Schizophrenia 3 Flashcards
What is a neuroleptic?
Reduces emotinoality and psychomotor activity without causing sedation
What is an antipsychotic drug?
Reduce positive symptoms of schiz but not cognitive/negative symptoms.
- ppl respond differently to different drugs, several need to be tested.
- continued drug maintenance reduces change of relapse
- patient compliance is often an issue.
What is the Law of Thirds?
Antipsychotic drugs where 1/3 people respond well, 1/3 show good improvement but need more help or relapse and 1/3 are treatment resistance
What do all antipsychotic drugs bind to?
All block D2 receptor to some degree
- strong correlation between D2 antagonist and effective dose
- D1 has no effect or worse effect
- can bind other receptors but no relationship between effectiveness and binding
What happens with initial antipsychotic is administered ?
Acute reduces hyperactive symptoms quickly, but see full effects at 2 weeks.
Initially, D2 antagonists block postsynaptic and autoreceptors. There is initial increase in DA release (autoreceptor blockage) but this this goes away after 2 weeks-the postsynaptic blockage prevents the DA increase from making symptoms WORSE.
What does chronic antipsychotic administration do?
Longer lasting changes in DA synthesis, release, metabolism
- Increase in DA neuron firing (blocking autoreceptors) leads to depolarization block (in rats this takes about 2 weeks, same time as max antipsychotic effect in humans)
- This explains lapse in effectiveness
Whats the bad part about antipsychotics?
Side effects cause they bind to a LOT of receptors.
- Parkinsonism
- Tardive dyskinesia
- Neuroendocrine
- Weight gain
- Anticholinergic
- Anti Adrenergic
Don’t show tolerance to side effects or the drug itself.
Describe parkinsonism?
Motor side effects because of effects on nigrostriatal DA pathway (extrapyramidal systems go through striatum not directly to spinal cord)
- Reduced Striatal DA function increases AcH activity which leads to motor effects.
USUALLY DA D2 inhibits ACh interneurons, which prevent GABA neurons from inhibiting Substantia nigra
- Reduced DA increases ACH firing that makes GABA interneurons on striatum more effective (inhibit Substantia nigra DA)
- LEADS TO OVERALL DECREASE IN DOPAMINE (for D1 and D2 receptors)
- drugs with anti-cholingergic action have fewer motor side effects, sometimes combine with antipsychotics to migigate motor symptoms
Describe Tardive dyskinesia (TD)
Iregular involuntary movements of face. 1/3 of patients on these drugs
- usually older patients
- effects persist after stopped taking the drug
- happens the longer you take the drug
- mechanism poorly understood
Describe neuroendocrine effect?
Tuboinfundibular pathway (DA) that innervates hypothalamus for hormone release
- decreased sex drive
- menstrual cycle disruption
- inhibit growth hormone
- increase prolactin (gives you boobs and lactation in both sexes)
- mediated by D2 antagonism
Describe weight gain effects
Mediated by 5-ht receptor action
Resistant to diet and exercise
Describe anticholenergic effects
dry mouth
blurred vision
hard time peeing
GI tract issues
Desdcrieb antiadrenergic effects
dizziness
faintness
blacking out
Describe antihistaminergic effects?
cause blacking out
What are atypical antipsychotics?
2nd generation without as many extrapyramidal effects. (no tardive dyskinesia or prolactin increase either)
- Broad spectrum antipsychotics: block other receptors besides just D2 (lots of 5ht receptor and less D2 affinity)
- Fewer but Still have bad side effects: weight gain (resistant to diet/exercise, insuilin resistance type 2 diabeties and cardiac issues) - Super selective D2 receptor antagonists: high D2 affinity (and D3) low for other receptors
- more mild autonomic/cardiovascular effects
- hormonoal side effects and risk of fatal blood disorders - DA stablilzers: partial DA agonists to reduce DA effect (higher affinity but less effective)
