Antiparkinsonian agents

Quick revision

Dopamine cannot be given as a medicine, so the whole class is built around getting its precursor into the brain and then defending it from the enzymes and the passage of time.

• Dopamine is useless as a treatment because it does not cross the blood-brain barrier; its precursor levodopa does, and is presumed to be converted to dopamine in the brain. (1)
• Levodopa taken orally is rapidly decarboxylated to dopamine in extracerebral tissues, so only a small portion of a given dose is transported unchanged to the central nervous system. (1)
• Carbidopa inhibits that peripheral decarboxylation, does not itself cross the blood-brain barrier, and thereby makes more levodopa available for transport to the brain. (1)
• Benserazide is the other peripheral decarboxylase inhibitor; with levodopa it forms co-beneldopa, sold as Madopar, and it blocks conversion outside the brain in the same way. (2)
• Sustained levodopa treatment brings motor complications: a wearing-off effect at the end of the dosing interval, and dyskinesias that may themselves force the dose down. (1)
• Dopamine agonists cause impulse control disorders including pathological gambling, hypersexuality, compulsive eating and compulsive shopping. (4) (13)
• Patients on dopaminergic drugs have fallen asleep without warning while operating a motor vehicle, sometimes causing accidents, which makes this a fitness-to-drive question. (4) (3)
• MAO-B inhibition blocks the catabolism of dopamine and so increases the net amount available, but selegiline and rasagiline carry long serotonergic and opioid contraindication lists. (6) (7)
• Among the COMT inhibitors only tolcapone carries a boxed warning for fatal fulminant liver failure and a defined transaminase monitoring schedule, which is why it is reserved. (10)
• Antimuscarinics such as trihexyphenidyl are licensed both for parkinsonism and for extrapyramidal disorders caused by antipsychotic medicines. (11)

Overview

Parkinson's disease is a failure of dopaminergic transmission, and every agent here addresses that failure from a different angle. The oldest and still the most effective approach is replacement, but dopamine itself cannot be used: its label-recorded ineffectiveness in Parkinson's disease is attributed to the fact that it does not cross the blood-brain barrier. Levodopa, the metabolic precursor of dopamine, does cross it and is presumably converted to dopamine within the brain, which is the entire reason the precursor rather than the transmitter is the drug. (1)

Levodopa given by itself is mostly wasted. Taken orally it is rapidly decarboxylated to dopamine in extracerebral tissues, so only a small portion reaches the central nervous system, and the dopamine generated outside the brain is what produces the vomiting. Adding an inhibitor of aromatic amino acid decarboxylase that cannot enter the brain solves both problems together: carbidopa inhibits decarboxylation of peripheral levodopa, does not cross the blood-brain barrier, does not affect levodopa metabolism within the central nervous system, and leaves more levodopa available for transport to the brain, with less nausea than levodopa alone. Benserazide performs the same job in the combination marketed as co-beneldopa. (1) (2)

Most of the rest of the class exists because levodopa's benefit becomes unstable over years. A wearing-off effect appears at the end of the dosing interval and dyskinesias emerge, so adjuncts are added to smooth the plasma curve or to act independently of it. Dopamine agonists stimulate the receptor without needing conversion; MAO-B inhibitors block the catabolism of dopamine already formed; and COMT inhibitors block the alternative methylation route, with entacapone licensed specifically for end-of-dose wearing-off. (1) (8) (6)

Two safety themes dominate teaching on this class. The first is behavioural: dopamine agonists carry impulse control disorders and episodes of sudden sleep as label warnings, not as curiosities, and UK regulators treat pathological gambling and increased libido as class effects that are generally reversible when the dose is reduced or the drug stopped. The second is that dopaminergic treatment is never withdrawn abruptly, because a symptom complex resembling neuroleptic malignant syndrome has been reported with rapid dose reduction or withdrawal of these agents. (13) (4) (1)

Classification and drug examples

Grouped by where each agent intervenes on the dopamine pathway: supplying the precursor, protecting it in the periphery, stimulating the receptor, or blocking the two enzymes that break dopamine and levodopa down. The antimuscarinics sit apart because they work on the opposing cholinergic arm rather than on dopamine at all.

Mechanism of action

One target, five ways of reaching it. The striatum is short of dopamine; levodopa supplies the precursor that can cross into the brain, a peripheral decarboxylase inhibitor protects that supply on the way, agonists bypass the synthesis step altogether, and the MAO-B and COMT inhibitors remove the two enzymes that would otherwise dispose of dopamine and levodopa. The antimuscarinics do none of this and instead damp the cholinergic side of the same circuit.

Molecular target

Striatal dopamine receptors, approached through precursor supply, direct receptor stimulation, or inhibition of the enzymes that metabolise levodopa and dopamine

Pharmacodynamic effect

Symptomatic replacement rather than disease-modifying

Effect kinetics

Benefit tracks plasma levodopa and receptor occupancy, which is why the response fluctuates as concentrations fall

1. Precursor loading across the blood-brain barrier

   Administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier. Levodopa, the metabolic precursor of dopamine, does cross it, and is presumably converted to dopamine in the brain. That single pharmacokinetic difference is why the precursor is the medicine. (1)

2. Blocking decarboxylation outside the brain

   When levodopa is administered orally it is rapidly decarboxylated to dopamine in extracerebral tissues, so only a small portion of a given dose is transported unchanged to the central nervous system. Carbidopa inhibits that peripheral decarboxylation, does not cross the blood-brain barrier, and does not affect the metabolism of levodopa within the central nervous system. Benserazide stops levodopa being changed to dopamine in the rest of the body in the same way. (1) (2)

3. Direct stimulation of the dopamine receptor

   Ropinirole is a non-ergoline dopamine agonist whose antiparkinsonian effect is related to its ability to stimulate dopamine D2 receptors within the caudate-putamen. Pramipexole is a nonergot agonist with full intrinsic activity at the D2 subfamily, binding with higher affinity to D3 than to D2 or D4 subtypes, and rotigotine delivers the same kind of stimulation continuously through the skin. (3) (4) (5)

4. Preventing the breakdown of dopamine by MAO-B

   Inhibition of monoamine oxidase type B blocks the catabolism of dopamine and so increases the net amount available. Rasagiline is a selective, irreversible MAO-B inhibitor that produces an increase in extracellular dopamine in the striatum, and selegiline acts as a selective type B inhibitor only while it is kept within its recommended dose range. (6) (7)

5. Closing the alternative COMT route

   COMT catalyses the methylation of levodopa to 3-methoxy-4-hydroxy-L-phenylalanine, better known as 3-O-methyldopa. Plasma levels of that metabolite are markedly and dose-dependently decreased by a COMT inhibitor, while levodopa levels become greater and more sustained, producing more constant dopaminergic stimulation in the brain. Tolcapone raises the relative bioavailability of levodopa roughly twofold, and opicapone raises peak and overall levodopa exposure by 43% to 44% and 62% to 94% respectively. (8) (10) (9)

6. Damping the cholinergic arm instead

   Trihexyphenidyl exerts a direct inhibitory effect upon the parasympathetic nervous system, and this antimuscarinic action is used both as an adjunct in all forms of parkinsonism and to control extrapyramidal disorders caused by central nervous system drugs. It restores nothing dopaminergic, which is why the group helps tremor more than it helps bradykinesia. (11)

Major clinical uses

Pharmacokinetics

• This page gives no dose regimens. Choosing, titrating and monitoring any of these medicines belongs to the treating clinician working from a current prescribing reference, because it depends on disease stage, age, cognition, comorbidity and everything else already prescribed.
• The COMT inhibitors have no pharmacology worth learning in isolation; what matters is the shape they give to the levodopa concentration curve and how much less levodopa is then needed. (8) (10)
• Ropinirole and rasagiline both depend on CYP1A2, so a single inhibitor of that enzyme can raise the exposure of either drug substantially. (3) (7)

Adverse effects

Common

• Nausea and vomiting: Generated by dopamine formed outside the brain, which is why the incidence of levodopa-induced nausea and vomiting is less with the carbidopa combination than with levodopa given alone. Benserazide reduces the same effects in the European combination. (1) (2)
• Somnolence and daytime sleepiness: Common across the dopaminergic agents and, at its extreme, becomes the sudden sleep episodes described in the serious column. Falling asleep during activities of daily living has been reported with levodopa preparations and with each of the agonists. (1) (3) (5)
• Orthostatic hypotension and syncope: Syncope, sometimes associated with bradycardia, was observed with ropinirole in patients with Parkinson's disease and in those treated for restless legs syndrome. Hypotension, both orthostatic and non-orthostatic, with syncope occurred in 5% of patients given opicapone. (3) (9)
• Dyskinesia: Levodopa alone, and the carbidopa combination, are both associated with dyskinesias, and their occurrence may require the dose to be reduced. Adjuncts make this worse rather than better: entacapone may cause or exacerbate pre-existing dyskinesia, and dyskinesia occurred in 20% of patients treated with opicapone. (1) (8) (9)
• Antimuscarinic effects with the anticholinergic group: Dryness of the mouth, blurring of vision, dizziness and mild nausea were reported in 30% to 50% of patients on trihexyphenidyl, together with constipation and urinary hesitancy or retention. (11)
• Diarrhoea with COMT inhibitors: Diarrhoea developed in 10% of patients on entacapone against 4% on placebo. With tolcapone it reached 16% and 18% on the two regimens studied against 8% on placebo, was regarded as severe in 3% to 4%, and typically presented six to twelve weeks after starting. (8) (10)

Serious adverse effects

• Impulse control disorders: Cases of pathological gambling, hypersexuality, compulsive eating including binge eating, and compulsive shopping have been reported with dopamine agonist therapy. UK regulators regard pathological gambling and increased libido including hypersexuality as rare class effects of dopamine agonists, generally reversible on reduction of the dose or discontinuation of treatment. Because patients may not recognise these behaviours as abnormal, labels direct prescribers to ask specifically about new or increased gambling urges, sexual urges, uncontrolled spending and compulsive eating; any change of treatment is a matter for the treating clinician. (4) (13) (3)
• Falling asleep during activities of daily living: Patients treated with pramipexole have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. With levodopa preparations, sudden onset of sleep has been reported as long as one year after treatment began. The ropinirole label states that the drug should ordinarily be discontinued if significant daytime sleepiness or episodes of falling asleep develop during activities that require active participation. (4) (1) (3)
• Fulminant hepatic failure with tolcapone: Its boxed warning reports that as of May 2005 three cases of fatal fulminant hepatic failure had been reported from more than 40,000 patient years of worldwide use, an incidence that may be ten to a hundred times higher than the background rate. The label requires that the drug not be used until the risks have been fully discussed and the patient has given written acknowledgement, and directs transaminase measurement at baseline and every two to four weeks for the first six months. (10)
• Hallucinations and psychotic-like behaviour: In three double-blind placebo-controlled trials in early Parkinson's disease, hallucinations occurred in 9% of patients receiving pramipexole against 2.6% on placebo. Postmarketing reports for rasagiline describe new or worsening mental status and behavioural changes that may be severe, including psychotic-like behaviour. A dopaminergic burden problem rather than a single-drug one, so the whole regimen is reviewed together; the decision rests with the treating clinician. (4) (7) (8)
• Neuroleptic malignant syndrome on withdrawal: Sporadic cases of a symptom complex resembling neuroleptic malignant syndrome have been reported with dose reduction or withdrawal of levodopa preparations. Four such cases were reported in tolcapone trials on abrupt withdrawal or dose lowering, and the same complex has followed rapid reduction of entacapone. This is the reason nothing in the class is stopped abruptly; patients are observed carefully when a dopaminergic dose is reduced, especially where a neuroleptic is also being given. (1) (10) (8)
• Dopamine agonist withdrawal syndrome: Insomnia, apathy, anxiety, depression, fatigue, sweating and pain have been reported during taper or after discontinuation of dopamine agonists including ropinirole. It is distinct from the neuroleptic malignant picture and does not respond to levodopa. Relevant whenever an agonist is being reduced, including reductions made because of impulse control problems. (3)
• Rhabdomyolysis with entacapone: Cases of severe rhabdomyolysis have been reported after the approval of entacapone, an uncommon but recognised postmarketing signal for this adjunct. Considered where an unexplained rise in creatine kinase or muscle pain appears in a patient on the drug. (8)

Drug-specific effects

• Rotigotine: Application site reactions, which occurred more often than with placebo in the dose-response studies; weight gain frequently associated with peripheral oedema, suggesting the patch may cause fluid retention in some patients; and sodium metabisulfite content, which can cause allergic-type reactions including anaphylactic symptoms in susceptible people. (5)
• Pramipexole: Augmentation in restless legs syndrome, meaning earlier onset of symptoms in the evening or afternoon, an increase in their intensity, and spread to other extremities. (4)
• Selegiline: Amphetamine and methamphetamine appear among its principal metabolites and have pharmacological actions of their own, which contributes to insomnia and to exacerbation of levodopa-associated effects. (6)
• Tolcapone and entacapone: Both discolour the urine; with entacapone the label describes a brownish-orange change that is not clinically relevant, and urine discoloration was reported by 7% of patients on the higher tolcapone regimen. (8) (10)
• Trihexyphenidyl: Incipient glaucoma may be precipitated, so gonioscope evaluation and close monitoring of intraocular pressures at regular periodic intervals are directed. Delusions, hallucinations, mental confusion, agitation and disturbed behaviour are described, and sensitivity rises after the age of sixty. (11)
• Opicapone: Impulse control disorders occurred in 1% and hallucinations in 3% of treated patients, showing that the behavioural liabilities of dopaminergic treatment follow the adjuncts as well as the agonists. (9)

Contraindications, precautions and interactions

Contraindications

• Nonselective monoamine oxidase inhibitors are contraindicated for use with carbidopa and levodopa, and the combination is also contraindicated in narrow-angle glaucoma and in known hypersensitivity to any component. (1)
• Rasagiline is contraindicated with meperidine, tramadol, methadone and propoxyphene because of the risk of serotonin syndrome, with dextromethorphan because of the risk of psychosis or bizarre behaviour, and with other MAO inhibitors because of the risk of non-selective MAO inhibition and hypertensive crisis. (7)
• Selegiline is contraindicated for use with meperidine, and its label notes that this contraindication is often extended to other opioids. (6)
• Concomitant use of opicapone with non-selective MAO inhibitors is contraindicated, although selective MAO-B inhibitors can be used alongside it. (9)

Precautions

• Tolcapone is not a routine adjunct. Its label restricts it to patients with symptom fluctuations who are not responding satisfactorily to, or are not appropriate candidates for, other adjunctive therapies, and directs withdrawal if no substantial clinical benefit appears within three weeks. (10)
• Driving and operating machinery is a live question for every patient on a dopaminergic drug, because sudden sleep has occurred without prior warning of sleepiness and, with levodopa preparations, as long as a year after treatment started. (1) (4)
• Dopaminergic treatment is not stopped or reduced abruptly, because a neuroleptic malignant syndrome-like complex has followed rapid dose reduction or withdrawal, and patients should be observed carefully when a levodopa dose is reduced, especially if a neuroleptic is being given. (1) (10)
• Antimuscarinics are a poor choice in older patients, in whom sensitivity to this drug type increases markedly after the age of sixty and confusion, delusions and hallucinations are described. (11)
• Antiparkinson agents do not relieve tardive dyskinesia and in some instances may aggravate it, which separates that movement disorder sharply from drug-induced parkinsonism. (11)
• Foods containing a very large amount of tyramine are avoided on rasagiline because of the potential for large increases in blood pressure, and selegiline's label explains the underlying mechanism: gut and liver MAO, mainly type A, normally protects against exogenous amines in what is called the cheese reaction. (7) (6)

Drug interactions

• Selective serotonin reuptake inhibitors and tricyclic antidepressants: Serious and sometimes fatal reactions have been reported when selegiline is combined with fluoxetine, sertraline or paroxetine, and its label directs that at least fourteen days elapse between stopping selegiline and starting a tricyclic or an SSRI. (6)
• Ciprofloxacin and other CYP1A2 inhibitors: Rasagiline plasma concentrations may increase up to twofold with ciprofloxacin, because CYP1A2 is the major isoenzyme involved in its metabolism; ropinirole depends on the same enzyme. (7) (3)
• Paroxetine and procyclidine: Daily paroxetine raised steady-state procyclidine exposure appreciably, with the trough concentration rising by 67%, and the paroxetine label directs that the procyclidine dose be reduced if anticholinergic effects are seen. (12)
• Pyridoxine (vitamin B6): Pyridoxine may reverse the effects of levodopa by increasing the rate of aromatic amino acid decarboxylation. Carbidopa inhibits this action of pyridoxine, which is why the interaction matters far less with the modern combination products. (1)
• Antipsychotic medicines: Extrapyramidal disorders caused by dibenzoxazepines, phenothiazines, thioxanthenes and butyrophenones are themselves an indication for an antimuscarinic, and the levodopa label separately warns that patients receiving a neuroleptic need particular care when a dopaminergic dose is reduced. (11) (1)
• Levodopa combined with an adjunct: Adding an adjunct usually means revisiting the levodopa itself: most patients in the entacapone studies required a decrease in daily levodopa dose, and selegiline's label anticipates the same need after it is started. (8) (6)

Comparison tables

High-yield exam pearls

• Dopamine is ineffective in Parkinson's disease apparently because it does not cross the blood-brain barrier, whereas its precursor levodopa does. (1) It is the single most asked question about this class, and it explains why a precursor rather than the transmitter itself is the drug.
• Carbidopa works precisely because it cannot get into the brain; it inhibits peripheral decarboxylation without affecting levodopa metabolism within the central nervous system. (1) Candidates routinely invert this and describe carbidopa as a central booster, which reverses the whole logic of the combination.
• Entacapone has no antiparkinsonian effect of its own, and most patients in its studies needed their daily levodopa dose reduced once it was added. (8) It fixes the idea that a COMT inhibitor is a pharmacokinetic modifier of levodopa rather than a treatment in its own right.
• Selegiline has no demonstrated benefit in controlled studies in the absence of concurrent levodopa, and its indication is limited to patients whose levodopa response has deteriorated. (6) The licensed wording is narrower than most students assume, and the restriction is examinable in its own right.
• Pramipexole binds with higher affinity to D3 than to D2 or D4, while ropinirole's effect is attributed to stimulation of D2 receptors within the caudate-putamen. (4) (3) Receptor detail is the usual way agonists are distinguished in written papers, and both statements come straight from the labels.
• Tolcapone alone among the COMT inhibitors carries a boxed warning for fatal fulminant liver failure, with three deaths reported from more than 40,000 patient years as of May 2005. (10) (8) (9) The contrast with entacapone and opicapone, neither of which carries such a warning, is the point of the comparison.
• Impulse control problems on dopamine agonists are generally reversible upon reduction of the dose or discontinuation of treatment. (13) Reversibility is what makes asking the question worthwhile, and it is the detail candidates most often omit.
• Pyridoxine can reverse the effects of levodopa by increasing aromatic amino acid decarboxylation, and carbidopa inhibits that action of pyridoxine. (1) A classic historical interaction that also tests whether the peripheral decarboxylation story has really been understood.

Common exam traps

• Trap: Suggesting that dopamine could be given directly if only the dose were high enough. Actually: No dose helps, because the barrier is anatomical rather than one of quantity; dopamine does not cross into the brain, which is why the precursor is used instead. (1)
• Trap: Describing carbidopa as an agent that increases levodopa's effect inside the brain. Actually: It acts only outside the brain. It does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system; the central gain is indirect, through more levodopa surviving the journey. (1)
• Trap: Treating all three COMT inhibitors as interchangeable. Actually: Only tolcapone carries a boxed warning for acute fulminant liver failure and a scheduled transaminase programme, which is exactly why entacapone and opicapone are used freely and it is not. (10) (9)
• Trap: Recording impulse control disorders as an unusual idiosyncrasy rather than a labelled warning. Actually: Pathological gambling, hypersexuality, compulsive eating and compulsive shopping appear in the agonist labels, and UK regulators advise that patients are warned about them before treatment starts. (4) (13)
• Trap: Stopping a dopaminergic medicine suddenly when a patient is admitted, is nil by mouth, or develops a side effect. Actually: A symptom complex resembling neuroleptic malignant syndrome has followed dose reduction or withdrawal of these agents, so any reduction is made deliberately and under observation. (1) (10)
• Trap: Reaching for an antimuscarinic when an antipsychotic-treated patient develops abnormal movements. Actually: It depends entirely on which movement disorder it is. Antimuscarinics are indicated for drug-induced extrapyramidal disorders, but antiparkinson agents do not relieve tardive dyskinesia and may aggravate it. (11)

Self-test questions

Answers are hidden until you open them. These questions are written from this page's cited content and are for study only — they are not clinical guidance.

1. Why is levodopa given rather than dopamine itself in Parkinson's disease?

   • Dopamine does not cross the blood-brain barrier, whereas levodopa does
   • Dopamine is destroyed by gastric acid, whereas levodopa is not
   • Dopamine has no affinity for striatal dopamine receptors
   • Levodopa is a more potent agonist at the D3 receptor
   Show answer

   Answer: Dopamine does not cross the blood-brain barrier, whereas levodopa does

   The label states that administration of dopamine is ineffective in the treatment of Parkinson's disease apparently because it does not cross the blood-brain barrier, while levodopa, the metabolic precursor of dopamine, does cross it and is presumably converted to dopamine in the brain. (1)

2. What is the pharmacological reason for combining levodopa with carbidopa?

   • Carbidopa inhibits decarboxylation of levodopa in the periphery and does not itself enter the brain
   • Carbidopa inhibits catechol-O-methyltransferase in the brain
   • Carbidopa is a dopamine agonist that supplements the levodopa effect
   • Carbidopa slows gastric emptying so that levodopa is absorbed more evenly
   Show answer

   Answer: Carbidopa inhibits decarboxylation of levodopa in the periphery and does not itself enter the brain

   Carbidopa inhibits decarboxylation of peripheral levodopa, does not cross the blood-brain barrier and does not affect the metabolism of levodopa within the central nervous system, so more levodopa is available for transport to the brain and nausea and vomiting are less frequent than with levodopa alone. (1)

3. A patient on a dopamine agonist for Parkinson's disease has begun gambling heavily and spending money uncontrollably. How should this be understood?

   • A recognised class effect of dopamine agonists that is generally reversible on dose reduction or withdrawal
   • An unrelated psychiatric illness with no bearing on the medicines
   • An early sign of levodopa-induced dyskinesia
   • A withdrawal phenomenon seen only when an agonist is being tapered
   Show answer

   Answer: A recognised class effect of dopamine agonists that is generally reversible on dose reduction or withdrawal

   Pathological gambling, hypersexuality, compulsive eating and compulsive shopping have been reported with dopamine agonist therapy, and UK regulators describe pathological gambling and increased libido as rare class effects that are generally reversible upon reduction of the dose or discontinuation of treatment. (4) (13)

4. Which COMT inhibitor carries a boxed warning for potentially fatal acute fulminant liver failure?

   • Tolcapone
   • Entacapone
   • Opicapone
   • Carbidopa
   Show answer

   Answer: Tolcapone

   The tolcapone label carries a boxed warning for potentially fatal acute fulminant liver failure and directs transaminase measurement at baseline and every two to four weeks for the first six months of therapy; entacapone and opicapone carry no equivalent warning. (10) (9)

5. Which statement about entacapone is correct?

   • It has no antiparkinsonian effect of its own and must be given with levodopa
   • It is effective as monotherapy in early Parkinson's disease
   • It requires transaminase monitoring every two weeks for six months
   • It acts by irreversibly inhibiting monoamine oxidase type B
   Show answer

   Answer: It has no antiparkinsonian effect of its own and must be given with levodopa

   The label states that entacapone should always be administered in association with levodopa and carbidopa and that entacapone has no antiparkinsonian effect of its own; it is licensed for end-of-dose wearing-off rather than as a primary treatment. (8)

6. A patient stabilised on rasagiline needs an antibiotic. Which agent most warrants caution because of an interaction with rasagiline?

   • Ciprofloxacin
   • Amoxicillin
   • Nitrofurantoin
   • Doxycycline
   Show answer

   Answer: Ciprofloxacin

   CYP1A2 is the major isoenzyme involved in rasagiline metabolism, and the label reports that rasagiline plasma concentrations may increase up to twofold when ciprofloxacin is given with it. (7)

7. An older patient on an antipsychotic develops rigidity and a resting tremor. Which agent is licensed for this drug-induced problem?

   • An antimuscarinic such as trihexyphenidyl
   • A COMT inhibitor such as opicapone
   • An MAO-B inhibitor such as rasagiline
   • A transdermal dopamine agonist such as rotigotine
   Show answer

   Answer: An antimuscarinic such as trihexyphenidyl

   Trihexyphenidyl is indicated for the control of extrapyramidal disorders caused by central nervous system drugs such as the dibenzoxazepines, phenothiazines, thioxanthenes and butyrophenones, although sensitivity to this class of drug increases after the age of sixty. (11)

8. Which of these is the correct description of selegiline's licensed place in treatment?

   • An adjunct for patients on levodopa with carbidopa whose response has deteriorated, with no evidence of benefit without levodopa
   • First-line monotherapy for newly diagnosed Parkinson's disease
   • A treatment for tardive dyskinesia caused by antipsychotic drugs
   • A peripheral decarboxylase inhibitor given with levodopa
   Show answer

   Answer: An adjunct for patients on levodopa with carbidopa whose response has deteriorated, with no evidence of benefit without levodopa

   Selegiline is indicated as an adjunct in the management of parkinsonian patients being treated with levodopa and carbidopa who exhibit deterioration in the quality of their response, and its label states there is no evidence from controlled studies of any beneficial effect without concurrent levodopa therapy. (6)

Frequently asked questions

References

1. CARBIDOPA AND LEVODOPA tablet — prescribing information DailyMed, U.S. National Library of Medicine
2. Common questions about co-beneldopa (levodopa with benserazide) National Health Service (NHS.UK)
3. ROPINIROLE tablet, film coated — prescribing information DailyMed, U.S. National Library of Medicine
4. MIRAPEX (pramipexole dihydrochloride) tablet — prescribing information DailyMed, U.S. National Library of Medicine
5. NEUPRO (rotigotine transdermal system) — prescribing information DailyMed, U.S. National Library of Medicine
6. SELEGILINE HYDROCHLORIDE capsule — prescribing information DailyMed, U.S. National Library of Medicine
7. AZILECT (rasagiline mesylate) tablet — prescribing information DailyMed, U.S. National Library of Medicine
8. COMTAN (entacapone) tablet, film coated — prescribing information DailyMed, U.S. National Library of Medicine
9. ONGENTYS (opicapone) capsule — prescribing information DailyMed, U.S. National Library of Medicine
10. TASMAR (tolcapone) tablet, film coated — prescribing information with boxed warning DailyMed, U.S. National Library of Medicine
11. TRIHEXYPHENIDYL HYDROCHLORIDE tablet — prescribing information DailyMed, U.S. National Library of Medicine
12. PAROXETINE hydrochloride tablet — prescribing information (procyclidine interaction) DailyMed, U.S. National Library of Medicine
13. Dopamine agonists: pathological gambling, increased libido, and hypersexuality Medicines and Healthcare products Regulatory Agency (GOV.UK Drug Safety Update), 2007

Related drug classes

• Typical antipsychotics
• Atypical antipsychotics
• Dementia agents

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