Pharmacology Flashcards
dialyzable toxins
Low molecular weight <500 daltons
High water solubility
Low protein binding
Low volume of distribution <1L/kg
Low endogenous clearance <4ml/min/kg
is lithium fast or slow absorbing
it’s fast absorbing because its water soluble.
Pharmacokinetics: rapidly absorbed, peak serum concentrations in a few hours. Bioavailability nearly 100%. Water soluble, thus neither protein bound not metabolized.
acute CV changes with lithium. Chronic CV changes?
prolonged QT
chronic: myocarditis
Which key organ does lithium damage over time
kidney.
Mechanism of action for Lithium:
Pharmacology/MOA: inhibits ___. This enzyme is involved in multiple signaling pathways (gene transcription, neuronal function), inadequately inhibited in patients with mood disorders. Lithium reduces functional output of the __ system.
Also inhibits ___ monophosphatase: involved in cellular signalling mechanisms. Inadequately inhibited in patients with mood disorders. Lithium blocks pathologic signaling from excessive myoinositol and leaves normal cellular signalling intact.
Pharmacology/MOA: inhibits GSK-3B. This enzyme is involved in multiple signaling pathways (gene transcription, neuronal function), inadequately inhibited in patients with mood disorders. Lithium reduces functional output of the mesolimbic system.
Also inhibits inositol monophosphatase: involved in cellular signalling mechanisms. Inadequately inhibited in patients with mood disorders. Lithium blocks pathologic signaling from excessive myoinositol and leaves normal cellular signalling intact.
2 main mechanisms of lithium toxicity
Excessive intake: intentional/unintentional ingestion
Impaired excretion: renal failure (decreased GFR), volume depletion, decreased sodium intake, drug interactions (NSAIDs, thiazides, ACE-I’s, ARBs)
mild, moderate, and severe neurological issues for lithium
Mild: weakness, lightheadedness, tremor
Moderate: fasciculations, tinnitus, altered LOC, hyperreflexia, slurred speech, clonus, nystagmus
Severe: stupor, coma, seizures
lithium toxicity definition
Lithium toxicity: elevated lithium toxicity (>4mEq/L with renal failure, or any lithium concentration with decreased LOC/seizures, arrhythmias/hemodynamically unstable)
management for lithium toxicity
HEMODIALYSIS!
- sodium polystyrene sulfonate
- WBI
- saline
traditional vs atypical antipsychotic
Receptor affinities, Antipsychotic effects:
traditionals/typicals: D2 dopamine antagonism
Atypicals: 5HT2A serotonin antagonism AND partial D2 antagonist. Treats both +/- sx of schizophrenia with less EPS
Antipsychotic:
__ protein bound
__ Vd’s
Relatively __ elimination half lives
Dialyzable?
Highly protein bound
High Vd’s
Relatively long elimination half lives
Therefore not dialyzable
5 key extrapyramidal side effects
- acute dystonia
- akathsia
- parkinsonism
- tardive dyskinesia
- neuroleptic malignant syndrome
5 key symptoms of neuroleptic malignant syndrome
Neuroleptic Malignant Syndrome: occurs within after 2-10 days after neuroleptic started, soon after a dose change or on a drug holiday
Criteria: MS change, hyperthermia, muscle rigidity, autonomic dysfunction, LEAD PIPE RIGIDITY
explain how NMS is different from serotonin syndrome
– ____ blockade, not overstimulation of ___ receptors
– ___ after exposure, not within ___ to __
– “__ __” rigidity, not ___/hyperreflexia
– Dopamine blockade, not overstimulation of serotonin receptors
– Days after exposure, not within minutes to hours
– “Lead pipe” rigidity, not myoclonus/hyperreflexia
for antipsychotics, ___ antagonism causes hypotension and miosis
alpha 1 antagonism
