Psychopharmacology MT 1

• Gross impairment in reality testing and creation of a new
unique reality that is not shared by others


• -Impairment in reality testing is manifested by:

• Disturbances in perception, thinking and speech including experiences not shared by others that occur in
the absence of any external stimulus
• 

-Delusions
:
• False fixed beliefs
• 

-Disturbances in behavior:

• Bizarre and inappropriate behavior may include doing something irrational or dangerous to accomplish a desired goal

• 1. Schizophrenia
• 2. Schizophreniform disorder
• 3. Schizoaffective disorder
• 4. Delusional disorder
• 5. Brief reactive psychosis
• 6. Psychotic disorder, NOS

• 1.Bipolar Disorder
• 2.Mood disorders with psychotic features
• 3.Parkinson’s disease & Idiopathic Parkinson’s
• 4. L-Dopa-induced psychotic disorder (build more DA in cortex.. Cause psychotic features)
• 5.Developmental disorders
• 6.Tourette’s

• -Typcially result of acute intoxication with or withdrawal from a drug or substance
• *Withdrawal from chronic alcohol abuse/dependence
• *Intoxication with or sustained use of: Stimulants or sympathomimetics

• 1. Endocrine Disorders
• 2. Metabolic Disorders
• 3. Neurological disorders
• 4. Auto-immune illnesses

• Intoxication with or sustained use of:
• 1-Hallucinogens: LSD
• 2-Dissociative anesthetics: PCP
• 3-Opiods: heroin, morphine, Vicodin, OxyContin
• 4-Anti-inflammatory drugs such as steroids
• 5-Anticholinergic drugs: used to treat Parkinson-like side
• effects of antipsychotic drugs

• 1. Affective flattening
• 2. Alogia
• 3. Avoiltion
• 4. Apathy
• 5. Anhedonia
• 6. Asociality
• (Correlated with more problems & Higher rates of permanent disability.)

• 1. Hallucinations
• 2. Delusions
• 3. Formal thought disorder
• 4. Bizarre behavior
• 5. Better response to medications
• (Less permanent disability)

• 1. Potent = use low doses

• Higher rate of extrapyramidal symptoms (EPS)



• 2. Weak = use in high doses can be longer lasting
Dopamine antagonists (DA blockers)

• Have potent side effects

• Neuroleptic drugs modify several neurotransmitter systems.
• 


• Despite this, a drugs efficacy in alleviating psychotic symptoms is best correlated with their effects on DA.
• 


• Effective antipsychotics interfere with DA transmission by:

• 1. Blocking post-synaptic DA receptors, and/or by
• 
2. Ultimately inhibiting DA release



• Evidence for actions on DA comes from
:
• 1. Their molecular structure
• 
2. Their side effects

• 3. Receptor binding and DA turnover

• 4. Neuroendocrine changes

-Classic neuroleptics have widespread effects on numerous receptor systems

-Even looking at a single receptor type (e.g., D2), neuroleptics will have differing effects in different areas of the brain

-Neuroleptics blocking D2 receptors in the pituitary gland stimulates prolactin secretion

-By antagonizing the normal DA-mediated inhibition of prolactin release

-The relationship between therapeutic benefit and side effect profiles may depend on actions at different receptor subtypes within different brain pathways

-The 3D configurations of the phenothiazines can be superimposed on the 3D structure of DA (bc shape so similar act at DA receptive sight)

-The common occurrence of Parkinsonian-like side effects (EPS) (permanent tarkidive Dysk.)indirectly suggests that neuroleptics reduce the normal DA-mediated activity in the striatum.

-At least six types of DA receptors have been identified and classified into two main groups. (Two main family D1 more motor D2 more psychotic).

- Neuroleptics have been shown to antagonize the D2L autoreceptors, effectively increasing the rate of firing, synthesis and release of DA

-They are also known to antagonize D2 post-synaptic receptors leading to up-regulation with chronic exposure

• 1. Neuroleptic Malignant Syndrome (rare)
• 2. Anticholinergic effects: (regonize!!!!)

• 

3. Extrapyramidal (EPS)
• 4. Tardive Dyskenesia (parkinsonian)
• 5. Anticholinergic effects, postural hypotension (esp. with aliphatics)
• 6. Lowered seizure threshold (all have alcohol lowers this,
• potentiate. )
• 7. Increased prolactin

• 1. Extrapyramidal (EPS):

• -
Acute dystonia
• -
Spasms of tongue, face, neck, back

• -Akathesia
• -
Restlessness with anxiety or agitation
• -
Akinesia
• -
Apathy
• -Parkinsonism


• With longer term use:
• -
Motor slowing, retarded facial movement, muscular rigidity (catalepsy), gait disturbance, resting tremor

• -High speed jitters more anxiety.

• 2. Neuroleptic Malignant Syndrome (rare):
Fatal in 20% of cases, High fever, Catatonia (bradykinesia) brady slow, taki fast. Stupor, Unstable blood pressureand pulse.
• 


• 3. Anticholinergic effects (recognize!!!!): Ataxia (loss ofcoordination), Burred vision, Confusion, Dry mouth, Dry skin, Constipation,Delayed urination, Weight gain, Sexual dysfunction.

• Duration of treatment
• -The longer a person takes an anti-psychotic, the more likely s/he is to develop TD
• -Only 4-6% of patients taking neuroleptics for one year develop TD (classics, lower potency higher dose)
• -However, if a patient takes the neuroleptic continuously for 10 years, s/he will have a 49% probability of developing TD.

• 1. -Drug free intervals:
• Patients who stop taking their neuroleptics, with or without consent of their physician, appear to be at higher risk than those who do not take “drug holidays”
• 2. -Age: Older adults are at higher risk than younger adults
• 3. -Gender: Women are at higher risk for TD than men
• 4. -Smoking tobacco appears to increase risk of TD
• 5. -Drinking alcohol increases the risk of TD

• -Discontinuing medication not effective (can even make worse)
• -EPS drugs will make it worse
• -No known medical treatment to cure, some possibilities for help:
• 1. Choline: (Water soluble B vitamin may be helpful, Still unclear if helpful)
• 2. Melatonin (Possibly helpful, but not clear)
• 3. Vitamin E (Not effective)

1. Inhibiting the action of liver enzymes (cytochrome P450 system)*. Certain drugs interact with the older typical neuroleptics to raise blood levels.

• 2. 







Inducing (speeding up) the action of
liver enzymes (cytochrome P450 system)* Because the metabolism of the neuroleptic is speeded up, less of the drug reaches the bloodstream and less is available for use at the brain
• receptor sites.
• 


• 
5.







Some drugs may interact with neuroleptics and cause increased sedation* Certain drugs/substances interact with the older typical neuroleptics to lower blood levels of the neuroleptic.

6. Other drug interactions with neuroleptics may put the patient at risk for very low blood pressure (hypotension; orthostasis)*

*More info on slides if need.

• 1. Atypical Neuroleptics are Multiple Receptor Antagonists

• -Designed to block D2 and one or more other receptors, for example clozapine (more information in notes)

• 2. Symptom-specific neuroleptics:
• -Develop more selective D2 receptor antagonists (e.g., sulpiride)
• -Develop more broad spectrum
• antipsychotics that antagonize multiple receptor systems

3. Specific D2 Receptor Antagonists - neuroleptics is mediated by a different population of receptor subtypes (e.g., D2,D3) than those mediating side effects (e.g., EPS).

• 4. Hypothesis of Action: Benefits for antipsychotic behavior while reducing side effects is a function of the ratio of antagonism for various receptors. As you
• balance may not get as many side effects.

5. Multiple Receptor Antagonists: Designed to block D2 and one or more other receptors.

• 1. 







Clozaril (clozapine)

 -Prototypic atypical antipsychotic


• -More effective than traditional
 antipsychotics


• -Especially good for refractory
patients and severe
• psychosis


• -Good with negative symptoms


• -Helps promote gains in social and 
occupational functioning 

• -Used to treat BD and Schizoaffective disorder

• -Used to treat Parkinson’s disease
related problems

2 -Agranulocytosis NB! (rare) 
high fever and a sharp drop in circulating granular white
blood cells

• -Interactions with other drugs likely
• -Definitely has dose-related EPS (inside dosing range pretty safe but if not can be dangerous) (Don’t want patients dosed over 10mg)
• -TD
• -Orthostatic hypotension
• -Sedation
• -Increases prolactin
• -Risperdal Consta: No greater association with EPS
• and TD

• 1. Zyprexa (olanzapine): Weight Gain <-know!
• 2. Abilify (aripiprazole): Minimal Weight Gain

-Has the patient been treated successfully in the past with an anti-psychotic drug?

-Is sedation needed to help manage this patient’s symptoms?

-The side effect profile of the drugs, the patient’s unique characteristics, and medical conditions

-Certain antipsychotic medications have more severe side effects than others

-The goal is to limit, minimize, and manage side effects so that the patient is able to tolerate the drug’s side effects

1. Asking a patient to monitor their medication-taking behavior is often enough to improve compliance 
e.g. in slides.

2.Clinicians can also help the patient set up contingencies, positive rewards for appropriate positive rewards for medication administration.