week 6- antipsychotics Flashcards
neurotransmission
- action potential leads to the release of NT into the synapse where they bind to post-synaptic receptors
- NT can be recycled through re-uptake or degradation
neurotransmitters
- chemical messengers that transport signals from neurons to other neurons, muscle cells or glands
- necessary for life
- at least 21 NT in the CNS and 3 in the PNS (Ach, NE, E)
classification of NT
monoamines, amino acids, purines, opioid peptides, non-opioid peptides, others
monoamines
dopamine, serotonin, epinephrine, norepinephrine
amino acids
GABA, glutamate
purines
adenosine, adenosine triphosphates
opioid peptides
endorphins, enkephalins
non-opioid peptides
oxytocin, vasopressin
others
acetylcholine, histamine
dopamine
- catecholamine hormone that is produced in the adrenal gland
- reward and motivation hormone
- low dopamine is correlated with movement disorders (parkinson’s)
receptors:
DA1- excitatory
DA2- inhibitory
dopamine functions
movement, memory, constriction/relaxation of BV and gut motility
serotonin
- produced in CNS (raphe nuclei in brainstem)
- low serotonin is correlated with depression, anxiety, mood disorders, panic disorder
receptors:
5HT1/5HT5- inhibitory
serotonin functions
mood, GI movement, sleep, bone health
acetylcholine
- excitatory NT
- produced by cholinergic neurons in basal forebrain
receptors:
nicotinic- memory and cognition
muscarinic- skeletal muscle movement and PSNS activity
epinephrine and NE
- catecholamine hormones, produced in adrenal gland
- epi is more potent and acts on SNS primarily
excitatory receptors:
alpha 1- BV constriction
beta 1- HR and force of contraction
inhibitory receptors:
alpha 2- SNS autoregulation
beta 2- bronchodilation
schizophrenia
- complex mental illness that is characterized by alterations in how a person thinks, feels and relates to others
- can include positive, negative or cognitive symptoms
etiology of schizophrenia
unknown but may be related to:
- genetics
- NT (hyperarousal of dopamine receptors)
- development (in-utero to adolescence)
- environmental factors
positive symptoms
exaggeration or distortion of normal function
ie. hallucinations, delusions, paranoia, agitation, tension (catatonia)
negative symptoms
loss or diminution of normal function
ie. amotivation, bunted affect, poor self-care, social withdrawal, poverty of speech
cognitive symptoms
include disordered thinking, a reduced ability to focus attention, prominent learning and memory difficulties
stages of schizophrenia
prodrome, acute, residual and long-term
prodrome schizophrenia
- not experienced by all
- social isolation, depression, anxiety, academic withdrawal
acute schizophrenia
delusions, hallucinations, feeling of being controlled, disordered thinking, blunt affect, impaired self-care
residual schizophrenia
- florid symptoms (hallucinations, delusions) dissipate
- less vivid symptoms remain
- suspicious, anxious, poor judgement/insight/motivation, limited capacity for self-care
long-term schizophrenia
episodic exacerbations, goal is to achieve stability and high functioning
management of schizophrenia
- suppress acute episodes
- prevent acute exacerbations
- maintain highest level of functioning
antipsychotic drugs
- used for a broad spectrum of psychiatric disorders
- their use has been revolutionary
- most are antagonists, blocking dopamine receptors
- first and second generation antipsychotics, both equally as effective
first generation antipsychotics
- typical or conventional
- classified by potency or chemical
- same ability to relieve symptoms
- differences in side effects
examples of FGAs
low-potency- chlorpromazine
medium potency- loxapine
high-potency- haloperidol
FGA mechanism of action
- block receptors for dopamine, Ach, histamine, NE in and out of CNS
- this results in many side effects
- goal is to block D2 receptors in the mesolimbic area of the brain
FGAs therapeutic use
- suppress symptoms in acute phase
- long-term use can reduce risk of relapse
- improves positive and negative symptoms, and reduces cognitive dysfunction
- not used for dementia psychosis
FGA extrapyramidal symptoms
acute dystonia, parkinsonism, akathisia, tardive dyskinesia, neuroleptic malignant syndrome
acute dystonia
- onset within days
- spasm in muscles of face, tongue, neck, back
- oculogyric gaze (fixed upward gaze)
- laryngeal dystonia
- treatment with anticholinergic drugs (IV or IM)
- requires rapid treatment
parkinsonism
- early onset
- bradykinesia, masked faces, drooling, tremor, shuffled gait
- treatment with anticholinergic drugs or amantadine
- blocking dopamine in basal ganglia, avoid levodopa
akathisia
- onset with 2 months
- pacing, constant movement
- treatment with anticholinergic drugs, beta blockers or switch to low-potency
- associated with high-potency FGAs
tardive dyskinesia
- late onset (years)
- twisting of tongue, impacts chewing/swallowing
- no reliable treatment, switch to lowest effective dose for shortest time
- occurs in 15-20% on long-term, high dose FGAs
neuroleptic malignant syndrome
- early onset (hours to days)
- lead-pipe rigidity, high fever, dysrhythmias, coma, death
- stop antipsychotic immediately, treat symptoms with dantrolene
- 5-20% mortality with NMS
other FGA adverse effects
- anticholinergic effects (can’t pee, can’t see, can’t shit, can’t spit)
- sedation
- orthostatic hypotension
- neuroendocrine effects (inc prolactin leads to breast growth and abnormal milk production, abnormal menstruation)
- arrythmias
- agranulocytosis
FGA contraindications
- dependence is rare, although symptoms will appear if stopped abruptly
- toxicity is rare, wide TI
- interactions with anticholinergics, CNS depressants and dopamine agonists
second generation antipsychotics
- atypical, introduced in 1990s
- overtook drug market, perceived better than FGAs
- different side effect profile (less EPS, metabolic symptoms)
- all approved for schizophrenia
clozapine (SGA) mechanism of action
- blocks dopamine, seretonin, NE, histamine and Ach receptors
- low affinity for D2 receptors (thought to decrease EPS)
- goal is blocking D2 receptors in mesolimbic area of brain
therapeutic use of clozapine
- highly effective
- improves positive and negative symptoms, and cognitive dysfunction
- not used for dementia psychosis
SGA adverse effects
- metabolic effects (weight gain, dyslipidemia, diabetes)
- agranulocytosis
- seizures
- orthostatic hypotension
- myocarditis
- EPS (sig reduced)
drug interactions with SGAs
immunosuppressants and drugs that influence cytochrome P450
antipsychotic administration
oral (pill, liquid suspension, sublingual formulation), IV solution, IM injection (depot medications), inhalation
key considerations when choosing an antipsychotic
- both SGAs and FGAs are equally as effective
- consider tolerability of adverse effects
- consider cost (SGAs 10-20x more expensive)
anxiety and insomnia
- caused by other mental health issues, external influences, medications, trauma, caffeine at night
- impacts dopamine, serotonin, glutamate, GABA
- treated with benzos
GABA
- found in limbic area of brain
- predominantly an inhibitory NT
- GABA-receptor complex opens channel for Cl, making cell more negative/unable to depolarize
receptors:
ligand gated ion channels or G-protein
benzodiazepines
- drug of choice for anxiety and insomnia
- also used for seizure management, muscle spasm, EtOH withdrawal, inducing anesthesia or conscious sedation
benzodiazepine mechanism of action
- enhance GABA by binding to GABA-receptor chloride channel complex
- not a GABA agonist, but intensifies the effect of endogenous GABA
benzodiazepine pharmacokinetics
- well absorbed orally
- lipid-soluble (crosses BBB and placenta)
- extensive metabolites (clinical response persists)
- time varies by drug, allows for targeted response based on indication
benzodiazepine adverse effects
- CNS depression (lightheaded/drowsy)
anterograde amnesia - complex and abnormal behaviours in sleep
- paradoxical effects
- respiratory depression
- IV administration is correlated with cardiac arrest
examples of benzos
lorazepam, clonazepam, diazepam, alprazolam
benzodiazepine considerations
- lower likelihood for abuse than other CNS depressants, but still a controlled substance
- dependence possible with LT use (gradual discontinuation)
- interacts with other CNS depressants leadings to respiratory depression and increased risk of toxicity
- antidote is flumazenil
