Alzheimers and 2nd gen antipsychotics

Question 1

How does chlorpromazine work and what are the side effects

Answer 1

a. D2 receptor antagonist
b. Anticholinergic side effects such as sedation
c. Extra pyramidal side effects

Question 2

4. How does haloperidol work and what are the side effects

Answer 2

a. V potent d2 antagonist
b. Takes 6-8 weeks for therapeutic effects
c. Little impact on negative symptoms
d. Extra pyramidal

Question 3

5. What are the second generation antipsychotics

Answer 3

a. Clozapine
b. Risperidone
c. Quetiapine
Aripiprazole

Question 4

6. How does clozapine work and what are the side effects

Answer 4

a. Potent antagonists of 5-HT2A receptors
b. Efficacy in resistant schizophrenia and negative symptoms
Neutropenia, agranulocytosis, myocarditis and weight gain

Question 5

How does risperidone work and what are the side effects

Answer 5

a. Potent antagonists of 5-HT2A and D2 receptors

b. More EPS and hyperprolactinaemia than other atypical antipsychotics

Question 6

8. How does quetiapine work and what are the side effects

Answer 6

a. Potent antagonist of H1 receptors

b. Lower incidence of EPS than others

Question 7

How does aripiprazole work and what are the side effect

Answer 7

a. Partial agonist of D2 and 5-HT1A receptors
b. No more efficacious than others
c. Reduced hyperprolactinaemia and weight gain than other antipsychotics

Question 8

1. What is the amyloid normal physiological processing

Answer 8

a. Usually APP is cleaved by alpha secretase
b. sAPPalpha released -> C83 fragment remains
c. C83 -> digested by gamma secretase
d. Products removed

Question 9

2. What is the pathophysiological processing of amyloid

Answer 9

a. APP cleaved by beta secretase
b. sAPPbeta release -> C99 fragment remains
c. C99 digested by gamma secretase releasing beta amyloid protein
d. Beta amyloid protein forms toxic aggregates (plaques)

Question 10

3. What is the physiology of tau

Answer 10

a. Soluble protein present in axons

b. Important for assembly and stability of microtubules

Question 11

4. What is the pathophysiology of tau

Answer 11

a. Hyperphosphorylated tau is insoluble -> self aggregates to form neurofibrillary tangles
b. Neurotoxic
c. Results in microtubule instability

Question 12

What is the inflammation hypothesis

Answer 12

a. Microglia inc release of inflammatory mediators and cytotoxic proteins, inc phagocytosis, dec levels of neuroprotective proteins

Question 13

6. What are the clinical symptoms of Alzheimer’s

Answer 13

a. Memory loss- esp of recently acquired information
b. Disorientation/confusion
c. Language problems
d. Personality changes
Poor judgement

Question 14

7. What are the risk factors for Alzheimer’s

Answer 14

a. Age
b. Genetics
a. Amyloid precursor protein -> early onset
b. ApoE -> late onset

Question 15

1. What drugs are used to treat alzheimers

Answer 15

a. Anticholinesterases

b. NMDA receptor blocker

Question 16

What anticholinesterases are used and how do they act

Answer 16

a. Donepezil
a. Reversible cholinesterase inhibitor
b. Long plasma half life
b. Rivastigmine
a. Pseudo-reversible AchE & BChE inhibitor
b. 8 hour half life
c. Also available as a patch
c. Galantamine
a. Reversible cholinesterase inhibitor which is also an alpha 7 nicotinic receptor agonist

Question 17

3. What is an example of an NMDA receptor blocker and how does it work

Answer 17

a. Memantine
b. Use dependent non-competitive NMDA receptor blocker with low channel affinity
a. More activated NMDA is, more effective the drug is
c. Only used in moderate-severe