Lecture 11: Neurology II

neurotransmitters are released where?

At a synapse

What do neurotransmitters bind to?

receptor on the post-synaptic neuron

Agonists/enzyme inhibitors increase what?

CNS neurotransmitters

Antagonists decrease what?

CNS neurotransmitter action

alterations of neurotransmitters causes what types of effects?

systemic effects

what type of neurotransmitter is epinephrine

excitatory:

\-drive

\-motivation

what type of neurotransmitter is dopamine

excitatory

* reward (pathway = pleasure)

what type of neurotransmitter is serotonin

inhibitory/complex-balance required

* mediator of fx
* balances mood

what type of neurotransmitter is GABA

increased Cl influx

* decreased cell activity

what type of neurotransmitter is glutamate

excitatory:

* memory learning

what type of neurotransmitter is substance P

excitatory

* synaptic communication

high levels of norepinephrine/epinephrine causes what?

paranoia

anxiety

stress

high levels of dopamine causes what

anxiety

psychosis

high levels of serotonin causes what?

mood swings

high levels of GABA causes what?

Lethargy

confusion

sedation

amnesia

high levels of glutamate causes what?

focus

anxiety

high levels of substance P can cause what?

pain

low levels of norepinephrine/epinephrine can cause ?

depression

lethargy

low levels of dopamine causes?

depression and

lethargy

low levels of serotonin

depression

OCD

mood swings

low levels of GABA causes?

anxiety

insomnia

low levels of glutamate

low focus

poor retention

Some traits of ADHD

Careless mistakes

problems organizing tasks

easily distracted

fidgets

talks tomuch

Describe dementia

Neurocognitive degenerative disorder

deficit in short and longterm memory

deficits in high cortical fx - judgement and personality

dx of dementia

direct is not possible, so need to rule out other possibilities

What possibilities do you need to rule out when trying to diagnose dementia

Drug s/e, depression, metabolic disease, declining sensory perception, brain lesion, infection/sepsis, anemia

Pathology of alzheimers

Abnormal breakdown and recycling of amyloid proteins → accumulation of b-amyloid deposits + protein fibre ‘tangles’ → amyloid plaques → loss of neurons and synapses, decreased Ach synthesis

S&S of alzheimers

Progressive symptoms of forgetfulness →

Behavioural changes →

Inability to complete ADLs

Tx of alzheimers

no cure, try to increase ACH

Medications for alzheimers disease

Cholinesterase inhibitors - decrease Ach breakdown

\-Rivastigmine

\-Galantamine

Parkinsons disease is the second most common form of ?

Dementia

Describe Parkinson’s disease

Accumulation of proteins: Lewy bodies

\-destruction of dopamine neurons → reduces dopamine transmission in basal ganglia → inability to filter out extra movements and focus purposeful movement

Defining S&S parkinsons

Rigidity

Jerking

Tremor

Tx for parkinsons

No cure - increase dopamine

Meds for parkinsons disease

Levodopa

Rotigotine (Neupro)

Structures of sleep

RAS, thalamus, cerebral cortex

Hypothalamic SCN (suprachiasmatic nucleus)

Pineal gland (melatonin synthesis)

Sleep: endocrine input

Melatonin

Describe the synthesis of melatonin

secreted by pinealocytes from the pineal gland (in the epithalamus)

* synthesized from tryptophan (amino acid)
* Diet acquired
* Is converted from serotonin

Describe attributes of melatonin

Feedback loop communicates with SCN

Higher synthesis at night

Production decreases w aging

What happens when there is excess melatonin

Drowsiness

Sleepiness

Lethargy

Depression

Circadian rhythm input

Decreased RAS/cortical stimulation → decreased excitatory neurotransmitter activity (norepi and ach) and increased inhibitory neurotransmitters (serotonin)

Sleep stages: nonREM 1-4

light to deep sleep progression

Sleep stages: REM

muscle paralysis

altered VS

dreaming

nightmares occur in this stage

What is insomnia

Difficulty with sleep initiation, quality, duration, and ability to resume sleep

S&S of insomnia

Fatigue

Decreased memory

GI upset

Irritabiltiy

Who is most effected by insomnia?

Elderly

Post-menopausal

Stimulants like caffeine, nicotine, ETOH

Drug side effects

DX of insomnia

Self assessment

Sleep study

EEG

VS - O2 sats

Treatment of insomnia

Melatonin - synthetic hormone, feedback loop < production

GAba binding - benzodiazepines, non-benzodiazepines, other

Insomnia meds: Benzodiazepines

Flurazepam (Dalmane)

Temazepam (Restoril)

Triazolam

Insomnia meds: non-benzodiazepines

Sonata

Ambien

Lunesta

Insomnia meds: other

sedation d/t CNS sedation

* antihistamines: diphenhydramine (benadryl)

what is obstructive sleep disorder?

Sleep related collapse of the upper airway (pharynx) → pharyngeal wall collapse, vocal cord approximation, tongue obstruction of the oropharynx

normal vs abnormal obstructive sleep apnea

normal - occasional snoring

abnormal - apnea frequency > 5 per hour, effects of apnea present

* headache, fatigue, irritability, poor memory, depression

Prominent risk factor for obstructive sleep apnea

OBESITY

* large neck girth, increased abdominal pressure → increased intra-thoracic pressure

tx of obstructive sleep apnea

decrease risk factors - weight loss

nighttime continuous airflow decides - NCPAP (nasal continuous positive airway pressure by an occlusive mask)

Headaches

a symptom

rule out pathology and diagnose - e.g fatigue, dehydration, hypoglycemia, lack of sleep, stress etc

Headache tx

DEPENDS ON CAUSE

* do not treat if not sure of dx

Acute and severe headaches

Attention to life threatening pathologies

Chronic headaches

Migraines

Chronic migraines etiology

Genetic link is common

Higher incidence in adult women

Criteria for migraines

>15 days/mth for 3 months

Pathology of chronic migraines

unknown

sequalae of migraines

trigeminal nerve irritation → inflammation within meningeal vasculature

main categories of migraines

without aura - most common

with aura - more pronounced visual disturbances and precede the headache

S&S of migraines

prodrome fatigue and irritability pre-migraine, N&V, intense unilateral headache, hypersensitivity to stimuli, sensory disturbances

Migraine tx analgesics

NSAIDS

Tylenol (acetaminophen)

Migraine tx serotonin agonsists

triptan drug class:

* sumatriptan
* zolmitriptan

migraine tx with botox

superficial scalp IM injections

* antiinflammatory actions, decreases neurotransmitter hyperstimulation

adjunct tx for migraines

caffeine

antiemetics

psychadelic drug examples

magic mushrooms

ecstasy

ketamine

what is anxiety

intense fear => SNS stimulation

S&S of anxiety

HPA axis stimulation

diaphoresis

elevated VS

fight-flight activated

Types of anxiety

Generalized, panic, social phobia

Generalized anxiety

Excessive, uncontrollable worry w systemic symptoms

Unable to modulate with present coping mechanisms

Panic anxiety

Instense fear with systemic systems

* CNS involvement w major emotional centres - amygdala, hippocampus, prefrontal cortex
* SNS stimulation - hypothalamus, brainstem HPA axis

Anxiety tx: increase GABA

benzodiazepines

* alprazolam (Xanax)
* Diazepam (valium)
* Lorazepam (ativan)
* Midazolam (versed)

Anxiety tx: increasing serotonin

balance of serotonin is desirable; imbalance - mood instability, manias, decreased ambition, depression

SSRIs

other tx for anxiety

behavioral and cognitive therapies

psychadelic tx

what is a psychiatric disorder

disorder characterized by a change in thoughts, mood, behavior which interfers with the persons life

common s&s of a psychiatric disorder

hallucinations

delusions

etiology of hallucinations

1. sensory block - stored images replace intel


1. neuronal dysfx - neuronal hyperactivity, pathway dysfx, disease

Hallucinations: sensory blocks are expected in ?

sensory deprivation

sensory dysfx

sensory classifications of hallucinations

visual

auditory

tactile

olfactory

what are delusions

false beliefs in facts and/or personal status

paranoias

etiology of delusions

present in some psychiatric disorders

caused by various environmental/existential influences

s&s of psychosis

hallucinations

delusions

lack of awareness of judgement

mood/affect alterations

etiology of psychosis

mental health illnessess

drug side effects/toxicity

electrolyte imbalances

sepsis

hospital induced overstimulation

what is schizophrenia

dysfunction of thoughts and language expression, a chronic illness, familial link is significant

s&s of schizophrenia

abnormal behaviors and movement

disorganized schizophrenia

incomprehensible speech, invented words, disconnected words and thought processes, disconnected/disorganized words

psychotic schizophrenia

hallucinations, delusions, agitaion

negative symptoms of schizophrenia

withdrawn and apathic, lack of motivation/happiness

* most difficult to treat, worse prognosis

etiology of schizophrenia

unknown - structural alterations present on MRI (hippocampus, frontal lobe, temporal lobe)

genetic predisposition

dpoamine excess

diagnosis of schizophrenia

at lease 2 of the s&S and 2 other functional alterations (e.g hygiene)

MOA of antipsychotics (aka neuroleptics)

targets limbic D2 receptors

* mood, behavior, emotion control
* degree of antagonism = success with therapy
* degree of specificity = fewer other effects

s/e of antipsychotics - D2 antagonism

D2 antagonism in basal ganglia - tardive dyskenisa, parkinsonism, tremors, restlessness, dystonias

s/e of antipsychotics - ACH blockage

anticholinergic s/e

* urinary retention
* dry mouth
* sexual dysfx

s/e of antipsychotics - neuroleptic malignant syndrome toxic reaction

* hyperthermia
* unstable BP
* diaphoresis
* incontinence

Typical antipsychotics: phenothiazines

e.g chlorprozamine

Typical antipsychotics - non-phenothiazines

e.g haloperidol