Free Shipping on orders over $99

Dopamine and Parkinsons Disease: Understanding the relationship

General, Mental Health | May 4, 2015 | Author: The Super Pharmacist

general, parkinsons

Dopamine and Parkinsons Disease: Understanding the relationship

In the brain, dopamine is a neurotransmitter that is released by nerve cells to send signals to other nerve cells. The degenerative impact of Parkinson’s disease causes a significant decrease in dopamine levels due to the loss of dopamine secreting neurons.

What are dopamine agonists?

The function of a dopamine agonist is to activate dopamine receptors in the absence of dopamine itself. They can be administered in a number of ways including tablets and capsules, prolonged release tablets, skin patches, injection or infusion.

Parkinson’s treatment is bespoke and offered on a personalised basis due to the complexity of the disease. Skin patches are beneficial for patients who have difficulty swallowing tablets, or those who have persistent drooling and gastritis (1). Injections or infusion is usually reserved for more advanced Parkinson’s and apomorphine is typically administered via this route. It is the strongest known dopamine agonist and is also a strong emetic (induces vomiting). As such, it is often an antiemetic such as domperidone is usually given 2-3 days before treatment starts and for at least another two weeks after it has been completed. More advanced Parkinson’s has been evidenced to respond better to intravenous treatments than those administered orally, and it is also used in patients who have sudden and unpredictable changes in symptoms (2).

Advantages and disadvantages of dopamine agonists

Studies suggest that dopamine agonists are effective treatments for several years when used alone. Single dopamine agonist use is also associated with longer control of symptoms than levodopa, although taken in conjunction with levodopa they can also increase the efficacy of levodopa and minimise the ‘on/off’ effect that individuals who take levodopa have often reported (3).

A range of dopamine agonists have also been evidenced to have a positive impact on symptoms of Parkinson’s that are not related to movement such as disturbed sleep, pain control and low mood (4).

Some of the older dopamine agonists that were previously used have since been evidenced to increase the risk of heart problems in some patients such as bromocriptine, pergolide and cabergoline (5). Due to this risk, these drugs are now usually only prescribed when no other dopamine agonists have been effective. More recently developed agonists such as apomorphine, pramipexole, ropinirole and rotigotine are not associated with any increased risk of heart problems.

Dopamine agonists can also induce excessive sleepiness, faintness and dizziness. This is particularly prevalent when people begin a course of drugs, although such effects are evidenced to wear off once a stable and appropriate dose is reached.

Some studies have reported an association between particular drugs and blurred vision (6).

If dopamine agonist treatment is halted abruptly, there is some preliminary research that suggests an increased risk of depression and / or anxiety (7). As such, it is recommended that any desire to stop medication, or to change to a different type of medication, is carefully managed in conjunction with an appropriate health professional.

Dopamine agonists, when administered alone, have also been linked through a number of studies to disinhibited and compulsive behaviours such as pathological gambling, hypersexuality and overeating.

What is Levodopa and How does it work?

Levodopa is an amino acid chemical precursor to dopamine. It is converted to dopamine through DOPA decarboxylase, a naturally occurring enzyme within the body. This occurs in both the Central Nervous System (CNS) and peripheral circulation after it crosses the blood brain barrier, a permeable barrier that separates circulating blood from extracellular fluid in the CNS. Once the central dopamine receptors in the brain are activated, the symptoms of Parkinson’s are improved. However, such an action also produces significant nausea and vomiting. For this reason, medication to inhibit DOPA decarboxylase is required to mitigate against the unwanted side effects of levodopa when it is administered in isolation, and this is most commonly carbidopa. Carbidopa inhibits the peripheral metabolism of levodopa, allowing a greater proportion of orally taken levodopa to cross the blood brain barrier for increased central nervous system effect. This combination of medication is sometimes referred to as levocarb or co-careldopa. Carbidopa is unable to cross the blood brain barrier, but it prevents the peripheral conversion of levodopa to dopamine and thus presents feelings of nausea and vomiting in patients. This results in a greater proportion of levodopa reaching the brain, increasing the efficacy of the drug in the process.

Evidence base for this combination 

Levodopa has been shown to be the most effective drug available for individuals with Parkinson’s disease, with virtually all patients responding to it either on its own or in conjunction with Carbidopa. There is no evidence to suggest that levodopa delays the onset of motor complications but it does successfully manage symptoms. However, the long term use of levodopa or combinations that include levodopa is well known to produce negative motor fluctuations (wearing off, dose failures and freezing) and dyskinesias (peak-dose dyskinesia, diphasic dyskinesia and dystonia) (8).

Severe fluctuations in motor capability may be helped through taking carbidopa in liquid form, and studies have also shown that the use of COMT inhibitors also improves motor impairment through increasing the efficacy of levodopa (9). There is an ongoing debate around which drug is the most effective treatment method during the early stages of Parkinson’s disease, or in patients who are newly diagnosed. Many individuals are now returning to dopamine agonists rather than levedopa as a first line treatment. Although levedopa is evidenced to work well in a wide range of patients with Parkinson’s, dopamine agonists carry less side effects and have been evidenced to be as effective in early use without the longer term side effects that levedopa causes such as significant motor fluctuations. As such, many patients now receive dopamine agonists only until it no longer relieves their symptoms, at which point patients usually switch to levodopa combination therapy.

www.superpharmacy.com.au  Australia’s best online discount chemist

References

1. Zhou CQ, Zhang JW, Wang M, Peng GG (2014) Meta-analysis of the efficacy and safety of long-acting non-ergot dopamine agonists in Parkinson’s disease J Clin Neurosci 21(7):1094-1101

2. Raz A, Lev N, Orbach-Zinger S, Djaldetti R (2013) Safety of perioperative treatment with intravenous amantadine in patients with Parkinsons disease Clin Neuropharm 36(5):166-9

3. Macleod AD, Taylor KS, Counsell CE (2014) Mortality in Parkinson’s disease: a systematic review and meta-analysis Mov Disord 29(13):1615-22

4. Ha AD, Jankovic J (2012) Pain in Parkinson’s disease Mov Disord 27(4):485-91

5. Andrejak M, Tribouilloy C (2013) Drug-induced valvular heart disease: an update Arch Cardio Dis 106(5):333-339

6. Hori N, Takamori M, Hirayama M, Watanabe H et al (2008) Pupillary sensitivity and visual disturbance in Parkinson’s disease Clin Auton Res 18(1):20-7

7. Connolly BS, Lang AE (2014) Pharmacological treatment of Parkinson’s disease: a review JAMA 311(16):1670-83

8. Schaeffer E, Pilotto A, Berg D (2014) Pharmacological strategies for the management of levodopa-induced dyskinesia in patients with Parkinson’s disease CNS Drugs 28(12):1155-84

9. Li CT, Palotti M, Holden JE, Oh J, Okonkwo O et al (2014) A dual-tracer study of extrastriatal 6-[18F]fluoro-m-tyrosine and 6-[18F]-fluoro-L-dopa uptake in Parkinson's disease Synapse 68(8):325-31

backBack to Blog Home