MBB TOLO – Week 5

 Overview: General anesthesia – reversible drug-induced coma – decreased state of consciousness

o General anesthetic affects synaptic transmissions whereas local anesthetic affect impulse conduction
o The ideal drug would not only decrease consciousness, but also:
 1. Induction of anterograde amnesia – patient doesn’t remember what happens
 2. SKM relaxation and immobility – easy to cut through during surgery
 3. Inhibition of undesired autonomic reflexes
 4. Analgesia – patient wakes up and wont feel pain
o Adverse effects: If you inhibit autonomic reflexes
 You could get systemic hypotension, or decrease breathing because skeletal muscle immobile
o Four stages of anesthesia
 1. Analgesia and Amnesia
 2. Delirium
 3. Surgical anesthesia – coma, and blocked somatic and ANS responses to painful stimuli
 4. Medullary depression – respiratory and CV depression
 We want stage 3 and get additional drug effects, so you need COMBO of drugs
 General anesthesia drug classes and adjuvants
o Adjuvants add to the ideal effects and also lower the
dose of the general anesthetics so you do not get
medullary depression
o General anesthetics decrease consciousnesses
 IV drugs – GABA target, and Adjuvants IV!!
o You get increase in chloride conduction and
hyperpolarization of the neuron
o Thiopental - barbiturates – increase affinity of GABAa
for GABA and increase the channel opening time
 Used for bolus injection for short surgeries
 INDUCTION of surgery
 (propofol can be used for induction and
maintenance)
 It goes into the brain immediately and when patient wake up, then it
redistributes into other parts of the body
 If you infuse for a long time, you will increase the half life of
thiopental, as opposed to propofol so if you infuse thiopental for a
long time, it will stay in the body for longer and patient will never
wake up
 Adverse effects: cause bronchospasm, hyperalgesic effects when
wake up, and avoid patients with abnormalities in HEME
o Propofol - not barbiturate or benzos – widely used for induction and maintenance of general anthesia
 Good if you do not know how long surgery will be
 Additional uses: sedation in the ICU, or procedural sedation (conscious sedation – decrease anxiety and
pain – like colonscopy)
 Adverse: decreases BP, initial apnea, and is made in a fat solution so it can cause allergies
o Etomidate- Non-barbituate. Low dose, normal decrease threshold, higher dose – prolongs the hyperpolarization
– small increase in half life with continued infusion
 Use: induce general anesthesia, intubation in ICU
 Advantages: No cardio or respiratory effects
 Adverse: endocrine problems – inhibits steroid synthesis by adrenal cortex so no using for maintenance
o Benzos – midazaloam, diazepam – increase affinity frequency of channel opening
 Use: Procedural sedation – increase anxiety, sedation, and amnesia
 Synergy with GA which can lower GA doses so decrease adverse effects and rapid waking up
 Advantages – water soluble so can use aqueous medium so decrease injection pain and has extremely short
half life among BDZ (midazolam) so can use infusion
 Also there is reversal adgent FLUMAZENIL
 o Upoiod receptor antagonist – Fentanyl
 Uses: used together during induce and maintenance – yay synergy and lower GA doses
 Increases parasympathetic tone to heart, so you get decreased HR, but same CO and organ perfusion – this
can be prevented if you pre-treat with atropine
 Disadvantages – respiratory depression, chest wall and jaw stiffness because basal ganglia are affected –
can administer neuromuscular blocking agent to fix this problem
o NMDA receptor antagonist - Ketamine – decrease glutamate and decrease potentiation
 Use: Produces hypnotic like state where patient is dissociated – can breathe and eyes can be open but are
unconsciousness, unresponsive, and no pain
 Induce and rarely maintenance of general anesthetics
 Advantages – increase BP and CO, (do not use if pt has HTN), and not much respiratory probs
 Disadvantages: Bad dreams and
hallucinations when waking up,
better if patient wakes up in quiet
place and give benzo before
ketamine – happens less with
kids
 Do not give to patient
with psychiatric
problem
 Increases ICP so bad in
eye surgery or if patient
has ICP

 Inhaled general anesthetics – added as gas
inhaled during procedure – NO!!!
o EC50 – measures the potency of the
drug, measure of the pressure that
produces 50% max response so lower
Ec means that you have to give less drug
o MAC – minimal alveolar concentration
–that blocks movement due to stimulus
in 50% of patients – so less is better
o MACBAR – minimal alveolar concentration to block autonomic response from noxious stimuli in 50% of patients
o Lower MAC and MACBAR means more potent because higher lipid solubility
o MOA – unclear, could interact with GABA or NMDA to affect synaptic transmission
o NO
 Use: used with combo with GA, low potency and light level of anesthesia
 Advantages – not irritating to airway but can cause nausea/vomiting long term, maintains BP
 Disadvantages – no skeletal muscle relaxation and can move into closed gas space (abdomen, air emboli)
o Desflurance /isofluorance (halogenated hydrocarbon)
 Use: widely used inhaled GA
 Advantages: rapid onset and recovery, moderate cardio depression, relax skeletal muscle, eliminated
mostly by ventilation but some by 0.02% by CYP
 Disadvantage – irritate airway and maybe malignant hyperthermia (esp with NM blocker), and the CYPS
could cause bad metabolites and lead to hepatic necrosis
 Neuromuscular blocking agents – important adjuvants for muscle relax
o Activate Nm receptor  Na comes in  depolarization  contraction
o Uses: skeletal muscle relax for skeletal muscle relax so you get intubation, ventilation, abdomen and thoracic
surgery
o 2 types of blockers:
 1. Competitive blocker – stop Ach from binding to Nm – flaccid paralysis
 2. Depolarization blocker – bind to Nm and keep activating them so the channels are persistently
depolarized – flaccid paralysis
o Vecuronium - competitive agent
 Prototype competitive agent is d-tubocurarine ( no longer used because it released histamine from mast
cells)
 Commonly used – more selective for Nm and fewer adverse effects
 Recovery: use competitive agent (AchE inhibitor or reversal agent) to outcompete the drug
o Succinylcholine – depolarization agent
 Rapid onset – for rapid intubation – metabolized by ChE in plasmas and liver – so short duration of agent
 Two phases of block
 Phase 1. Persistent depolarization – rapidly reversed – recover 5-10 minute
 Phase 2. Occurs with prolonged administration because you get desensitization so 20 min
recovery
 Not recommended for long surgery
 Disadvantages – Significant K+ efflux and get hyperkalemia, + also get malignant hyperthermia
 No reversal agent, do not need for phase 1 block

 Malignant hyperthermia
o Contraction and stiffness of
SKM leads to hyperthermia
because SKM contraction
o You get increased
metabolism, and metabolic
acidosis (increased lactic acid)
and tachycardia
o Caused by uncontrolled Ca
release from SR in SKM –
leading to abnormal and
sustained contraction and
increased suspectibility if kid
has genetic abnormality of
RyR1 (stores Ca in SR)
o Rare but can happen if you
use halogenated hydrocarbon
and succinylcholine together
o Treatment – stop giving drug
and give IV dantrolene (which blocks Ca release)
 Dantrolene normally for anti-spasticity
 Approaches to anesthesia
o Look what they need, how long surgery is, give lots of different drugs and limit side effects
Lecture 33 – Higher brain function: language and ideomotor praxis – can also happen with thalamic lesions
 Hemispheric Specialization
o 99% right handed people use language on left, 70% of left handed use language on left
o Left – verbal, analytic, temporal processing
 Temporal – lots of information that is presented over time that you can push it together
o Right – nonverbal, holistic, spatial processing
 Spatial – lots of information that is presented at once and putting it together
o Localizations and lesions – Localization of function
 Cortical or subcortical syndrome
 Subcortical – axons that come from cortical, or deep grey structures
 Disconnection syndrome -Brain regions need to talk to each other with white tracks
 Neuroanatomy of language
o Broca’s area – anterior to precentral gyrus – important for language output
o Wernicke’s area – near the auditory cortex – language comprehension network
 These two are connected by the arcuate fasiculus
o The supramarginal gyrus, and angular gyrus are important for reading and writing
 Disorders of language
o Aphasia – not uncommon, an acquired disorder of language due to brain damage
or dysfunction
 Recognize something
 Anomia – inability to name recognized object
 Paraphasic error – a wrong word that obeys the rules for a word
 Alexia – cannot read
 Agraphia – Cannot write
 Usually due to lesion of dominant angular gyrus or supramarginal gyrus Alexia without agraphia
is due to disconnection syndrome with lesion of left occipital lobe and splenium of corpus
collusum
 Dyslexia – congenital/developmental cannot read, learning disability
o Broca’s Aphasia – bad output, relatively good comprehension
 Language output is slow and effortful, have dysarthria, less words/min and patient is aware of deficit
 Agrammatic or telegraphic – suppose you had bad phone and you pay 10 dollars for each word you
send so they talk like this – use common nouns and adjectives and not words in between
 Prosidy is absolutely normal
o Wernicke’s Aphasia – lots of output, bad comprehension
 Language output is fluent – lots of words/min, good use of small connecting grammatical words” but
cannot find nouns
 Bad anomia – cannot name words and could speak slower if cant figure out the word
 Are not aware that this is happening so could be going on
 Paraphasic errors
 Letter fluency (“F”) – damage to frontal lobe
 Category fluency (animals)
o Types of aphasia - lots of aphasia
 1. Conduction aphasia – cannot repeat words– disconnection
syndrome
 2. Subcortical Aphasia – lesions of left caudate or left thalamus
o Aprosodia- common with parkinsonism or cortical problems
 Melody of speech, emotional component of language
 Right hemisphere’s contribution to language
 Prosody is preserved in aphasia
 Right hemisphere lesions – lesion is more diffuse and can lead to
aprosodia problems with output or comprehension
 Treatment: education
 Disorders of ideomotor praxis – pretend to brush hair – one sided stroke
o Parietal lobe problem in left hemisphere which normally travels by corpus collusum to the other side to make the
action – know what to do and how to do it but cannot, can do it maybe spontaneously
Lecture 34 – Higher brain functions- Spatial Cognition and Recognition
 Balint’s syndrome – very rare
o Bilateral lesions of the occipital parietal (where) visual system – cannot localize what they see into mental
presentation of space – can put hearing and feeling into mental space – so if you snapped with their eyes
closed, they would know where it is
 Cannot saccade to a particular place and cannot see big picture view
o Cannot point to head of a man, and will look around the picture until by chance, they see the man’s head
 Hemi-inattention, or neglect – temporary lesion that usually goes away
o Neglect of space contralateral to lesion, in the cerebral hemisphere or thalamus, problem with the awareness
o Right hemisphere lesion is worse than left
o If you show them the side they are neglecting, they are not shocked
o Treatment – behaviorally – tell people to interact with the patient on the left side
o Patient may have neglect, homonymous hemianopia, or both – it isn’t because they cannot see
 Constructional Apraxia – not localizing at all – tell patient to draw a cube
o Praxis – you should be able to do something and you can do it
o Apraxia – you should be able to do something that you cannot
o Constructional apraxia – use language, motor, sensory abilities to put parts together into a whole, but you
cannot – understood the task, have the sensory modalities to get information to do it, but cannot do it
 Can be seen with cortical, or subcortical lesions of either cerebral hemisphere, or thalamus
 If you have a group of people with lesions on the same side, then you can localize
 Gnosis and Agnosia
o Gnosis – ability to recognize and know something
o Agnosis – inability to recognize something that is presented in a specific sensory modality even tho that
sensory modality is fine – MODALITY SPECIFIC
 Look at a picture of a pig, and not know what it is, but hear or smell a pig and know what it is
o Visual Agnosia – patient with bilateral lesions of occipital temporal (what) visual system – have good visual
acuity and visual fields but cannot recognize object
o Prosopagnosia – inability to recognize familiar face, associated with visual agnosia
 Intelligence works and voice works, can recognize animals are animals, but not which animal, and
can draw the animal
Lecture 35 – Higher Brain functions – Executive Function and Memory – decide whether or not to do something
 The frontal lobe syndrome – really common in previously young healthy people
o Medial – difficulty with initiation and continuation of motor acts - cannot get going and keep going
o Orbital – inappropriate and disinhibited behavior – what you want to do now vs long term consequences
o Dorsolateral – difficulty with abstraction and problem solving – most of the frontal cortex
o Patient example:
 Patient no longer doesn’t have any fear – has cancer, experiences less pain even though it hurts just as
much – in the past would use to give people frontal lobe syndrome for neuropathic pain
 Is aware of motor commands but cannot do it – this patient has a really bad lesion – metastatic cancer
 Perserveration – repetition of an old behavior despite need to change to new behavior
o May see in prefrontal lesions, but could be seen in other brain lesions and in people without lesions
o Draw square and circle, and repeat, then asked to draw one spiral and keeps drawing more spirals even though
he wasn’t asked for it
 Memory
o Temporal lobe - Hippocampal formations
 Parahippocampal gyrus (anterior portion is entorhinal cortex)
 Entorhinal cortex is where Alzheimer’s starts
 Subiculum
 Hippocampus (CA1 and CA3) – CA1 is vulnerable to ischemia
 Any lesion in any of these regions will lead to a memory not being laid down by the cerebral cortex
o Medial Diencephalic Structures
 Mammillary bodies
 Mediodorsal nucleus of thalamus
 Related structures: Fornix, mammillothalamic tracts, anterior nucleus of thalamus
 Just as important as the temporal but the localization is not as well worked out
o Modality specific – usually get diffuse lesions so probably not localize to one side of the other
 Left structures- verbal fact and event short term memory – memorize a fact
 Right structures – short term memory of nonverbal facts and events – spatially learned a new route
 Memory
o Immediate, short-term, long-term
 Immediate memory is something that you can repeat, and then if you get distracted, and then are asked to
recall it, all the temporal lobe and medial diencephalic structures have put it to short term memory
o Declarative (temporal and diencephalic structure), procedural
 Different parts – forget the training sessions but the procedures learned normally
o The basic amnesia syndrome
 Anterograde amnesia – going forward in time, you cannot learn new things or make short term memory
 All people that have anterograde amnesia also have some degree of retrograde amnesia
 Retrograde amnesia (almost but not always) – do not remember things that happened before onset of
amnesia
 Typically with temporal gradient – always remember childhood
 Normal immediate memory
 Normal procedural memory – benzo make you forget during colonscopy
 Will not affect immediate memory
o Amnesia patients will give confabulation
 To quickly and confidently give wrong answer that is not recognize to be wrong
 Typically do not know answer (because of amnesia) or say the first thing that comes to mind (because of
disinhibition due to frontal or diffuse brain dysfunction)
 A diffuse lesion – group of patients with transient global amnesia
o This is usually due to transient dysfunction of bilateral medial temporal lobe structures important for memory
o During the episode, they cannot remember a story you told them, and cannot look at diagrams
o After the episode, they recover back to normal
o So for transient global amnesia, you get dysfunction of both temporal lobe structures, left and right
o Also get some retrograde amnesia – but eventually after recovering they can know the information again so it
was a problem with accessing the material
Lecture 36- Neuropsychological Testing
 Neuropsychological Testing – extension of the bedside mental status examination
o Might be considered for any focal, multifocal, or diffuse brain-based impairment in higher cognitive function
o Also important to evaluate neuropsychiatric disorders
 Major neurocognitive disorder (aka dementia used to be this)– significant cognitive decline
o Many causes – significant cognitive decline (most common in Alzhiemer’s)
 One or more domains, somebody has to be concerned about it, substantial impairment (could be at
risk but have not gotten it yet)
o Interferes with independence in everyday activities
o Not due to delirium, or another mental disorder such as major depressive disorder
 Hallucination – sensory experience that occurs without external stimulation
o Can happen in any sensory modality
o May be recognized as unreal (nonpsychotic) or may be thought to represent true external events (psychotic)
 If you think it is real problem, then it is psychotic hallucination but if you know its not, its
nonpsychotic
o Can happen to many normal people without disease
o Release hallucinations – hallucinations in a given sensory modality that comes if you have a lesion in the
pathway and it no longer works or is receiving any input. The decreased input leads to a release in
SPONTANEOUS activity of CNS structure that mediate the hallucination
 Characteristics:
 Min- hour, not sterotyped
 Often find detectable defect in a primary sensory modality, typically lateralized if the defect
is lateralized
 Can be modified by environmental changes, such as redirecting gaze
o Hallucinations due to neurochemical effects
 LSD acts on serotonin receptors (5-HT)
 Anticholinergic toxicity also has hallucinations or if neurodegenerative leads to cholinergic
deficiency, also sometimes get hallucinations
 Excess dopamine or dopaminergic drugs too
 So in general, increased serotonin, dopamine, or less Ach can cause hallucinations
o Hallucinations due to dreams
 Occur during REM, or waking state of narcolepsy
 Alcohol withdrawal – could be related dreaming mechanism
o Ictal hallucinations
 Due to seizure – relatively stereotyped, many seconds – min, and cannot be changed if you change
environment
o Migraine Hallucinations – aura
o Hallucinations with primary psychiatric disorder
 Schizophrenia (auditory psychotic), psychotic depression (mood congruent), or PTSD (flashbacks)
o Unformed (flashing lights) vs formed (mouse running across room) hallucinations
 Whether a hallucination is unformed or formed does not aid in localization
o Modality and Etiology of hallucinations
 Visual hallucinations  neurological disorder
 Auditory hallucination  primary psychiatric disorder
 Delusion – false belief that is firmly head despite evidence to contrary and not endorsed by culture
o Delusions are ALWAYS psychotic
o Could be primary due to psychiatric illness, or secondary (due to neurological disorder)
o Anosognosia – delusional denial of their own illness or the severity
 Could be complete or partial
 Associated with unilateral neglect and posterior cerebral hemispheric lesion
o Capgras Syndrome – delusion that an important person (spouse) has been replaced by identical imposter
 Often in schizophrenia
 Often delusion due to various neurologic disorder, especially on right side
o Reduplicative paramnesia – delusion that one is simultaneously at two locations
 Usually one location is correct and another is closer to home
 Common with delirium or TBI but also in right hemisphere with frontal dysfunction
 Psychosis – Loss of reality, psychotic hallucination, delusion, or both
o Primary psychosis is primarily psychiatric disorder, secondary is due to neurological lesion
 Usually affect cerebral hemisphere or thalamus  secondary psychosis
 Conversion symptoms/signs and related disorders
o A relatively persistent loss of alteration in sensory or voluntary motor function that cannot be explained by a
physical disorder or pathophysiological mechanism
 If it is a cognitive problem, it is a CONVERSION-LIKE disorder and you treat the same way
o MOA- could be due to unconscious self hypnosis by a distressed mind
o Conversion-like disorders affect cognitive and other behavioral functions
o Sometimes called functional, or psychogenic, but not hysterical
o If you tell these patients that you will help them and get to the bottom of this, they typically get better
 If it is malingering, then the patient will be concerned that you are onto them and find someone else
 Factiious disorder
o Patient intentionally fakes an illness perhaps due to unconscious desire to occupy the sick role
o Patient really wants to be a patient so they do sometimes to themselves or their kids to make them sick so they
will be patients
o Munchausen’s syndrome – extreme form of this illness
 Malingering
o Conscious faking of neurologic illness, typically for specific purpose
o Different from conversion symptom only by confession
Lecture 37 – Drugs for Psychotic Disorders, cognitive enhancers