Psycho pharm ch 6 Flashcards
In schixophrenia
Too much dopamine causes positive symptoms (delusions,hallucinates, paranoid thinking). Therefore, a dopamine receptor blocker is needed to help with positive s/s.
Decreasing dopamine can cause hypo kinetic problems. Dopamine blockers may decrease positive symptoms but may compound negative symptoms.
In Parkinsons
Too little dopamine due to dopamine-neuronal death in substance nigra. Dopamine is essential for normal movement and support for normal movements. PD occurs when 80% of neurons die off.
A balance between acetylcholine and dopamine is needed and a decline in dopamine levels leads to imbalance between these two NT.
Tx - increase dopamine. ie. levodopa, precursor to dopamine.
Increasing dopamine can cause schizophrenia like problems
Traditional Antipsychotics
High potency antipsychotics block D2 dopamine recceptors. Anticholinergic meds block acetylcholine.Therefore creating a balance between these two and decreasing risk of EPS.
SE of FGA anti psych (1 good, 3 bad) :
- EPS
- ^PROLACTIN - due to D2 receptor blockage in ant pituitary. s/s impotence, galactorreha, amenorrhea, gynecomastia, lowe sperm ct, feminzation.
- ^NEGATIVE/cognitive symptoms -traditional antipscy can block dopamine and cholinergic receptors. Aceytlcoholine has a role in learning and memory, so if blocked, then issues with memory and learning.
- Decreased positive event
Chlorpromazine - also has anticholinergic properties and does not need benztropine.
Low potency meds block non-dopamine receptors.
Atypical Antipsychotics
Pathways related to the bad SE due to dopamine D2 blockade:
- Mesolimbic dopamine pathway - positive symptoms.
- Nigrostriatal “ “ - EPS.
- Tuberoinfundibular tract - ^ prolactin.
- Mesocortical dop. path - increased negative/cognitive symptoms.
SGAs do not block and may increase dopamine in #2-4, while blocking D2 receptors in #1 mesolimbic.
SGAs antagonize 5HT2a receptors which are found on terminal of neurons that produce dopamine. When serotonin activates receptors, then dopamine release decreases. Therefore, block serotonin receptors to avoid activation and increasing dopamine release.
SGAs affect areas 2-4, while blocking dopamine in 1.
SGA types
Clozapine - Agranulocytosis.
Riperidone - hgiher affinity for D2 receptors than clozapine. Known to cause EPS and ^ prolactin.
Paliperidone - metabolite of risperidone with same MOA.
Olanzapine - popular, tx bipolar and schizophrenia. Causes wt gain, DM.
Quetiapine - has anxiolytic and sedative effect.
Ziprasidone - QTc interval prolongation, get EKG, must take with large meal, significant activation of 5HT1a receptors therefore can dcrease anxiety, decrease depressive s/s, improve negative symptoms via non dopamine avenue.
Aripiprazole - dopamine partial agonist. Levels off dopamine availability everywhere in brain (decreases where dopamine overactivity, increases with dopamine hypo activity) , decreases in 1, increases in 2-4
Problems - wt gain, sedating, metabolic syndrom, elevated lipids, htn, orthostasis.
Antidepressants
Top sellers: escitalopram, venlafaxine, duloxetine.
- All (except for MAOIs and NaSSAs) increase serotonin, NE, DA levels or a combination of these by blocking reuptake.
- Effect in 2-4 weeks.
- Newer Antidep are not better, just less SE.
Classes:
1. TCA - has anticholinergic (muscarinic receptors blocked, antihistaminic (leads to sedation and wt gain), and antiadrenergic (if blocked blood vessels lose ability to constrict leading to hypotension effects. Possibly arrhythmias and seizures with very high doses due to Na channel disruption. Bad for suicidal pts.
- SSRI - GI & Sexual dysfunction common. May lead to non adherence. Sexual dysf due to dopamine inhibition by serotonin in mesolimbic. (citalopram, fluoxetine, paroxetine, escitalopram, fluvoamine, sertraline)
- SNRI - (desvenlafaxine, venlafaxine, duloxetine) increases serotonin at lower dosages, and increase NE at mid range doses, increases dopamine at higher doses.
Venlafaxine- lower affinity for muscarininc, histaminic, and adrenergic receptor but problem with high BP in some. Desvenlafaxine is a metabolite of ven. Duloxetine - same as venlafaxine, used to tx diabetic neuropathy. - NRI - atomoxetine.
- NDRI - bupropion. the only antidep with dopamine reuptake inhibition and do not affect serotonin. Impacts adrenergic system and can cause overstimulation, insomnia, and agitation, possible seizures. zyban for smoking cessation.
- NaSSAs - noradrenergic and specific serotnonerigc antidepressants. Mirtazapine, antagonist at a2 auto receptor therefore release more serotonin and NE. It also antagonizes ht2-3 receptors. Causes wt gain, increased appetite, dizziness. at lower doses, used for sedation, at higher doses, drowsiness decreases. Also useful for sex dysf, those with poor appetite, insomnia.
Serotonin syndrome
almost identical to NMS. Hyperthermia, rigidity, altered mental status, and autonomic changes.
Symptoms precipitated by serotonin elevations, usually drug interactions.
Excessive 5HT1A and2 receptors may cause serotonin syndrome.
Antimanic drugs
mood stabilizers include lithium, divalproex, anticonvulsants, and antipsychotics.
Lithium - naturally occurring element. Gold std for bipolar. typical dosage 600mg tid, with serum level between 0.6 -1.2.
Anticonvulsants
Divalproex -more rapid onset than lithium and better tolerated. SE hair loss, wt gain, GI problems, dose related thrombocytopenia.
Carbamezapine, lamotrigine, gabapentin, oxcarbazepine, topiramate.
antipsychotics - olanzapien, risperidone, aripiprazole, ziprasidone, quetiapine.
Antianxiety
Benxodiazepine - anxiolytic response by enhancing GABa receptors. Important thing is metabolism, especially in elderly. Highly bound to serum proteins and have active metabolites, lipophilic. See table on pg 179.
Tolerance develops. SE imclude sedation, reduced coordination, very disinhibiting. May have paradoxical effect of agitation, anxiety, insomnia. Have wide therapeutic index.
Withdrawal s/s:
HA, pain, tingling, weakness, twitches, tremors, dizzines, tinnitus. Excitability, insomnia, anxiety, depersonalization, depression. aggression, poor memory and concentration, hallucinations and SEIZURES.
SSRIs
Buspirone - anxiolytic effect like lorazepam, nonsdating. Not a quick fix, takes time for full effects 3-6 weeks.
