P

Parkinson’s Disease Treatment

USES

To slow or stop clinical progression of Parkinson’s disease and to improve function and quality of life in pts with Parkinson’s disease, a progressive neurodegenerative disorder.

ACTION

Normal motor function is dependent on the synthesis and release of dopamine by neurons projecting from the substantia nigra to the corpus striatum. In Parkinson’s disease, disruption of this pathway results in diminished levels of the neurotransmitter dopamine. Medication is aimed at providing improved function using the lowest effective dose.

TYPES OF MEDICATIONS FOR PARKINSON’S DISEASE DOPAMINE PRECURSOR

Levodopa/carbidopa:

Levodopa: Dopamine precursor supplementation to enhance dopaminergic neurotransmission. A small amount of levodopa crosses the blood-brain barrier and is decarboxylated to dopamine, which is then available to stimulate dopaminergic receptors.

Carbidopa: Inhibits peripheral decarboxylation of levodopa, decreasing its conversion to dopamine in peripheral tissues, which results in an increased availability of levodopa for transport across the blood-brain barrier.

COMT INHIBITORS

Entacapone, tolcapone: Reversible inhibitor of catechol-O-methyltransferase (COMT). COMT is responsible for catalyzing levodopa. In the presence of a decarboxylase inhibitor (carbidopa), COMT becomes the major metabolizing enzyme for levodopa in the brain and periphery. By inhibiting COMT, higher plasma levels of levodopa are attained, resulting in more dopaminergic stimulation in the brain and lessening the symptoms of Parkinson’s disease.

DOPAMINE RECEPTOR AGONISTS

Bromocriptine: Stimulates postsynaptic dopamine type 2 receptors in the neostriatum of the CNS.

Pramipexole: Stimulates dopamine receptors in the striatum of the CNS.

Ropinirole: Stimulates postsynaptic dopamine D2 type receptors within the caudate putamen in the brain.

MONOAMINE OXIDASE B INHIBITORS

Rasagiline, Selegiline: Increase dopaminergic activity due to irreversible inhibition of monoamine oxidase type B (MAO B). MAO B is involved in the oxidative deamination of dopamine in the brain.

MEDICATIONS FOR TREATMENT OF PARKINSON’S DISEASE

Name	Type	Availability	Dosage	Side Effects
Amantadine	Dopamine agonist	C: 100 mg Syrup: 10 mg/ml T: 100 mg	100 mg 2 times/day. May increase up to 400 mg/day in divided doses	Cognitive impairment, confusion, insomnia, hallucinations, levido reticularis
Carbidopa/levodopa (Parcopa, Rytary, Sinemet, Sinemet CR)	Dopamine precursor	OD (Parcopa): 10/100 mg, 25/100 mg, 25/250 mg Immediate-release (Sinemet): 10/100 mg, 25/100 mg, 25/250 mg Extended-release (Sinemet CR): 25/100 mg, 50/200 mg (Rytary): 23.75 mg/95 mg, 36.25 mg/145 mg, 48.75 mg/195 mg, 61.25 mg/245 mg	Parcopa: 300–1,500 mg levodopa in divided doses Sinemet: 300–1,500 mg levodopa in divided doses Sinemet CR: Initially, 400 mg/day in 2 divided doses. May increase up to 1,600 mg levodopa in divided doses Rytary: Initially, 23.75 mg/95 mg 3 times/day. May increase up to 612.5 mg/2,450 mg per day in divided doses	Anorexia, nausea, orthostatic hypotension initially; hallucinations, confusion, sleep disturbances with chronic use, constipation, dry mouth, headache, dyskinesia
Entacapone (Comtan)	COMT inhibitor	T: 200 mg	200 mg 3–4 times/day up to maximum of 8 times/day (1,600 mg)	Dyskinesias, nausea, diarrhea, urine discoloration
Pramipexole (Mirapex, Mirapex ER)	Dopamine agonist	T: 0.125 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, 1.5 mg ER: 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3 mg, 3.75 mg, 4.5 mg	T: Initially, 0.125 mg 3 times/day. May increase q5–7 days. Usual dose: 0.5–1.5 mg 3 times/day ER: Initially, 0.375 mg once daily. May increase q5–7 days by 0.75 mg/dose up to 4.5 mg once daily	Nausea, drowsiness, lower extremity edema, postural hypotension, confusion, toxic psychosis (avoid use in pts with dementia)
Rasagiline (Azilect)	MAO B inhibitors	T: 0.5 mg, 1 mg	0.5–1 mg once daily	Nausea, orthostatic hypotension
Ropinirole (Requip, Requip XL)	Dopamine agonist	T: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, 5 mg XL: 2 mg, 4 mg, 6 mg, 8 mg, 12 mg	T: Initially, 0.25 mg 3 times/day. May increase at weekly intervals to 0.5 mg 3 times/day, then 0.75 mg 3 times/day, then 1 mg 3 times/day. May then increase by 1.5 mg/day up to 9 mg/day, then by 3 mg/day up to total dose of 24 mg/day in divided doses XL: Initially, 2 mg/day for 1–2 wks, then increase by 2 mg/day at weekly intervals	Nausea, drowsiness, lower extremity edema, postural hypotension, confusion, toxic psychosis (avoid use in pts with dementia)
Rotigotine (Neupro)	Dopamine agonist	Transdermal patch: 1 mg/24 hrs, 2 mg/24 hrs, 3 mg/24 hrs, 4 mg/24 hrs, 6 mg/24 hrs, 8 mg/24 hrs	Early stage: Initially, 2 mg/24 hrs up to 6 mg/24 hrs Advanced stage: Initially, 4 mg/24 hrs up to 8 mg/24 hrs	Peripheral edema, dizziness, fatigue, application site reactions, sleep disturbances, dyskinesia, nausea, arthralgia
Selegiline (Eldepryl, Zelapar)	MAO B inhibitor	C (Eldepryl): 5 mg OD (Zelapar): 1.25 mg	C: 5 mg with breakfast and lunch OD: 1.25–2.5 mg daily in the morning	Nausea, orthostatic hypotension
Tolcapone (Tasmar)	COMT inhibitor	T: 100 mg	Initially, 100 mg 3 times/day. May increase to 200 mg 3 times/day	Dyskinesias, nausea, diarrhea, urine discoloration

C, Capsules; COMT, catechol-O-methyltransferase; ER, extended-release; I, injection; MAO B, monoamine oxidase B; OD, orally disintegrating; T, tablets; XL, extended-release.

Proton Pump Inhibitors

USES

Treatment of various gastric disorders, including gastric and duodenal ulcers, gastroesophageal reflex disease (GERD), pathologic hypersecretory conditions.

ACTION

Suppresses gastric acid secretion by specific inhibition of the hydrogen-potassium-adenosine triphosphatase (H⁺/K⁺ ATPase) enzyme system, which transports the acid at the gastric parietal cells. These agents do not have anticholinergic or histamine receptor antagonistic properties.

PROTON PUMP INHIBITORS

Name	Availability	Indications	Usual Dosage	Side Effects
Dexlansoprazole (Dexilant)	C: 30 mg, 60 mg	Erosive esophagitis, heartburn associated with nonerosive GERD	30–60 mg/day	Diarrhea, abominal pain, nausea, upper respiratory tract infection, vomiting, flatulence
Esomeprazole (Nexium)	C: 20 mg, 40 mg I: 20 mg, 40 mg	Helicobacter pylori eradication, GERD, erosive esophagitis	20–40 mg/day	Headaches, diarrhea, abdominal pain, nausea
Lansoprazole (Prevacid)	C: 15 mg, 30 mg T (ODT): 15 mg, 30 mg	Duodenal ulcer, gastric ulcer, NSAID-associated gastric ulcer, hypersecretory conditions, H. pylori eradication, GERD, erosive esophagitis	15–30 mg/day	Diarrhea, skin rash, pruritus, headaches
Omeprazole (Prilosec)	C: 10 mg, 20 mg, 40 mg	Duodenal ulcer, gastric ulcer, hypersecretory conditions, H. pylori eradication, GERD, erosive esophagitis	20–40 mg/day	Headaches, diarrhea, abdominal pain, nausea
Omeprazole and Sodium Bicarbonate (Zegerid)	P: 20 mg, 40 mg	Duodenal ulcer, benign gastric ulcer, GERD, erosive esophagitis	20–40 mg/day	Headaches, abdominal pain, diarrhea, nausea
Pantoprazole (Protonix)	T: 20 mg, 40 mg I: 40 mg	Erosive esophagitis, hypersecretory conditions	40 mg/day	Diarrhea, headaches
Rabeprazole (Aciphex)	T: 20 mg S: 5 mg, 10 mg	Duodenal ulcer, hypersecretory conditions, H. pylori eradication, GERD, erosive esophagitis	20 mg/day	Headaches

C, Capsules; GERD, gastroesophageal reflux disease; I, injection; NSAID, nonsteroidal anti-inflammatory drug; ODT, orally disintegrating tablets; P, powder for suspension; S, sprinkles; T, tablets.

Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease associated with progressive disability, systemic complications, early death, and socioeconomic costs. RA affects most joints and their surrounding tissues. RA is characterized by synovial inflammation and hyperplasia, autoantibody production (e.g., rheumatoid factor), cartilage and bone destruction, and systemic features (e.g., cardiovascular, pulmonary, psychological, skeletal disorders). The clinical hallmark of RA is polyarticular synovial inflammation of peripheral joints (typically in the hands, resulting in pain, stiffness, and some degree of irreversible joint damage; deformity; and disability).

Medications used in RA include disease-modifying antirheumatic drugs (DMARDS) and biologic agents, including tumor necrosis factor (TNF) inhibitors.

DMARDS

Name	Dosage	Side Effects/Comments
Hydroxychloroquine (Plaquenil)	Induction: 400–600 mg/day for 4–12 wks Maintenance: 200–400 mg/day	Side Effects: nausea, epigastric pain, hemolysis may occur in pts with G6PD deficiency, retinal toxicity with long-term use
Leflunomide (Arava)	Induction: 100 mg/day × 3 days Maintenance: 10–20 mg/day	Side Effects: diarrhea, respiratory tract infection, hypertension, headache, reversible alopecia, rash, myelosuppression, and/or elevated hepatic enzymes Comments: contraindicated for use during pregnancy
Methotrexate (oral) (Rheumatrex, Trexall) Methotrexate (injectable) Otrexup, Rasuvo)	Induction: 7.5–10 mg PO once/wk Maintenance: 7.5–25 mg PO once wkly Induction: 7.5 PO once wkly Maintenance: 10–25 mg IM or SQ once wkly	Side Effects: stomatitis, anorexia, nausea, vomiting, diarrhea, abdominal cramps, hepatic enzyme elevations, thrombocytopenia Comments: not recommended in pts with CrCl <30 ml/min; should not be prescribed for women who are or may become pregnant
Sulfasalazine (Azulfidine)	Induction: 3–4 g/day in divided doses Maintenance: 2 g/day in divided doses	Side Effect: headache, nausea, anorexia, rash, hemolysis may occur in pts with G6PD deficiency

BIOLOGIC AGENTS

TNF Inhibitors

Name	Dosage	Side Effects/Comments
Adalimumab (Humira)	40 mg SQ once wkly or q2wks	Side Effects: headache, skin rash, positive ANA titer, antibody development, injection site reaction (erythema, itching, pain, swelling), upper respiratory tract infection Comments: increased risk for serious infections (e.g., tuberculosis, invasive fungal infections), avoid use in pts with recent history of malignancy or pre-existing demyelinating disorders
Certolizumab (Cimzia)	Induction: 400 mg SQ at 0, 2, 4 wks Maintenance: 200 mg SQ every other week or 400 mg q4wks	Side Effects: nausea, infection, upper respiratory tract infection, skin rash Comments: see adalimumab
Etanercept (Enbrel)	25 mg SQ 2 times/wk or 50 mg SQ once/wk	Side Effects: headache, skin rash, diarrhea, injection site reactions (e.g., erythema, swelling), upper respiratory tract infection, rhinitis Comments: see adalimumab
Golimumab (Simponi, Simponi Aria)	Simponi: 50 mg SQ once monthly Simponi Aria: Induction: 2 mg/kg IV at 0 and 4 wks Maintenance: 2 mg/kg IV q8wks	Side Effects: positive ANA titer, upper respiratory tract infection (e.g., nasopharyngitis, rhinitis) Comments: see adalimumab
Infliximab (Remicade)	Induction: 3 mg/kg IV at 0, 2, and 6 wks Maintenance: 3 mg/kg IV q8wks	Side Effects: nausea, diarrhea, abdominal pain, increased ANA titer, upper respiratory tract infection, sinusitis, cough, pharyngitis Comments: see adalimumab

OTHER BIOLOGIC AGENTS

Name	Dosage	Side Effects/Comments
Abatacept (Orencia)	IV: 500 mg, 750 mg, or 1,000 mg IV at 0, 2, and 4 wks, then q4wks SQ: 125 mg SQ once/wk	Side Effects: nausea, UTIs, acute exacerbation of COPD, hypertension, headache, dizziness Comments: may increase risk of serious infections (e.g., pneumonia, pyelonephritis, cellulitis, diverticulitis)
Rituximab (Rituxan)	1,000 mg IV twice, 2 wks apart	Side Effects: hypotension, peripheral edema, abdominal pair anemia, arthralgia, infusion site reactions Comments: Pts at high risk for hepatitis B virus infection should be screened before beginning therapy
Tocilizumab (Actemra)	IV: Induction: 4 mg/kg IV q4wks Maintenance: 8 mg/kg q4 wks SQ: Induction: 162 mg SQ every other week Maintenance: 162 mg once wkly	Side Effects: hypertension, upper abdominal pain, increased ALT/AST, injection site reactions, neutropenia, dyslipidemia Comments: severe complications including GI perforation and hypersensitivity with anaphylaxis have been reported
Tofacitinib (Xeljanz)	5 mg PO bid	Side Effects: diarrhea, nasopharyngitis, upper respiratory infections, headache hypertension, increased LFT, dyslipidemia, cytopenias have been reported Comments: screening for tuberculosis recommended, increased incidence of solid cancers detected

ANA, Antinuclear antibodies; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; GI, gastrointestinal; UTI, urinary tract infection.