1A2 inhibitor (don’t take w fluvoxamine/ciprofloxacin)
Cyclobenzaprine adverse effects
Concomitant MAO
Acute recovery phase of MI
Patients w heart block or congestive heart failure
Cyclobenzaprine adverse effects
Hallucinations
Dantrolene MOA
blocks RYR1 channels in SR of SKM
Botulinum Toxin MOA
inhibits synaptic exocytosis of vesicles via cleaning SNAP-25 or synaptobrevin-2
Malignant hyperthermia treatment
Dantrolene
Dantrolene adverse effects
Hepatotoxicity
Contraindication concomitant use of meperidine
Selegiline
Rasagiline
Amantadine MOA
increase dopamine release and decrease dopamine uptake (exact MOA unknown)
Amantadine adverse Effects
Orthostatic hypotension
Urinary retention
Peripheral edema
Benztropine MOA
muscarinic and histamine antagonist
Benztropine contraindication
Children <3 yo
Trihexyphenidyl MOA
muscarinic and histamine antagonist
Adjunctive PD therapy w on-off phenomena
Selegiline
Trihexyphenidyl adverse effect
Glaucoma
Pramipexole MOA
D3 agonist
Cylclobenzaprine contraindication
Concomitant MAO
Acute recovery phase of MI
Patients w heart block or congestive heart failure
Vigabatrin MOA
Irreversibly inhibits GABA-T
Vigabatrin adverse effects
Permanent Visual field loss (Black Box)
Tiagabine MOA
selective inhibitor of the GAT-1 GABA transporter
Tiagabine adverse effects
Dizziness, drowsiness, nervousness, lack of concentration
Perampanel MOA
non-competitive antagonist of the AMPA receptor on post-synaptic neurons, a main mediator of synaptic excitation in the central nervous system
Perampanel adverse effects
aggression, hostility, irritability, and anger
**Alcohol use may exacerbate the level of anger
Selegiline
Rasagiline adverse effects
anxiety and insomnia
what special about Oxcarbazepine
no cyp interactions
Phenytoin adverse effects
diplopia
ataxia
gingival hyperplasia
hirsutism
Lamotrigine indication
Conversion to monotherapy in adults with partial-onset seizures
Topiramate adverse effects
Decreased serum bicarbonate
impaired expressive language function
Topiramate contraindication
alcohol use
patients with metabolic acidosis
Valproic Acid/Valproate/Divalproex contraindication
pregnancy
liver failure
Lacosamide MOA
Selectively binds fast-inactivated state of sodium channels
Ethosuximide MOA
inhibition of low-voltage activated T-type calcium channels in thalamocortical neurons
Lamotrigine adverse effect
insomnia
Gabapentin MOA
avidly binds to alpha-2-delta-1 (α2δ) subunit of voltage-gated calcium channels
Gabapentin adverse effects
somnolence
ataxia