370: Cognitive Patho Flashcards
Which neurotransmitter is most prevalent in the brain?
Glutamate
Negative symptoms of schizophrenia
Decreased motivation
Blunted affect
Poor self-care
Social withdrawal
4 A's: Apathy / Ambivalence Affect blunted Associative loosening Autism
Positive symptoms of schizophrenia
Paranoia
Hallucinations
Agitation
Delusions
(PHAD)
Cognitive symptoms of schizophrenia
Disordered thinking
Memory and learning
Lack of focus
Pathophysiology of schizophrenia
- Dysregulation of dopamine (up or down)
2. Imbalance of dopamine and serotonin
First generation antipsychotics (FGA)
- D2 antagonists (decrease dopamine transmission)
2. Blockade on receptors for: Serotonin Histamine Acetylcholine Norepinephrine Dopamine (SHAND)
- Classified by potency
Second generation antipsychotics (SGAs) aka Atypical agents
- Decreased serotonin transmission
- Low affinity for D2 receptors
(Serotonin has inhibitory effects on DA)
Medicated cooperative stage
1st week of antipsychotic action
Decreased agitation, hostility
Improved socialization stage
2-6 week of antipsychotic action
Obeys rules, attends meetings, etc
Elimination of thought disorder stage
2 weeks - months of antipsychotic action
Decreased delusions, hallucinations, thought disturbances
Maintenance Stage of antipsychotic action
Achieves baseline level of functioning
Positive symptoms of schizophrenia
Too much dopamine in MESOLIMBIC area
Treat with FGAs (D2 blockers) or SGAs
Negative symptoms of schizophrenia
Not enough dopamine in MESOCORTICAL area
Treat with SGAs (restore balance between serotonin and dopamine)
What is a protype of a First Gen Antipsychotic (FGA)?
Chlorpromazine
Low potency agents of FGA
(Low D2 affinity, non selective)
Sedation, orthostatic hypotension, anticholinergic effects, weight gain
High potency agents of FGAs
(High D2 affinity/selectivity)
Extrapyramidal symptoms, prolactin release, arrhythmias
What is a prototype of a high potency agent of FGA?
Haloperidol
Extrapyramidal Symptoms
- Movement disorders
- Due to blockade of D2 receptors in nigrostriatal region
- Low DA, high Ach
Extrapyramidal movement disorders
High potency agents, occur early:
- Acute dystopia (muscle spasms)
- Akinesia (Parkinsonism)
- Akathesia (internal motor restlessness)
Prolonged med use:
4. Tardive Dyskinesia (invol muscle movements)
(AAAT)
Severe spasm of muscles in tongue, face, neck, back
Acute dystopia
Treated with anticholinergics
Tremor, rigidity, slow shuffling gait
Akinesia / Parkinsonism
Treated with anticholinergics
Profound restlessness, pacing, movement
Akathisia
Treated with anticholinergics
Involuntary twisting, writhing movements of face, tongue; may be irreversible, no reliable treatment
Tardive Dyskinesia
Treated with anticholinergics
Anticholinergics
(Benztropine, diphenhydramine)
Restore balance between DA and Ach
Neuroleptic Malignant Syndrome (NMS)
- More likely with high potency antipsychotics
Sudden fever, muscle rigidity, sweating, increased HR, labile BP, altered LOC, confusion, seizures, coma, arrhythmia, death
D/c antipsychotics, no antidote
What is a prototype of a Second Gen Antipsychotics (SGA)?
Olanzapine
Others: Risperidobe, Clozapine
Blockade of 5-HT2 receptors (restore DA/5HT balance)
Side effects: weight gain
Side effects of Second Gen Antipsychotics (SGA)
Weight gain, diabetes, increased cholesterol, prolonged QT interval
Clozapine
Risk of agranulocytosis
Agranulocytosis
Drop in blood cell counts
Could be fatal due to sepsis
Monitor WBC and neutrophil counts
Monoamine hypothesis of depression
Deficit of one or more NE, 5HT, or DA neurotransmission
Principal symptoms of depression
Depressed mood, loss of interest/pleasure
Respond by 4 weeks
Somatic symptoms of Depression
Sleep pattern, changes in appetite, weight changes, fatigue
Respond in 1-3 weeks
Antidepressant drug classes
- SSRIs
- SNRIs
- TCAs
- Atypical/Antidepressants
- MAOIs
What is a prototype of SSRIs?
fluoxetine (Prozac)
- Blocks neuronal reuptakr of 5HT
- Long half-life
SSRI Side effects
- Serotonin Syndrome
- Sexual dysfunction
- Nausea, HA, weight gain
- CNS stimulation (nervousness, insomnia, anxiety)
- Headache
Serotonin Syndrome
- Altered mental status (confusion, agitation, hallucination)
- Increased muscle tone
- Tremor
- Rigidity
- Sweating
- Fever
What is a prototype of TCA antidepressants?
Amitriptyline (Elavil)
- Blocks neuronal reuptake of NE/5HT
- Long half-lives
- Second-Line therapy
What are side effects of TCAs?
(TCAS) Thrombocytopenia Cardiac (arrhythmia, MI, stroke) Anticholinergic (tachycardia, urinary retention, etc) Seizures
Side effects of TCAs antidepressants
- Sedation (H1 receptor blockade)
- Orthostatic hypotension (blockade of alpha1-adrenergic receptors)
- Anticholinergic effects (dry mouth, blurred vision, constipation, urinary retention, tachycardia, etc) (muscarinic cholinergic receptor blockade)
- Weight gain (5HT2 receptor blockade)
- Cardiac toxicity (arrhythmias)
- Diaphoresis (sweating)
- Seizures
- Hypomania
What is a prototype of SNRI antidepressants?
Venlafaxine (Effexor)
- Block reuptake of NE and 5HT
Side effects: nausea, HA, insomnia, weight loss/anorexia, sexual dysfunction, increased BP
What is a prototype of an atypical antidepressant?
Bupropion (Wellbutrin)
- Blocks DA and NE reuptake. Also works on nicotine receptors.
- Shorter half life
Side effects: agitation, HA, nausea, dry mouth, insomnia, constipation, weight loss, psychosis (rare)
