PHARMACOLOGY- AUTONOMIC NERVOUS SYSTEM

SUBJECTIVE EXAM ANSWER KEY

By MEDTRIX

ACUTE CONGESTIVE GLAUCOMA TREATMENT

A. Hyperosmotic Agents

Drugs:

Mannitol (20%) – IV infusion (1.5-2 g/kg)to dehydrate the vitreous and lower IOP rapidly.
Glycerol (10%) – Oral alternative, 50% glycerine retention enema may also be used

Mechanism of Action

These agents increase plasma osmolality, drawing water out of the vitreous humor, thereby reducing
intraocular pressure.

Adverse Effects:

Mannitol: Dehydration, Headache, Electrolyte imbalance, Pulmonary edema, Heartfailure

Glycerol: Nausea, Vomiting, Hyperglycemia(caution in diabetics).

B. Carbonic Anhydrase Inhibitors

Drug:

Acetazolamide – IV (500 mg bolus), followed by oral administration (250 mg every 6 hours).

Mechanism of Action

Inhibits carbonic anhydrase in the ciliary body, reducing aqueous humor production and lowering
IOP.

Adverse Effects: Metabolic acidosis, Hypokalemia, Paresthesia, Renal calculi, Drowsiness,

Sulfonamide hypersensitivity reactions.

C. Miotic Agents (Parasympathomimetics)

Drug:

Pilocarpine (1-4%) – Instilled every 10 minutes initially, then at longer intervals.

Mechanism of Action:

Di tl ti l t i i t (M3) i th i i hi t l i ill
 Directly stimulates muscarinic receptors (M3) in the iris sphincter muscle, causing pupillary
constriction (miosis). This pulls the peripheral iris away from the trabecular meshwork, facilitating
aqueous humor drainage.

Adverse Effects: Blurred vision, Brow ache, Retinal detachment (rare), Nausea, Sweating, Bradycardia,
Increased salivation

D.Topical β-Blockers

Drug:

Timolol (0.5%): Administered(one drop) every 12 hours to reduce aqueous humor production:

Mechanism of Action:

Blocks β2 receptors in the ciliary epithelium, reducing aqueous humor production.

Adverse Effects: Bradycardia, Hypotension, Bronchospasm (caution in asthma/COPD), Depression,

Fatigue.

Timolol is preferred because:

1. Acts as a local anesthetic/partial agonist

2. Doesn't affect pupil size (accommodation)

3. Has a longer duration of action

4. Well tolerated

5. Less expensive

E. Other Adjunctive Drugs

Drug:

Apraclonidine (1%) – Adjunct therapy.

Mechanism of Action:

Stimulates α2 receptors, decreasing aqueous humor production and increasing uveoscleral

outflow.

Adverse Effects: Ocular irritation, Dry mouth, Dizziness,Hypotension, Conjunctival hyperemia.

F. Prostaglandin Analogs

Drug:

Latanoprost (0.005%) – Once daily.

Mechanism of Action:

Increases uveoscleral outflow of aqueous humor by relaxing ciliary muscle.

Adverse Effects: Iris pigmentation changes (brown discoloration), Eyelash growth, Eye redness, Mild
irritation.
Definitive Surgical or Laser Treatment
Laser Iridotomy or Surgical Iridectomy: Once the acute attack is controlled, definitive treatment is
required to prevent recurrence.
In chronic cases, a miotic or other ocular hypotensive drug may be used long-term, but surgery is
often necessary

MYASTHENIA GRAVIS
A. Anticholinesterase Drugs (First-line therapy)

These drugs inhibit acetylcholinesterase (AChE), allowing acetylcholine (ACh) to act for a longer
duration at the neuromuscular junction.
Neostigmine: 15 mg orally every 6 hours, with dose adjustments based on response.
Pyridostigmine: Preferred due to a longer duration of action, requiring less frequent dosing.

Adverse Effects: Nausea, Diarrhea, Sweating, Bradycardia (managed with atropine if needed)

B. Corticosteroids (For cases not responding to anticholinesterases)

Prednisolone: 30-60 mg/day initially, then tapered to 10 mg/day or on alternate days.

Mechanism of action

Suppresses autoimmune response and decreases AChR antibody production.

Adverse Effects: Osteoporosis, Hyperglycemia, Immunosuppression, Weight gain

C. Immunosuppressants (For severe or refractory cases)

Azathioprine, Cyclosporine: Inhibit antibody production by suppressing T-cells.

Adverse Effects: Bone marrow suppression, Hepatotoxicity, Increased infection risk

Management of Myasthenic Crisis

1. Myasthenic crisis is characterized by severe respiratory muscle weakness requiring ventilatory

support.
2. IV Methylprednisolone pulse therapy with plasmapheresis or IVIG for rapid improvement.
3. Temporary discontinuation of anticholinesterases, as overdose may cause cholinergic crisis
(which worsens weakness).

Why are Anticholinesterases the First-line Treatment?

Directly improve muscle strength by enhancing neurotransmission.

Act rapidly (Pyridostigmine onset: 30-60 min, duration: 3-6 hours).
Non-immunosuppressive, unlike corticosteroids and immunosuppressants.
They counteract the primary defect—reduced ACh receptor availability by enhancing synaptic ACh
levels, leading to improved muscle strength and function.

ORGANOPHOSPHATE POISONING
Organophosphate poisoning occurs due to inhibition of acetylcholinesterase, leading to excessive
acetylcholine accumulation at synapses.

Treatment Approach

Supportive Care
a. Airway Protection & Oxygenation: Mechanical ventilation if needed.
b. Decontamination: Remove contaminated clothing and wash skin.
Pharmacological Treatment
a. Atropine (Anticholinergic)
i. Mechanism of Action: Blocks muscarinic effects of excess acetylcholine.
ii. Dose: 2–5 mg IV every 5–15 minutes until secretions dry up.
iii. Adverse Effects: Tachycardia, urinary retention, hyperthermia
b P lid i (Ch li t R ti t )
 b. Pralidoxime (Cholinesterase Reactivator)
i. Mechanism of Action: Reactivates acetylcholinesterase if given early.
ii. Dose: 1–2 g IV over 30 minutes, repeated every 6–12 hours.
iii. Adverse Effects: Hypertension, nausea, muscle weakness.
c. Benzodiazepines (Diazepam)
i. Mechanism of Action: Controls seizures and reduces anxiety.
ii. Dose: 5–10 mg IV.
iii. Adverse Effects: Drowsiness, respiratory depression.
Monitoring
a. Serial measurement of cholinesterase levels.
b. Observation for intermediate syndrome (muscle weakness 24–96 hours post-exposure).

1 A tid t & R t
1. Antidote & Route
a. Atropine (IV) & Pralidoxime (IV).
2. Monitoring Adequacy of Atropine
a. Parameters: Heart rate, drying of secretions.
3. Why Not Give Pralidoxime Late?
a. It works only before the aging of enzymes.
4. Atropine-Induced Delirium
a. Managed with physostigmine.
CASE BASED
1. 32-year-old man with RTA and blood loss – Inotropic support for impending renal
shutdown.
a. Name the inotrope of choice and mention the dose.
i. Dopamine is the inotrope of choice.
ii. Dose: 2–5 mcg/kg/min (for renal perfusion)
iii. Given via continuous IV infusion.
b. Mechanism of renal protective effect.
i. Dopamine exerts a renal protective effect through: Dopaminergic (D1 receptor) activation →
Vasodilation of renal, mesenteric, and coronary arteries → Increased renal blood flow →
Enhanced urine output.
ii. Beta-1 adrenergic stimulation (at moderate doses) → Increases cardiac output → Improves
renal perfusion.
c. Consequences of doubling the dose
i. At higher doses (5–10 mcg/kg/min), dopamine predominantly stimulates beta-1 receptors,
increasing heart rate and contractility.
ii. At doses >10 mcg/kg/min, alpha-adrenergic effects dominate, causing vasoconstriction,
which may reduce renal perfusion, worsening renal function instead of protecting it.
2. 55-year-old man with chronic open-angle glaucoma
a. Two strategies for reducing intraocular tension.
i. Reducing aqueous humor production (e.g., beta-blockers, carbonic anhydrase inhibitors,
alpha-2 agonists).
ii. Enhancing aqueous humor outflow (e.g., prostaglandin analogs, cholinergic agonists).
b. Drug of choice and reason.
i. Prostaglandin analogs (e.g., Latanoprost 0.005% eye drops once daily at night).
ii. Reason: Most effective in reducing intraocular pressure (IOP) by increasing uveoscleral
outflow.
c. Mechanism of IOP reduction and adverse effects.
i. Mechanism: Prostaglandins increase the breakdown of extracellular matrix in the
uveoscleral pathway, enhancing aqueous humor drainage.
ii. Adverse effects: Iris pigmentation (brown discoloration), Eyelash growth (hypertrichosis),
Conjunctival hyperemia.

1. 40-year-old woman with myasthenia gravis

a. Drug of choice and its group
i. Pyridostigmine (preferred over Neostigmine).
ii. Group: Reversible anticholinesterase inhibitors.
b. Reason for preference
i. Pyridostigmine has a longer duration of action (4–6 hours) than neostigmine.
ii. Fewer gastrointestinal and muscarinic side effects compared to neostigmine.
c. Management of diarrhea, cramps, and salivation
i. These symptoms indicate excessive cholinergic activity.
ii. Reduce Pyridostigmine dose slightly.
d. Give Atropine (0.2–0.3 mg PO) to counteract muscarinic effects.

4.35-year-old man with anaphylaxis due to lignocaine

a. Drug of choice and justification.
i. Epinephrine (Adrenaline) is the drug of choice.
b. Justification:
i R b h (b t 2 ff t)
 i. Reverses bronchospasm (beta-2 effect).
ii. Increases blood pressure (alpha-1 effect).
iii. Reduces histamine release from mast cells (beta-2 effect).
c. Dose, strength, and route. Why preferred?
i. Dose: 0.3–0.5 mg
ii. Strength: 1:1000 (1 mg/mL)
d. Route: Intramuscular (IM) in anterolateral thigh
i. Reason: IM route provides rapid absorption and avoids cardiovascular complications seen with
IV use.
e. Why is it dispensed as a pen injector?
i. Ensures rapid and accurate self-administration during anaphylaxis.
ii. Used in emergency situations where immediate action is needed (e.g., EpiPen).

Drug Selection & Justification

1. Mydriasis for fundoscopic examination.
a. Drug: Tropicamide (0.5–1% eye drops)
b. Short-acting anticholinergic that dilates the pupil.
c. Preferred over Atropine (which has a long duration).
d. Precautions: Avoid in narrow-angle glaucoma.
2. 12-year-old with nasal congestion.
a. Drug: Oxymetazoline or Phenylephrine nasal spray
i. Alpha-adrenergic agonist causing vasoconstriction → Decreases nasal congestion.
ii. Precautions: Avoid prolonged use (>5 days) to prevent rebound congestion.
3. 32-year-old woman with colicky abdominal pain.
a. Drug: Dicyclomine (Antispasmodic)
i. Anticholinergic that relaxes GI smooth muscles, relieving spasm.
ii. Precautions: Avoid in intestinal obstruction and glaucoma.
4. 50-year-old man requiring muscle relaxant for laparotomy.
a. Drug: Vecuronium or Atracurium (Non-depolarizing muscle relaxants)
b. Provides longer muscle relaxation with less histamine release than succinylcholine.
c. Precautions: Monitor neuromuscular function; use neostigmine + atropine for reversal.
5. 20-year-old man with stage anxiety.
a. Drug: Propranolol (10–40 mg PO, 30–60 min before performance)
b. Beta-blocker reduces adrenergic symptoms (tremors, palpitations, sweating).
c. Precautions: Avoid in asthma and bradycardia.
6. Belladonna Poisoning
a. Symptoms: Symptomatic treatment, Gastric lavage with tannic acid, Keep in dark, quiet room,
Cold sponging to reduce body temp, Physostigmine (1–3 mg SC or IV) – Risk of arrhythmias

Contraindications

1. Infants and children predisposed to hyperthermia

2. Benign Prostatic Hyperplasia (BPH)

3. Angle-closure glaucoma

Uses and Adverse Drug Reactions (ADR)

1. Uses of Alpha Agonists: 1.Hypotension & Shock – Norepinephrine, Phenylephrine

(vasoconstriction to raise BP).
2. Nasal Decongestants – Phenylephrine, Oxymetazoline (vasoconstriction reduces nasal
congestion).
3. Ophthalmic Use – Brimonidine (reduces intraocular pressure in glaucoma).
4. ADHD & Hypertension – Clonidine (reduces sympathetic outflow).
5. Anaphylaxis – Epinephrine (bronchodilation & vasoconstriction).

Adverse Drug Reactions (ADR) of Alpha Agonists:

1 H t i & R fl B d di D t t i ti
 1. Hypertension & Reflex Bradycardia – Due to vasoconstriction.
2. Arrhythmias & Palpitations – Due to excessive adrenergic stimulation.
3. Urinary Retention – Especially in BPH patients.
4. Rebound Congestion – With prolonged use of nasal sprays (Rhinitis Medicamentosa).
5. CNS Effects – Anxiety, tremors, insomnia (especially with Clonidine withdrawal).

Contraindications:

1. Hypertension (may worsen BP control)

2. Severe cardiovascular disease (risk of arrhythmias and ischemia)
3. Hyperthyroidism (increased sensitivity to catecholamines)
4. Glaucoma (especially narrow-angle glaucoma, due to increased intraocular pressure)
5. Pheochromocytoma (risk of excessive catecholamine release)
6. Peripheral vascular diseases (vasoconstriction may worsen ischemia)
7. Renal impairment (risk of altered drug metabolism and excretion)

Uses of Alpha Blockers:

1. Hypertension – Prazosin, Doxazosin (α1-blockers cause vasodilation and reduce blood pressure).
2. Benign Prostatic Hyperplasia (BPH) – Tamsulosin, Alfuzosin (relax prostate smooth muscle and
improve urine flow).
3. Pheochromocytoma – Phenoxybenzamine, Phentolamine (used to control hypertension due to
catecholamine excess).
4. Raynaud’s Phenomenon – Prazosin (reduces vasospasm and improves blood flow).
5. Heart Failure – Carvedilol (α & β-blocker) (reduces afterload and improves cardiac output).
6. Erectile Dysfunction – Yohimbine (α2-blocker that increases penile blood flow).

Adverse Drug Reactions (ADR) of Alpha Blockers:

1. Postural Hypotension – Especially with first doses (First-dose phenomenon in Prazosin).

2. Reflex Tachycardia – Due to compensatory sympathetic activation.
3. Nasal Congestion – Due to vasodilation.
4. Dizziness & Fatigue – Due to reduced blood pressure.
5. Edema – Due to fluid retention (common with non-selective blockers).
6. Inhibition of Ejaculation – Seen with Tamsulosin and other uroselective α1-blockers.

Contraindications:

Hypotension (can lead to severe dizziness and syncope)

Severe cardiac failure (risk of reflex tachycardia and worsening heart function)
Orthostatic hypotension (may exacerbate postural BP drops)
Severe renal impairment (altered drug clearance)
Patients undergoing cataract surgery (risk of intraoperative floppy iris syndrome)

Uses of Beta Agonists:

1. Bronchial Asthma & COPD – Salbutamol, Terbutaline, Formoterol, Salmeterol (β2-agonists cause
bronchodilation).
2. Preterm Labor (Tocolysis) – Ritodrine, Terbutaline (β2-agonists relax uterine smooth muscle).
3. Anaphylaxis – Epinephrine (β2 for bronchodilation, β1 for cardiac stimulation).
4. Cardiogenic Shock & Heart Failure – Dobutamine (β1-agonist increases cardiac contractility).
5. Bradycardia & Heart Block – Isoprenaline (β1 and β2 action increases heart rate).

Adverse Drug Reactions (ADR) of Beta Agonists:

1. Tachycardia & Palpitations – Due to β1 stimulation.

2. Tremors – Common with β2-agonists (due to skeletal muscle stimulation).
3. Hypokalemia – Due to β2-mediated shift of potassium into cells.
4. Hyperglycemia – β2 stimulation increases glycogenolysis.
5. Headache & Dizziness – Due to vasodilation effects.
6. Increased Oxygen Demand – Can worsen angina in heart disease patients.

7 A h th i E i ll ith hi h d i di d i di id l
 7. Arrhythmias – Especially with high doses or in predisposed individuals.

Contraindications:

Tachyarrhythmias (can increase heart rate further)

Uncontrolled hypertension (may exacerbate BP elevation)
Hyperthyroidism (increased sensitivity to catecholamines)
Severe coronary artery disease (may precipitate angina)
Hypertrophic obstructive cardiomyopathy (may worsen outflow obstruction)
Glaucoma (especially non-selective beta agonists, due to increased intraocular pressure)

Uses of Beta Blockers: ( extremely important)

1. Hypertension – Reduces cardiac output and renin secretion (e.g., Metoprolol, Atenolol).
2. Angina Pectoris – Reduces myocardial oxygen demand (e.g., Propranolol, Metoprolol).
3. Myocardial Infarction (Post-MI Protection) – Reduces mortality (e.g., Carvedilol, Metoprolol).
4. Heart Failure (HFrEF) – Improves survival and prevents remodeling (e.g., Bisoprolol, Carvedilol).
5. Arrhythmias – Controls atrial fibrillation, ventricular arrhythmias (e.g., Esmolol, Sotalol).
6. Glaucoma – Reduces aqueous humor production (e.g., Timolol, Betaxolol).
7. Migraine Prophylaxis – Prevents attacks (e.g., Propranolol).
8. Thyrotoxicosis – Controls symptoms like tachycardia and tremors (e.g., Propranolol).
9. Pheochromocytoma (with Alpha Blockers) – Controls hypertension (e.g., Propranolol).
10. Anxiety & Essential Tremors – Controls symptoms (e.g., Propranolol).

Adverse Drug Reactions (ADR) of Beta Blockers:

1. Bradycardia & Hypotension – Due to β1 blockade.

2. Heart Failure Worsening (Initially) – Especially in acute decompensated HF.
3. Bronchoconstriction – β2 blockade worsens asthma and COPD.
4. Masking of Hypoglycemia – Can delay recognition of hypoglycemic symptoms in diabetics.
5. Fatigue & Depression – Common with lipid-soluble beta blockers (e.g., Propranolol).
6. Impotence & Sexual Dysfunction – Due to reduced sympathetic activity.
7. Cold Extremities & Raynaud’s Phenomenon – Due to vasoconstriction.
8. Dyslipidemia – Some older beta blockers (e.g., Propranolol) increase triglycerides and lower HDL.
9. Sudden Withdrawal Syndrome – Can cause rebound hypertension and tachycardia if stopped
abruptly.

Contraindications:

Asthma and COPD (can induce bronchoconstriction, especially non-selective beta blockers)
Bradycardia (risk of severe heart rate reduction)
Heart block (2nd or 3rd degree, unless pacemaker is present)
Cardiogenic shock (may worsen myocardial depression)
Severe peripheral vascular disease

Uses of Atropine and Anticholinergics (System-Wise)

1. Central Nervous System (CNS)

Parkinsonism – Central anticholinergics (e.g., Trihexyphenidyl, Procyclidine) are used to reduce
tremors and rigidity
Motion Sickness – Hyoscine (Scopolamine) is used to prevent nausea and vomiting associated
with motion sickness
Drug-Induced Extrapyramidal Symptoms – Used to treat antipsychotic-induced dystonia (e.g.,
Trihexyphenidyl)

2. Cardiovascular System (CVS)

Bradycardia and Heart Block – Atropine is used to increase heart rate in cases of sinus
bradycardia and AV block
V l Att k U dt t fl lb d di d i di l
 Vasovagal Attacks – Used to prevent reflex vagal bradycardia during surgery or myocardial
infarction

3.Respiratory System

Bronchial Asthma and COPD – Ipratropium, Tiotropium are inhaled M3 blockers used as
bronchodilators in asthma and COPD
Preanesthetic Medication – Atropine is used before surgery to reduce airway secretions and
prevent laryngospasm

4. Gastrointestinal (GI) System

Peptic Ulcer – Pirenzepine (selective M1 antagonist) is used to reduce gastric acid secretion
(rarely used today)
Irritable Bowel Syndrome (IBS) and Spasmodic Colic – Dicyclomine, Hyoscine Butylbromide are
used as antispasmodics
Diarrhea (As Adjunct) – Atropine is combined with diphenoxylate (Lomotil) to reduce intestinal
motility

5. Genitourinary System

Urinary Incontinence and Overactive Bladder – Oxybutynin, Tolterodine, Solifenacin reduce

bladder contractions in urge incontinence
Neurogenic Bladder – Atropine and other anticholinergics help increase bladder capacity

6. Ocular System

Mydriatic for Fundoscopy – Tropicamide, Atropine are used to dilate the pupil for eye examinations
Cycloplegic Refraction – Atropine, Cyclopentolate are used to paralyze accommodation for
refractive testing
Treatment of Uveitis & Iritis – Atropine, Homatropine relieve ocular pain and prevent synechiae
formation

7. Miscellaneous Uses

Organophosphate Poisoning – Atropine is the antidote for organophosphate poisoning by

blocking excess muscarinic activity
Hyperhidrosis (Excessive Sweating) – Atropine is sometimes used to reduce sweating

Aging of Enzyme in Organophosphate Poisoning

Definition:

Aging refers to the irreversible modification of the acetylcholinesterase (AChE) enzyme after it has
been inhibited by organophosphate compounds. This prevents the enzyme from being reactivated,
making the poisoning permanent unless new enzyme synthesis occurs.

Mechanism of Aging:

1. Organophosphates (e.g., Malathion, Parathion, Sarin gas) phosphorylate the serine hydroxyl
group at the active site of acetylcholinesterase.
2. Over time, the phosphate group loses an alkyl or alkoxy group (dealkylation), making the enzyme
irreversibly bound to the organophosphate.
3. Once aging occurs, cholinesterase reactivators like Pralidoxime (2-PAM) can no longer restore
enzyme function, leading to permanent inhibition.

Clinical Importance of Aging:

Time-Dependent Process: Different organophosphates have different aging times:

Soman (Nerve Gas) → Ages in minutes.
Sarin, Parathion → Ages in hours.
Malathion → Ages in days.
Treatment Implications:
Pralidoxime (2-PAM) must be administered before aging to successfully reactivate
acetylcholinesterase.
If aging has already occurred, only new enzyme synthesis can restore function, which may take
weeks.