The document presents a comprehensive overview of drugs and chemicals that influence autonomic functions, detailing cholinergic and adrenergic agents, as well as their pharmacological effects. It highlights the mechanisms through which these substances can either reduce or stimulate autonomic activity, including adverse effects associated with various therapeutic and illicit compounds. Additionally, it discusses the impact of chronic exposure to certain toxins and drugs on autonomic neuropathy and dysfunction.

1. 1
Drugs and Chemicals affecting
Autonomic Functions
Presenter : Dr. Saran A. K.
Preceptor : Prof. (Dr.) Tribhuwan Kumar
DM Seminar | 31 January 2025
DEPT. OF PHYSIOLOGY, AIIMS PATNA

2. Autonomic (adj)
/ tə n m k/
ɔː ˈ ɒ ɪ
self governing, functionally independent

3. DEPT. OF PHYSIOLOGY, GMCM 3

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Complementary, my dear Watson!

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7. DEPT. OF PHYSIOLOGY, AIIMS PATNA 7
Overview
1. Autonomic System Pharmacology
• Cholinergic Agonists and Antagonists
• Adrenergic Agonists and Antagonists
2. Drugs, Chemicals and Toxins
• Direct reduction of autonomic activity
• Reduction of autonomic activity due to autonomic neuropathy
• Stimulation of excess autonomic activity
3. Points to Consider in Autonomic Function Testing
4. Summary

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Cholinergic Agonists (Parasympathomimetic)
Class Examples
Esters of Choline
Acetylcholine, Methacholine,
Carbachol, Bethanechol,
Cevimeline
Cholinomimetic Alkaloids Pilocarpine, Muscarine
Reversible Anticholinesterases
Physostigmine, Neostigmine,
Edrophonium, Donepezil,
Rivastigmine
Irreversible Anticholinesterases
Organophosphorous compounds
(Dyflos, Parathion, Ecothiophate)

10. DEPT. OF PHYSIOLOGY, AIIMS PATNA 10

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12. Pharmacological Actions of Parasympathomimetic
System Effect
Effects Mediated Via Muscarinic Receptors – M1 (Neuronal), M2 (Cardiac), M3 (Secretory glands/smooth muscles)
Heart
Decrease in heart rate and A.V nodal conduction,
negative inotropic action, decrease in mean arterial
BP
Blood Vessels
M3 mediated endothelial NO release - arteriolar
dilatation
Gastrointestinal Tract Increased tone and motility – cramps and diarrhea
Urinary Bladder
Detrusor contraction and relaxation of trigone -
Voiding
Bronchial Smooth Muscles Contraction
Secretory Glands
Enhanced secretion – sweat, salivary, lacrimal,
gastric, intestinal
Eyes
Miosis (contraction of circular smooth muscles of
iris); spasm of accommodation, reduced intraocular
tension (i.o.t)

13. DEPT. OF PHYSIOLOGY, AIIMS PATNA 13
Anti Cholinergic Drugs
• Natural alkaloids — Atropine, scopolamine
• Semi-synthetic — Homatropine, Ipratropium, Tiotropium
• Synthetic
• Mydriatic — Tropicamide
• Anti-secretory/ anti-spasmodic — Pirenzepine, Dicyclomine
• Anti-parkinsonian — Trihexyphenidyl, benztropine
• Vesicoselective — Oxybutynin, darifenacin

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Adrenergic Agonists (Sympathomimetics)
By Mode of Action
Directly acting
Sympathomimetics –
Direct agonists at
adrenergic receptors
Indirectly acting
Sympathomimetics –
Increase NT levels at
synaptic cleft by
inhibiting NE transporter
or displacing NT from
storage vesicles
Amphetamine,
Cocaine,
Reserpine,
Tricyclic Anti depressants
Epinephrine ,
Norepinephrine,
Dopamine,
Phenylephrine
Metaraminol

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Adrenergic Antagonists

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Drugs acting on Adrenergic Receptor Subtypes
Receptor Sub-type α₁ α₂ β₁ β₂
Agonists
Phenylephrine,
Methoxamine,
Metaraminol
Clonidine Isoprenaline,
Dobutamine
Salbutamol,
Terbutaline
Antagonists Prazosin Yohimbine Propranolol,
Metoprolol
Propranolol
Receptor Location
Post-synaptic
smooth muscle
(arteries, bladder,
uterus)
Pre-synaptic CNS,
Post-synaptic
intestinal SMC
Heart, Kidney (J-G
cell)
Post-synaptic
bronchial smooth
muscle; skeletal
muscle; hepatic
tissue
2nd Messenger
System
Phospholipase, Ca
flux alteration
Inhibition of
adenylyl cyclase
Stimulation of
adenylyl cyclase
Stimulation of
adenylyl cyclase

18. DEPT. OF PHYSIOLOGY, AIIMS PATNA 18
• Many drugs, chemicals, and toxins are capable of interacting
with the autonomic nervous system to alter autonomic function in
humans.
• While acute exposure may cause autonomic overactivity, the
chronic effect of most such compounds is a reduction in
autonomic activity.

19. DEPT. OF PHYSIOLOGY, AIIMS PATNA 19
1. Drugs and other chemicals that reduce autonomic activity,
• either directly by inhibiting the activity of otherwise
functional autonomic nerve fibers and/or receptors, or
• indirectly by causing an autonomic neuropathy.
2. Drugs and compounds, including naturally occurring toxins
and venoms, that cause an abnormal increase in
autonomic activity.

20. DEPT. OF PHYSIOLOGY, AIIMS PATNA 20
A. Direct reduction of autonomic activity
1. Therapeutic drugs
• Sympathetic inhibitors
• Parasympathetic inhibitors
• Centrally acting drugs
2. Other drugs and toxins
• Nicotine
• Long lasting anticholinesterase compounds
• Herbal remedies
• Illicit Drugs
• Snake Venoms

21. DEPT. OF PHYSIOLOGY, AIIMS PATNA 21
1. Therapeutic Drugs (↓ of autonomic activity)
1. Drugs - pharmacodynamic effects depend on direct antagonism of
autonomic neurotransmission.
2. Those drugs that have antagonist activity within the autonomic nervous
system in addition to their primary pharmacodynamic effect.
Drugs commonly used by the elderly often cause autonomic
dysfunction, with sympathetic and parasympathetic inhibition having greater
impact in older adults.

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Sympathetic Inhibitors

24. DEPT. OF PHYSIOLOGY, AIIMS PATNA 24
• Drugs with alpha-antagonist properties (such as the
phenothiazines and tricyclic antidepressants) cause orthostatic
hypotension, particularly when used in combination in elderly.
• A less common complication reversible urinary incontinence
caused by antagonism of sympathetic activity in the internal bladder
sphincter, most commonly in elderly women.

25. DEPT. OF PHYSIOLOGY, AIIMS PATNA 26
• Beta-blockers can exacerbate cardiac failure due to their negative
inotropic effects.
• When combined with drugs like digoxin or verapamil, beta-blockers
may cause significant atrioventricular conduction delay, even in
individuals with normal baseline ECGs.
• Exacerbation of symptoms of obstructive airways disease is also
well recognized as a complication of the use of beta-blockers in
susceptible people.

26. DEPT. OF PHYSIOLOGY, AIIMS PATNA 27
• Local administration of drugs with autonomic effects may also cause
systemic symptoms.
• Timolol eye drops for glaucoma can exacerbate bronchospasm or
cardiac insufficiency due to systemic beta-blocker effects.
• Schweitzer et al. (2008) documented severe depression in a patient
with a history of depression treated with ocular timolol for glaucoma,
which resolved only after discontinuing timolol.

27. DEPT. OF PHYSIOLOGY, AIIMS PATNA 28
Parasympathetic Inhibitors
• Class I antiarrhythmic agents such as quinidine and disopyramide
have significant antimuscarinic effects in addition to their sodium
channel blocking activity.
• Protriptyline and amitriptyline, potent muscarinic antagonists
among tricyclic antidepressants, may contribute to urinary retention
or constipation.
• Newer antidepressants like fluoxetine and venlafaxine have the
advantage of minimal alpha- and muscarinic receptor antagonism.

28. DEPT. OF PHYSIOLOGY, AIIMS PATNA 29
• Anticholinergic drugs like benztropine and oxybutynin are
used for Parkinson’s, antipsychotic-induced movement
disorders, and overactive bladder.
• In all of these cases the drug is administered systemically and
can be expected to have widespread autonomic effects.

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• Antimuscarinic drugs can cause blurred vision, particularly
in younger individuals with preserved lens accommodation.
• Common side effects include dry mouth, severe
constipation, and urinary retention, especially in elderly
males with prostatic hypertrophy.
• At high doses, they may inhibit gastric emptying and
secretion, leading to epigastric discomfort.

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Centrally acting drugs
• Centrally acting drugs can affect autonomic function, with
levodopa and D2 agonists (bromocriptine, pergolide) linked to
early-phase orthostatic hypotension in Parkinson’s treatment.
• Peripheral dopaminergic stimulation, along with increased
natriuresis and diuresis, causes orthostatic intolerance only in the
presence of impaired baroreflex and sympathoneural dysfunction
in Parkinson’s disease.

31. DEPT. OF PHYSIOLOGY, AIIMS PATNA 33
• Centrally acting antihypertensives (alpha-methyldopa, clonidine,
moxonidine, rilmenidine) lower blood pressure by reducing tonic
sympathetic outflow (Sica, 2007).
• Rilmenidine reduces blood pressure, baseline sympathetic activity, and
peripheral resistance but preserves reflex sympathetic responses to
stress and head-up tilt (Esler et al., 2004).
• Alpha-methyldopa and clonidine more frequently cause postural
hypotension, dry mouth, somnolence, and constipation compared to
imidazoline agonists.

32. DEPT. OF PHYSIOLOGY, AIIMS PATNA 34
• Guanfacine, a centrally acting alpha2-adrenoceptor agonist,
was initially an antihypertensive but is now used for tics, ADHD,
anxiety, and PTSD.
• Overdose may cause initial hypertension followed by
persistent orthostatic hypotension.

33. DEPT. OF PHYSIOLOGY, AIIMS PATNA 35
Other drugs and toxins
1. Nicotine
• Nicotine has a variety of pharmacological actions in the central and
peripheral nervous systems
• Short-term administration enhances several cognitive functions,
including attention and working memory.
• It may also have central neuroprotective effects, for example in
Parkinson’s disease.

34. DEPT. OF PHYSIOLOGY, AIIMS PATNA 36
• In the periphery, nicotine binds to nicotinic receptors in
autonomic ganglia, as well as at neuromuscular junctions, and
stimulates them
• Acute autonomic effects include increased heart rate, blood
pressure, and cutaneous vasoconstriction

35. DEPT. OF PHYSIOLOGY, AIIMS PATNA 37
• Exposure to toxic doses (e.g. in tobacco workers or those exposed to
nicotine-containing pesticides) can result in ganglionic paralysis
with bradycardia, hypotension, coma, and eventual respiratory
muscle paralysis.
• The specific role of nicotine in the toxic effects of long-term tobacco
smoking remains unclear.

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2. Long lasting anticholinesterase compounds
• Compounds with anticholinesterase activity, such as
organophosphorus esters and carbamate compounds, are
commonly used in agriculture as insecticides.
• Acute ingestion by humans causes increased activity at
autonomic ganglia and parasympathetic terminals.

37. DEPT. OF PHYSIOLOGY, AIIMS PATNA 39
• In some circumstances, however, they may reduce autonomic
function.
• WWII workers exposed to organophosphorus compounds experienced
persistent autonomic dysfunction for years.
• Chronic exposure to organophosphorus insecticides may have lasting
effects, though evidence is controversial.

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3.. Herbal Remedies
Many freely available proprietary herbal remedies contain
alkaloids such as atropine and scopolamine and there have
been case reports of anticholinergic poisoning resulting in
confusion, dry mouth, tachycardia, and dilated pupils

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3. Illicit Drugs
• Amphetamine-induced suppression of vasomotor outflow can
cause severe orthostatic hypotension while preserving normal
vagal function.
• Symptoms, including pronounced drowsiness and hypotension, -
10 hours post-ingestion and resolved spontaneously over 3 days.
• Differential diagnosis in cases of acute autonomic neuropathy.

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• Contaminated illicit drugs can cause acute autonomic
dysfunction.
• E.g. acute anticholinergic poisoning in individuals using street
"heroin" mixed with scopolamine.
• Symptoms include hallucinations, tachycardia, pupillary
dilation, dry skin, and urinary retention, which respond quickly to
physostigmine treatment

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3. Snake Toxins
• α-Neurotoxins bind specifically to nicotinic acetylcholine receptors
at the neuromuscular junction, causing flaccid paralysis and
respiratory arrest.
• Autonomic ganglionic nicotinic receptors are less affected by α-
neurotoxins but are targeted by κ-neurotoxins like κ-
bungarotoxin and κ-flavitoxin.
• κ-Neurotoxins cause complete and prolonged autonomic
ganglion blockade even at low doses.

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B. Reduction of autonomic activity due to
autonomic neuropathy
• Therapeutic Drugs
• Cytotoxic agents used in cancer chemotherapy
• Other therapeutic drugs
• Occupational exposure
• Others forms of exposure
• Alcohol
• Botulinum Toxin

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• Autonomic neuropathy from drugs or toxins should be
considered in chronic autonomic dysfunction.
• Neurotoxic compounds have selective effects; not all peripheral
neuropathies affect autonomic function.
• Examples: Arsenic causes sensory neuropathy; lead toxicity
affects motor function and CNS with little autonomic impact.

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Therapeutic drugs
1. Cytotoxic Agents Used in Cancer Chemotherapy
• Vincristine and Vinblastine
• Cause dose-dependent peripheral sensory neuropathy (Vincristine
more than Vinblastine).
• Induce axonal degeneration due to their effect on microtubules.

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Mechanism of Action
• Bind to tubulin, preventing its polymerization into microtubules.
• In neurons, microtubules facilitate rapid transport of essential
proteins from the cell body to the axon.
• Disruption of this transport leads to axonal degeneration.
Clinical Features of Neuropathy
• Longer fibers are more vulnerable, leading to distal sensory loss.
• The vagus nerve is particularly susceptible to damage.

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• Case reports indicate orthostatic hypotension, constipation,
paralytic ileus, and urinary retention.
• Both sympathetic and parasympathetic systems are affected. (Hirvonen
et al., 1989).
• No significant effect on Valsalva ratio, heart rate variability with
deep breathing, or systolic blood pressure response to head-up tilt
(Lahtinen et al., 1989).
• Long-term follow-up in young sarcoma patients found no persistent
autonomic abnormalities at 8 months post-treatment (Earl et al., 1998).

47. DEPT. OF PHYSIOLOGY, AIIMS PATNA 51
• Doxorubicin may rarely cause toxicity in peripheral neurons,
particularly in the dorsal root ganglia and autonomic ganglia
leading to degeneration.
• Cisplatin frequently causes a predominantly sensory peripheral
neuropathy, can also affect the autonomic nervous system,
though this is relatively rare.
• Two patients showed abnormal heart rate responses to both the
Valsalva maneuver and deep breathing, indicating parasympathetic
dysfunction (Hansen, 1990).

48. DEPT. OF PHYSIOLOGY, AIIMS PATNA 52
• Paclitaxel, used for breast and ovarian cancer, disrupts axonal
microtubule dissociation, affecting fast axonal transport.
• Can cause autonomic dysfunction along with peripheral sensory
neuropathy.
• Reported cases of acute severe orthostatic hypotension (Jerian et al.,
1993).
• Abnormalities in Parasympathetic dysfunction indicated by abnormal
heart rate response to the Valsalva maneuver and deep breathing.
• Sympathetic dysfunction evidenced by loss of normal pressor
response to isometric hand grip.

49. DEPT. OF PHYSIOLOGY, AIIMS PATNA 53
• Another study - Reduced diastolic blood pressure variability
observed, but no significant changes in deep breathing, Valsalva
maneuver, or orthostasis (Eckholm et al., 1997).
• Considerable inter-individual variability in susceptibility to taxane-
induced autonomic dysfunction.
• Paralytic ileus and orthostatic hypotension are the most common
manifestations.
• Patients with diabetes mellitus may be more susceptible to
autonomic complications.

50. DEPT. OF PHYSIOLOGY, AIIMS PATNA 54
2. Other therapeutic drugs
• Perhexiline can cause peripheral sensorimotor neuropathy and,
in some cases, autonomic dysfunction (postural hypotension,
abnormal heart rate control).
• Amiodarone may lead to sensory peripheral neuropathy and
possible autonomic dysfunction (orthostatic hypotension),
though evidence is inconclusive.

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• Pentamidine, used for Pneumocystis carinii pneumonia in
AIDS, can cause acute autonomic insufficiency.
• Manifests as severe orthostatic hypotension with a fixed
heart rate.
• Leads to complete loss of heart rate responsiveness to
deep breathing and the Valsalva maneuver.

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Occupational exposure
1. Organic Solvents
• Long-term low-level exposure to carbon disulphide (e.g., in the
viscose/rayon industry) may affect autonomic function.
• Parasympathetic dysfunction, assessed via HRV and responses
to deep breathing and the Valsalva maneuver, is observed in some
workers.

53. DEPT. OF PHYSIOLOGY, AIIMS PATNA 57
2.Acrylamide
• Acrylamide toxicity causes distal symmetrical axonopathy,
affecting both somatic and autonomic nerves, likely by
interfering with fast axonal transport.
• Longer fibers are most vulnerable, with the vagus nerve being the
first affected, leading to early impairment of heart rate control and
gastrointestinal function before blood pressure regulation.
• Autonomic disturbances are rare in humans but well-studied in
experimental animals.

54. DEPT. OF PHYSIOLOGY, AIIMS PATNA 58
3. Heavy Metals
• Chronic exposure to lead is known to cause a peripheral
neuropathy with axonal degeneration, particularly affecting
motor fibres.
• Whether or not the autonomic nervous system is also
involved is controversial.

55. DEPT. OF PHYSIOLOGY, AIIMS PATNA 59
4.Pesticides
• Organochlorine insecticides (e.g., DDT) primarily impact
sensory and motor nerves with minimal autonomic effects,
regardless of acute or chronic exposure.

56. DEPT. OF PHYSIOLOGY, AIIMS PATNA 60
Other forms of exposure
1. Alcohol
• Acute alcohol exposure reduces parasympathetic modulation of heart
rate, possibly via central cardiovascular control alterations rather than
direct vagal effects.
• Chronic alcohol abuse leads to axonal neuropathy, affecting both somatic
and autonomic nerves, predominantly impairing vagal function.
• Impact: About 25% of chronic alcohol abusers show parasympathetic heart
rate control abnormalities, with sympathetic dysfunction occurring later.

57. DEPT. OF PHYSIOLOGY, AIIMS PATNA 61
• Chronic alcohol-induced autonomic dysfunction can lead to
orthostatic hypotension and anhidrosis due to impaired
sympathetic responses.
• Reduced sympathetic activity in alcoholics is evident in blunted
blood pressure responses to pressor stimuli (cold pressor test,
isometric exercise, Valsalva phase IV) compared to controls.
• Nerve damage severity correlates with total lifetime ethanol
intake, though abstinence may lead to gradual improvement over
months to years.

58. DEPT. OF PHYSIOLOGY, AIIMS PATNA 62
Long-term follow-up of chronic alcohol abusers suggests
that the presence of autonomic abnormalities on clinical
testing is associated with an increased mortality.

59. DEPT. OF PHYSIOLOGY, AIIMS PATNA 63
2. Botulinum Toxin
• Botulinum toxin (type B) poisoning should be considered in acute
autonomic neuropathy, especially with predominant
parasympathetic dysfunction.
• Mechanism: The toxin blocks acetylcholine release at cholinergic
synapses by inhibiting calcium-mediated exocytosis, affecting
neuromuscular junctions and autonomic ganglia.
• Dysautonomia cases involving cholinergic pathways have been
reported even in the absence of typical motor abnormalities.

60. DEPT. OF PHYSIOLOGY, AIIMS PATNA 64
C. Stimulation of excess autonomic activity
• Therapeutic Drugs
• Sympathetic Stimulation
• Parasympathetic Stimulation

61. DEPT. OF PHYSIOLOGY, AIIMS PATNA 65
• Excessive autonomic activity is frequently seen in individuals with
denervation hypersensitivity (e.g. due to pre-existing autonomic
neuropathy) during treatment with autonomic agonists.
• A toxic compound may cause abnormally increased autonomic
activity in an individual with previously normal autonomic function.

62. DEPT. OF PHYSIOLOGY, AIIMS PATNA 66
• Organophosphate poisoning inhibits acetylcholinesterase, leading to
excessive cholinergic activity.
• Muscarinic effects include increased secretions,
bronchoconstriction, miosis, abdominal cramps, and
bradycardia.
• Nicotinic effects involve hypertension, muscle fasciculations,
tremors, and eventual paralysis due to receptor overstimulation
at autonomic ganglia and neuromuscular junctions.

63. DEPT. OF PHYSIOLOGY, AIIMS PATNA 67
Therapeutic drugs
Sympathetic stimulation
• Neuroleptic Malignant Syndrome (NMS) is caused by altered central
dopaminergic transmission, leading to increased sympathetic outflow.
• Symptoms include hyperthermia, muscle rigidity, and unstable blood
pressure and heart rate; it occurs in <1% of antipsychotic users but can
be fatal if untreated.
• Similar toxicity is seen with Ecstasy (MDMA) and amphetamines,
sometimes resulting in fatalities

64. DEPT. OF PHYSIOLOGY, AIIMS PATNA 68
• Antidepressants (NA/5-HT reuptake inhibitors) interact with
tyramine, causing excessive catecholamine release.
• Result: Increased neurotransmitter levels in sympathetic
synapses lead to sympathetic hyperactivity.
• Symptoms: Sweating, tachycardia, severe hypertension, with
risk of intracranial hemorrhage.

65. DEPT. OF PHYSIOLOGY, AIIMS PATNA 70
Ketamine, neurolept anaesthetic/analgesic agent
• It has a direct negative inotropic effect on the myocardium in
isolated organ studies.
• In intact systems, sympathetic stimulation counteracts this,
increasing blood pressure, heart rate, and cardiac output.
• Additional effect: Bronchodilation, likely mediated by increased
sympathetic outflow.

66. DEPT. OF PHYSIOLOGY, AIIMS PATNA 71
Parasympathetic Stimulation
• Bethanechol-induced cholinergic toxicity was reported in a
patient with diabetic autonomic neuropathy.
• Symptoms: Shivering, salivation, dyspnea, profuse sweating, and
pinpoint pupils, requiring atropine treatment.
• Cause: Denervation hypersensitivity, leading to an exaggerated
response to normal doses.

67. DEPT. OF PHYSIOLOGY, AIIMS PATNA 73
• Venom-induced autonomic storm from snakes and scorpions causes
sympathetic hyperactivity, leading to acute hypertension and
hypertensive encephalopathy.
• Treatment: Prazosin is effective in managing venom-induced
hypertension.
• Mechanism: Some venoms contain dendrotoxin, which enhances
catecholamine release, while others directly activate alpha-
adrenoceptors.

68. DEPT. OF PHYSIOLOGY, AIIMS PATNA 74
Parasympathetic Stimulation
• Muscarinic toxicity occurs after poisoning with certain wild
mushrooms and herbal remedies containing muscarinic
agonists.
• Cholinomimetic herbal toxins can also cause papillary constriction,
diarrhea, sweating, rhinorrhea, and cardiovascular effects.

69. 75
Ziemssen T, Siepmann T. The
Investigation of the Cardiovascular
and Sudomotor Autonomic Nervous
System-A Review. Front Neurol. 2019
Feb 12;10:53. doi:
10.3389/fneur.2019.00053.
Points to Consider in Autonomic Function Testing

70. DEPT. OF PHYSIOLOGY, AIIMS PATNA 76

71. DEPT. OF PHYSIOLOGY, AIIMS PATNA 77
Cardiovascular Drugs
Class of Drugs Examples Clinical Use Effects
Beta Blockers Propranolol, metoprolol,
atenolol
Hypertension,
arrhythmias, heart failure
Reduce sympathetic tone
→ blunted HRV, impaired
orthostatic responses.
Mask tachycardia during
tilt-table testing.
Alpha-Blockers Prazosin, doxazosin Hypertension, benign
prostatic hyperplasia
(BPH)
Cause vasodilation →
orthostatic hypotension.
May blunt sympathetic
vasoconstriction during
Valsalva maneuver
Calcium Channel Blockers Amlodipine, diltiazem,
verapamil
Hypertension, angina,
arrhythmias
Mild reduction in
sympathetic tone.
Verapamil/diltiazem may
cause bradycardia.
ACE Inhibitors/ARBs Lisinopril, losartan Hypertension, heart
failure, diabetic
nephropathy
Minimal direct ANS
effects but may cause
orthostatic hypotension

72. DEPT. OF PHYSIOLOGY, AIIMS PATNA 79
Neurological/Psychiatric Drugs
Class of Drugs Examples Clinical Use Effects
Tricyclic Antidepressants
(TCAs)
Amitriptyline,
nortriptyline
Depression, neuropathic
pain
Strong anticholinergic
effects → reduced HRV,
orthostatic hypotension.
SSRIs/SNRIs Fluoxetine, venlafaxine Depression, anxiety Mild anticholinergic
effects; may alter HRV
Antipsychotics Amlodipine, diltiazem,
verapamil
Schizophrenia, bipolar
disorder
Anticholinergic effects →
reduced HRV, orthostatic
hypotension.
α-blockade → impaired
vasoconstriction.
Antiepileptics Gabapentin, pregabalin,
carbamazepine
Epilepsy, neuropathic pain May cause autonomic
neuropathy with chronic
use.
Mild anticholinergic
effects.

73. DEPT. OF PHYSIOLOGY, AIIMS PATNA 80
Respiratory Drugs
Class of Drugs Examples Clinical Use Effects
Beta-2 Agonists Albuterol, salmeterol Asthma, COPD Increase sympathetic tone
→ elevated HR, reduced
HRV
Anticholinergics Ipratropium, tiotropium COPD, asthma Reduce parasympathetic
tone → blunted HRV
Class of Drugs Examples Clinical Use Effects
Anticholinergics Dicyclomine, hyoscyamine Irritable bowel syndrome
(IBS), peptic ulcers
Reduce parasympathetic
tone → dry mouth,
reduced HRV
Prokinetics Metoclopramide,
domperidone.
Gastroparesis, nausea Dopamine antagonism →
mild autonomic effects
Gastrointestinal Drugs

74. DEPT. OF PHYSIOLOGY, AIIMS PATNA 81
Pain Management
Class of Drugs Examples Clinical Use Effects
Opioids Morphine, fentanyl,
tramadol
Chronic pain, post-
surgical pain
Reduce sympathetic tone →
orthostatic hypotension,
constipation
NSAIDs Ibuprofen, naproxen Pain, inflammation Minimal direct ANS effects
but may cause fluid retention
→ orthostatic hypotension.
Class of Drugs Examples Clinical Use Effects
Decongestants Pseudoephedrine,
phenylephrine
Nasal congestion Sympathomimetic →
elevated HR, reduced HRV
Antihistamines Diphenhydramine,
loratadine
Allergies, insomnia Anticholinergic effects
(especially
diphenhydramine) →
reduced HRV.
Others

75. DEPT. OF PHYSIOLOGY, AIIMS PATNA 82
Others
Class of Drugs Examples Clinical Use Effects
Chemotherapy Agents Vincristine, cisplatin Anti-cancer Drug Autonomic neuropathy →
orthostatic hypotension,
reduced HRV
Practical Tips for Autonomic Testing
1. Screen for Medications: Always review the patient’s medication list, including OTC drugs and
supplements.
2. Discontinuation Protocol: Stop ANS-acting drugs 5 half-lives before testing (if safe).
3. Document Effects: Note any drugs that cannot be stopped and their potential impact on test
results.
4. Patient Education: Advise patients to avoid caffeine, nicotine, and heavy meals before testing

76. DEPT. OF PHYSIOLOGY, AIIMS PATNA 83

77. DEPT. OF PHYSIOLOGY, AIIMS PATNA 84
Summary

78. 85
References
1. Autonomic Failure A Textbook of Clinical Disorders of the Autonomic Nervous
System Fifth Edition Edited by Christopher J. Mathias and Roger Bannister
2. Tripathi, K. D. (2018). Essentials of medical pharmacology (8th ed.). Jaypee
Brothers Medical.
3. Pharmacology for Medical Graduates, 4th Updated Edition Tara V. Shanbhag,
Smita Shenoy
4. Ziemssen T, Siepmann T. The Investigation of the Cardiovascular and
Sudomotor Autonomic Nervous System-A Review. Front Neurol. 2019 Feb
12;10:53. doi: 10.3389/fneur.2019.00053.
5. Sudo SZ et al, Diabetes-induced cardiac autonomic neuropathy: impact on
heart function and prognosis. Biomedicines. 2022;10(12):3258.

79. DEPT. OF PHYSIOLOGY, AIIMS PATNA 86
THANK YOU !
saran.adhoc@gmail.com