Dementia, Alzheimer's Flashcards
What are the symptoms of dementia?
Memory loss, problems with reasoning and communication, personality change, and a reduced ability to carry out daily activities.
He’s forgetting his past. He’s forgetting how to think, and how to speak. He’s a changed man. He’s even forgotten how to do the dishes.
Alzheimer’s pathphysiology - the TRIAD
Neuronal loss - decreased levels of acetylcholine
Senile plaques
Neurofibrillary tangles
What neurotransmitter is deficient in patients with Alzheimer’s?
Acetylcholine.
That’s why we use acetylcholinesterase inhibitors (muscarinic agonists). This enzyme (cholinesterase) breaks down acetylcholine therefore there is more acetycholine (a neurotransmitter) whose targets are Muscarinic receptors (M1-M5) and Nicotinic receptors (at the neuromuscular junction and at the ganglia neuron).
What are the acetylcholinesterase inhibitors that are used in Alzheimer’s?
Rivastigmine, galantamine and donepezil.
What are the NMDA (glutamate) receptor antagonists used in Alzheimer’s?
Memantine.
Mild-to-moderate Alzheimer’s treatment,
Rivastigmine, galantamine or donepezil is first line.
Memantine if these acetylcholinesterase inhibitors are not tolerated or contra-indicated in MODERATE Alzheimer’s.
Moderate-to-severe Alzheimer’s already on acetylcholinesterase inhibitors. What can be added?
Memantine.
The MHRA/CRA has reported that antipsychotic drugs cause an increase risk of what in elderly patients with dementia?
Stroke and death
What are the adverse effects associated with the use of acetylcholinesterase inhibitors (muscarinic agonists)? [MUSCARINIC RECEPTORS]
DUMBBELSS!
Diarrhoea, urination, miosis (pupil constriction), bronchospasm, emesis (vomiting), lacrimation (tears), sweating, and salivation.
Think about it. It makes sense.
Why bronchospasm? There are muscarinic receptors (M3) on the bronchial smooth muscle. Acetylcholine (neurotransmitter) acts as an agonist of these receptors, and leads to bronchial contraction.
Similarly, muscarinic receptors are located in the sweat & salivary glands, and the smooth muscles of the urinary bladder, GI, and the eye.
Generally speaking, activating these receptors lead to gland secretion and smooth muscle contraction but it’s important to remember that this is not always the case, inhibitory effects from muscarinic receptor activation can occur, such as through the muscarinic receptors in the heart where bradycardia is the outcome (reflex tachycardia can occur as a counter-action).
Antimuscarinics therefore lead to conditions such as urinary retention, constipation and dyspepsia, dry mouth & eye (visual disturbances), hyperthermia and/or flushing (heat loss through sweat inhibited). They can also be used to relieve bronchospasm (LAMA) or to treat overactive bladder (solifenacin), or even glaucoma & Sjorgen’s (pilocarpine).
What other conditions would you expect from someone who has Alzheimer’s?
Gastro-intestinal disorders (constipation, dyspepsia, gastroenteritis, gastric infections), nutritional deficiency, bladder disorders, erectile dysfunction, dyspnoea, cardiovascular diseases (hypertension, tachycardia, arrhythmia).
It makes sense.
People with Alzheimer’s have low levels of acetylcholine (neurotransmitter) that acts as an agonist (muscarinic and nicotinic) at several sites throughout the body. Internal communication systems (peripheral nervous system) are failing.
What are the adverse effects associated with the use of acetylcholinesterase inhibitors (muscarinic agonists)? [NICOTONIC RECEPTORS]
Acetylcholine also stimulates nicotinic receptors (N1 and N2) found in the CNS and skeletal muscle.
Activation of these receptors leads to CNS stimulation
and skeletal muscle excitation
What classes of medication should be avoided with Alzheimer’s?
Medication with anti-muscarinic activity such as some antidepressants (e.g. amitriptyline, paroxetine), antihistamine aka H1 antagonists (e.g. chlorphenamine, promethazine), antipsychotics aka dopamine antagonists (e.g. olanzapine and quetiapine), and urinary antispasmodics aka anti-muscarinic (e.g. solifenacin and tolterodine).
Acetylcholinesterase inhibitors should not be given to the elderly with a medical history of?
Bradycardia (less than 60bpm), heart block, recurrent unexplained syncope, and medication that reduces the heart rate
If somebody is on rivastigmine (oral) and experiences vomiting and nausea, what can you do?
Consider transdermal.
Withhold until resolution of vomiting and nausea (causes dehydration) and re-titrate dose if required
What medication can be given to reverse excessive muscarinic stimulation by an acetylcholinesterase inhibitor?
Atropine.
Duh, It’s an antimuscarinic.
