Persistent RLS

• Moderate to severe discomfort
• Sx occur at least 2 x per week
• Requires daily tx

RLS - Treatment

-non pharm measures for mild sx

engage in alertness activities

avoid caffeine, alcohol, nicotine,

try massage, hot baths, exercise

manage drug causes

pharm choices for intermitent RLS

-iron replacement therapy if ferritin levels <75mcg/l

-consider intermittent use of levodopa or benzos or low potency opioids

treatment for chronic RLS

note -if first drug not effective, switch to another in same class and if that fails switch to another class

-iron replacement therapy if ferritin levels <75mcg/l

-consider daily use of Nonergoline dopamine agonists e.g pramipexole, ropinole, or transdermal rotigotine(consider pt factors) or GABA derivative (pregabalin, gabapentin)

-

what do u do if lack of effect or drug is not tolerated?

-treat as refractory RLS

Refractory RLS- treatment

-unresponsive to monotherapy with 1st line-line agents for chronic persistent RLS

recheck serum ferritin -restart iron replacement therapy if ferritin levels <75mcg/l-if poor absorption consider IV iron

-consider and correct other possible exacerbating factors i.e changes in medications, lifestyle or other causes of sleep disturbance

-consider combination therapy with agents from different classes:- ie dopamine agonists, GABA derivatives, benzos, low or high potency opioids

in severe refractory RLS resistant to other trtments- what do u do?

- consider monotherapy with high potency opioids (oxycodone, hydrocodone or methadone)

WHAT IS PARKINSON’S DISEASE?

Progressive
• Neurodegenerative
• Effect on the extrapyramdial motor system

DIAGNOSIS of PD

Clinical diagnosis
– No definitive diagnostic test
– History
– Clinical signs and symptoms

PD Hallmark Symptoms

-bradykinesia(masked face, reduced arm swing)

-rest tremor-early -asymmetrical pill rolling, increased

-gait disturbance -shuffling gait, stooped posture

-rigidity -cogwheel or lead-pipe rigidity on clinical exam

what are the hidden symptoms of PD

-constipation

-soft speech

-panic attacks

-loss of smell

-hypontension

-impulse control disorder and delusional disorder

-sleep disturbances

-bladder disfunction

-anxiety

-hallucinations

-sweating

-dementia

-erectile difficulties

DIFFERENTIAL DIAGNOSIS for PD

-Multi-System Atrophy
• Progressive Supranuclear Palsy
• Corticbasalar degeneration
• Lewy Body Dementia
• Wilson’s Disease
• Drug-related Parkinsonism

Drugs Causing Parkinsonism

Antipsychotics
• Conventional agents - higher potency agents have greater risk (e.g. haloperidol) but
also seen with moderate to low potency agents related to dose
• Atypicals
• Those with higher potency (e.g. risperidone)
• Can also be observed with other agents at higher doses

Antiemetics
• Metoclopramide versus domperidone (crosses BBB vs not expected to cross BBB)

whic drugs have a low risk of causing PD

SSRIs – low risk

why does metoclopramide not cause PD

crosses BBB

How Does Drug-Induced Parkinsonism Differ from Parkinson’s Disease

• Tends to be symmetrical versus asymmetrical
• Less likely associated with tremor
• Amiodarone, lithium, levetiracetam & valproate generally cause tremor without other
symptoms
• Tends to remain static and does not progress
• Poor response to levodopa compared to idiopathic PD
• Improvement in symptoms with withdrawal of offending agent

Treatment Goals

A. Cure disease
• No cure at present
B. Slow disease progression
• No evidence for Vitamin E, Coenzyme Q , dopamine agonists or MAOIs for neuroprotection
• Early use of CR Sinemet does not ↓ motor complications
C. Reduce severity/frequency of symptoms
• Present treatments

Early use of ... does not ↓ motor complications

CR Sinemet

Non-Pharmacologic Interventions

• Physical therapy
• Speech therapy
• Occupational therapy
• Counseling/education
• Fall precautions

When to Initiate PD Drug Therapy?

• When functional impairment is present
• Not necessarily at time of diagnosis
• Ability to carry out activities of daily living in home, social and/or
occupational setting is impaired

Approach to Drug Therapy

-Balance b/w therapeutic &
adverse effects becomes
more difficult with disease
progression

Initial treatment depends on:
• Severity of sx
• Functional decline
• Cost
• Patient specific factors – including preference
• Treatment evolves as disease progresses
• Managing side effects

Initial Therapy

what to do when no mild impairment for some one <50yrs and willing to accept 50% risk of impulse control disorder

use a dopamine agonist stimulate the parts of the brain influenced by dopamine-less likely to cause dyskenesia

While levodopa is converted in the brain into dopamine, ......mimic the effects of dopamine without having to be converted.

dopamine agonists

consider age and risk of impulse disorders

-pramipixole(mirapex)

-ropinirole

-apomorphine

-rotigotine-neupro

....... are involuntary, erratic, writhing movements of the face, arms, legs or trunk. They are often fluid and dance-like, but they may also cause rapid jerking or slow and extended muscle spasms. They are not a symptom of Parkinson's disease (PD) itself. Rather, they are a complication from some Parkinson's medications.

Dyskinesias

Common Side Effects of Dopamine Agonist

• Excessive daytime sleepiness or sudden sleep attacks
• Confusion or visual hallucinations
• Low blood pressure or lightheadedness
• Leg swelling and discoloration
• Dyskinesia
• Compulsive behaviors (such as uncontrolled shopping, gambling, eating, and sexual urges)

what to do when no mild impairment for some one <50yrs but not willing to accept 50% risk of impulse control disorder

-use levodopa-there are some levodopa associated complications.

what to do when someone is using dopamine agonists but there is a lack of efficacy or unacceptable side effects?

use levodopa-

what do you give when there is mild functional impairment

consider MAO-I-B

-rasagiline

-selegiline

which MAO-I-B is not indicated in early PD disease?

safinamide

does levodopa CR delay motor complication

no

which drug shud not be considered according to canadian PD guide line

-amantadine

-anticholinergics

Levodopa

Gold standard treatment
• Monotherapy or combination therapy
• Early or late disease
• Precursor drug converted to dopamine in CNS & periphery
• Therapeutic effect & adverse effects
• Dopa Decarboxylase Inhibitors coadministered

Dopa Decarboxylase Inhibitors

-are competitive inhibitors of aromatic amino acid decarboxylase (AAAD) that do not penetrate brain. They have become a mainstay for anti-Parkinsonian therapy with levodopa.

Carbidopa
Benserazide

Enhances distribution to brain – enhances treatment of motor sx’s
- ↓ nausea – vomiting - ↑ DDC dose if motor sx’s controlled but N/V

Dopa Decarboxylase Inhibitors

what do u do if the motor sx are controlled but N/V- while using Dopa Decarboxylase Inhibitors?

↑ DDC dose if motor sx’s controlled but N/V

when to initiate levodopa

Depends on severity of symptoms
• Delay levodopa= delay motor complications
• Improving motor disability vs. limiting motor complications
• Previously thought young patients (< 60-70 yrs) may delay levodopa with
other medications until symptoms interfere with daily activities
BUT
This is now changing

Protein and levodopa

• Amino acids from protein can compete for absorption in gut and at BBB
• Should not reduce daily protein intake
• May be able to overcome with increase in levodopa dose

what is Effect of food on levodopa

• May delay or vary absorption
• If patient complains of delayed onset or variable effectiveness → administer 1 hr before or after meal

what is the impact of Iron supplements on levodopa

• Iron supplements can ↓ absorption
• Consider supplements, multivitamins
• Separate administration

Vitamin B6 can reverse effects of levodopa but.......this effect
• generally not clinically important

DCC inhibits

levodopa May precipitate B12 deficiency-what do u do in this case?

• Supplement with Vitamin B12

Levodopa – Drug Interactions

1.Antihypertensives
• Contribute to orthostatic hypotension – consider modification of
antihypertensive therapy if symptomatic
2• Non-selective MAOIs
• Hypertensive crisis
3• Dopamine antagonists or depleters
4• Iron

Levodopa Dosing

Initial dose - depends on experience of prescriber and patient specific
factors
• 100/25 mg 1-3 x daily
• ↑ by 100/25 mg every 3-4 days
• Maximum daily dose is pt dependent
• Usually does not exceed 2000 mg/day

daily dose of levodopa

Usually does not exceed 2000 mg/day

why do we give levodopa CR at night?

Because CR formulation has unpredictable absorption generally
reserved for night-time doses
• IR formulation 30 minute onset
• CR formulation 1-3 hour onset

Levodopa – Motor Complications

Dyskinesia
• Wearing off
• On-off phenomenon
• Unpredictable fluctuations in mobility
• Unrelated to timing of doses
• ↑ over time - 3-5 years
• Ability to regulate dopamine levels declines

Levodopa – Mechanism of Motor
Fluctuations

• Progressive loss of dopaminergic neurons=loss of ability to regulate and store striatal dopamine
• Response becomes dependent on plasma levels
• Dopamine’s short t1/2 (1.5-2 hours)
• Dopamine receptors are exposed to high and low concentration of dopamine
• With disease progression striatal dopamine levels depend on peripheral
concentrations

Wearing Off Syndrome

• Return of symptoms before next dose
• ↑shortened duration of benefit from dopamine dose
• Related to timing of doses
• Loss of neuronal storage capacity for dopamine

Dyskinesia

• Common problem - 30 to 80% of patients
• involuntary movements involving the face, neck, trunk and upper
extremities
• Peak dose
• Associated with peak dopamine concentrations
• Diphasic
• Dyskinesias before and after therapeutic concentrations of dopamine are
achieved

Managing Motor Complications

Best evidence with entacapone & MAOI-B agents(Rasagiline or selgiline)
• Consider availability of MAOI-B agents

Managing Motor Complications

when predominant issue is dyskinesia-for mild or no wearing

-add amantadine or decrease levodopa

-discontinue anticholinergic

-discontinue MAO-B inhibitor

Managing Motor Complications

when predominant issue is moderate dyskinesia

-add amantadine

or increase frequency but smaller doses of levodopa

or -decrease levodopa and add dopamine agonist

if the above cause side effects or is inneffective-then consider surgical or intrajejunal levodopa/carbidopa infusion

Managing Motor Complications

what to do when predominant issue is end of dose "wearing off"-mild or no dyskinesia

-increase freq of levo

or add antacapone

or add dopamine agonist

or add nasagiline or safinamide(consider availaibility)

or change to slow release levodopa

Managing Motor Complications

what to do when predominant issue is end of dose "wearing off"-but in the case of moderate dyskinesia

-add amantadine

or increase frequency but smaller doses of levodopa

or -decrease levodopa and add dopamine agonist

Medical Cannabis in PD – Is there a role in managing dykinesia

• Nabilone has limited data in refractory dyskinesia
• 7 patients
• 0.03 mg/kg (no upper dosing limit mentioned)
• Short-term data only
• No long-term adverse event data
• Off-label indication

Medical Cannabis in PD – Is there a role in
managing dykinesia
• Nabilone has limited data in refractory dyskinesia
• 7 patients
• 0.03 mg/kg (no upper dosing limit mentioned)
• Short-term data only
• No long-term adverse event data
• Off-label indication

• Adverse effects
• CNS effects
• Dysphoria
• Somnolence
• Hallucinations/para
noia
• Exacerbate autonomic
instability
• Orthostatic hypotension

Duo-Dopa (Carbidopa/Levodopa) Intestinal
Gel

NS program in place - ~ $60,000 per year

Indicated for severe, refractory motor complications – including dyskinesia
• Direct administration via PEG-J tube
• Requires specialized team
• Extensive patient education

Duo-Dopa (Carbidopa/Levodopa) Intestinal Gel Starting dose

1:1 ratio from oral tablet formulation
• Morning bolus dose (usually 100-200 mg levodopa)
• Maximum bolus is 300 mg
• Continuous maintenance dose (usually 40-120 mg/hr x maximum 16 hr)
• Adjust by 2 mg/hr

Duo-Dopa (Carbidopa/Levodopa) Intestinal Gel Maximum bolus is ....

300 mg

Dopamine Agonists

• Simulate dopamine at postsynaptic dopamine receptors
• Do not require conversion to active form
• Longer t1/2- provide more continuous stimulation of dopamine
receptors
• Less likely to cause motor fluctuations

Dopamine Agonists

• Bromocriptine
• Ergot based – generally not used
• Pramipexole
• Renal dosing
• Ropinirole
• CYP450 metabolism- CYP 1A2 (e.g. ciprofloxacin)
• Rotigotine
• Patch
• Apomorphine
• Discontinued by manufacture

Dopamine Agonists – Adverse Effects

Orthostatic hypotension
• α antagonism
• Consider pharmacodynamic drug
interactions
• Avoid apomorpine with 5HT3
antagonists (e.g. ondansetron)
• Severe hypotension
• Edema
• Constipation
• Hallucinations
• Confusion
• Somnolence – sleep attacks
• Implications for driving
• Compulsive disinhibitory
behavior
• Gambling, shopping,
hypersexuality

COMT Inhibitors

• Entacapone (Comtan®)
• Tolcapone - removed from market (hepatotoxic)
• Opicapone – available in Europe & US but not yet on Canadian market

↓ peripheral metabolism of levododa → ↑ CNS concentrations

- Only beneficial in combination with levodopa

COMT Inhibitors – Adverse Effects

-changes urine color to -orange-brown colour

Potentiate side effects of levopdopa
• dyskinesia, nausea-vomiting, orthostatic hypotension
• Consider ↓ levodopa dose 10-20% if start entacapone
• Entacapone
• Urine discoloration – orange-brown colour

Consider ↓ levodopa dose 10-20% if u start .....

entacapone

COMT Inhibitors – Dosing

• Dosing
• 200 mg tablets - 200mg TID-QID, max 1.6 g/day
• Available in combination with levodopa (Stalevo®) - dose of levodopa varies

COMT Inhibitors-Counseling tips

• Take/administer at the SAME TIME as levodopa
• Take with EACH levodopa dose
• Do not break/crush tablets

MAOI-B Selective Inhibitors

Selectively & irreversibly inhibit MAO-B metabolism of dopamine
• Selegiline, rasagiline
• Rasagiline not covered by NS Pharmacare

what MAO-B is a selective & reversible inhibitor-not indicated in early disease.

• Safinamide
• Not covered by NS Pharmacare
• Indicated only in late disease

MAOI-B Selective Inhibitors- Place in therapy

Early disease as monotherapy – manage mild symptoms
• Selegiline & rasagiline only
• Combination with levodopa in late disease
-Selegiline, rasagiline and safinamide

Selegiline

•First generation
• Amphetamine metabolites-insomnia, agitation
-Zelaplar- transbuccal tablet available in U.S. with less amphetamine metabolites
• Side effects- nausea, dizziness, orthostatic hypotension, rash, dyskinesia
• Initial dose- 2.5 (with levodopa) -5 (as monotherapy) mg daily
- ↑ gradually to 5 mg twice daily – maximum dose
• Available as 5 mg tablets

Rasagiline

• Second generation
• Side effects- headache, arthralgias, dyspepsia, depression, orthostatic
hypotension, chest pain, dyskinesia (when used with levodopa)
• Initial dose- 0.5 (with levodopa) to 1 mg (monotherapy) daily
• Available as 0.5 and 1 mg tablets
• CYP 1A2 inhibitors (e.g. ciprofloxacin)
• Not covered in NS

Safinamide

• Metabolism primarily non-CYP P450
• Pharmacodynamic interactions similar to other MAOI-Bs
• Side effects similar to other MAOI-Bs
• Indicated in late disease only
• “off” periods
• Start at 50 mg daily & increase to 100 mg at 2 weeks if partial response & tolerated
• Not covered in NS

MAOI-B Agents – Potential Drug Interactions

1.Serotonin syndrome – use with caution if combined with:
• SSRIs, SNRIs, TCAs, MAOIs
• Meperidine – avoid
• Other opioids can be used
• Tramadol
• Cyclobenzaprine
• Dextromethorphan – cough and cold preparations
• St. John’s Wort
• Chlorpheniramine & brompheniramine
2• Severe hypertension – hypertensive crisis
• Alpha-agonists - cough and cold preparations

how do we treat depression in PD patients?

• Meperidine – avoid
• Other opioids can be used
• Tramadol
• Cyclobenzaprine
• Dextromethorphan – cough and cold preparations
• St. John’s Wort
• Chlorpheniramine & brompheniramine

Serotonin Syndrome

• Toxicity caused by excessive
serotonin levels that result
from a drug overdose or a
drug interaction

What to Do?

AVOID: Group A + Group A

Group A

Non-selective & irreversible
MAOi A & B
• Isocarboxazide
• Isoniazid
• Phenylzine
• Trancyclopromine

AVOID: Group A + Group B ??

Group B

Antidepressants
• SSRIs
• SNRIs
• TCAs – imipramine &
cloimpramine

CAUTION: > 2 Group B drugs
especially if ONE used at a high
dose

Non-selective & reversible
MAOi A&B
• Linezolid

Opioids-Group B
• Tramadol
• Meperidine
• Methadone
• Fentanyl

MONITOR:

If 2nd Group B drug
added to Group B drug, start low,
go slow & monitor symptoms x
24-48 hours after every change

MONITOR: If 2nd Group B drug
added to Group B drug, start low,
go slow & monitor symptoms x
24-48 hours after every change

Group B

Antidepressants
• SSRIs
• SNRIs
• TCAs – imipramine &
cloimpramine

Opioids
• Tramadol
• Meperidine
• Methadone
• Fentanyl

Cough, Cold & Allergy
• Dextromethorphan
• Chlorphenriamine
• Brompheniramine

NHPs
• St. John’s Wort
• L-tryptophan

serotonin syndrome-What the Evidence Says

Meta-analysis
• 8 studies overall
• Retrospective cohort – 1504 patients – no serotonin syndrome
• Parkinson’s study group – 4568 patients – 11 cases of probable serotonin
syndrome with selegiline and antidepressants (including SSRIs)
• Conclusion
• Concomitant use of SSRIs and MAO-Bs is generally well tolerated
• Selegiline and rasagiline doses within therapeutic range
• Lower end of therapeutic doses of SSRI
• Consider use of multiple agents with serotoninergic activity
• Monitoring parameters for serotonin syndrome

• Concomitant use of SSRIs and MAO-Bs is generally well tolerated
• .............doses within therapeutic range
• Lower end of therapeutic doses of SSRI
• Consider use of multiple agents with serotoninergic activity
• Monitoring parameters for serotonin syndrome

Selegiline and rasagiline

how do u assess patient for serotonin syndrome

sx start within hours to 1 day of increasing the dose or adding another drug

-assess the drugs(all)-most cases involve 2 drugs that increase serotonin in different ways:rx drugs, OTC and natural drugs, illicit drugs

-rule out other things-serotonin can look like other things: diagnosis requires accurate drug history.

MILD sx of serotonin syndrome :

nervousness

insomnia

nausea/diarrhea

tremor

big ppils

68 year old female with 6 month history of PD presents to the
pharmacy with prescriptions for:
• Selegiline 5 mg BID (refill – taking x 3 months)
• Citalopram 10 mg once daily (new prescription for depression)
Drug interaction between the 2 agents pops up on the pharmacy
software.
What factors does the pharmacist need to consider in determining if
both prescriptions should be filled?

-age

-duration of therapy

-frequency and dose

-sx

-type interaction -absolute of relative??

Amantadine-not the drug of choice

Place in therapy

• Monotherapy in early disease for mild sxs (~1-2 yrs) – not drug of first choice
• Combination with levodopa in late disease for dyskinesia

Amantadine-not the drug of choice -dosing??- adjust dose for renal impairment

• 100 mg capsules or 100mg/10 ml syrup
• 100 mg daily (if other PD drugs) or twice daily
• Maximum dose – 400 mg daily
• Adjust dose for renal impairment

Amantadine-

not the drug of choice -dosing??- adjust dose for renal impairment

-used in early disease or in combo with levodopa for dyskinesia

Amantadine – Adverse Effects

CNS (dizziness, insomnia, confusion, nightmares) especially in older
patients
•
• Dry mouth, nausea
• Leg edema, orthostatic hypotension
• Ataxia – falls
• Livido reticularis (molting of skin)

Anticholinergic Agents-avoid in older patients

-Generally, are not
recommended-as first line

Benztropine

procyclidine

trihexyphenyidyl

Younger patients with severe, prominent tremor????
• Effectiveness?? – not recommended as first line therapy
• Avoid in older persons

Anticholinergic Agents
• Benztropine, procyclidine, trihexyphenyidyl

Adverse effects limit use
• Blurred vision
• Exacerbate narrow angle glaucoma
• Dry mouth
• Urinary retention
• Constipation
• Confusion

Anticholinergic Agents
• Benztropine, procyclidine, trihexyphenyidyl

Adverse effects limit use
• Blurred vision
• Exacerbate narrow angle glaucoma
• Dry mouth
• Urinary retention
• Constipation
• Confusion

Deep Brain Stimulation

Small electric shocks delivered to the globus pallidus rendering
it inactive without surgically destroying it.

Best results
• Adequate response to dopaminergic therapy
• Presence of on–off fluctuations
• Age < 70 yr
• Dyskinesia impairing quality of life
• Medication-resistant tremor
• Reasonable cognitive function

Non-Motor Symptoms

• Neuropsychiatric
- Dementia
- Psychosis – hallucinations
• Autonomic
- Constipation
- Orthostatic hypotension

Parkinson’s Disease Dementia (PDD)

↑ risk of dementia compared to general population
• develops at least 1 year after motor symptoms present
• Risk ↑ with ↑disease duration, severity, and age
• Slow progressive cognitive decline
• Discontinue cognitive unfriendly drugs
• Anticholinergic agents (consider total anticholinergic burden) – including TCAs & urinary agents
• Sedative-hypnotics
• Consider cholinesterase inhibitors
• Rivastigmine or donepezil

Psychosis=Common reason for nursing home placement

• Frequency ↑ as PD progresses
• Common reason for nursing home placement
• May be due to underlying dementia or medication induced
• Medications induced – visual hallucinations
• Dementia related psychosis – delusions (especially paranoid delusions)
• Treat distressing symptoms – not those that are not distressing to
patient

Managing Psychosis

Treat precipitating
illnesses (e.g. infection,
heart failure)

Lower doses or
discontinue precipitating
medications

Add antipsychotic agent
for unresponsive,
distressing sx’s

Medication-Related Psychosis

Non-essential contributing medications

ALWAYS taper down to discontinuation/ dont stop abruptly
-Anticholinergics &/or nabilone
-Amantadine
-Dopamine agonists
-MAOI-B
-Levodopa

Entacapone alone

does not cause
confusion but can contribute to effect
of levodopa

DO NOT STOP DOPAMINERGIC THERAPY
ABRUBTLY!!!!!!!

• Risks to the patient
• neuroleptic malignant-like syndrome
• Aspiration → pneumonia
• deep vein thrombosis/pulmonary embolism
• Painful

Drugs with Anticholinergic Activity to
Remember

• Tri-Cyclic Antidepressants
• Drugs to treat urinary incontinence
• Tolterodine, oxybutynin, darifenacin, solefenacin, trospium
• 1st generation anti-histamines
• Includes dimenhydrinate, diphenhydramine, doxylamine, chlorpheniramine

Pharmacologic Management of Psychosis

Treat if hallucinations/delusions are distressing to the patient or may cause
harm to themselves or others
• Typical antipsychotics should not be used due to extrapyramidal symptoms
(EPS)

Pharmacologic Management of Psychosis-do not use typical antipstchotics

Atypical antipsychotics may be considered
• Best evidence with clozapine – not practical – required blood work
• Quetiapine is a reasonable alternative
• Pimavanserin shows promise but not yet available in Canada

Constipation

• Common – occurs up to 80% of patients
• Consider discontinuing any medications that may contribute to
constipation (e.g. agents with anticholinergic properties)
• Treatment includes:
• High fiber diets +/- bulking agents (usually insufficient as monotherapy)
• Ensure adequate hydration
• ↑ physical activity
• Laxatives
• Senna, isosomotic agents (PEG), lactulose
• Domperidone – prokinetic agent that does not cross BBB

Orthostatic Hypotension

Fall in systolic BP of 20-30/10 mmHg or more between lying and
standing

Orthostatic Hypotension

Treatment

Treatment
• ↓ non-PD contributing medications, including antihypertensives
• ↑ salt & water intake (avoid dehydration)
• Compression stockings
• Elevating the head of the bed by 10-30 degrees
• Leg exercises prior to standing
• Avoid large meals (post-prandial effect), alcohol, excessively warm
environments

Orthostatic Hypotension – Pharmacologic
Intervention

• ↓ dose or d/c contributing medications whenever possible – including
antihypertensives
• Consider risk/benefit of strict antihypertensive control
-Options
- Fludrocortisone – mineralcorticoid → Na + H2O retention
- Midodrine – alpha-agonist
Both can cause supine hypertension
- Pyridostigmine – cholinesterase inhibitor- Useful in presence of supine hypertension
- Some case reports suggesting domperidone helpful

Orthostatic Hypotension – Pharmacologic
Intervention

• Fludrocortisone (Florinef®)
- Mineralocorticoid
- ↑ sodium retention (think about precautions/contraindications)
- Reduces serum potassium – potassium supplements usually necessary
- Start at 0.1mg/day and gradually increase – generally max 1 mg per day
• Midodrine
- α1 agonist
- ↑BP by ↑ peripheral vascular resistance
- Cardiac precautions
- Starting dose 2.5mg/day and gradually increase (max 10mg TID)
- Don’t take after 6 pm, especially if supine hypertension

Midodrine

α1 agonist-used to treat ortho-hypotension

• ↑BP by ↑ peripheral vascular resistance
• Cardiac precautions
• Starting dose 2.5mg/day and gradually increase (max 10mg TID)
• Don’t take after 6 pm, especially if supine hypertension

Fludrocortisone (Florinef®)

mineral corticorticoid

used to treat ortho-hypotension

• ↑ sodium retention (think about precautions/contraindications)
• Reduces serum potassium – potassium supplements usually necessary
• Start at 0.1mg/day and gradually increase – generally max 1 mg per day

Pyridostigmine

Orthostatic Hypotension – Pharmacologic Intervention

• Useful as monotherapy in mild orthostatis
• 30 mg BID to TID - may increase to 60 mg
• Sometimes combined with low dose midodrine

Pharmacist’s Role

• Work to your full scope of practice
• Observe patients presenting with Parkinsonian sx’s
• Tremor, rigidity, bradykinesia +/- postural hypotension
• Refer to primary care provider for assessment
• Review medications for drug-induced parkinsonism
• Provide education (written & verbal) to patients & caregivers – tailor individually
• Develop therapeutic goals in collaboration with pt & team
• Assist pt & team with appropriate dosing, administration & timing of PD medications
• Actively assess PD medications for effectiveness, adverse effects & affordability
• Assess adherence
• Assist pts & team with dosing adjustments