Neuropharmacology Flashcards
Which class of medications has the highest rate of being prescribed?
antidepressants
List the 6 major categories of psychiatric disorders:
- neurosis
- psychosis
- depression
- schizophrenia
- Tourette’s syndrome
- dementia
Which types of psychological disturbances are categorized under “neurosis”?
mild forms of mental disorders
- anxiety
- hysteria
- hypochondria
- phobias
- OCD
- panic disorders
- PTSD
Diseases classified as “psychosis”:
- schizophrenia
- organic psychoses
- bipolar disorder
- psychotic depression
- drug-induced psychoses
How is the word “psychosis” derived?
psyche = mind/soul
osis = abnormal condition
Pharmacological treatment of depression presumes…
a brain deficiency in dopamine, norepi, serotonin, or altered receptor activities
Positive symptoms of schizophrenia:
- delusion
- hallucinations
- disorganized speech/thinking
- grossly disorganized behaviors/catatonic behaviors
Negative symptoms of schizophrenia:
- lack of emotion
- lack of interest/motivation
- flat affect
- alogia
- inappropriate socializing/isolation
Cognitive symptoms of schizophrenia:
- disorganized thinking
- slow thinking
- difficulty understanding, expressing
- poor concentration & memory
How is dopamine related to schizophrenia?
- schizophrenic individuals produce more dopamine than typical brain
- increased activity at D2 receptor
4 dopamine pathways in the brain:
1) mesolimbic
2) mesocortical
3) nigrostriatal
4) tuberoinfundibular
Location of the mesolimbic pathway:
from the tegmentum (midbrain) to the nucleus accumbens (limbic system)
Blocking the mesolimbic dopamine pathway has what effect?
decrease in positive symptoms
Location of the mesocortical pathway:
from tegmentum (midbrain) to frontal & limbic cortex
Effect of blocking the mesocortical dopamine pathway:
may produce or worsen negative symptoms d/t an increase in 5HT which inhibits dopamine release
*explains why negative symptoms are unaffected or worsened by drugs that only block dopamine receptors
Location of the nigrostriatal pathway:
from the substantia nigra (midbrain) to basal nuclei
Importance of the nigrostriatal pathway:
regulates posture and voluntary movement
*first gen antipsychotics block receptors here and cause parkinson’s-like syndrome (EPS)
Location of the tuberoinfundibular pathway:
from hypothalamus to anterior pituitary
Effect of blocking the tuberoinfundibular pathway:
dopamine inhibits prolactin release, so blocking dopamine here may lead to galactorrhea, amenorrhea, sexual dysfxn
Where do FGAs work? What symptoms are they most successful at treating?
- block D2 receptors in limbic system
- (muscarinic, adrenergic, & histaminergic receptors affected too)
- most effective against positive symptoms but may cause EPS
Most potent FGA?
Least potent FGA?
most = haloperidol
least = chlorpromazine
Clozapine effects and benefits?
- effective for both positive and negative symptoms
- no parkinsons-like symptoms
- blocks D2 and 5HT receptors
Adverse effect of clozapine:
agranulocytosis
Common adverse effects of SGAs:
- sedation
- weight gain
- orthostatic hypotension
- EPS
- parkinsonism
Activation of 5-HT2 receptors causes what?
blocks release of dopamine
Blocking 5-HT2 receptors causes what?
increases release of dopamine
Effect of blocking 5-HT in each of the 4 dopamine pathways:
- nigrostriatal: increased DA release = less EPS than FGAs
- mesocortical: increased DA release improves negative symptoms
- tuberoinfundibular: increased DA release = less prolactinemia than FGAs
- mesolimbic: less effect here than other 3 pathways; SGAs block DA receptors and improve positive symptoms
How does tardive dyskinesia differ from EPS?
- TD may be irreversible/take years to resolve
- incidence higher in elderly with FGAs (53%)
- lower incidence in elderly with SGAs (5)
Which drug produces a zero incidence of tardive dyskinesia?
Clozapine
Descibe parkinsonism:
- tremor
- rigidity
- akinesia/bradykinesia
- cognitive fxn eventually declines
- s/s d/t degeneration of inhibitory DA pathway from substantia nigra to caudate nucleus in striatum
Treatment for parkinson’s disease?
- replacement therapy
- Levodopa = drug of choice
Why don’t we give dopamine to Parkinson’s patients?
cannot cross the BBB
Why is Levodopa successful in treating Parkinson’s disease?
- precursor to dopamine that can cross the BBB
- orally effective (large doses)
- decreases tremor and akinesia
Drugs that interact with Levodopa:
- Pyridoxine (Vit. B6) increases peripheral metabolism of levodopa -> DA (reverses effect)
- Carbidopa, a peripheral decarboxylase inhibitor, decreases peripheral metabolism of leveopda
- therefore, most effective treatment for Parkinson’s dz = sinemet (carbidopa:levodopa)
Anesthetic considerations for patients on antiparkinsonian drugs:
- hemodynamic instability
- gastric aspiration
- laryngospasm
- postop cognitive dysfxn
- upper airway obstruction
- sensitive to CV and resp depressant effects of anesthetics
- caution with Fentanyl & Neostigmine
- continue PD meds the AM of sx
How is dopamine related to psychosis?
- increase in DA
- located in the limbic system
- treatment is to block DA receptors
- adverse effects = parkinsonism
MOA of SSRIs:
selectively block neuronal reuptake of serotonin at presynaptic membranes with little effect on other neurochemical systems
How long does it take SSRIs to work?
1-4 weeks (maybe up to 12 weeks for some patients)
Most important advantage of SSRIs compared to TCAs?
relative safety when taken in an overdose
List some common SSRIs:
- Fluoxetine
- Paroxetine
- Sertraline
- Citalopram
MOA of SNRIs:
inhibit NE transporter as well as SERT
Which antidepressant class is preferred for patients with heart dz?
SNRIs
Body processes regulated by serotonin:
- GI motility
- genital arousal
- vascular tone
- hematopoeisis
- PLT aggregation
- parts of the inflammatory response
SE of SNRIs:
- nausea
- dry mouth
- somnolence
- HA
- sexual dysfxn
One way SNRIs are superior to SSRIs:
chronic pain treatment
MOA of TCAs:
inhibit synaptic reuptake of NE and serotonin at presynaptic terminals; also affect other neurochemical systems (histaminergic and cholinergic)
SE of TCAs:
- postural hypotension
- cardiac dysrhythmias (contraindicated in prolonged QT)
- urinary retention
Major TCA:
Amitriptyline
MOA of MAOIs:
heterogenous group that block the enzyme that metabolizes biogenic amines (monamine oxidase A & B), increasing the bioavailability of catecholamines and serotonin in the CNS and peripheral ANS
MAIOs are typically (first/second/third) line treatment, except in which patient population?
typically second/third except in atypical depression (first line)
List 2 MAOIs:
phenelzine & tranylcyrpromine
Major SE of MAOIs:
HTN crisis
- treat clinically with a peripheral vasodilator
- patients should promptly report serious HA, N/V, CP
Lithium toxicity s/s:
- skeletal muscle weakness
- ataxia
- sedation
- widened QRS
- AV heart block
- hypotension
- seizures
Cause of neuroleptic malignant syndrome:
rapid increase or over administration of high doses of antipsychotics (esp haldol)
4 main syndromes characterized “extrapyramidal syndromes”:
1) acute dystonia
2) akathisia
3) parkinsonism
4) tardive dyskinesia
s/s of discontinuation syndromes:
- N/V
- anorexia
- general somatic distress
- insomnia
- anxiety
- agitation
Drugs that can cause serotonin syndrome:
- SSRIs
- atypical & cyclic antidepressants
- MAOIs
- opiates
- antibiotics
etc
s/s of serotonin syndrome:
- agitation
- delirium
- autonomic hyperactivity
- hyperreflexia
- clonus
- hyperthermia
What causes mortality with serotonin syndrome?
rhabdomyolysis (renal failure, hyperK+, DIC, ARDS)
Which neuropharmacological drug potentiates the action of NDMRs & succs?
Lithium
Most common antidepressants used for chronic pain:
- TCAs
- SSRIs
- SNRIs
Effect of rhodiola:
relieve occasional anxiety and support body during stress
Effect of valerian root:
promotes relaxation to relieve nervousness, tension, occasional anxiety
Effect of winter cherry:
thought to relieve intermittent anxiety
