A 38-year-old woman from Mumbai presents with a 6-month history of recurrent episodes of palpitations, anxiety, and dry mouth. During an episode, her heart rate is 105/min, blood pressure 155/95 mmHg, and she has marked salivary dryness. Her pupils are dilated and she reports blurred vision. Thyroid function tests and cardiac workup are normal. A diagnosis of panic disorder with autonomic hyperactivity is made. Which neurotransmitter-receptor system is most likely dysregulated to cause the constellation of sympathetic and anticholinergic features observed?

Explanation

## Autonomic Dysregulation in Panic Disorder ### Clinical Presentation Analysis The patient exhibits a dual autonomic pattern: 1. **Sympathetic hyperactivity:** tachycardia, hypertension, anxiety, dilated pupils 2. **Parasympathetic hypoactivity:** dry mouth (reduced salivation), blurred vision (mydriasis dominates) This is **not** parasympathetic excess — it is sympathetic dominance with relative parasympathetic withdrawal. ### Pathophysiology of Panic Disorder **Key Point:** Panic disorder involves dysregulation of the **locus coeruleus-noradrenergic system**, which is the brain's main source of norepinephrine and controls arousal, threat detection, and autonomic output. ### Noradrenergic System in Panic **High-Yield:** The locus coeruleus projects widely to: - Amygdala (fear/threat processing) - Prefrontal cortex (cognitive control — reduced in panic) - Hypothalamus (autonomic regulation) - Brainstem autonomic nuclei Excessive noradrenergic tone → **simultaneous activation of:** - **α1 receptors** → vasoconstriction, mydriasis, piloerection - **β1 receptors** → tachycardia, increased contractility - **β2 receptors** → tremor, anxiety **And relative withdrawal of parasympathetic tone** → loss of salivation, accommodation defects, unopposed sympathetic effects on heart rate and blood pressure. ### Why This Is NOT the Other Options | Feature | Sympathetic Excess (Correct) | Parasympathetic Excess (Wrong) | | --- | --- | --- | | Salivation | ↓ (dry mouth) | ↑ (drooling) | | Pupils | Dilated (mydriasis) | Constricted (miosis) | | Heart rate | ↑ (tachycardia) | ↓ (bradycardia) | | Vision | Blurred (mydriasis) | Sharp (miosis) | | Anxiety | ↑ (noradrenergic) | ↓ (calming) | **Clinical Pearl:** Dry mouth + dilated pupils + tachycardia = **sympathetic dominance**. If this were parasympathetic excess, you would see salivation, miosis, bradycardia, and bronchospasm — the opposite picture. ### Mnemonic: SYMPATHETIC PANIC SIGNS **S**weat, **Y**ellow pupils (dilated), **M**outh dry, **P**ounding heart, **A**nxiety, **T**remor, **H**ypertension, **E**xcitation, **T**achycardia, **I**ncreased arousal, **C**onstricted airways (sometimes) ### Treatment Rationale **Key Point:** SSRIs and SNRIs (which reduce noradrenergic hyperactivity in the locus coeruleus) are first-line treatments for panic disorder — confirming the noradrenergic hypothesis. [cite:Harrison 21e Ch 418]