AChE inhibitors Flashcards
What are the indications of AChE inhibitors?
Monotherapies for managing mild to moderate Alzheimer’s disease
What are the names of the different AChE inhibitors available?
Donepezil
Galantamine
Rivastigmine
What is the usual dose of donepezil prescribed?
Initially 5mg OD at bedtime
Increased if tolerated and necessary to a max of 10mg daily after 1 month
What is the usual dose of galantamine prescribed?
Most people = 8mg capsule OD for 4 weeks, then 16mg OD for at least 4 weeks
Maintenance dose is 16-24mg OD
What is the dose of galantamine prescribed for those with hepatic impairment?
Initially 8mg on alternate days, preferably in the morning, for 7 days
Then 8mg OD for 4 weeks
Daily dose should not exceed 16mg
What is the usual oral dose of rivastigmine prescribed?
Initially 1.5mg BD
Increased in steps of 1.5mg BD at intervals of at least 2 weeks according to response and tolerance up to a max of 6mg BD
If Tx is interrupted for more than several days, oral rivastigmine should be re-titrated from 1.5mg BD
What is the usual transdermal dose of rivastigmine prescribed?
Initially 4.6mg/24 hours patch - applied to clean, dry, non-hairy, non-irritated skin on the back, upper arm or chest
Should be removed after 24 hours
After at least 4 weeks, if well tolerated, the dose should be increased to the usual maintenance dose of 9.5mg/24 hours patch daily
After a further 6 months, if well tolerated and cognitive deterioration or functional decline are demonstrated, the dose can be increased to 13.3mg/24 hours patch daily (should be done with caution in people who weigh < 50kg)
If Tx is interrupted for more than 3 days, transdermal rivastigmine should be re-titrated from a 4.6mg/24 hours patch
What are the contraindications for donepezil?
Hypersensitivity to donepezil hydrochloride, piperidine derivatives or any excipients used in the formulation
Pregnancy and breastfeeding
What are the contraindications for galantamine?
Hypersensitivity to galantamine or any of the excipients
Severe renal impairment (eGFR < 9mL/min/1.73 m^2)
Severe hepatic impairment (Child-Pugh score > 9)
People who have both significant renal and hepatic dysfunction
Urinary outflow obstruction
GI obstruction
During recovery from bladder or GI surgery
Pregnancy and breastfeeding
What are the contraindications for rivastigmine?
Hypersensitivity to rivastigmine, other carbamate derivatives, or any other excipients
Previous Hx of application site reactions suggestive of allergic contact dermatitis with the rivastigmine patch
Pregnancy and breastfeeding
What are the cautions for AChE inhibitors?
Hx of bradycardia, heart block, recurrent unexplained syncope
Concurrent Tx with drugs that reduce heart rate
What are the cautions for donepezil?
Sick sinus syndrome or other supraventricular conduction abnormalities
Susceptibility to peptic ulcers including concurrent NSAID use
Asthma and COPD
Hepatic impairment
Concomitant antipsychotic Tx - increased risk of neuroleptic malignant syndrome (NMS)
What are the cautions for galantamine?
Renal and hepatic impairment
Cardiac disease (inc. sick sinus syndrome, supraventricular conduction abnormalities, post-MI, unstable angina, new onset AF, second degree HB or greater, congestive heart failure)
Or in those that use meds that significantly reduce heart rate concomitantly e.g., digoxin and beta-blockers
QTc interval prolongation or taking drugs that prolong the QTc interval
Electrolyte disturbances (e.g., hyperkalaemia or hypokalaemia)
Susceptibility to peptic ulcers including concomitant use of NSAIDs
Hx of severe asthma, COPD or pulmonary seizures
Hx of seizures
What are the cautions for rivastigmine?
Hepatic impairment
Renal impairment
Gastric or duodenal ulcers (or susceptibility to ulcers)
Sick sinus syndrome or conduction abnormalities
Hx of asthma or COPD
Hx of seizures
Bladder outflow obstruction
What are the common adverse effects of donepezil?
N+V
Reduced appetite
Diarrhoea
Fatigue
Headache
Dizziness
Syncope
Abnormal dreams
Hallucinations
Agitation
Aggression
Muscle cramps
Urinary incontinence
Rash
Pruritus
What are the rare adverse effects of donepezil?
Extrapyramidal symptoms
Sinoatrial block
AV block
Liver dysfunction (inc. hepatitis)
NMS (if someone develops this, donepezil should be discontinued)
What are the common adverse effects of galantamine?
Vomiting
N+V
Abdo pain
Diarrhoea
Dyspepsia
Decreased appetite
Weight loss (monitor the patient’s weight)
Bradycardia
HTN
Syncope
Hallucinations
Depression
Dizziness
Tremor
Headache
Fatigue
Malaise
Muscle spasm
What are the less common adverse effects of galantamine?
Retching
Dehydration
Hypotension
Flushing
Palpitation
Arrhythmias
First-degree AV block
Taste disturbance
Paraesthesia
Seizures
Hypersomnia (increased sleepiness)
Muscular weakness
Blurred vision
Tinnitus
Sweating
What are the rare adverse effects of galantamine?
Exacerbation of Parkinson’s disease
Hepatitis
Serious skin reactions (galantamine should be stopped at the first appearance of a skin rash)
What should you warn patients on galantamine and their carers about?
Signs of serious skin reactions inc.
- Stevens-Johnson syndrome
- erythema multiforme
- acute generalised exanthematous pustulosis
What is Stevens-Johnson syndrome?
A rare, serious disorder of the skin and mucous membranes
Usually a reaction to medication that starts with flu-like symptoms, followed by a painful rash that spreads and blisters
Then the top layer of affected skin dies, sheds and begins to heal after several days
It needs to be treated immediately often in ITU
What are the common adverse effects of rivastigmine?
N+V
Dyspepsia
Anorexia
Weight loss
Abdo pain
Bradycardia
Dizziness
Headache
Drowsiness
Gait abnormalities
Fall
Malaise
Agitation
Anxiety
Tremor
Insomnia
Parkinsonism
Syncope
Skin reactions
UTI
Urinary incontinence
Sweating
What are the less common adverse effects of rivastigmine?
AF
AV block
Depression
Aggression
What are the rare adverse effects of rivastigmine?
EPS
Gastric and duodenal ulceration
Pancreatitis
Angina
Seizures
What are the frequency unknown adverse effects of rivastigmine?
Dehydration
Hallucinations
Hepatitis
Restlessness
Sick sinus syndrome
Tachycardia
HTN
What effect does AChE inhibitors have on the ability to drive?
A minor or moderate influence on the ability to drive (esp in the 1st weeks after starting Tx or when the dose increases)
AChE inhibitors can cause fatigue, dizziness, sleepiness and muscle cramp and can induce syncope or delirium
Routinely assess the person’s ability to drive
What drugs can interact with AChE inhibitors?
Antimuscarinic drugs (e.g., TCAs) - antagonise the effects of AChE
- using 2 or more antimuscarinic drugs together can increase adverse effects (e.g., dry mouth, urine retention, and constipation) and can cause confusion in the elderly
Antipsychotics (e.g., olanzapine) - using together with AChE inhibitors increases risk of NMS
- if this happens stop Tx
Beta-blockers (e.g., atenolol) or other bradycardia agents (e.g., CCB, class III antiarrhythmics) - if concurrent is necessary be alert for bradycardia
What are the specific drug interactions for donepezil?
CYP3A4 inhibitors e.g., ketoconazole and possible itraconazole and erythromycin and CYP2D6 inhibitors e.g., quinidine and possibly fluoxetine = inhibit donepezil metabolism
Liver enzyme inducers e.g., rifampicin, phenytoin, carbamazepine and alcohol = reduced plasma levels of donepezil
What are the specific drug interactions for galantamine?
CYP3A4 inhibitors e.g., ketoconazole and erythromycin and CYP2D6 inhibitors e.g., quinidine and fluoxetine = increased plasma [galantamine]
What are the specific drug interactions for rivastigmine?
Metoclopramide
- concurrent use of rivastigmine and metoclopramide could increase the risk of EPS adverse effects
- be alert for movement disorders and signs of NMS
Sources
https://cks.nice.org.uk/topics/dementia/prescribing-information/acetylcholinesterase-inhibitors/
https://go.drugbank.com/categories/DBCAT000815
https://www.nice.org.uk/guidance/NG97/chapter/Recommendations#pharmacological-management-of-alzheimers-disease
https://www.nhs.uk/medicines/donepezil/
