| 1 | Levodopa: The most effective drug to treat motor symptoms is mainly bradykinesia, but it can also be used for tremors and rigidity. | Levodopa; levodopa-carbidopa (to enhance the effectiveness of levodopa and minimize its adverse effects) | Nausea, sleepiness, dizziness, headache; others: confusion, hallucinations, delusions, agitation, psychosis; long-term (5 to 10 years) use can be associated with motor fluctuations and dyskinesia. | Risk of Parkinsonism-hyperpyrexia syndrome (PHS) on acute withdrawal; short half-life: Will require enteral administration in prolonged procedures; avoid halothane as it may sensitize the heart to catecholamines which may cause levodopa-induced arrhythmias |
| 2 | Monoamine oxidase B inhibitors (MAOBIs): It works by obstructing the activity of MAOB enzymes, which deactivate dopamine. | Selegiline; rasagiline; safinamide | Selegiline commonly causes nausea, headaches, and insomnia. Additionally, in elderly Parkinson’s patients, its use may be restricted due to the potential for confusion. | Risk of serotonin syndrome (agitation, muscle rigidity, and hyperthermia) with opioids such as meperidine (pethidine); risk of exaggerated vasoconstrictor effects in patients taking direct-acting sympathomimetics and MAOBIs |
| 3 | Dopamine agonists (ergot or non-ergot): It functions by directly activating the dopamine receptors in the brain to replicate the effects of dopamine. | Pramipexole; ropinirole; rotigotine (trans-dermal); apomorphine (SC infusion) | Nausea, sedation, leg swelling, visual hallucinations, impulse control disorders, orthostatic hypotension; apomorphine is highly emetogenic. | Risk of dopamine agonist withdrawal syndrome (DAWS) on acute withdrawal; to prevent the use of medications such as metoclopramide, butyrophenones (haloperidol, droperidol), and phenothiazines (promethazine, prochlorperazine) that have anti-dopaminergic effects, which may exacerbate Parkinson’s disease symptoms |
| 4 | Catechol-O-methyl transferase inhibitors (COMTIs): To prolong and enhance the effect of levodopa by preventing the breakdown of dopamine by COMT | Tolcapone; entacapone | Dyskinesia, hallucinations, confusion, nausea, diarrhoea, orange discoloration of the urine, and postural hypotension; tolcapone can cause deranged LFTs and potential hepatotoxicity. Hence entacapone should be used in those at risk of hepatotoxicity. | Risk of exaggerated sympathetic response when used together with drugs metabolized by COMT pathway, e.g., adrenaline, hence the need to reduce the dose when used concurrently |
| 5 | Anticholinergics: They are used to reduce symptoms of tremors in PD patients aged 70 and below who do not have significant akinesia or difficulty walking. | Trihexyphenidyl; benztropine; orphenadrine; procyclidine; biperiden | Dry mouth, blurred vision, constipation, nausea, difficulty emptying the bladder, impaired sweating, tachyarrhythmia, delirium, memory issues, hallucinations | Centrally-acting anticholinergic drugs, like atropine, may trigger central anticholinergic syndrome, which can cause confusion, drowsiness, and agitation. As a result, glycopyrrolate, a peripherally acting alternative, is a safer choice. |
| 6 | N-methyl-D-aspartate (NMDA) receptor antagonist: The antiviral drug was initially developed to prevent influenza but was found to improve mild symptoms (tremors, akinesia, rigidity) by an indirect dopamine-stimulating effect. | Amantadine | Visual hallucinations, confusion livedo reticularis (blotchy, purple-colored areas of skin found on the wrists and legs), ankle swelling | |
| 7 | Treatment for non-motor symptoms: Anti-depressants; medications for PD dementia | TCAs (amitriptyline, nortriptyline); SSRIs (citalopram, paroxetine, sertraline); SNRIs (venlafaxine, duloxetine); acetylcholinesterase inhibitors (rivastigmine, donepezil) | Risk of extrapyramidal side effects with SSRIs and SNRIs | The use of TCA anti-depressants may potentiate levodopa-induced arrhythmias.; risk of serotonin syndrome with concurrent use of MAOB and some anti-depressants; the use of acetylcholinesterase inhibitors, such as rivastigmine, donepezil, and galantamine, in Parkinson’s disease dementia patients has been linked to extended succinylcholine effects, which can last up to 50 minutes, as well as heightened resistance to non-depolarizing neuromuscular blocking drugs. |