Parkinson's and Dementia (Alzheimer's)

Question 1

Donepezil

tabs Aricept, Aridon, Aridon APNa, Arazil

Answer 1

1. Anticholinesterase/ acetylcholinesterase inhibitor
2. Alzheimer’s disease
3. 5-10mg once daily, same time each day.
   Usually at night but consider mane dosing if more convenient or if insomnia or vivid dreams occur.
   10mg provides ↑ benefit but ↑ risk of A/Es.
4. • severe A/Es (severe vomiting)= if persist dose ↓ may be needed .
   • poor compliance
   • clinical benefit lack of stabilisation/improvement of smx
     Stop tx if above occurs
   • NMS Rare (<0.1%)
   • BP= brady

Anticholinergic meds (e.g. TCAs, sedating antihistamines): can antagonise effects of donepezil and worsen cognitive function. Avoid.

C/I= Active PUD or GI or ureteric obstruction.
Hx of PUD, seizures, heart block, bradyarrhythmias, Parkinson’s, asthma, COPD= risk of aggravation.

5. LABELs: 12, 16
   This medicine can cause nausea, vomiting, diarrhoea, muscle cramps and insomnia.

Infrequent or rare
inappropriate sexual behaviour (rare; most published cases have been with donepezil)

Question 2

Galantamine
capsules (CR) Galantyl, Gamine XR, Reminyla

↑↓△

Answer 2

1. Anticholinesterase/ acetylcholinesterase inhibitor
2. Mild-to-moderate Alzheimer’s disease
3. 8-24mg MANE with FOOD.
   ↓ dose in hepatic impairment. Max= 16 mg daily.

4. hepatic fn
renal fn
- severe A/Es (severe vomiting)= if persist dose ↓ may be needed .
- poor compliance
- clinical benefit lack of stabilisation/improvement of smx
Stop tx if above occurs
- NMS Rare (<0.1%)
- BP= brady

Medicines with anticholinergic activity (e.g. TCAs, sedating antihistamines): can antagonise effects of donepezil and worsen cognitive function. Avoid.

C/I= Active PUD or GI or ureteric obstruction.
Hx of PUD, seizures, heart block, bradyarrhythmias, Parkinson’s, asthma, COPD= risk of aggravation.

5. LABELs: 12, A, B
   This medicine can cause nausea, diarrhoea, loss of appetite, dizziness, drowsiness and headaches.
   NandV, most common A/Es, generally persist for less than a week.

Question 3

Rivastigmine

cap, 1.5 mg, 56, Exelon, PBS‑A1
cap, 3 mg, 56, Exelon, PBS‑A1
cap, 4.5 mg, 56, Exelon, PBS‑A1
cap, 6 mg, 56, Exelon, PBS‑A1
patch, 4.6 mg/24 hours, 30, Exelon 5, PBS‑A1
patch, 9.5 mg/24 hours, 30, Exelon 10, PBS‑A1
patch, 13.3 mg/24 hours, 30, Exelon 15, PBS‑A1

Answer 3

1. Anticholinesterase/ acetylcholinesterase inhibitor
2. Alzheimer’s disease
3. Capsules= 1.5-6mg BD

Patch= 1 patch applied once daily.
4.6mg/24 hours-13.3 mg/24 hours once daily.

The patch may be suitable for patients intolerant of oral therapy; nausea and vomiting are less common with the patch than with oral rivastigmine

Conversion from capsules to patch, use patch of closest strength to established oral daily dose. Start patch on the day after the last oral dose. See product information for further details.

4. hepatic fn
   renal fn
   - severe A/Es (severe vomiting)= if persist dose ↓ may be needed .
   - poor compliance
   - clinical benefit lack of stabilisation/improvement of smx
   Stop tx if above occurs
   - BP= brady

Medicines with anticholinergic activity (e.g. TCAs, sedating antihistamines): can antagonise effects of donepezil and worsen cognitive function. Avoid.

C/I= Active PUD or GI or ureteric obstruction.
Hx of PUD, seizures, heart block, bradyarrhythmias, Parkinson’s, asthma, COPD= risk of aggravation.

5. LABELs: Capsule= 12, B. patch= 12, 21, K
   Capsules= take with morning and evening meals.

Patch= apply to clean, dry, hairless skin on the back, upper arm or chest. When changing the patch, gently remove the old patch and apply a new one to a different place (avoid re-using the same area within 2 weeks). Make sure you know how to dispose of patches safely, out of the reach of children.

This medicine can cause nausea, diarrhoea, abdominal pain, loss of appetite, weight loss, headaches and increased sweating.

Patch: can cause redness and itching at the application site.
Rare (<0.1%)
skin hypersensitivity reactions (including allergic contact dermatitis with patch)

Caregivers should be advised of the strong likelihood of nausea and vomiting, and the possibility of anorexia and weight loss. They should be encouraged to monitor for these and tell the doctor if they occur.

This medicine can cause nausea, diarrhoea, loss of appetite, dizziness, drowsiness and headaches.
NandV, most common A/Es, generally persist for

Question 4

Memantine

Answer 4

1. NMDA antagonist
2. Moderate-to-severe Alzheimer’s disease
3. 5-20mg MANE.
   Dose ↓ in renal impairment
4. Renal fn
   Hx of seizures= C/I
   Regular review of behavioural and functional status is important; drug treatment should continue only if these stabilise or improve.
5. LABEL: 12†
   This medicine is usually trialled for 6 months to determine whether it will be effective.
   This medicine may make you feel drowsy or dizzy; avoid operating machinery.
   This medicine can cause drowsiness, dizziness, headaches, vomiting and diarrhoea.

Common (>1%)
confusion, dizziness, drowsiness, headache, insomnia, agitation, hallucinations, dyspnoea, hypersensitivity

Infrequent (0.1–1%)
vomiting, anxiety, hypertonia, VTE

Rare (<0.1%)
seizures, rash, renal failure, cholestatic hepatitis, heart failure, bradycardia

Question 5

Levodopa with benserazide or carbidopa
Drug of choice for initial treatment of Parkinson’s disease
Conventional products
Controlled release products
Intestinal gel= reserved for uncontrolled advanced disease.
Fixed-dose combination with carbidopa and entacapone

Dispersible tabs= for pts w/swallowing difficulties and provide rapid response for managing early morning stiffness.
Do not break Stalevo® tablets in half as they may not work properly.

Answer 5

1. dopamine precursor with decarboxylase inhibitor
2. Parkinson’s disease= replenishes depleted striatal dopamine.
3. 100/25 1 tab 2-3 times a day and can be increased to 800 in divided doses up to 3-5 times a day.

Dosage is expressed as levodopa.
Take doses at the SAME time each day, in the same way (eg always before food).

4. Monitor for development of impulse control disorders (e.g. pathological gambling, hypersexuality, compulsive buying, binge eating)
   Mood changes (e.g. depression, suicidality).
   Regular skin exams to monitor for melanomas.
   Dopamine dysregulation syndrome= Characterised by compulsive overuse of levodopa (more than is needed to control motor symptoms) which may cause dyskinesias, psychiatric effects including psychosis and impulse control disorders. It is estimated to occur in 3–4% of patients with advanced Parkinson’s disease and appears to be more likely in those with early-onset Parkinson’s disease.
   Non-selective MAOIs= C/I
   Caution with:
   - PUD
   - CVD
   - arrhythmia
   - psychiatric disorders
   - Angle-closure glaucoma
   Tx w/dopamine antagonists (eg antipsychotics, metoclopramide)= may worsen control of Parkinson’s disease.
5. LABELs= Caps/MRcaps/tabs: 4a (delete dairy products), 9, 12, 16, A (except normal tabs); intestinal gel: 6, 9, 12 13, 16.
   S/Es= N,V, constipation, muscle cramps, insomnia or sleepiness/drowsiness, and palpitations. ↓ or disappear w/continued use.
   Tell dr, if sudden onset of DAYTIME SLEEP.
   Do not stop abruptly= risk of w/drawal syndrome (e.g. fever, muscle rigidity, rhabdomyolysis, tachycardia, tachypnoea, agitation).
   High-PROTEIN meal ↓ absorption. Can initially be taken w/food to ↓ GI effects. In later stages of disease, taking it on an empty stomach helps to minimise motor fluctuations.

Question 6

Pramipexole
Sifrol= 125, 250, 375, 750mcg, 1, 1.5, 2.25, 3, 3.75, 4.5mg CR

Rotigotine
patch, 2 mg/24 hours, 28, Neupro, PBS‑R1
patch, 4 mg/24 hours, 28, Neupro, PBS‑R1
patch, 6 mg/24 hours, 28, Neupro, PBS‑R1
patch, 8 mg/24 hours, 28, Neupro, PBS‑R1

Answer 6

1. non-ergot dopamine agonist
2. Parkinson’s disease
   Restless legs syndrome
3. with food
   Parkinson’s= 125microg-1.5mg TDS. Increase dose each week by 250 micrograms TDS.
   XR= use same total daily dose, taken once daily.
   Restless legs syndrome: (conventional tablets) 125-750 microg 2-3hrs before bedtime.
   Slowly titrate up to limit adverse effects.
4. Renal fn= pramipexole
   Hepatic fn= ↓ dose
   Psychiatric adverse effects= Hallucinations and confusion
   Dopamine dysregulation syndrome
   Impulse control disorders
   Withdrawal syndrome= monitor pt closely when discontinuing a dopamine agonist, as wdrawal syndrome may occur.
   Do not stop abruptly= ↓ dose gradually bc of risk of smx resembling NMS (fever, muscle rigidity, rhabdomyolysis, profuse sweating, tachycardia, tachypnoea, agitation)

Rotigotine= Regular ophthalmological examinations are recommended= visual disturbance. Monitor BP.

5. LABELs= tab: 1, 9, 12, 16, A (CR ONLY)
   With FOOD to ↓ chance of nausea or stomach upset.
   S/Es= N, constipation and confusion. ↓ w/continued use.
   Tell dr, if sudden onset of DAYTIME SLEEP or hallucinations and avoid driving.
   Tell dr if △ in behaviour, impulsive, etc.
   Warn pts/carers of possibility impulse control disorders/compulsive behaviours such as gambling.

Rotigotine= 1, 9, 12, 16, 21, K
Redness, itching and a rash at the application site.
Apply at the same time each day to non-irritated, clean, dry, hairless skin on the hip, abdomen, thigh, upper arm or shoulder. When changing the patch, remove the old patch and apply a new one to a different place (avoid applying to the same place for 14 days). Make sure you know how to dispose of patches safely.

Question 7

Cabergoline
tab, 500 mcg (scored), 2, 8, Dostinex, PBS‑R[2]1/PBS‑R[8]2
tab, 1 mg (scored), 30, Cabaser
tab, 2 mg (scored), 30, Cabaser

Bromocriptine
tab, 2.5 mg (scored), 30, Parlodel

Answer 7

1. ergot-derived dopamine agonist
2. Parkinson’s disease
3. Parkinson’s disease: 0.5-1mg daily, ↑ gradually to 2-3 mg daily.
4. Fibrotic effects= cardiac fibrosis
   Perform regular cardiovascular evaluations (e.g. 6-monthly echocardiograms).
   Hepatic fn= ↓ dose
   Psychiatric adverse effects= Hallucinations and confusion
   Dopamine dysregulation syndrome
   Impulse control disorders
   Withdrawal syndrome= monitor pt closely when discontinuing a dopamine agonist, as wdrawal syndrome may occur.
   Do not stop abruptly= ↓ dose gradually bc of risk of smx resembling NMS (fever, muscle rigidity, rhabdomyolysis, profuse sweating, tachycardia, tachypnoea, agitation)
5. LABELs= 12†, 16, 21, A, B
   Take with food, starting at night.
   S/Es= NV, constipation drowsiness, light-headedness, insomnia and headaches. ↓ w/continued use.
   Tell your doctor if you develop SOB, cough or chest pain.
   Tell dr, if sudden onset of DAYTIME SLEEP or hallucinations and avoid driving.
   Tell dr if △ in behaviour, impulsive, etc.
   Warn pts/carers of possibility impulse control disorders/compulsive behaviours such as gambling.

Bromocriptine= 5, 12, 16, B (Rarely used for Parkinson’s disease, more for a cromegaly, hyperprolactinaemia)
S/Es= NV, nasal congestion, headaches, and fatigue. ↓ w/continued use.
Tell dr if cough, chest pain, difficulty breathing, back pain, swollen ankles, confusion, or black/bloody stools.

Question 8

Rasagiline
tab, 1 mg, 30, Azilect, Rasalecta, PBS‑R1

Safinamide
tab, 50 mg, 30, Xadago, PBS‑R1
tab, 100 mg, 30, Xadago, PBS‑R1

Selegiline
tab, 5 mg (scored), 100, Eldepryl, PBS‑R1

Answer 8

1. selective irreversible MAO-B inhibitor= They reduce breakdown of dopamine and may also block dopamine reuptake.
2. Parkinson’s disease= adjuncts to levodopa in later disease
3. Oral, 1 mg once daily.
   Safinamide= 50-100mg OD.
   Selegiline= 2.5mg daily to 5mg BD.

4. Hepatic fn
Tyramine
BP
retinal damage= Safinamide
Dry mouth= Selegiline
Sleeping= insomnia

5. LABELs= 5, 9, 21, A
   S/Es= h/aches, flu-like smx, dyspepsia, loss of appetite/weight and joint pains.
   Orthostatic hypotension, depression, vertigo, hallucinations, rash, weight loss, arthralgia, angina.

Avoid eating tyramine (matured cheese/wine) while you are taking this medicine.

Selegiline= 5, 12, B
S/Es= dry mouth, h/aches, NV,, insomnia and joint pains.
For temporary relief of dry mouth, use sugarless gum or sweets, or a saliva substitute.

Question 9

Amantadine

cap, 100 mg, 100, Symmetrel, PBS‑R1

Answer 9

1. NMDA antagonist, dopaminergic antiviral
2. Parkinson’s disease
   Prevention of influenza type A in non-immunised people
3. usually >65 years, oral 100mg OD.
4. Renal fn= dose reduce
   Epilepsy— ↑ risk of seizures.
   HF, recurrent eczema, prostatic enlargement, confusion, hallucinations, psychosis, peptic ulcer disease, orthostatic hypotension= risk of aggravation.
   Do not stop abruptly reduce dose gradually because of the risk of smx resembling NMS (fever, muscle rigidity, rhabdomyolysis, profuse sweating, tachycardia, tachypnoea, agitation)
   Impulse control disorders
5. LABELs= 9, 12, 16, B
   Take with food to reduce stomach upset.
   Impulse control disorders

Depression, anxiety, insomnia, nightmares, hallucinations, anorexia, peripheral oedema, orthostatic hypotension, nausea, anticholinergic effects
(e.g. dry mouth, constipation, blurred vision), livedo reticularis (purplish-red mottling of the skin caused by dilation of capillaries), impulse control disorders (e.g. pathological gambling, hypersexuality, compulsive spending/eating).

Question 10

Entacapone

Answer 10

1. catechol-O-methyltransferase inhibitor
2. Parkinson’s disease as an adjunct to levodopa in patients with motor fluctuations
3. 200mg w/each dose of levodopa/decarboxylase inhibitor. Max 2g daily.
   Take this medicine at the same time as each dose of levodopa.
4. Hepatic fn
   NMS= hx C/I
5. This medicine may increase some side effects of levodopa such as:
   dizziness (if you stand up too quickly)
   drowsiness (if affected, do not drive or operate machinery).
   Your urine may be a reddish-brown colour while taking this medicine (but this is harmless).
   S/Es= NV, abdo pain, constipation, diarrhoea and dry mouth. ↓ or disappear w/continued use.
   Tell dr if persistent diarrhoea, loss of appetite or weight loss, or sudden onset of DAYTIME SLEEP.
   Do not stop abruptly reduce dose gradually because of the risk of smx resembling NMS (fever, muscle rigidity, rhabdomyolysis, profuse sweating, tachycardia, tachypnoea, agitation)

nausea, vomiting, dry mouth, diarrhoea, abdominal pain, constipation, discoloured urine, hallucination, confusion, paranoia, dyskinesia

Rare (<0.1%)
skin, hair or nail discolouration, rash, increase in liver enzymes, hepatitis, colitis

Question 11

Benzatropine (benztropine)
tab, 2 mg (scored), 60, Benztrop

Trihexyphenidyl (benzhexol)
tab, 2 mg (scored), 200, Artane, PBS
tab, 5 mg (scored), 200, Artane, PBS

Answer 11

1. Anticholinergic
2. Parkinson’s disease
   Drug-induced extrapyramidal disorders (except tardive dyskinesia)
   Acute dystonic reaction
3. Oral, 0.5-1mg daily, increase gradually up to 6mg daily.

Trihexyphenidyl= oral 1 mg daily; increase gradually to 5–15 mg daily in 3 or 4 doses.

4. Cognitive impairment= may worsen smx; monitor mental status during tx.
   dry mouth may reduce ability to adhere to fluid restriction in heart failure and severe renal failure
   monitor for decreased sweating and hyperthermia, especially in hot weather; risk is increased if combined with other drugs with this effect
   Monitor intra-ocular pressure regularly.
5. 1, 9 (long-term regular therapy)
   Side effects: This medicine can cause dizziness, blurred vision, nausea, dry mouth and constipation.

may increase the effects of alcohol; if affected, do not drive or operate machinery.

This medicine may also reduce or prevent sweating. Tell your doctor if this happens to you as it may affect your body’s ability to cool down, especially in hot weather.

Parkinson’s disease: do not stop taking this medicine suddenly unless your doctor tells you to.