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What are the two main types of stroke?

Haemorrhagic and ischaemic


What's the difference between the two types of stroke?

Haemorrhagic is a bleed, ischaemic is a blockage caused by a clot


Main cause of stroke?

Atherosclerotic plaque


Incidence/outcomes of stroke?

23% of people die within one month, 3rd leading cause of death in UK
60-70% of people die within 3 years
80% strokes are preventable


WHO definition of stroke?

Rapidly developing clincial signs of disturbance of cerebral function lasting more than 24 hours (or leading to death) with no other apparent cause than that of vascular origin


What is ischaemic stroke?

70% of all strokes, cerebral thrombosis from atherosclerotic disease (or distal embolism from cardioembolic disease)


What is haemorrhagic stroke?

Intracerebral haemorrhage (ruptured vessel in brain) or subarachnoid haemorrhage (ruptured intercranial aneurysm in subarachnoid space)


Symptoms of stroke

Face - drooping/can they smile
Arms (or legs) - weakness, can they raise both arms
Speech - is it clear
Time - to call 999


What other conditions can present similarly to a stroke?

Seizures, drug toxicity (e.g. overdose), brain tumour, migraine, spinal cord lesion (e.g. multiple sclerosis)


Stroke risk factors: non-modifiable

Age - risk doubles with every decade over 55
Gender - more common in men, more women die
Family History
Afro-caribbean ethnicity


Stroke risk factors: modifiable

Hypertension - antihypertensives reduce risk by 40%
Atrial Fibrillation - implicated in 15% of strokes. Anticoagulation reduces risk of stroke by 70%
Diabetes - 2-2.5x more likely to suffer stroke
Hyperlipidaemia - statins reduce risk
Smoking - doubles risk


Investigations for suspected stroke?

CT scan - ASAP
- haemorrhage clearly visible, ischaemic stroke harder to spot but hypodense zone

MRI scan - useful for investigating TIA

Other: BP, ECG, FBC, U&Es, blood glucose, inflammatory markers


What is a TIA?

Symptoms of stroke that resolve within 24 hours


Acute stroke treatment at presentation?

Transfer to hyperacute stroke unit ASAP. No acute treatment can be administered until CT results are back as treatments for the two types of stroke are v different


Acute treatment for ischaemic stroke?

Thrombolysis (alteplase) must be given within 4.5 hours of onset, twice as effective if given within 1.5h

Antiplatelet: 300mg aspirin asap (via PR or NG if necessary) and continue for 14 days


Antiplatelet therapy for patients who have been thrombolysed?

Wait 24 hours before giving any apsirin, and CT must be repeated to ensure no haemorrhagic transformation


Criteria for alteplase?

- age over 18 years old (no upper age limit)
- Symptoms of acute stroke with a clear onset time
- Thrombolysis can be administered within 4.5 hours of symptom onset
- Haemorrhage excluded on neuro-imaging

- Major surgery in last 14 days
- GI or urinary tract bleeding in last 21 days
- History of intracranial haemorrhage, Intra-cranial malignancy or intracranial AVM
- Symptoms suggestive of subarachnoid bleed (even if CT Head clear)
- BP greater than >185 systolic or >110 diastolic unresponsive to medical treatment (see page 6)
- INR >1.7
- Hyperglycaemia (>20) or Hypoglycaemia (<3)
- Stroke or head injury in last 3 months
- Use of anti-coagulation in last 24 hours


Acute treatment for haemorrhagic stroke?

- neurosurgical intervention sometimes necessary
- anticoagulants stopped and reversed if INR >1.4 (vitamin K and prothrombin complex)


Lipid lowering treatments for stroke?

Can be given for both types of stroke

Ischaemic: high intensity statin (20-80mg) as soon as patient can swallow safely
Haemorrhage: only if indicated according to CV risk, when patient can swallow safely


General acute treatments and measures?

- SALT assess ability to swallow, pharmacist advise on medication ROA (drug administration via feeding tubes)


Acute control of blood pressure in ischaemic stroke?

- fluctuating BP common after acute stroke
- body detects it so pumps more blood to brain to try and oxygenate, hence hypertension. up to 185/110 is ok - only manage if hypertensive crisis. should be below this for thrombolysis so lower if eligible


Acute control of blood pressure in haemorrhagic stroke?

treat if higher than 150mmHg systolic, aim for 140mmHg for at least 7 days.


Suitable agents to acutely control blood pressure in stroke?

short acting anthypertensive infusion, e.g. nicardipine, labetalol, GTN


Why use short acting antihypertensive in acute management in stroke?

so they can be stopped quickly if needed


Secondary prevention of further stroke

Antiplatelet (or anticoagulant in embolic stroke) - aspirin/clopidogrel - ischaemic only
- control hypertension
- control blood glucose


Possible stroke complications?

- swallowing problems
- depression
- dry mouth/sialorrhoea
- seizures
- spasticity


Long term antiplatelet treatment for ischaemic stroke?

once 14 days of aspirin complete, clopidogrel (generally for life)
- aspirin + MR dipyridamole if clopidogrel not tolerated
- MR dipyridamole if aspirin and clopidogrel not tolerated


Long term anticoagulant treatment for stroke?

in embolic stroke/AF score more than 2

Direct-acting Oral Anticoagulant (apixaban, rivaroxaban etc) or warfarin


Long term antihypertensive treatment for stroke?

Reduce risk of stroke in both hypertensive and previously normotensive patients - follow NICE guidance
- BP less than 130mmHg systolic


Long term lipid lowering treatment for stroke?

Reduces risk of ischaemic stroke
Simvastatin 40mg, consider atorvastatin if target of <4mmol/L not met
- only used in haemorrhagic stroke if patients has hyperlipidaemia or CV risk needing treatment


Long term management of swallowing difficulties after stroke?

NG/PEG feeding may be required, puree diet, thickened fluids (all assessed by SALT)
- medication must be reviewed for appropriate formulation and administration (only crush tablets or open caps if safe and no alternative)


Management of dry mouth after stroke?

Artificial saliva, good oral hygiene


Management of sialorrhoea after stroke?

Oral glycopyrronium, atropine eye drops into mouth, hyoscine patch


Management of depression after stroke?

Screen all patients (30% will experience), treat as per NICE (SSRI first line)


Management of seizures after stroke?

- common problem, up to 67% late onset seizures post ischaemic stroke
- give prophylactic antiepileptic drugs if recurrent diagnosed at epilepsy


Management of spasticity after stroke?

skeletal muscle relaxants - baclofen, tizanidine

botulinum toxin recommended by RCP stroke guidelines


Pathophysiology of Parkinson's disease?

- chronic progressive neurodegerative disease
- degeneration of the dopaminergic neurones in the nigro-striatal pathway
- 50-80% loss before symptoms become apparent
- presence of Lewy bodies in neurones
- changes in the GABA glutamate pathway


Incidence of Parkinsons?

- 1 in 500 people in the UK
- average onset is 60 years, 5-10% early onset
- Men more commonly affected, 3:2 ratio


Risk factors for Parkinson's?

- Complex interaction of factors, including genetic factors, head injury and exposure to neurotoxins


Motor symptoms of Parkinson's?

Tremor, rigidity, bradykinesia


Non-motor symptoms of Parkinson's?

- Microphagia, monotone voice
- Swallowing and speech problems
- Drooling, loss of smell, excessive sweating
- Depression, memory problems, sleep disturbances
- Constipation and urinary problems
- Dizziness and falls
- dementia


When should drug treatments be started for Parkinson's?

Once symptoms affect a patient's ability to function on a daily basis


What do drug treatments for Parkinson's aim to do?

Increase dopamine levels in the brain through a variety of mechanisms. Not curative or disease-modifying, symptomatic treatment only


What types of drugs can be used to treat motor symptoms of Parkinson's?

- MAO-B inhibitors
- Dopamine agonists
- Levodopa
- COMT inhibitors
- Amantadine
- Anticholinergics


How is Levodopa given for treatment of Parkinson's?

Combined with a dopa-decarboxylase inhibitor e.g. Madopar (co-beneldopa), Sinemet (co-careldopa), Duodopa


Why does levodopa need to be administered with a dopa-decarboxylase inhibitor?

To prevent peripheral metabolism of levodopa to dopamine - so it can be metabolised after crossing the BBB


What symptoms does Levodopa treatment relieve?

Motor (tremor, bradykinesia, rigidity) - the most effective treatment


How is dosing for Levodopa done?

started low then titrated up - to limit side effects of postural hypotension, nausea, vomiting and psychiatric effects


When should levodopa be started?

When symptoms interfere with daily activities. Until then, use other first line (due to long term problems)


Examples of MAO-B inhibitors for Parkinson's?

Selegiline and Rasagiline


How do MAO-B inhibitors work?

Prevent metabolism of dopamine, so increased at receptors


Place of MAO-B inhibitors in Parkinson's treatment?

Can be used as monotherapy in early disease, better in milder symptoms.

Also useful in advanced disease to lower the dose of levodopa


Which MAO-B inhibitor is preferred?

Rasagiline. Selegiline can cause hallucinations and insomnia due to amphetamine like metabolites (last dose must be before 1pm)


Types of dopamine agonists for Parkinson's?

Non-ergot: ropinirole, pramipexole, rotigotine
Ergot: pergolide, lisuride, bromocriptine, cabergoline

Ergot are older and not really used anymore


Place of dopamine agonists in Parkinson's treatment?

Useful initial monotherapy - fewer long term problems than levodopa but less effective for motor symptoms

used with levodopa in advanced disease


How is dosing for dopamine agonists done?

Slow initial dose titration needed


Formulations of dopamine agonists?

Most available as tablets

rotigotine available as 24 hour transdermal patch, apomorphine s/c


Side effects of dopamine agonists? Ergot specific

Lung and cardiac valve fibrosis


Side effects of dopamine agonists? General

- Nausea and vomiting
- psychiatric (psychosis)
- Postural hypotension
- Sudden sleep onset
- Rare: dopamine dysregulation syndrome (gambling, hypersexuality, binge eating) - more common in young males w history of mental illness


How does response to drug treatment change with Parkinson's progression?

- response to treatment declines
- patients experience more noticeable effects (rigidity, akinesia) when the drugs wear off
- patients also experience motor complications (dyskinesia, dystonia) when drug levels peak. fluctuations between peak and trough and the effects are known as on-off


How is the declining response to treatment managed in Parkinson's?

use drug combinations or shorten the interval between doses


What is the order of recommended treatments for Parkinson's?

1. Dopamine agonist or levodopa monotherapy
2. dopamine agonist and levodopa combination therapy
3. add entacapone or rasagiline if unsatisfactory control. can also add amantadine or antimuscarinic for dyskinesia
4. consider apomorphine or duodopa intestinal gel


What are COMT inhibitors?

Catechol-O-Methyl Transferase inhibitors


How are COMT inhibitors used in Parkinson's disease and how do they work?

in combination with Levodopa

prevent metabolism of levodopa to 3-O-methyldopa


Example of COMT inhibitor?


In combination with levodopa and carbidopa combination product - Stalevo. allows a reduced levodopa dose


Side effects of COMT inhibitors?

Dyskinesias, nausea, diarrhoea


What is amantadine?

Glutamate agonist at the NMDA receptor


How is amantadine used in Parkinson's?

To treat dykinesias in later stage disease
efficacy decreases after several months and higher doses are required, so not suitable in early stages


Side effects of amantadine?

- Psychiatric e.g. confusion, hallucinations
- GI effects (n&v)
- Oedema
- Skin rash (livedo reticularis)


Place of anticholinergics in Parkinson's treatment?

Only used for tremor - especially good in younger patients
avoid in elderly


Examples of anticholinergics used for Parkinson's?

Trihexyphenidyl, orphenadrine


Side effects of anticholinergics?

constipation, urinary retention

psychiatric e.g. confusion


Important note for stopping anticholinergics?

Do not stop abruptly due to rebound effects


What is duodopa and what is it used for?

Intestinal gel containing carbidopa and levodopa - administered via PEG tube (after NG trial).

Used for Parkinson's with severe motor fluctuations and dyskinesia, as can be used for up to 16 hours a day


What is apomorphine?

Dopamine agonist given s/c. useful for on-off fluctuations, but specialist supervision is needed


Side effects of apomorphine?

Nausea/vomiting (pretreat with domperidone PR for 3 days), yawning, drowsiness, abscess/nodule formation


Treatment for complications: early morning bradykinesia

Dispersible levodopa taken on wakening, or night time dose of dopamine agonist or MR levodopa


Treatment for complications: dyskinesias

- decrease levodopa dose
- add dopamine agonist or COMT inhibitor and decrease levodopa dose
- add amantadine
- Duodopa infusion


Treatment for complications: on-off

- add dopamine agonist
- apomorphine
- decrease protein intake to increase levodopa absorption


Treatment for non-motor symptoms: sialorrhoea

Hyoscine patches or sublingual atropine drops


Treatment for non-motor symptoms: restless legs syndrome

Ropinirole or pramipexole


Treatment for non-motor symptoms: REM sleep behaviour disorder

Clonazepam 500mcg at night


Treatment for non-motor symptoms: depression

SSRI (with care)


Treatment for non-motor symptoms: constipation

As per BNF


Treatment for non-motor symptoms: psychosis

- review Parkinson's meds
- quetiapine or clozapine
- not typical antipsychotics


Treatment for non-motor symptoms: dementia



Treatment for non-motor symptoms: sexual dysfunction

PDE inhibitors e.g sildenafil


Role of the pharmacist in Parkinson's management?

- monitor for interactions e.g. iron and levodopa
- compliance aids and timing devices
- managing adverse effects
- alternatives in swallowing difficulty


What are some of the future treatments appearing for Parkinson's?

- Deep brain stimulation (subthalamic