Module 14a - Part 2 Flashcards
Most common form of dementia
Alzheimer’s disease
Symptoms of Alzheimer’s disease
Memory loss, problems with language, judgement and behaviour
Early symptoms are centered around confusion and problems with routine tasks, but as the disease progresses, patients have difficulty with ______ activities.
daily
The pathophysiology of AD is characterized by a degeneration of neurons in the _______ ______.
AD is linked to decreased ________ nerve function.
Patients with advanced AD have only __% of the ________ function of healthy subjects.
cerebral cortex
cholinergic
10%
cholinergic
How is a definitive AD diagnosis given?
After death, during brain autopsy
These are the hallmark structures of AD.
Neurofibrillary tangles
neuritic plaques
Form inside neurons when MT arrangement is disrupted.
Caused by abnormal production of ____ protein.
Neurofibrillary tangles
tau
Protein responsible for forming cross-bridges between MTs, keeping their structure
Tau protein
Found outside of neurons, and are composed of a core protein fragment called beta amyloid
neuritic plaques
Shown to kill hippocampal cells and cause Alzheimer’s-like symptoms when injected into monkeys
Beta amyloid
Patients with two copies of this gene are at increased risk for developing AD.
apoE4
How is apoE4 involved in the development of AD?
ApoE4 is involved in the production of beta-amyloid, a component of neuritic plaques
______ injury is also a risk factor for developing AD.
head injury
There are currently only two classes of drugs used to treat AD. What are they?
Cholinesterase inhibitors
NMDA receptor antagonists
Block NMDA mediated increases in intracellular calcium
NMDA receptor antagonists
Inhibit the metabolism of ACh by acetylcholinesterase
Cholinesterase inhibitors
Why do cholinesterase inhibitors only show modest improvement on memory?
They only work on the remaining, healthy neurons
What are the common adverse effects of cholinesterase inhibitors?
Nausea and vomiting
diarrhea
insomnia
The NMDA receptor is a _______ channel that is blocked by __________ at rest.
When _______ binds to the NMDA receptor, ________ dissociates, allowing calcium to enter the post-synaptic neuron
calcium
magnesium
glutamate
magnesium
In AD, there is excess _________ release so the NMDA receptor remains _____, allowing excess ______ to enter the cell
glutamate
open
calcium
How is excess calcium detrimental in AD?
1 - detrimental to learning and memory (overpowers the normal calcium signal)
2 - causes degradation of neurons (too much calcium is toxic)
What are the adverse effects of NMDA antagonists?
Very well tolerated; side effect profile identical to those taking placebos
Disease in which it becomes difficult to distinguish between real and false experiences, to think logically, to have normal emotional responses, and to behave normally in social settings.
Schizophrenia
Schizophrenia usually begins in _________ or _______ ________.
The prevalence is roughly __%.
adolescence
early adulthood
1%
Symptoms that exaggerate or distort normal neurological function
positive symptoms
Symptoms where there is loss of normal neurological function
negative symptoms
For the following, indicate if positive or negative: 1 - disorganized speech/thinking 2 - Paranoia 3 - Poverty of speech 4 - Emotional withdrawal 5 - Poor insight/judgement 6 - Combativeness 7 - Social withdrawal 8 - Agitation
1 - positive 2 - positive 3 - negative 4 - negative 5 - negative 6 - positive 7 - negative 8 - positive
What are some factors that predispose a person to schizophrenia?
Family history
Drug abuse - crystal meth, PCP, LSD
low birth weight
Low IQ
Involved in movement and emotions
In schizophrenia, thought to play a role in paranoia and hallucinations
basal ganglia
Involved in problem solving and insight
Thought to be involved in disorganized thoughts and difficulty planning actions in schizophrenia
Frontal lobe
Involved with emotions
Contributes to agitation in schizophrenia
limbic system
Overactive in hallucinations in schizophrenia (voices)
Auditory system
Schizophrenia is thought of as a disorder with increased ________ nerve transmission (i.e. the opposite of ____)
dopaminergic
PD
Drugs that block dopamingeric nerve function decrease some of the _______ symptoms of schizophrenia.
Positive
What other NTs play a role in schizophrenia?
5-HT (serotonin), glutamate
Patients with schizophrenia have a decreased number of ______ and an increased number of ________ receptors in the _______ cortex.
5HT2A (less)
5HT1A (more)
frontal
How do we know glutamate is involved in schizophrenia?
PCP is a strong antagonists of the NMDA receptor, can cause similar symptoms to schizophrenia
Additionally, patients with schizophrenia have less NMDA receptors in certain brain regions (recall that glutamate binds to, and activates the NMDA receptor)
What is the definitive test for schizophrenia?
There is none
The basis for treatment of schizophrenia is blocking ______, ______ and/or _______ neurotransmission in the brain.
dopamine, serotonin, glutamate
Act primarily by blocking dopanine 2 (D2) receptors primarily in the mesolimbic area of the brain.
conventional antipsychotics
To a lesser degree, conventional antipsychotics also block receptors for these signalling molecules.
NE, ACh, histamine
The potency of conventional antipsychotics is directly proportional to what?
Ability to inhibit the D2 receptors
Conventional antipsychotics are more effective at treating the ______ symptoms of schizophrenia, than the _______ symptoms.
positive (should be intuitive as the positive symptoms are due to excess dopamine, which this blocks)
negative
The initial effect of conventional antipsychotics is seen in as few as __ or ___ days, but substantial improvement usually takes between __ and __ weeks.
1-2 days
2-4 weeks
What are the side effects of conventional antipsychotics?
Vent = smell
ESO ASS Extrapyrimidal symptoms Sudden high fever Orthostatic hypotension Anticholinergic effects Sedation Skin reactions
Extrapyrimidal symptoms (EPS) are due to blockade of ____ receptors.
D2
Involuntary spasm of the muscles in the face, tongue, neck or back. Typically occurs EARLY in therapy.
Acute dystonia
Bradykinesia, mask-like faces, rigidity, and stooped posture are common.
Parkinsonism
How is parkinsonism treated?
What must be avoided?
Anti-cholinergics
Avoid use of L-DOPA
pacing, squirming and a desire to continually be in motion. Typically occurs EARLY in treatment
Akathesia
occurs in about 20% of patients on long-term therapy. Is irreversible so early detection is essential. Symptoms include involuntary twisting and writing of the face and tongue along with lip-smacking.
tardive dyskinesia
Patients developing tardive dyskinesia should be switched to what?
Atypical antipsychotic
Block both D2 receptors and the 5-HT1a and 5HTa receptors.
Atypical antipsychotics
easy to remember since A - atypical - HT1/2a
The therapeutic action of Atypical antipsychotics is mostly attributed to what?
Blockade of 5-HT receptors, as it has poor ability to block D2 receptors
What are the benefits of atypical antipsychotics?
No EPS! (since D2 receptors aren’t blocked as much)
As efficacious against positive symptoms
More efficacious against negative symptoms
What are the AEs of atypical antipsychotics?
WORSA Weight gain (sometimes severe) Orthostatic hypotension Risk of developing type II diabetes (think of it related to weight gain) Sedation Anticholinergic effects
