2/18: Drug Syndromes Flashcards
Serotonin syndrome + epidemiology
newborns to elderly, ppl who have overdosed on SSRIs (single SSRI dose can produce the syndrome)
Serotonin syndrome + precipitating factors
concurrent CYP2D6 and 3A4 inhibitors, withdrawal of concurrent drug tx; agonism of 5-HT2a receptors contribute substantially to the clinical condition
serotonergic neurons in the CNS
midline raphe nuclei: brainstem from midbrain –> medulla
serotonergic neurons in the CNS: rostral end of the raphe nuclei
assists in regulation of wakefulness, affective behavior, food intake thermoregulation, migraine, emesis, and sex behavior
serotonergic neurons in the CNS: raphe in the lower pons and medulla
participate in regulation of nociception and motor tone
peripheral serotonergic neurons in the CNS
assist in regulation of vascular tone and GI motility
spectrum of findings in serotonin syndrome
from mild –> life-threatening:
akathisia, tremor, AMS, clonus (inducible–> sustained), muscular hypertonicity), hyperthermia
management of serotonin syndrome
- discontinue use of all potential precipitating drugs
- provide supportive management
- control agitation
- admin serotonin antagonist (cyproheptadine)
- control autonomic instability
- control hyperthermia
- reassess the need to resume the use of the serotonergic agent once the sx have resolved
Lithium
used in the tx of bipolar disorder; reported to inc serotonin metabolites in the CSF and my interact PD with SSRIs, resulting in serotonin syndrome
drugs assoc with serotonin syndrome: SSRIs
sertraline, fluozetine, fluvoamine, paroxetine, citalopram
drugs assoc with serotonin syndrome: antidepressants
trazodone, nefazodone, busipirone, clomipramine, venlafaxine
drugs assoc with serotonin syndrome: MAOIs
phenelzine, isocarboxazid
drugs assoc with serotonin syndrome: AEDs
valproate
drugs assoc with serotonin syndrome: analgesics
meperidinem fentanyl, tramadol, pentazocine
drugs assoc with serotonin syndrome: antiemetics
ondansetron, graniestron, metoclopramide
drugs assoc with serotonin syndrome: anti migraine drugs
sumatriptans
drugs assoc with serotonin syndrome: dietary supplements and herbal products
tryptophan, st. john’s wort, ginseng
neuroleptic malignant syndrome: MOA + sx
blockade of D2 receptors in hypothalamus –> HYPERTHERMIA
blockade of inhibitory actions of dopamine on the SNS –> ANS dysfx
Blockade of nigrostriatal dopamine –> inc muscle rigidity/tremor via extrapyramidal pathways (possible direct muscle toxx via an inc in Ca2+ release from the SR)
MC RF for NMS
high-dose and high-potency antipsychotic agents (haloperidol»>clozapine, but both), during rapid dose escalation, and with depot forms (IM) of drug release
other RF for NMS
concomitant use of predisposing drugs (anti-depressants, anticholinergics, lithium), w/drawal of anti-Parkinsonian agents, previous hx of NMS, inc ambient temp or dehydration, catatonia or agitation, history of affective disorders or physical disorders of brain that cause a dec in mental fx
management of NMS
withdraw causative drug and institute supportive care
management of NMS: avoid the following Cx
rhabdomyolysis, renal and respiratory failure, recurrence
management of NMS: common drug approaches
1) dopamine agonists: bromocriptine»_space; amantadine
2) dantrolene: sk.mm. relaxant (also used to treat malignant hyperthermia)
3) lorazepam: reduce psychosis, agitation and anxiety; act as an anticonvulsant
management of malignant hyperthermia
admin dantrolene IV (to restore IC management of Ca levels), correct metabolic acidosis, monitor serum K+ (admin insulin + glucose + CaCl or gluconate + IV lidocaine for arrhythmia), cool body to <38˚C, maintain urinary output (cold fluids, furosemide and mannitol, if needed)
