Neuro-psych Drugs Flashcards
Role of tertiary amines in TCAs
Have two methyl groups in side chain with dominant effect on serotonin reuptake
Role of secondary amines in TCAs
Single methyl group with dominant effect on norepinephrine reuptake
TCA pharmacokinetics
Good GI absorption but high first pass (50%)
Large Vd
Liver metabolism
Long half-life >24hrs
Adverse effects of TCAs
Dry mouth (xerostomia)
Urinary hesitancy
Decreased gastric motility
Blurred vision
Orthostatic hypotension
Cardiac effects of TCAs
Increased Arrhythmogenicity
-tachycardia/palpitations
-Prolonged QTc
-narrow therapeutic index should be considered in patients with suicidal ideation
Anesthesia Implications: TCAs
Exaggerated response to indirect Sympathomimetics- ephedrine
Prolonged use- adrenergic desensitization and catecholamine depletion=vasoplegia
Pro-arrhythmic effect with volatiles
SSRI mechanism
5-HTT inhibition and modulation of post synaptic 5-HT receptors
Also production of neuroprotective proteins along with anti-inflammatory effects
SSRI pharmacokinetics
Hepatic metabolism
Most have inactive metabolites
Half-life about a day- can take weeks for adverse reactions to resolve completely
SSRI adverse effects
Mostly well tolerated
Sexual dysfunction, weight changes, dizziness, sleep disturbances
Serotonin syndrome- agitation-increased sympathetic outflow, can mimic malignant hyperthermia, -usually occurs in combination with other drugs modulating serotonin activity
SSRI anesthetic considerations
Prolonged QTC
Inhibit platelet aggregation
Serotonin syndrome
MAOI mechanism
Irreversibly binds MAO, inhibits enzyme for up to two weeks
MAO-A
Metabolizes via deamination: serotonin, epinephrine, norepinephrine, melatonin, dopamine, tryptamine
MAO-B
Metabolizes via deamination: phenylethylamine, tyramine, dopamine, tryptamine,
Adverse effects of MAOIs
Avoid foods containing large amounts of tyramine
Orthostatic hypotension
MAOI drug interactions
Indirect acting Sympathomimetics may case hypertensive crisis
AVOID ephedrine
AVOID phenylpiperidine opioids, especially meperidine=life threatening hypertensive crisis
Morphine is opioid of choice
First generation antipsychotics
Blockade of D2 dopamine receptors
Compazine
Phenergan
Haldol
Reglan
Not commonly given due to high incidence of adverse effects
Extrapyramidal symptoms
Involuntary movement disorders
Dystonia-acute spasm/muscle contraction-give anti cholinergic to reverse- can occur after one dose
Akathesia- restlessness-same treatment
Pseudoparkinsonism- generally reversible- typically don’t give dopamine antagonists with Parkinson’s since it exacerbates symptoms
Tardive dyskinesia
Choreoathetoid movements (wormlike)
From Chronic therapy
Anticholinergic agents may worsen TD
Administration of D2 antagonist will exacerbate TD
Neuromalignant syndrome
Closely resembles malignant hyperthermia and serotonin syndrome
Mortality 50%, rare, rhabdo in severe cases
Treatment- dantrolene and supportive care- with addition of a dopamine agonist (bromocriptine)
Clozapine (clozaril)
2nd Gen
Dopamine Antagonist (D4) and 5-HT 2c/2a serotonergic receptors
Schizophrenia
Adverse effects:
agranulocytosis-low wbcs
Myocarditis
Orthostatic hypotension, ketoacidosis
Olanzapine (zyprexa)
2nd gen
Dopamine antagonist, 5-HT2a, & alpha1-adrenergic antagonism…. Also weak GABAa agonist
Bipolar
Adverse: POTENTIATION OF BENZOS
Weight gain, diabetogenesis
EPS
Quetiapine (Seroquel)
2nd Gen
Less D2, high affinity for 5-HT2a and H1 histamine=sedation
Schizophrenia/ bipolar-polar
Adverse effects:
Sedation
Weight gain
Diabetogenesis
Aripiprazole (abilify)
2nd gen
Schizophrenia/ bipolar
Partial antagonism/agonism of serotonin and dopamine systems
Risperidone (Risperdal)
2nd Gen
High affinity for 5-HT2a
Schizophrenia/bipolar
Well tolerated generally
Lithium
Narrow therapeutic index= increased toxicity
Thiazide diuretics/ACEI/ARA blockers/NSAIDS all increase blood levels
Prolongs NMBDs duration of action
Valproate (depakote)
Anticonvulsant
Hepatitis/pancreatitis
Thrombocytopenia/platelet dysfunction
Increases metabolism of NMBDs
Carbamazepine (Tegretol)
Anticonvulsant
Blood dyscrasias
SIADH
Increased metabolism of NMBDs as well as versed/fentanyl/tramadol
Lamotrigine (lamictal)
Anticonvulsant
Severe derm reactions
Increased metabolism of NMBDs
Amphetamine MOA
enhances dopaminergic/serotnergic and noradrenergic release
Methylphenidate MOA
Norepi and dopamine reuptake inhibitor
ADHD/Narcolepsy/obesity
Levodopa Mechanism
Converted to dopamine in CNS- normalizing dopamine levels in corpus striatum and binding pre/post dopamine receptors
Why is levodopa administered with carbidopa?
Carbidopa is a AAAD (aromatic L-amino acid decarboxylase)
Prevents accumulation of dopamine in the periphery and increases cerebral bioavailability of levodopa
Levodopa anesthetic considerations
Continue in perioperative period due to short half-life
Give just before surgery and just after- have patient bring it in
Consider NG for longer procedures for intraop admin
Pramipexole
Adjunct with levodopa/carbidopa
No major anesthetic considerations
Treating Myasthenia Gravis
In addition to immunomodulators, anticholinesterases are used to increase ACh at the NMJ
-primarily pyridostigmine
Interference with NMBDs and potential to prolong ester-local anesthetics and succinylcholine
SSRI with active metabolite
Fluoxetine- extends typically SSRI half-life from 1 to 2-3 days
Phenothiazine examples and class
First generation antipsychotics
Prochlorperazine (compazine)
promethazine (phenergan)
Chlorpromazine (Thorazine)
Butyrophenones
First Gen antipsychotics
Haloperidol (haldol)
Droperidol (Inapsine)
Benzamide class and example
Metoclopramide (reglan)
Clozapine (clozaril) adverse effects
Agranulocytosis
Myocarditis/cardiomyopathy
Hyperglycemia/DKA
2nd gen antipsychotic with benzo potentiation
Olanzapine (zyprexa)
Also weak gaba receptor agonist
Reason for sedation with seroquel
Histamine 1 receptor affinity
Interesting thing about aripiprazole (abilify) MOA
Partial AGONIST of D2 and 5HT, also strong antagonism of other Dopamine/serotonin receptors…
Compared to clozapine, Risperidone (risperdal) has:
20-50 times higher affinity for 5HT and D2 receptors
Well tolerated/no QT prolongation
Avoid chronic NSAIDs with this antipsychotic
Lithium
QTC prolongers
SSRIs
TCAs
Ondansetron
Granosetron
Dolanosetron
Promethazine
Diphenhydramine
Dimenhydrinate
Droperidol
Haloperidol
Metoclopramide
NOT: palonosetron/aprepitant or scopolamine
