Module 14a - Part 2

Question 1

Most common form of dementia

Answer 1

Alzheimer’s disease

Question 2

Symptoms of Alzheimer’s disease

Answer 2

Memory loss, problems with language, judgement and behaviour

Question 3

Early symptoms are centered around confusion and problems with routine tasks, but as the disease progresses, patients have difficulty with ______ activities.

Answer 3

daily

Question 4

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.

Answer 4

cerebral cortex
cholinergic
10%
cholinergic

Question 5

How is a definitive AD diagnosis given?

Answer 5

After death, during brain autopsy

Question 6

These are the hallmark structures of AD.

Answer 6

Neurofibrillary tangles

neuritic plaques

Question 7

Form inside neurons when MT arrangement is disrupted.

Caused by abnormal production of ____ protein.

Answer 7

Neurofibrillary tangles

tau

Question 8

Protein responsible for forming cross-bridges between MTs, keeping their structure

Answer 8

Tau protein

Question 9

Found outside of neurons, and are composed of a core protein fragment called beta amyloid

Answer 9

neuritic plaques

Question 10

Shown to kill hippocampal cells and cause Alzheimer’s-like symptoms when injected into monkeys

Answer 10

Beta amyloid

Question 11

Patients with two copies of this gene are at increased risk for developing AD.

Answer 11

apoE4

Question 12

How is apoE4 involved in the development of AD?

Answer 12

ApoE4 is involved in the production of beta-amyloid, a component of neuritic plaques

Question 13

______ injury is also a risk factor for developing AD.

Answer 13

head injury

Question 14

There are currently only two classes of drugs used to treat AD. What are they?

Answer 14

Cholinesterase inhibitors

NMDA receptor antagonists

Question 15

Block NMDA mediated increases in intracellular calcium

Answer 15

NMDA receptor antagonists

Question 16

Inhibit the metabolism of ACh by acetylcholinesterase

Answer 16

Cholinesterase inhibitors

Question 17

Why do cholinesterase inhibitors only show modest improvement on memory?

Answer 17

They only work on the remaining, healthy neurons

Question 18

What are the common adverse effects of cholinesterase inhibitors?

Answer 18

Nausea and vomiting
diarrhea
insomnia

Question 19

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

Answer 19

calcium
magnesium
glutamate
magnesium

Question 20

In AD, there is excess _________ release so the NMDA receptor remains _____, allowing excess ______ to enter the cell

Answer 20

glutamate
open
calcium

Question 21

How is excess calcium detrimental in AD?

Answer 21

1 - detrimental to learning and memory (overpowers the normal calcium signal)
2 - causes degradation of neurons (too much calcium is toxic)

Question 22

What are the adverse effects of NMDA antagonists?

Answer 22

Very well tolerated; side effect profile identical to those taking placebos

Question 23

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.

Answer 23

Schizophrenia

Question 24

Schizophrenia usually begins in _________ or _______ ________.
The prevalence is roughly __%.

Answer 24

adolescence
early adulthood
1%

Question 25

Symptoms that exaggerate or distort normal neurological function

Answer 25

positive symptoms

Question 26

Symptoms where there is loss of normal neurological function

Answer 26

negative symptoms

Question 27

``` 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 ```

Answer 27

``` 1 - positive 2 - positive 3 - negative 4 - negative 5 - negative 6 - positive 7 - negative 8 - positive ```

Question 28

What are some factors that predispose a person to schizophrenia?

Answer 28

Family history Drug abuse - crystal meth, PCP, LSD low birth weight Low IQ

Question 29

Involved in movement and emotions | In schizophrenia, thought to play a role in paranoia and hallucinations

Answer 29

basal ganglia

Question 30

Involved in problem solving and insight | Thought to be involved in disorganized thoughts and difficulty planning actions in schizophrenia

Answer 30

Frontal lobe

Question 31

Involved with emotions | Contributes to agitation in schizophrenia

Answer 31

limbic system

Question 32

Overactive in hallucinations in schizophrenia (voices)

Answer 32

Auditory system

Question 33

Schizophrenia is thought of as a disorder with increased ________ nerve transmission (i.e. the opposite of ____)

Answer 33

dopaminergic | PD

Question 34

Drugs that block dopamingeric nerve function decrease some of the _______ symptoms of schizophrenia.

Answer 34

Positive

Question 35

What other NTs play a role in schizophrenia?

Answer 35

5-HT (serotonin), glutamate

Question 36

Patients with schizophrenia have a decreased number of ______ and an increased number of ________ receptors in the _______ cortex.

Answer 36

5HT2A (less) 5HT1A (more) frontal

Question 37

How do we know glutamate is involved in schizophrenia?

Answer 37

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)

Question 38

What is the definitive test for schizophrenia?

Answer 38

There is none

Question 39

The basis for treatment of schizophrenia is blocking ______, ______ and/or _______ neurotransmission in the brain.

Answer 39

dopamine, serotonin, glutamate

Question 40

Act primarily by blocking dopanine 2 (D2) receptors primarily in the mesolimbic area of the brain.

Answer 40

conventional antipsychotics

Question 41

To a lesser degree, conventional antipsychotics also block receptors for these signalling molecules.

Answer 41

NE, ACh, histamine

Question 42

The potency of conventional antipsychotics is directly proportional to what?

Answer 42

Ability to inhibit the D2 receptors

Question 43

Conventional antipsychotics are more effective at treating the ______ symptoms of schizophrenia, than the _______ symptoms.

Answer 43

positive (should be intuitive as the positive symptoms are due to excess dopamine, which this blocks) negative

Question 44

The initial effect of conventional antipsychotics is seen in as few as __ or ___ days, but substantial improvement usually takes between __ and __ weeks.

Answer 44

1-2 days | 2-4 weeks

Question 45

What are the side effects of conventional antipsychotics? | Vent = smell

Answer 45

``` ESO ASS Extrapyrimidal symptoms Sudden high fever Orthostatic hypotension Anticholinergic effects Sedation Skin reactions ```

Question 46

Extrapyrimidal symptoms (EPS) are due to blockade of ____ receptors.

Answer 46

D2

Question 47

Involuntary spasm of the muscles in the face, tongue, neck or back. Typically occurs EARLY in therapy.

Answer 47

Acute dystonia

Question 48

Bradykinesia, mask-like faces, rigidity, and stooped posture are common.

Answer 48

Parkinsonism

Question 49

How is parkinsonism treated? | What must be avoided?

Answer 49

Anti-cholinergics | Avoid use of L-DOPA

Question 50

pacing, squirming and a desire to continually be in motion. Typically occurs EARLY in treatment

Answer 50

Akathesia

Question 51

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.

Answer 51

tardive dyskinesia

Question 52

Patients developing tardive dyskinesia should be switched to what?

Answer 52

Atypical antipsychotic

Question 53

Block both D2 receptors and the 5-HT1a and 5HTa receptors.

Answer 53

Atypical antipsychotics | easy to remember since A - atypical - HT1/2a

Question 54

The therapeutic action of Atypical antipsychotics is mostly attributed to what?

Answer 54

Blockade of 5-HT receptors, as it has poor ability to block D2 receptors

Question 55

What are the benefits of atypical antipsychotics?

Answer 55

No EPS! (since D2 receptors aren't blocked as much) As efficacious against positive symptoms More efficacious against negative symptoms

Question 56

What are the AEs of atypical antipsychotics?

Answer 56

``` WORSA Weight gain (sometimes severe) Orthostatic hypotension Risk of developing type II diabetes (think of it related to weight gain) Sedation Anticholinergic effects ```