S A M A R S TAT E U N I V E R S I T Y

PHARMACOTHERAPY
OF AUTONOMIC
SYSTEM DISORDER

Clinpharm | Group 2
The autonomic nervous system (ANS) is a
complex network responsible for regulating
involuntary bodily functions like heart rate,
blood pressure, digestion, and temperature
control. When this system malfunctions, it
can lead to a range of debilitating
conditions known as autonomic system
disorders (ASDs)
PHARMACOTHERAPY- is defined as the treatment and prevention of disease
through the administration of drugs. It involves the use of pharmaceutical
compounds to treat health conditions, alleviate symptoms, and improve patient
outcomes (DiPiro et al., 2020).
 Diagnosis of Autonomic System Disorder

Diagnosing Autonomic system disorder is a multifaceted process

that involves a combination of ;

• Clinical evaluation (Medical History, Physical examination)

• Laboratory testing (Autoantibody Testing,Comprehensive Blood
Panels)
• Autonomic function assessments(Tilt Table Test,Heart Rate
Variability (HRV) Analysis
• Neuroimaging (Magnetic Resonance Imaging (MRI) Positron
Emission Tomography (PET) Scan)
Neurocardiogenic syncope
Other Name: vasovagal syncope
Is a condition where the body’s autonomic nervous system (ANS)
temporarily malfunctions in response to specific triggers, such as
standing for long periods, emotional distress, or pain. This
malfunction causes a sudden drop in blood pressure and heart
rate, leading to reduced blood flow to the brain and resulting in
fainting (syncope).
 Occurrence of abnormal
Triggered by stimuli such reflexes such as;
as; Sudden decreases in
Emotional distress Heart Rate( Bradycardia)
Pain Sudden decreases in
Prolonged standing Blood pressure
( Hypotension)

PATHOPHYSIOLOGY

Loss of consciousness Reduced blood flow to

( Syncope) the brain
Signs and symptoms

Pre-syncope (Before fainting)

1.Dizziness
2. Nausea
3. Blurry or tunnel vision
4. Weakness

Syncope (During fainting)

1. Sudden loss of consciousness
2. Limpness or collapse
3. Slow or weak pulse (bradycardia)
4. Pale and cool skin

Post-syncope (After fainting)

1. Confusion or disorientation
2. Fatigue or tirednes
3. Headache
DIAGNOSIS METHODOLOGY

1. Clinical History: Including symptoms, triggers, and frequency

of episodes.
2. Physical Examination: To assess vital sign such as Blood
pressure and heart rate
3. Tilt Table Test: To observe the cardiovascular system's
response to changes from lying down to standing.
4. Electrocardiogram (ECG): To assess heart rhythm and identify
any other cardiac issues.
5. Echocardiogram: To evaluate cardiac structure.
Assessment

Primary Diagnosis: Neurocardiogenic Syncope (Vasovagal Syncope)

•Triggered by prolonged standing and warm environments.
• Tilt Table Test confirms diagnosis with a drop in blood pressure and
heart rate.
• Rule out structural heart disease or arrhythmia as causes

Medication:
Mineralocorticoid - fludrocortisone
Non Selective Beta adrenergic agonist- Isoproterenol
Alpha 1 adrenergic Agonist - Midodrine
SOAP PHARMACOTHERAPY PLAN FOR PATIENTS WITH NEUROCARDIOGENIC SYNCOPE
Patient: Miko cutie
Age: 27
Diagnosis: Neurocardiogenic Syncope

SUBJECT

Chief Complaint: "I've been fainting a lot recently, especially after standing for a long time or when
it’s hot.

History of Present Illness:

John reports experiencing recurrent episodes of fainting over the past six months. He describes a
sensation of lightheadedness, nausea, palpitations, and sweating before losing consciousness. He
has had about 4 fainting episodes in the past month. Each episode lasts only a few seconds to a
minute, and he quickly regains consciousness without confusion or seizure activity. His symptoms
are often triggered by prolonged standing or being in a warm environment.
Past Medical History: No known cardiovascular
or neurological disorders.
Medications: None
Social History: No alcohol or drug use.
Family History: No family history of heart
disease or syncope.
Review of Systems: Positive for lightheadedness
and fainting. No chest pain, shortness of breath,
or recent illness
 Objective

Vital Signs:
Blood Pressure (supine): 110/70 mmHg
Blood Pressure (standing): 85/55 mmHg
Heart Rate (supine): 75 bpm
Heart Rate (standing): 60 bpm

Physical Examination:

General: Alert and oriented, no acute distress.

Cardiovascular: Normal heart sounds, no murmurs.
Neurological: No focal deficits, no tremors.

Diagnostic Tests:

Tilt Table Test: Positive result, with a significant drop in blood pressure and heart rate, leading to
syncope.
ECG: Normal sinus rhythm, no arrhythmias.
Echocardiogram: Normal, no structural abnormalities.
Assessment

Primary Diagnosis: Neurocardiogenic Syncope (Vasovagal

Syncope)
•Triggered by prolonged standing and warm environments.
• Tilt Table Test confirms diagnosis with a drop in blood
pressure and heart rate.
• Rule out structural heart disease or arrhythmia as causes
PLAN
1. Medication : Midodrine (5 mg TID):
Chosen to increase blood pressure by promoting vasoconstriction, which will help prevent
episodes of syncope by improving peripheral vascular tone. This medication is often effective for
patients with neurocardiogenic syncope as it helps counteract the excessive vasodilation that
leads to fainting.

2. Lifestyle Modifications:
• Increase fluid and salt intake to help maintain blood pressure.
• Avoid prolonged standing and warm environments.
• Wear compression stockings to promote venous return and improve circulation.

3. Follow-up
• Reassess symptoms in 4 weeks to determine if midodrine is effective in reducing syncope
episodes.
• Monitor for potential side effects, such as excessive hypertension or goosebumps, which can be
caused by midodrine.
Education:
• Educated the patient on how midodrine works, its purpose in
managing neurocardiogenic syncope, and potential side effects.
• Encouraged John to track his blood pressure regularly at
home and note any changes in symptoms.

Further Testing:
If symptoms do not improve, consider additional testing (e.g.,
tilt table test repetition or a Holter monitor) to reassess the
diagnosis and adjust treatment accordingly.
 Autoimmune Autonomic Ganglionopathy (AAG)

Autoimmune Autonomic Ganglionopathy (AAG) is a rare disorder in which the body's immune
system mistakenly attacks the autonomic ganglia—the nerve cell clusters that relay signals
within the autonomic nervous system (ANS). This impairs the normal functioning of the ANS,
which regulates involuntary bodily functions such as heart rate, blood pressure, digestion, and
temperature control.

Pathophysiology
AAG results from an autoimmune attack on the autonomic ganglia, specifically
targeting nicotinic acetylcholine receptors (nAChRs) located on postganglionic
neurons. The disruption of cholinergic transmission impairs signal relay within the
autonomic nervous system, leading to widespread autonomic failure.
The pathogenesis of AAG is complex and not fully understood. It's likely a combination of
genetic predisposition and environmental triggers. Possible triggers include:

- Infections: Viral or bacterial infections can trigger an autoimmune response.

- Cancer: AAG can be associated with certain cancers, particularly small cell lung cancer,
thymoma, and lymphoma.

- Other autoimmune disorders: Individuals with other autoimmune disorders, such as

rheumatoid arthritis or lupus, may be at increased risk for AAG.

- Drugs: Certain medications, such as anticholinergics, can trigger AAG in susceptible

individuals.
 Signs and Symptoms of AAG
The symptoms of AAG can vary widely from person to person, but they are generally
related to dysfunction of the autonomic nervous system. Some of the most common
symptoms include:
• Severe orthostatic hypotension (low blood pressure upon standing)
• Fainting (syncope)
• Constipation
• Dry mouth and dry eyes (sicca syndrome)
• Urinary retention:
• Gastrointestinal dysmotility
• Fatigue
 Overview of Pharmacotherapy in AAG

Pharmacotherapy for AAG is multifaceted, targeting both the autoimmune

processes driving the disease and the symptomatic manifestations resulting
from autonomic dysfunction. The primary objectives are:

1. Immunomodulatory and Immunosuppressive Therapies -To reduce or

eliminate the autoimmune attack on autonomic ganglia.

2. Symptomatic Management -To alleviate the diverse autonomic

symptoms, thereby improving the patient's quality of life.
 These therapies can be categorized as follows:
1. Plasmapheresis (Plasma Exchange)
involves the removal and replacement of the plasma component of blood.
Mechanism of Action (MoA): Removal of Autoantibodies: By physically removing
plasma, plasmapheresis reduces the concentration of pathogenic autoantibodies
in the bloodstream.
2. Intravenous Immunoglobulin (IVIG)
IVIG involves the administration of pooled immunoglobulins from healthy
donors to modulate the immune system.
Mechanism of Action (MoA): Neutralization of Autoantibodies: IVIG can bind to
and neutralize pathogenic autoantibodies.
Example Drug:
Gamunex-C® (Immune Globulin Intravenous [Human])
 Symptomatic Treatments
These treatments target specific autonomic symptoms such as orthostatic
hypotension, gastrointestinal dysfunction, and secretory abnormalities.
1. Midodrine - Is an alpha-adrenergic agonist used primarily to manage orthostatic
hypotension.
Mechanism of Action (MoA): Alpha-1 Adrenergic Stimulation: Midodrine
stimulates alpha-1 receptors on vascular smooth muscle, causing vasoconstriction
Example Drug: ProAmatine® (Midodrine)

2.Beta-Blockers
Mechanism of Action (MoA): Beta-Adrenergic Receptor Blockade: Beta-blockers inhibit beta-
adrenergic receptors in the heart, reducing heart rate and myocardial contractility.
Example Drugs: Propranolol® (Propranolol) ,Metoprolol® (Metoprolol)
 FARM PHARMACOTHERAPY WITH PATIENT HAVING AUTOIMMUNE
AUTONOMIC GANGLIOPATHY

Case Overview
Patient: Female, 45 years old
Diagnosis: Autoimmune Autonomic Ganglionopathy
Symptoms: Orthostatic hypotension, severe fatigue, gastroparesis, dry
mouth, and blurred vision.
Medications: Midodrine (for hypotension), Pyridostigmine (to enhance
autonomic function), IVIG (Intravenous immunoglobulin), and
Prednisone (immunosuppression).
 Findings
Autonomic Dysfunction: The patient exhibits multiple signs of dysautonomia,
including orthostatic hypotension (drop in blood pressure when standing),
gastroparesis (delayed gastric emptying), and reduced sweating.

IVIG Therapy: Patient has been receiving monthly IVIG treatments with
moderate symptom improvement.

Side Effects: Complaints of tremors, mood swings, and increased appetite

attributed to corticosteroid use (Prednisone).

Blood Pressure Control: Blood pressure still fluctuates despite the use of
Midodrine and Pyridostigmine.
 Assessment
Disease Management: The patient’s autoimmune autonomic ganglionopathy is only
partially controlled. Symptom burden is high, and there is inconsistent response to
treatment.

Medication Side Effects: The corticosteroid (Prednisone) is causing adverse effects like
tremors and mood changes, which may necessitate dose adjustment or an alternative
therapy.

Orthostatic Hypotension: Persistent orthostatic hypotension indicates that Midodrine

may require a dose titration or adjunct therapy to better stabilize blood pressure.

Overall Quality of Life: Patient continues to experience significant fatigue and digestive
symptoms, impacting daily function and quality of life
 Recommendations
Adjust Medications: Consider reducing Prednisone dose to minimize side effects, possibly
introducing a steroid-sparing immunosuppressant like Azathioprine.

Optimize BP Management: Increase Midodrine dose slightly to better manage orthostatic

hypotension. Consider adding Fludrocortisone to expand blood volume.

Non-pharmacological: Encourage dietary modifications such as frequent small meals for

gastroparesis, and increased salt and fluid intake to help stabilize blood pressure.

Mental Health Support: Given the side effects of mood swings, a referral to a mental health
specialist to manage potential steroid-induced psychiatric symptoms.
 Monitoring
Blood Pressure: Regular home blood pressure monitoring, especially after standing.
Consider ambulatory blood pressure monitoring for better tracking.

Symptom Log: Encourage the patient to maintain a log of symptoms like fatigue,
dizziness, and digestive issues to help track progress.

Follow-up Labs: Regular monitoring of antibodies, blood sugar (due to steroid use),
and kidney function, especially if Fludrocortisone is initiated.

Medication Review: Follow-up in 1 month to reassess the response to medication

adjustments and to evaluate the need for further modifications.
Pure Autonomic Failure (PAF)
- Rare and debilitating neurological disorder that affects the autonomic
nervous system (ANS). PAF is characterized by a progressive
degeneration of the autonomic nervous system, leading to widespread
autonomic dysfunction.
Pathophysiology:
The pathophysiology of PAF is not fully understood, but it is believed to
involve:
1) Neurodegeneration
2) Inflammation
3) Oxidative stress
Clinical Features:
Common symptoms include:

1) Orthostatic hypotension
2) Urinary retention
3) Erectile dysfunction
4) Gastrointestinal dysfunction
5) Sudomotor dysfunction
6) Cardiovascular dysfunction
 Pharmacotherapy:
Focuses on symptom management, particularly addressing orthostatic hypotension and
other autonomic dysfunctions. There is no cure for PAF, so treatment aims to improve
quality of life and alleviate symptoms. Here's a comprehensive overview of
pharmacotherapy for PAF:

1. Treatment of Orthostatic Hypotension

Orthostatic hypotension is the most disabling feature of PAF and is the primary target of
pharmacotherapy.
a. Fludrocortisone (Mineralocorticoid)
• MOA: Retain sodium and increase blood volume by acting on the kidneys.
• Dosage: 0.1 to 0.2 mg daily, titrated based on the patient's response and tolerance.
• Adverse Effects: Hypertension in the supine position, hypokalemia (low potassium levels),
and edema.
b. Midodrine (Alpha-1 Agonist)
• MOA: Causes vasoconstriction by stimulating alpha-1 adrenergic receptors,
which helps to increase blood pressure, especially when standing.
• Dosage: 2.5 to 10 mg three times daily (avoid dosing close to bedtime to
prevent supine hypertension).
• Adverse Effects: Supine hypertension, piloerection (goosebumps), scalp
tingling, and urinary retention.

c. Droxidopa (Northera)
• MOA: Droxidopa is a prodrug converted to norepinephrine, which increases
blood pressure by enhancing vasoconstriction.
• Dosage: Typically started at 100 mg three times a day and titrated up to 600
mg three times a day based on the response.
• Adverse Effects: Supine hypertension, headache, dizziness, and nausea.
.
d. Octreotide (Somatostatin Analog)
• MOA: Inhibits the release of vasodilatory peptides, thereby promoting
vasoconstriction and increasing blood pressure.
• Dosage: 25-100 mcg subcutaneously before meals and when upright.
• Adverse Effects: Gastrointestinal disturbances (nausea, bloating), gallstones,
and the risk of hypoglycemia.

e. Pyridostigmine (Acetylcholinesterase Inhibitor)

• MOA: Enhances cholinergic transmission, which can increase vascular
resistance and help improve blood pressure, particularly during standing
without causing supine hypertension.
• Dosage: 30-60 mg orally, 2-3 times daily.
• Adverse Effects: Diarrhea, abdominal cramping, and increased salivation.
2. Treatment of Supine Hypertension
A common complication in PAF patients treated for orthostatic
hypotension is supine hypertension (elevated blood pressure
when lying down). This needs careful management as it can
exacerbate cardiovascular risks, especially at night.
• Short-acting antihypertensives: Medications like nitroglycerin
patches or clonidine may be used during nighttime to manage
supine hypertension without worsening daytime hypotension
.
3. Treatment of Other Autonomic Symptoms
PAF can also cause various other autonomic dysfunctions, which may require additional
pharmacological management:

a. Constipation:
• Laxatives or stool softeners such as polyethylene glycol (PEG) can help manage chronic
constipation.
Prokinetic agents like prucalopride can also be used.
b. Urinary Retention:
• Alpha-blockers (e.g., tamsulosin) can help relax the bladder neck and prostate to
improve urine flow.
c. Erectile Dysfunction:
• Phosphodiesterase type 5 inhibitors (PDE5 inhibitors): Medications like sildenafil can
help manage erectile dysfunction by improving blood flow to the penile tissue.
d. Sweating abnormalities:
• Antiperspirants or medications like glycopyrrolate can be used if patients experience
excessive sweating.
.
SOAP PHARMACOTHERAPY WITH PATIENT HAVING Pure Autonomic
Failure (PAF)

S (Subjective):
A 65-year-old male patient presents with complaints
of frequent dizziness, especially when standing up from a
sitting or lying position. He reports feeling lightheaded
and occasionally fainting. The patient also mentions
experiencing constipation, heat intolerance, and reduced
sweating. These symptoms have been progressively
worsening over the past two years.
O (Objective):
- Vital signs:
- Blood pressure: 110/70 mmHg (supine), 80/50
mmHg (standing)
-Heart rate: 68 bpm (supine), 72 bpm (standing)
-Respiratory rate: 14 breaths/minute
-Temperature: 37.0°C (98.6°F)
- Physical examination
- Orthostatic hypotension confirmed
- Skin appears dry with minimal sweating
- No signs of external injuries from reported falls
- Neurological examination:
-No motor or sensory deficits
- Pupillary responses normal
- Recent autonomic function tests show impaired
cardiovascular reflexes and sudomotor function.
A (Assessment): Based on the patient's symptoms,
physical examination findings, and autonomic function
test results, the assessment is consistent with Pure
Autonomic Failure (PAF). The key features supporting this
diagnosis are:

1. Orthostatic hypotension without compensatory heart

rate increase
2. Progressive autonomic symptoms (constipation, heat
intolerance, reduced sweating)
3. Absence of other neurological signs or symptoms
4. Gradual onset and progression over years

Differential diagnoses to consider:

- Multiple System Atrophy (MSA)
- Parkinson's disease with autonomic failure
P (Plan):
1. Education:
-Explain the nature of PAF to the patient and discuss its chronic, progressive
course.
2. Non-pharmacological management:
- Advise on gradual position changes and avoiding prolonged standing
- Recommend compression stockings to improve venous return
- Suggest increasing salt and fluid intake to maintain blood volume
- Encourage small, frequent meals to minimize postprandial hypotension
3. Pharmacological management:
-Initiate fludrocortisone 0.1 mg daily to enhance sodium retention and
increase blood volume
- Consider midodrine 2.5 mg three times daily for vasoconstriction, titrating
as needed
4. Monitoring and follow-up:
- Schedule regular blood pressure checks, both supine and standing -
Monitor for potential side effects of medications
- Follow up in 4 weeks to assess response to treatment and adjust as
necessary