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Anti-psychotics
anti psychotics
41
Accounting
Pre-School
10/13/2014

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Cards

Term
Positive Symptoms
Definition
Delusions, hallucinations, disorganized speech, catatonic behavior
Term
Negative Symptoms
Definition
Affective flattening (decrease in range of emotion), decrease in fluency of speech and avolition
Term
Dopamine Hypothesis
Definition

Schizophrenia caused by increased dopamine transmission in the brain (based on fact that effectiveness of typicals correlates with blocking dopamine receptors) 

 

Hallucinations are also a side effect of L-DOPA therapy in Parkinsons


DA levels in subcortical areas of the brain were found to be twice as high in schizophrenic patients compared to controls 

Term
LSD
Definition
stimulates 5HT2A receptors which causes hallucinations similar to those of schizophrenia
Term
4 Dopaminergic Pathways in CNS
Definition

Nigrostriatal Pathway (extrapyramidal nervous and controls nervous and controls motor function)

Mesolimbic (midbrain VTA --> nucleus accumbens); thought to be overactive

Mesocortical (midbrain VTA --> cortex); though to be underactive --> apathy, withdrawal, lack of motivation, and pleasure

Tuberoinfundibular pathway: hypothalamus --> anterior pituitary (decreases prolactin secretion) 

Term
High Potency Typical Antipsychotics
Definition

Haloperidol, Fluphenazine

EPS - high

Anticholinergic - low non neurologic side effects

Term
Medium Potency Anti-psychotics
Definition

Perphenazine 

Medium EPS and anti-cholinergic effects

Term
Low potency anti-psychotics
Definition

Chlorpromazine and Thioridizine

Low EPS, High anti-cholinergic effects

Term
Distinguishing features of typicals + pharmacokinetics
Definition

High extrapyramidal symptoms compared to atypicals

Enhancement of negative symptoms by blocking reward symptoms of mesolimbic system 

 

Ability to cause effective and long lasting blockade of dopamine D2 receptors in all dopaminergic pathways, leading to undesirable effects

Term
Early onset and reversible side effects of typicals
Definition
Acute dystonia, Parkinsonian symptoms, Akathisia
Term
Late onset and irreversible side effects of typicals
Definition
Tardive dyskinesia
Term
Acute Dystonia
Definition

Involuntary contractions of face, neck, tongue, and extraocular muscles 

Will respond to anticholinergics or diphenhydramine (Benadryl has anti-muscarinic properties)

Low potency antipsychotics with significant anticholinergic effects are LESS likely to cause acute dystonia 

Term
Parkinsonianism
Definition

Akinesia, muscle rigidity, tremor, shuffling gate (due to blockade of nigrostriatal pathway)

Must be treated with anticholinergics or amantadine

Term
Akathisia
Definition

Motor restlessness and urge to move

Reduce dose, treat with propranolol

May be treated with benzodiazepines (increase GABA) **Gaba B receptor agonist; baclophen to reduce muscle spasticity**

 

Term
Tardive Dyskinesia
Definition

Late onset and sometimes irreversible

exposed to antipsychotics 3 months or longer 

Involuntary movements of lips, face, tongue, and limbs

Due to supersensitivity of dopamine receptors in caudate

Treated by reducing dose, discontinuing drug, or switching to an atypical

Patients with dystonia are more likely to develop tardive dyskinesia 

 

 

Term
Other common side effects of typical anti-psychotic drugs
Definition

Blockade of alpha -- orthostatic hypotension, male sexual dysfunction

Blockade of muscarinic - constipation, dry mouth, urinary retention, and visual problems 

Blockade of histamine and muscarinic receptors - sedation

Blockade of dopamine D2 in pituitary - increased prolactin --> galactorrhea and amenorrhea 

Weight gain (atypicals more)

Decreased seizure threshold

Thioridazine retinal deposits and arrhythmias

Term
Thioridazine side effects
Definition
Retinal deposits and arrhythmias
Term
Rare side effect of typicals + lab findings
Definition

Neuroleptic malignant syndrome - similar to malignant hyperthermia, extreme muscle rigidity, dystonia, akinesia, agitation, hyperthermia, and autonomic instability 

 

Increased WBC count and creatinine phosphokinase

 

Rx: Dantrolene and dopamine agonists like bromocriptine 

Term
Distinguishing features of Atypicals
Definition

Comparatively low extrapyramidal symptoms

Effective for both positive and negative symptoms relative to typicals which mostly only treat positive 

Term
Pharmacologic properties of Atypicals
Definition

Serotonin antagonist at 5HT2A receptors

D2 antagonists with rapid dissociation

Dopamine D2 partial agonist (only aripiprazole)

Term
Serotonin antagonist at 5HT2A receptors
Definition

1) Reduction of EPS symptoms

2) Reduction of negative symptoms

3) Reduction of positive symptoms

4) Inhibiton of prolactin release 

Term
Atypicals and EPS
Definition

Stimulation of 5HT2A normally inhibits dopamine release (directly or through GABA release) 

Inhibition of 5HT2A will enhance dopamine release which will compete with atypical at D2 receptor

Since there is competition, there are less extrapyramidal effects 

 

Still a substantial block of D2 receptors in mesolimbic system, but is somewhat attenuated due to this effect 

Term
Atypicals and reduction of negative symptoms
Definition

Schizophrenics have decreased dopaminergic activity in prefrontal cortex (responsible for some negative symptoms)

Blockade of 5HT2A will increase dopamine from mesocortical (originating in VTA) neurons terminating in prefrontal cortex

Density of dopamine D2 receptors in the prefrontal cortex is low relative to the striatum so the ratio of 5HT2A to D2 blockade is large and the serotonin effect predominates 

Term
5HT2A antagonism and reduction of positive symptoms
Definition

Pyramidal cells in cortex have glutamate and project back to dopaminergic cell bodies in mesolimbic pathway in mesolimbic pathway 

Blocking 5HT2A blocks gluatmate which indirectly inhibits mesolimbic system which reduces positive symptoms 

May be possible to attenuate overactivity in mesolimbic pathway while minimizing side effects of dopamine blockade 

Term
Typicals and prolactin secretion
Definition
Normally inhibits prolactin release, thus, blockade of D2 receptors enhances prolactin release, but 5HT2a blockade has bigger effect, so there is actually less prolactin release 
Term
Dopamine D2 agonists with rapid dissociation
Definition
dopamine d2 receptor antagonists are bound long enough to cause antipsychotic action but not long enough to cause EPS
Term
Dopamine D2 Partial agonist
Definition

Aripiprazole

Causes signal transduction to be intermediate between full output and zero output 

Maybe could attneuate signal transduction at DA D2 mesolimbic pathway and simulate in nigrostriatal pathway 

Term
General side effects of atypical drugs
Definition

Generally decreased APS and decreased anti-cholinergic effects

Cardiometabolic risk

Sedation 

Term
Cardiometabolic risk of atypicals
Definition

Blockade of both histamine and 5HT2C receptors in hypothalamus will cause an increased appetite - increased intake - increased triglycerides, insulin resistance, diabetes, and CV events 

 

Some atypicals will elevate these without any relation to increased weight gain

 

Monitor weight, waist circumference, glucose, lipids, and triglycerides 

Term
Only atypical agent that will cause increased prolactin secretion
Definition
Risperidone
Term
Only atypical without EPS
Definition
Quetiapine
Term
Significant weight gain with atypicals
Definition

Olanzapine, Clozapine

Quetiapine second 

 

All of them cause weight gain doe 

Term
Sedation with atypicals
Definition

Many antipsychotics will block muscarinic, histamine, and alpha adrenergic receptors 

 

Blockade of these receptors will cause sedation and somnolence 

 

May be preferrable early on but later on can cause cognitive impairment 

Term
Clozapine SE
Definition

Atypical

Can be effective in patients who don't respond to other treatment

Big side effect is agranulocytosis - WBC need to be monitored, therefore only reserved for patients who really don't respond to anything else

 

Also causes a large increase in salivation and seizures 

Term
Ziprasidone
Definition

Cardiac arrhythmia and has risk of death

Rare side effect due to prolongation of QT interval by inactivation of fast acting delayed rectifier channels 

May lead to torsades arrhythmia 

Problem in higher doses and older patients 

Term
Risperidone SE
Definition

Only one to cause hyperprolactinemia

 

Also will cause EPS at higher doses 

Term
Pharmacokinetics of Atypicals
Definition
These drugs are metabolized by cytochrome P450 so inducers of the system may need higher doses
Term
If the patient complains of sexual dysfunction, don't give them..
Definition
Typicals (can cause sexual dysfunction by blocking alpha receptors), and risperidone (hyperprolactinemia)
Term
If patient already has signs of tardive dyskinesia, you would use one of the ...
Definition

Newer atypical drugs like quetiapine (decreased EPS) 

 

Generally patients that suffer from acute dystonia with typical antipsychotics will be more likely to get tardive dyskinesia 

Term
Injectables for patient compliance
Definition

Typicals: Fluphenazine, halperidol

Atypicals: Risperidonze, Ziprasidone 

Term
Other uses for antipsychotics
Definition
Psychosis from other dementias, mood stabilizers, off label augmentation of antidepressants in treatment resistant depression and augmentation of anxiolytics in resistant anxiety disorders, autism (aggression control), Tourette's syndrome - chronic tics, severe agitation in mentally retarded Alzheimers patients
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