Ropinirole PRESENTATION

Ropinirole

A Dopamine Receptor Agonist

ADME

Dosage

Learning objectives

Pharmacokinetics

How much is too much?

Content

Finding Information

Side Effects

Indications

What's it used for?

What we don't want

What we'll be covering in today's lecture

Summary

Parkinson's

Interactions

A general overview

Drugs it doesn't get on with

In the future

Contra- indications

Method of Action

Kahoot

People it doesn't get on with

How does ropinirole help?

Learning Objectives

• To understand what ropinirole is used for

• A basic knowledge of Parkinson's disease

• How ropinirole can help with Parkinson's

• Reasons why it sometimes isn't used

• Know where to look for information in the future

Indications

Non-ergoline dopamine receptor agonists are used to treat a variety of central nervous system disorders.

• Parkinson's Disease

Can be used on its own or in conjunction with other medications such as co-careldopa or co-beneldopa Ropinirole is used for when the patient's quality of life is not impaired by the motor symptoms they are suffering from

• Restless Leg Syndrome

(moderate to severe)

CNS Diseases

03

02

Parkinson's

01

Non-motor Symptoms

Motor Symptoms

Risk Factors

Neurodegenerative death of dopamine-containing cells of the substantia nigra

Non-movement related

Movement and visible symptoms

Decrease of dopamine in the brain causes cognitive and motor decline Affects 1 in 500 in the UK Can have 'On' and 'Off' periods

Age >80 Male > Female Family History Brain Trauma Hispanic origin (in USA)

Bradykinesia : Slow movement Resting Tremours Stiff Joints Postural Instability General Rigidity

Sleep disorders: Insomnia, terrors, RLS Constipation Urinary Incontinence Psychosis Dementia Depression + Anxiety

Mechanism of Action

D2 Receptor Agonist

Ropinirole is a non-ergot dopamine receptor agonist. Being non-ergoline means that it is more specific for dopamine receptors and thus less side effects Actively binds to D2 receptors in the central and peripheral nervous systems The activated D2 GCPR now inhibits the adenylyl cyclase pathway and eventually Ca 2+ channels whilst activating K+ channels Resulting in ropinirole's physiological activity

dopamine receptors range from 1-5

Quiz

Ropinirole

Start

Question 1/4

Ropinirole's physiological effect is associated with what type of receptor?

Dopamine 2

Dopamine 1

Dopamine 5

Question 2/4

Ropinirole should not be prescirbed when motor symptoms are not impacting QoL?

True

False

Question 3/4

What is the maximum dose of ropinirole in a day?

24mg

2.4mg

2400μg

Question 4/4

Parkinson's disease affects roughly how many people in the UK?

1/250

1/600

1/500

wrong

Unlucky, maybe next time

Back

congratulations!

A true ropinirole know-it-all

The End?

Initially 750μg daily in 250μg TDS

Increased to 3 mg daily in 3 divided doses in 4 weeks

Usual dose 9–16 mg daily in 3 divided doses

Immediate rELEASE

Initially 2 mg once daily

Increased to 4 mg once daily

Increased in steps of 2 mg at intervals of at least 1 week, up to 8 mg once daily

pROLONGED RELEASE

Dosing Advice

Missed Doses

Driving Skills

Sudden Sleep

Need to be counselled on the risk of driving or operating machinery. If sedation occurs, stop immediately.

Increased daytime sleepiness can occur with all dopamine agonists. Could be exacerbating an underlying cause whih needs to be treated.

If treatment is missed for >1 day, re-titration of dosing should be considered by HCP.

Impulse Control Disorders: Gambling, Binge eating & Complusive spending/Buying

Never immediately stop treatment, as this carries a small risk of neuroleptic malignant syndrome. Slowly decrease dose over a 7 day period to also help with withdrawal symptoms

Associated with all dopamine agonists Patient counselling is key

A common side effect which can be dealt with OTC medication if needed

Headaches + Dizziness

Sudden Tiredness

Usually only occur during the first few days of treatment Can occur with any dopamine agonist

Ropinirole can be taken with food just before bedtime in an attempt to decrease any GI discomfort caused

GI Discomfort

Hypotension

A common side effect which can be dose dependant Starting on a low dose and increasing should subside symptoms

Long-term use can worsen psychotic symptoms, which may already be present in Parkinson's Close monitoring is needed

Nausea + Vomiting

PSYCHOTIC SYMPTOMS

Pregnancy

Breast Feeding

Interactions + Contraindications

Avoid unless potential benefit outweighs risk—toxicity in animal studies Would need to be discussed with medical team

AVOID in breastfeeding mothers as can decrease and suppress lactation

Interactions can be found in the BNF! Let's try and find some together!

Hepatic

Renal

Avoid in patients with hepatic impairment Especially if history of alcohol as well

Avoid if creatinine clearance less than 30 mL/minute

A D M E

Peak plasma concentration is about 1 to 2 hours. With 50% of the drug first-pass metabolized, and the absolute bioavailability around 50%. It reaches steady-state concentrations within two days of initiating ropinirole. A high-fat diet may delay absorption

Ropinirole has an apparent volume of distribution 7.5 L/kg, and 40% of the drug is bound to plasma proteins

Cytochrome P450 1A2 is the primary enzyme involved in the metabolism of ropinirole to active renally-excreted metabolites SK&F-104557 and SK&F-89124

The elimination half-life of the ropinirole immediate-release tablet is approximately 6 hours, and less than 10% of the orally administered drug is excreted as an unchanged drug in urine

When undergoing first-pass metabolism, ropinirole is heavily metabolsied by the liver. Through N-despropylation and hydroxylation reactions to form inactive metabolites which are then excreted

Will you remember this outside of the classroom?

probably not

So, we're going to teach how to learn and discover the information yourself In your trusty BNF

Summary

Ropinirole can be a key dopamine receptor agonist drug in giving symptomatic relief to patients with Parkinson's disease With a complex dosing regime and multiple adverse effects and interactions, caution and close working with HCP are needed. Multiple sources of information are available to help both HCP and patient.

Looking Forward

Learnt about how we need to take in all factors about when we can use certain types of drug and when it may not be the most optimal treatment route Knowing where to look for information and using a wide range of resources in order to cross-reference We will use the variety of sources in the future to know the guidelines, the appropriateness of the drug, how it works and knowledge if the patient has any concerns. All in order to give the best possible patient care.

References

• Joint Formulary Committee. British National Formulary. 80 ed. London: BMJ Group and Pharmaceutical Press; 2020
• Ropinirole 2 mg film-coated tablets - Summary of Product Characteristics (SmPC) - (emc) [Internet]. www.medicines.org.uk. [cited 2022 Dec 12]. Available from: https://www.medicines.org.uk/emc/product/9911/smpc
• Choi J, Horner KA. Dopamine agonists.
• Dopamine agonists (pramipexole, ropinirole) | Parkinson’s UK [Internet]. Parkinsons.org.uk. 2019. Available from: https://www.parkinsons.org.uk/information-and-support/dopamine-agonists-pramipexole-ropinirole

“Study without desire spoils the memory, and it retains nothing that it takes in.”

— Leonardo da Vinci

THANK YOU!