Drug therapy
Jeremy Playfer, John Hindle, Andrew Lees in Parkinson's Disease in the Older Patient, 2018
Apomorphine is a unique drug for use in late-stage PD. It is the most effective dopamine agonist and has clinical efficacy almost equivalent to levodopa. It is given by the subcutaneous route by intermittent injection using a Penject injection. The intermittent injection rescues the patient from the ‘off’ state within 5–15 minutes of administration, and the effects last for about one hour. In more advanced cases, where more than eight ‘rescue’ injections are needed each day, apomorphine can be given by continuous subcutaneous infusion using an ambulatory syringe driver. The dosage of apomorphine needs to be titrated for individual patients. The dose range is very wide, from a few milligrams per day by intermittent injection up to 150 mg a day by continuous infusion (the current licence recommends up to 100 mg). Continuous infusion over a period of months, together with reduction of other dopaminergic drugs, may significantly reduce dyskinesias.76 Most patients ultimately progress from inter mit tent injections to continuous infusion of apomorphine.
Behavioral effects of amphetamines and related stimulants: the importance of species differences as demonstrated by a study in the marmoset
John Caldwell, S. Joseph Mulé in Amphetamines and Related Stimulants: Chemical, Biological, Clinical, and Sociological Aspects, 2019
In rats the effects of amphetamine and apomorphine, as seen by direct observation, are similar in quality, though differing in time course and dose effect in so far as both produce stereotypic and locomotor effects.75 In the marmoset, the effect of apomorphine differed qualitatively from that of amphetamine. The biphasic effect of apomorphine complicates direct comparison but the increase in checking and decrease in activities in the early phase after apomorphine follows the amphetamine effect. Since it is supposed that apomorphine acts directly on the dopamine receptor, both these effects may be dopaminergic. But it is noteworthy that, although doses of apomorphine that were sufficient to disrupt behavior more than the disruption caused by amphetamine were used, the effect on checking and activities was never as large as that caused by amphetamine. It could be argued that checking (and loss of other activities) should not be considered to be purely a dopamine effect but could, for example, result from a product of dopamine and other, possibly noradrenergic, effects. Alternatively, it could be supposed that amphetamine and apomorphine exert different partial agonist effects on the dopamine system.
Examine the gait
Hani TS Benamer in Neurology for MRCP PACES, 2019
Q: What is the treatment? Drugs are the main form of treatment.Dopamine agonists, especially in the early stages of the disease and in young patients (ropinirole, pramipexole and rotigotine).Levodopa is still the main and most effective treatment.Monoamine oxidase B inhibitors (rasagiline and selegiline).Catechol-O-methyl transferase (COMT) inhibitors (entacapone).Apomorphine injection and infusion.Surgery, mainly deep brain stimulation. Patient selection is crucial. Patients should have positive responsiveness to dopamine therapy with no cognitive or psychiatric problems.
Rationale and patient selection for interventional therapies in Parkinson’s disease
Published in Expert Review of Neurotherapeutics, 2018
Junaid Siddiqui, Zakiyah Aldaajani, Raja Mehanna, Barbara Kelly Changizi, Danish Bhatti, Ziyad Ghazi Al-Johani, Aparna Wagle Shukla, Hubert H. Fernandez, Jawad A. Bajwa
At present, apomorphine is not FDA-approved for infusion in the USA and is undergoing a randomized trial. However, it is FDA approved as a solution of 10 to 20 mg/mL for intermittent SC injection. In Europe and the Middle East, apomorphine has been available for both intermittent injections and also as a continuous subcutaneous infusion (APO-go, by Britannia Pharmaceuticals). The device consists of a small battery driven pump that is worn on a waist belt or around the neck, which is connected to a subcutaneous catheter. Typically, initiation and adjustment of CSAI requires the patient to be hospitalized and then followed up on an outpatient basis by their physician. CSAI is typically administered 12–24 h per day at a dose of 4 to 7 mg/hour, most typically for 16 waking hours. Figure 3 gives a step-wise approach to CSAI assesment and placement.
An evaluation of subcutaneous apomorphine for the treatment of Parkinson’s disease
Published in Expert Opinion on Pharmacotherapy, 2020
The number of daily bolus injections depends on the frequency and severity of ‘OFF’ states. A single subcutaneous injection may be applied to the lower abdomen or outer thigh at the moment of first signs for the onset of an ‘OFF’ episode. Absorption differs in the various injection sites within a single individual. Accordingly, the optimum dosage of apomorphine hydrochloride varies between individuals. Once established, it may remain constant only for a certain interval, further titration is often needed. Treatment response is typically observed within a range between 3 and 30 mg apomorphine daily. The total daily apomorphine hydrochloride dose shall not exceed 100 mg, an individual bolus injection shall not be higher than 10 mg. Once an apomorphine treatment regimen has been established, domperidone, if available, may gradually and cautiously be reduced. Domperidone therapy may rarely eliminate without concomitant, transient reappearance of vomiting or nausea [24–26].
An update on emerging drugs for the treatment of erectile dysfunction
Published in Expert Opinion on Emerging Drugs, 2018
U. Milenkovic, J. Campbell, E. Roussel, M. Albersen
A non-selective dopamine receptor agonist, developed for the treatment of Parkinson’s disease, apomorphine acts centrally by activating D2-receptors in hypothalamic neurons [68]. It is most effective in mild to moderate ED but is less effective than PDE5-I. Erections occur about 20 min after sublingual administration. Most frequent, dose-limiting, adverse effects are nausea and vomiting caused by non-selective binding to other dopamine receptor types. The main reason for treatment discontinuation is ineffectiveness, which is the case for about two-thirds of patients stopping treatment. Thus, apomorphine SL was never approved by the FDA and has been discontinued since in the United Kingdom [69].
Related Knowledge Centers
- Aporphine
- Dopamine Agonist
- Ligand
- Morphine
- Receptor Antagonist
- Binding Selectivity
- D2-Like Receptor
- D1-Like Receptor
- 5-Ht2 Receptor
- Adrenergic Receptor