Dementia Flashcards
Define Dementia
Umbrella term for a progressive and irreversible syndrome of widespread impairment of mental function
What are the various types of Dementia? Define each of these (3)
Alzheimers Disease
Vascular Dementia
Dementia with Lewy bodies
What are the COGNITIVE symptoms of dementia? (4)
Memory loss
Language impairment
Poor concentration
Disorientation/Confusion
What are the NON-COGNITIVE symptoms of dementia? (4)
Anxiety
Depression
Sleep disturbances
Delusion
What drug treatments are available for cognitive symptoms? 1st line and 2nd?
1st line - Acetylcholinesterase inhibitors e.g. Donepezil hydrochloride, Galantamine, Rivastigmine
2nd line - Memantine Hydrochloride
When is Memantine hydrochloride used?
It is used as an alternative when Acetylcholinesterase inhibitors are contra-indicated or not tolerated.
1st line choice for severe Alzheimer’s disease.
In which type of dementia is pharmaceutical treatment not recommended for cognitive symptoms?
Vascular dementia
What is the treatment of choice for non-cognitive symptoms (unless severe)?
Non-pharmalogical treatments such as multi-sensory stimulation or aromatherapy
Counselling
Anti-psychotics are reserved only for severe symptoms. What is the MHRA advice on their use in dementia patients?
MHRA states that there is increased risk of stroke and a small increased risk of death when anti-psychotics used in elderly with dementia.
How should antipsychotic treatment be started?
Lowest effective dose and slowly titrated upwards with regular review every 6 weeks
What can be used in severe aggression, violence and extreme agitation apart from anti-psychotics?
Benzodiazepines
e.g. haloperidol, lorzepam, olanzapine.
Diazepam and chlorpromazine are not recommended.
What is the drug class and the mechanism of action of Donepezil hydrochloride ?
Acetylcholinesterase (AChE) inhibitor.
Reversible inhibitor of acetylcholinesterase.
What is the dose of donepezil hydrochloride for mild/moderate dementia in Alzheimer disease?
Initially 5mg ON for a month and then can be increased to upto 10mg daily if needed.
Why should donepezil hydrochloride be given for at least one month?
To allow earliest clinical response to treatment to be assessed & allow steady state concentration to be achieved.
Is donepezil hydrochloride suitable for
- 18 and under
- Renal impairment
- Hepatic impairment
- Pregnancy
- Breastfeeding
- No
- Yes - as clearance of donepezil is not affected by renal impairment.
- Depends on patient’s tolerability - due to possible increased exposure in mild/moderate hepatic impairment. No results in severe.
- No data. Should not be used unless clearly necessary
- Should NOT be used. No studies.
V. common (3) & common(10) side effects on donepezil?
V. common:
Diarrhoea, Nausea, Headache,
Common:
Common cold, Aggression, Agitation, Vomiting, Dizziness, GI disorders, Muscle cramp, Fatigue, Insomnia, Hallucination
Cautions to using Donepezil? (3)
- Respiratory - Asthma, COPD - due to chol
- Cardiovascular - Sick Sinus Syndrome/ Supraventricular conduction (Sinoatrial/Atrioventricular block) This is because cholinesterase inhibitors may have vagotonic effects on heart rate (bradycardia/slower)
- GI conditions - increased risk of peptic ulcers (e.g. concurrent NSAID use, history of peptic ulcer = monitoring)
Notable interactions with donezepil
Reduce (4)
Increase (2)
Reduce levels of Donepezil : Enzyme inducers such as Rifampicin Phenytoin Carbamazepine Alcohol
Increase levels:
Enzyme inhibitors such as:
Ketoconazole
Quinidine
What is the indication and mechanism of action of Galantamine ?
Mild to moderately severe dementia of the Alzheimer type
Reverisible inhibitor of acetylcholinesterase
Dosing schedule of Galantamine?
Immediate release and prolonged release
Immediate release:
4mg BD for 4 weeks
then increased to 8mg BD for at least 4 weeks
Maintenance dose = 8-12mg BD
Prolonged release:
8mg OD for 4 weeks, increased to 16mg OD for at least 4 weeks.
Maintenance = 16-24mg OD
Is galantamine suitable for:
- 18 and under
- Renal impairment
- Hepatic impairment
- Pregnancy
- Breastfeeding
- No
- Avoid if eGFR less than 9ml/min/1.73m (Galantamine plasma concentrations may be increased in pts with moderate to severe renal impairment )
- Galantamine plasma concentrations may be increased in moderate to severe hepatic impairment
moderately impaired hepatic function (Child-Pugh score 7-9), dosing should begin with 8 mg PR capsule once every other day (in morning) for one week. Thereafter, should proceed with 8 mg once-daily for four weeks. daily dose max 16 mg.
Immediate release - 4mg OD for 7 days. then 4mg BD for 4 weeks. Max 8mg BD
Severe hepatic impairment (Child-Pugh score greater than 9), the use of galantamine is contraindicated
No dosage adjustment in mild hepatic impairment
- Use with caution - toxicity in animal
- Avoid - no info
What serious skin reaction should patients be made aware of with galantamine?
Stevens-Johnson syndrome (red man syndrome) - stop using it at first sign of skin rash or reaction
Cautions with Galantamine? (4)
Cardiac disorder (same with donepezil) - sick sinus syndrome, supraventricular cardiac disturbances or those on medicines which reduce heart rate e.g. digoxin and beta blockers, or pts with uncorrected electrolyte disturbances e.g. hyperkalaemia, hypokalaemia.
GI disturbances - peptic ulcers. Not used in those with GI blockages or recovering from GI surgery.
Resp - asthma, COPD
Urinary/Renal - should NOT be used in those with urinary outflow obstruction or recovering from bladder surgery.
Most common side effects of galantamine? (7)
Nausea
Vomiting
Fatigue Bradycardia Hypertension Abdominal pain Diarrhoea
Indication and MoA of rivastigmine
Mild/Moderate dementia in Alzheimer’s disease & Parkinson’s disease
Reversible non-competitive inhibitor of acetylcholinesterases.
What is the dosing schedules of Rivastigmine for Alzheimer and Parkinsons
A.D & P.D
ORAL- Initially 1.5mg BD then can be increased every 2 weeks depending on tolerance.
Usual dose 3-6mg BD
Max dose 6mg BD
If treatment interrupted for several days - needs retitrate from 1.5mg BD
PATCH
4.6mg/24hr daily for at least 4 weeks, increased to 9.5mg/24hr for 6 months, then if necessary to 13.3mg/24hr
Need to retitrate from 4.6mg if treatment stopped for more than 3 days.
Use Rivastigmine with caution in patients with a body weight less of…
50kg.
What is the dose equivalence if you wanted to switch from oral rivastigmine to patch?
3-6mg orally = 4.6mg/24hr
9mg orally = 9.5mg/24hr
12mg orally = 9.5mg/24hr
If not tolerated titrate up from 4.6mg patch. First patch should be applied the day after last oral dose.
Is rivastigmine suitable for:
- 18 and under
- Renal impairment
- Hepatic impairment
- Pregnancy
- Breastfeeding
- No
- Yes - no adjustments req.
- Titrate depending on individual tolerability.
- No - unless clearly necessary
- No
Specific side effects of Rivastigmine?
(6)
Rare (2)
Oral: Confusion Hallucinations Gait abnormal Malaise Parkinsonism Sleep disorder
Rare: Angina pectoris (chest pain due to CHD), GI disorder/haemorrhage
What should be monitored with Rivastigmine? and in Alzheimer’s disease in general.
Weight
Risk of transdermal patches of Rivastigmine?
Fatal overdose
What is the drug class, MOA and indication of Memantine hydrochloride?
Drug class: NMDA receptor antagonists
MoA: glutamate receptor antagonist
Indication: moderate to severe dementia in Alzheimer’s disease
What is the dose of memantine?
Start at 5mg OD then increased in steps of 5mg every week.
Usual & max dose 20mg OD
It is titrated up to reduce risk of adverse effects.
Is memantine hydrochloride suitable for
- 18 and under
- Renal impairment
- Hepatic impairment
- Pregnancy
- Breastfeeding
- No
- Avoid in severe renal impairment less than 5ml/min
eGFR 5-29ml/min daily dose 10mg.
eGFR 30-49ml/min dose should be 10mg per day and if well tolerted after at least 7 days then can be increased to 20mg following titration
- Yes, no dose adjustment required in mild/moderate heaptic. Severe - no data.
- Avoid in preg
- Avoid
Common side effects of Memantine? (7)
Balance impaired Constipation Dizziness Dyspnoea Headache Hypersensitivity Hypertension
Cautions with memantine? (3)
Epilepsy
History of convulsions
Risk factors for epilepsy
NICE guidelines on the prescribing of donepezil, galantamine, rivastigmine and memantine? (3)
- Treatment should be initiated on advice of a specialist
- ensure local arrangements for prescribing follow guidelines
- treatment should continue only if it is considered to have a worthwhile effect on cognitive, global function or behavioural symptoms
Directions for administration of Rivastigmine (Exelon) patches?
Apply patches to clean, dry non-hairy non-irritated skin on back, upper arm, or chest, removing after 24 hours.
Make sure to remove previous patch before new one is put on a different area avoid using same area for 14 days.
Acetylcholinesterase inhibitors may have STOPP criteria in elderly - which categories may they be inappropriate?
- Pts with a known history of persistent bradycardia (heart rate less than 60 beats per minute)
- Heart block
- Recurrent unexplained syncope
- Concurrent treatment with drugs that reduce heart rate
