Why Parkinson folks need to pay attention to 'low' blood pressure

Great example of orthostatic hypotension in an article by the Mayo clinic in 2018.

Every time you visit your primary care doctor a ‘blood pressure measurement is checked’ usually to proactively check for ‘high blood pressure’ also known as hypertension. If you have Parkinson’s disease, it is also vital that your blood pressure is checked on every visit, however your neurologist is more interested in ‘low blood pressure,’ also referred to as hypotension. Some experts talk about the ‘silver lining’ of Parkinson’s disease as the opportunity to reduce or discontinue hypertension medications. In this month’s parkinsonsecrets.com blog I will review what is orthostatic hypotension, how to proactively screen for it and how to avoid the million dollar workup. I will also offer some practical tips for blood pressure management in Parkinson’s disease. These tips when employed can prevent falling and passing out.

Jonny Acheson reminds us the importance of checking blood pressure.

How common is orthostatic hypotension in the elderly?

Though the prevalence of orthostatic hypotension is low 7% in the elderly population, when you consider other illnesses it dramatically climbs. Orthostatic hypotension can occur in 30% of folks with other medical problems and in half of folks who have previously had a stroke(s).

Masaki and Long recently reviewed how common orthostatic hypotension can be especially if other medical illnesses are present.

When Parkinson folks ‘pass out’ and head to the emergency room what is the biggest mistake doctors make?

When you enter an emergency department after ‘passing out’ which is also referred to by doctors as ‘syncope’ the single biggest mistake is assuming the problem is with the ‘heart.’ If you have Parkinson’s disease, the vast majority of ‘passing out’ is caused by autonomic nervous system dysfunction in combination with dopaminergic medications. The degenerative changes in your brain circuits add up to an overall reduction in your blood pressure. In addition levodopa and dopamine agonists reduce your blood pressure. The mistake emergency departments make over and over is ordering expensive cardiac workup’s, instead of simply managing Parkinson’s autonomic symptoms and medications.

I love this process for identification and treatment of orthostatic hypotension proposed by Gibbon’s in 2017.

What are the symptoms of low blood pressure?

The American Heart Association lists the following symptoms as important potential indicators of low blood pressure (hypotension):

• Confusion

• Dizziness or lightheadedness

• Nausea

• Fainting leading to falling (medical doctors call this syncope)

• Fatigue

• Neck or back pain

• Headache

• Blurred vision

• Heart palpitations, or feelings that your heart is skipping a beat, fluttering, or beating too hard or too fast

What Parkinson’s medications lower blood pressure?

Here is a list of some of the big offending drugs which may result in orthostatic hypotension.

Far and away the two most common Parkinson’s medications which may lower blood pressure are levodopa (dopamine) and dopamine agonists.

The other medications to watch out for, may include Parkinson’s folks who are on tricyclic antidepressants for depression or sleep.

The non-Parkinson’s medications which are the biggest offenders— no surprise they are most commonly antihypertensives.

What is the correct way to check for orthostatic hypotension?

A total of three blood pressure readings should be performed.

It is far cheaper to start the work-up of ‘low blood pressure’ by checking what are called ‘orthostatics’ as the first step in a workup. Orthostatic blood pressures are checked by performing blood pressure when laying down, followed by sitting up for 1-3 minutes, and then followed by a BP when standing for 3 minutes. In some cases you may need to repeat for longer than 1-3 minutes in each position.

What plays out in Parkinson’s is when we get out of bed or stand up from a chair— the blood pressure drops.

The body may keep this response in check by releasing a chemical called norepinephrine or norepi. Norepi causes your blood vessels to contract or tighten. When norepi is released, blood is redirected from the legs to the brain. When this process occurs the hope is that enough blood gets to your brain so you do not ‘pass out.’

If you have Parkinson’s disease you have less norepinephrine and the response of your autonomic nervous system to release norepinephrine may be impaired.

When your blood pressure drops when you change position we called that ‘orthostatic hypotension.’ If it is caused by a neurological disease like Parkinson’s, we refer to it as neurogenic orthostatic hypotension.

What are other causes of orthostatic hypotension?

If you have Parkinson’s disease, you are at risk for orthostatic hypotension, however there may be other causes which contribute to worsening of your symptoms. Here are a few to watch out for:

• Dehydration

• Antidepressants

• Diuretics

• Drugs used for folks who have trouble urinating

• Drugs used for erectile dysfunction

• Drugs for high high blood pressure.

• Heart problems

• Anemia

How do we define worrisome orthostatic hypotension?

Here are the key tips I teach folks in my practice:

• If you experience lightheadedness, dizziness or weakness when you stand up after sitting or lying down, check for orthostatic hypotension.

• If you have a drop of at least 20 millimeters of mercury in systolic blood pressure (top number) and 10 millimeters of mercury in diastolic blood pressure (bottom number) within three minutes of sitting up or standing up— you have orthostatic hypotension.

• Many people just use the standing drop, however in Parkinson’s, I find it useful to monitor sitting drops in blood pressure, and to educate folks that this may be the first warning sign (dizziness or lightheadedness when sitting up).

How do you treat orthostatic hypotension?

I prioritize treatment for each person with orthostatic hypotension. I always prioritize fall prevention as the number one goal.

• Hydration is important. One cold glass of water in the morning wakes up the autonomic nervous system.

• 6-8 glasses or bottles of water a day.

• Education of slow and steady position changes from laying to sitting, and from sitting to standing. Slow and steady, with a plan to sit back down if dizzy or lightheaded, is a key to success.

• Discussion with the general doctor about the risks and benefits of reduction or elimination of antihypertensive medications.

• Discontinuation of dopamine agonists and using a levodopa only regimen if possible.

• Elimination of other medications which may be contributing (e.g. TCA antidepressants, prostate drugs, etc.)

• Compression stockings or an abdominal binder.

• Consideration of fludrocortisone, midodrine or droxidopa.

• Sometimes in severe cases eating small, frequent meals, reduce alcohol consumption and avoiding hot drinks and hot foods may help.

• Increasing salt intake for those who the general doctor agrees it is appropriate and safe (e.g. pretzels).

• Limit exposure to outside activities when a high heat index.

What are counter-maneuvers you can employ when you first detect orthostatic hypotension symptoms ‘coming on?’

Yes there are physical counter-maneuvers you can learn and employ for orthostatic hypotension. You can use them as soon as symptoms appear. You can proactively use them if you know you will be standing for a long period of time.

• Contracting muscles below the waist (hold contractions for ~20-30 seconds)

• Toe-raising

• Leg-crossing and contraction

• Thigh muscle co-contraction

• Bending at the waist, however this one we usually don’t recommend for Parkinson’s.

• Slow marching in place

• Leg elevation

What are some treatment tips for ‘tricky’ orthostatic hypotension cases?

Similar to other medical diagnoses there are straight-forward cases of orthostatic hypotension and there are those which are tricky or difficult to manage.

Here is a list of tips from an article written by Figueroa, Basford and Lowe in the Cleveland Clinic Medical Journal.

Figueroa and colleagues have offered some suggestions for challenging cases of orthostatic hypotension.

Here is a nice screening group of 10 questions from the Parkinson’s Foundation.

What do I need to know about the drug midodrine?

Here is a nice summary of recent studies showing the evidence base for use of midodrine.

• Midodrine is what is referred to as a vasopressor. It contracts blood vessels.

• Starting dose is 2.5-5 mg three times a day. It is common to reach doses of 10mg three times a day.

• It is very short acting and only lasts a few hours.

• This drug is less effective if plasma volume is reduced.

• Most experts prescribe it first thing in the morning or as close to arising as possible; just before lunch and in the middle of the afternoon.

• Supine hypertension or high blood pressure when laying down is the biggest fear for prescribing clinicians. I encourage folks on midodrine to always be up at at least a 30 degree angle when in bed or when seated (avoid lying flat).

• Common side effects include scalp paresthesias and goose-bumps on the skin.

What do I need to know about fludricortisone for the treatment of orthostatic hypotension?

• Fludrocortisone is referred to as a synthetic mineralocorticoid.

• How does it increase blood pressure? It both expands plasma volume and increases alpha-adrenoceptor sensitivity. These receptors are located inside the blood vessels.

• If your plasma volume does not improve even when you add salt (pretzels and other salty foods) this drug is useful.

• This drug can be used as the first medication to treat orthostatic hypotension or it can be added to other drugs.

• The drug can also be added to midodrine to treat more severe cases of orthostatic hypotension

• The starting dose is usually 0.1 to 0.2 mg/day. In more severe cases doses may be escalated to 0.4 to 0.6 mg/day.

• Fludrocortisone may lead to 3-5 pounds of weight gain.

• This drug is usually not administered if you have congestive heart failure or chronic renal failure.

• Low potassium is a potential side effect and many experts will add potassium to the diet to address this potential challenge.

• Supine hypertension similar to midodrine may occur (try not to lay flat).

What treatment tips do I need to know for using droxidopa?

Here are some recent trials by Kaufmann and Hauser showing the evidence base for droxidopa.

• Droxidopa is a synthetic amino acid. It is identical to levodopa with an added hydroxyl group.

• The drug gets decarboxylated into norepinephrine.

• The norepinephrine acts to bring ‘up’ blood pressure.

• A starting dose of droxidopa is 100 mg three times daily.

• Over time and if needed one can increase droxidopa to up to 600 mg three times a day and occasionally higher.

• In some cases, experts administer only the morning or both morning and before lunch.

• Carbidopa actually blocks the conversion of droxidopa to norepinephrine so folks on high doses of carbidopa levodopa may have less benefit.

• Headache and nausea are common side effects.

• Supine hypertension is common and the same precautions as midodrine and fludrocortisone are employed.

What do I need to know about use of pyridostigmine for treatment of orthostatic hypotension?

4 steps to treat orthostatic hypotension.

• Pyridostigmine is a cholinesterase inhibitor.

• Folks use this drug in orthostatic hypotension because it may improves neurotransmission in the baroreflex pathway which is important in blood pressure.

• This drug is less effective than midodrine or fludricortisone and is thus usually only administered in mild cases.

• A typical starting dose is 30 mg twice or three times a day. The dose can be increased to 60 mg three times a day if needed.

• Side effects particularly at higher doses include abdominal cramping and diarrhea.

• You may recognize this drug as well as its anticholinergic side effects, as it is a common medication used in myasthenia gravis.

Do I need a tilt table and a million dollar workup for “passing out’ and low blood pressure with Parkinson’s?

In most cases you probably do not need a tilt table to diagnose and treat Parkinson’s disease orthostasis.

Probably not necessary to get a tilt table and autonomic testing in most cases. In our practice we skip the tilt tables and expensive cardiac tests and EEG’s, and we focus on the basics of diagnosis and treatment. In severe or tricky cases we may pursue tilt tables and autonomic testing.

What is the bottomline for addressing low blood pressure in Parkinson’s?

• Your blood pressure should be checked at every visit.

• If you are getting lightheaded or dizzy have your doctor check blood pressure in three positions.

• Both medications and the Parkinson’s itself can contribute to orthostatic hypotension.

• The number one priority in treating orthostatic hypotension is preventing falls and fall related morbidity.

• There are conservative measures and more aggressive medication regimens which can be employed.

• Drink lots of water and remember to take your blood pressure 1 hour after taking your levodopa as that is when your blood pressure will be at its minimal level.

• I tell folks to drink a bottle of water every time they take a levodopa dose as this will combat the effects of levodopa in lowing blood pressure.

• There are very severe cases which may require autonomic testing, tilt tables and consideration of specialty medicines (octreotide a somatostatin analogue for low blood pressure after eating).

Michael Okun is the author of this blog post and the co-editor of parkinsonsecrets.com.

Jonny Acheson is the artist for the parkinsonsecrets.com blog. He is also a doctor and a person with Parkinson’s.

Selected references:

Wieling W, Kaufmann H, Claydon VE, van Wijnen VK, Harms MPM, Juraschek SP, Thijs RD. Diagnosis and treatment of orthostatic hypotension. Lancet Neurol. 2022 Aug;21(8):735-746. doi: 10.1016/S1474-4422(22)00169-7. PMID: 35841911; PMCID: PMC10024337.

Seppi K, Ray Chaudhuri K, Coelho M, Fox SH, Katzenschlager R, Perez Lloret S, Weintraub D, Sampaio C; the collaborators of the Parkinson's Disease Update on Non-Motor Symptoms Study Group on behalf of the Movement Disorders Society Evidence-Based Medicine Committee. Update on treatments for nonmotor symptoms of Parkinson's disease-an evidence-based medicine review. Mov Disord. 2019 Feb;34(2):180-198. doi: 10.1002/mds.27602. Epub 2019 Jan 17. Erratum in: Mov Disord. 2019 May;34(5):765. PMID: 30653247; PMCID: PMC6916382.

Freeman R, Abuzinadah AR, Gibbons C, Jones P, Miglis MG, Sinn DI. Orthostatic Hypotension: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Sep 11;72(11):1294-1309. doi: 10.1016/j.jacc.2018.05.079. PMID: 30190008.

Palma JA, Kaufmann H. Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies. Mov Disord. 2018 Mar;33(3):372-390. doi: 10.1002/mds.27344. PMID: 29508455; PMCID: PMC5844369.

Gibbons CH, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R, Isaacson S, Karabin B, Kuritzky L, Lew M, Low P, Mehdirad A, Raj SR, Vernino S, Kaufmann H. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017 Aug;264(8):1567-1582. doi: 10.1007/s00415-016-8375-x. Epub 2017 Jan 3. PMID: 28050656; PMCID: PMC5533816.