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Neuro pharm 4


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- tricyclic ring typicals
- binds D1 and D2
- includes Chlorpromazine, thioridazine, trifluoperazine, perphenazine, Prochlorperazine
- overdosing can be fatal in
thioridazine, mesoridazine
- most noted for CV SE's like prolonged QT
low potency phenothiazine, typical
low potency phenothiazine, typical
higher potency phenothiazine, typical
higher potency phenothiazine, typical
phenothiazine that doesn’t pass BBB, so its only an anti-emetic, would be typical
Haloperidol, Pimozide, droperidol - typicals
- typical partially selective for D2 vs D1
- only used in long-term psych care and acute situations where rapid control needed
– EP SEs are a big problem
– approved for Tourette's and severe ADHD
typical very selective for D2 and used for Tourette's
typical used w/ fentanyl for anesthesia until “black box”
- 1st atipcal w/ minimal SEs
– v. effective, risk of agranulocytosis, so monitor blood
- may block D2, D4, 5-HT
– SE's sedation, wt gain, postural hypotension, anticholinergic effects, arrhythmias
- atypical like clozapine, but only causes but wt gain and can give /w amantadine in 1st month to reduce it
– gets (+) and (-) sx and – approved for of acute mania of bipolar
– also for agitation and psychotic sx in dementia (Alzheimer’s)
- atypical that blocks HT2C and D2 – gets mesocortical tract and stops (-) sx
– SE's low unless > 6 mg/day, then highest risk of EP SEs
- atypical potent blocker of 5-HT2 and only mildly gets D2
- get (+) and (-) w/out EP SEs
- blocks H1 and α1 so wt gain, sedation and postural hypotension
- atypical, better w/ wt gain and depressive Sx of SCZ
– inhibits S/NE reuptake, activates 5-HT1A, and blocks 5-HT1D
– greatest risk of prolonged QT
- atypical, partial agonist at D2, 5-HT1A and blocks 5-HT2A, stabilizing D and S
– improves (+) and (-) sx
- EP sx low
EP SE's Tx
- from too much GABA
- switch to atypicals, or give anti-muscarinic drugs
– try benztropine and trihexyphenidyl (they will act on PNS)
TD tx
- from not enough GABA
- discontinue or reduce current ASY and try atypical
– discontinue drugs w/ ACh action in CNS, like antiparkinsonism drugs and TCI’s
– add benzodiazepine may enhancing GABA
Neuroleptic malignant syndrome (NMS)
- in v. sensitive pts, esp w/ Haloperidol and phenothiazines
- 1st muscle rigidity, then severe motor dysfunction, hyperthermia, altered consciousness, leukocytosis, and elevated CP
- stop therapy, then give amantadine (indirect D agonist) and bromocriptine (direct D agonist)
– muscle relaxants, like diazepam and dantrolene, are often also helpful
ASY pharmokinetics
- single daily dosing OK
- metabolized by p450

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