Central Nervous System Pharmacology

Central Nervous System Pharmacology Indian Medical PG Question 1: Erenumab was approved by FDA in 2018 for which condition?

• A. Phenylketonuria
• B. Migraine (Correct Answer)
• C. Hypertension
• D. Glycogen storage disorders

Central Nervous System Pharmacology Explanation: **Explanation:** **Erenumab** is a breakthrough therapeutic agent in the management of **Migraine**. It is a fully human monoclonal antibody that specifically targets and blocks the **Calcitonin Gene-Related Peptide (CGRP) receptor**. CGRP is a potent neuropeptide and vasodilator that plays a central role in the pathophysiology of migraine by mediating pain transmission and neurogenic inflammation in the trigeminal system. By antagonizing this receptor, Erenumab effectively prevents the initiation of migraine attacks. It was the first FDA-approved drug (2018) in this class specifically for the **prophylaxis** of migraine in adults. **Analysis of Incorrect Options:** * **A & D (Phenylketonuria & Glycogen storage disorders):** These are metabolic/genetic disorders. Phenylketonuria is typically managed with dietary restriction or drugs like Sapropterin. Glycogen storage diseases are managed through nutritional support or enzyme replacement therapy (e.g., Alglucosidase alfa for Pompe disease), not monoclonal antibodies targeting neuropeptides. * **C (Hypertension):** While CGRP is a vasodilator, Erenumab is not used for hypertension. In fact, because it blocks a vasodilator, a potential side effect of Erenumab is a slight increase in blood pressure. **High-Yield Clinical Pearls for NEET-PG:** * **Mechanism:** CGRP Receptor Antagonist (Contrast this with *Fremanezumab* and *Galcanezumab*, which bind to the CGRP **ligand** itself). * **Route:** Administered via subcutaneous injection once monthly. * **Indications:** Prophylaxis of both episodic and chronic migraine. * **Side Effects:** Most common are injection site reactions and constipation. * **Other "Gepants":** Oral CGRP antagonists (e.g., Rimegepant, Ubrogepant) are used for acute treatment or prevention.

Central Nervous System Pharmacology Indian Medical PG Question 2: All except one are centrally acting muscle relaxants. Which one is not?

• A. Meprobamate
• B. Baclofen
• C. Diazepam
• D. Dantrolene sodium (Correct Answer)

Central Nervous System Pharmacology Explanation: **Explanation:** Skeletal muscle relaxants are broadly classified into two categories based on their site of action: **Centrally acting** (acting on the CNS) and **Peripherally acting** (acting at the neuromuscular junction or directly on the muscle fiber). **1. Why Dantrolene Sodium is the correct answer:** Dantrolene is a **peripherally acting** muscle relaxant. Unlike the other options, it does not work by depressing the central nervous system. Instead, it acts directly on the skeletal muscle by binding to the **Ryanodine Receptor (RyR1)** on the sarcoplasmic reticulum. This inhibits the release of calcium ions into the cytosol, thereby preventing muscle contraction (excitation-contraction uncoupling). **2. Analysis of Incorrect Options:** * **Meprobamate:** A carbamate derivative primarily used as an anxiolytic; it acts as a central depressant with muscle relaxant properties. * **Baclofen:** A **GABA-B agonist** that acts at the spinal cord level to reduce spasticity by inhibiting monosynaptic and polysynaptic reflexes. * **Diazepam:** A Benzodiazepine that acts via **GABA-A receptors** in the CNS to increase chloride conductance, leading to hyperpolarization and muscle relaxation. **Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** Dantrolene is the DOC for **Malignant Hyperthermia** (caused by halothane/succinylcholine) and **Neuroleptic Malignant Syndrome (NMS)**. * **Baclofen** is the DOC for spasticity in Multiple Sclerosis but is ineffective in stroke. * **Tizanidine** is another high-yield centrally acting relaxant that works as a central **$\alpha_2$ agonist**. * **Side Effect:** A major side effect of Dantrolene is hepatotoxicity (monitor LFTs).

Central Nervous System Pharmacology Indian Medical PG Question 3: Which of the following drugs has the highest potential to cause metabolic syndrome?

• A. Clozapine (Correct Answer)
• B. Risperidone
• C. Quetiapine
• D. Aripiprazole

Central Nervous System Pharmacology Explanation: **Explanation:** Metabolic syndrome—characterized by significant weight gain, hyperlipidemia, and hyperglycemia (Type 2 Diabetes)—is a major adverse effect of **Second-Generation Antipsychotics (SGAs)**. **1. Why Clozapine is correct:** Clozapine (along with Olanzapine) carries the **highest risk** of metabolic syndrome. The underlying mechanism involves potent antagonism of **H1 (histamine)** and **5-HT2C (serotonin)** receptors, which leads to increased appetite, sedation, and direct interference with insulin sensitivity. Clozapine is associated with the most profound weight gain and the highest incidence of new-onset diabetes among all antipsychotics. **2. Analysis of incorrect options:** * **Quetiapine:** Also carries a high risk of metabolic syndrome, but it is clinically ranked lower than Clozapine and Olanzapine. * **Risperidone:** Carries a moderate risk. It is more notorious for causing hyperprolactinemia (due to D2 blockade in the tuberoinfundibular pathway) than severe metabolic derangement. * **Aripiprazole:** This is a partial D2 agonist and has the **lowest risk** (metabolically neutral) along with Ziprasidone and Lurasidone. **3. NEET-PG High-Yield Pearls:** * **Hierarchy of Metabolic Risk:** Clozapine = Olanzapine > Quetiapine > Risperidone > Aripiprazole = Ziprasidone. * **Monitoring:** Patients on Clozapine require mandatory monitoring of BMI, fasting blood glucose, and lipid profiles. * **Clozapine "Must-Knows":** It is the drug of choice for **resistant schizophrenia**, but its use is limited by **agranulocytosis** (requires regular CBC monitoring) and a lowered seizure threshold.

Central Nervous System Pharmacology Indian Medical PG Question 4: Which of the following medications are used for migraine prophylaxis?

• A. Verapamil
• B. Valproate
• C. Amitriptyline
• D. All of the above (Correct Answer)

Central Nervous System Pharmacology Explanation: Migraine prophylaxis is indicated when patients experience frequent attacks (usually >2-3 per month), severe disability, or failure of acute treatments. The goal is to reduce the frequency, severity, and duration of attacks. Why "All of the above" is correct: The medications listed represent three different pharmacological classes, all of which are first-line or second-line agents for migraine prevention: * **Verapamil (Option A):** While Beta-blockers (like Propranolol) are the most common cardiovascular drugs used, Verapamil (a Calcium Channel Blocker) is an effective alternative, particularly in patients with contraindications to beta-blockers or those with cluster headaches. * **Valproate (Option B):** Anticonvulsants like Sodium Valproate and Topiramate are highly effective. Valproate works by enhancing GABAergic inhibition and modulating glutamate, thereby reducing neuronal hyperexcitability [1]. * **Amitriptyline (Option C):** This Tricyclic Antidepressant (TCA) is a mainstay for prophylaxis. It works by inhibiting the reuptake of Serotonin and Norepinephrine and is particularly useful in patients with co-existing tension-type headaches or insomnia [2]. **High-Yield Clinical Pearls for NEET-PG:** * **Drug of Choice (DOC):** Propranolol is generally considered the first-line agent for migraine prophylaxis. * **Topiramate:** Often preferred in obese patients as it causes weight loss, whereas Valproate and Amitriptyline cause weight gain. * **Teratogenicity:** Avoid Valproate in women of childbearing age due to the risk of neural tube defects. * **Newer Agents:** CGRP antagonists (e.g., Erenumab) and Botox injections are used for chronic, refractory migraines. * **Acute Attack DOC:** Triptans (5-HT 1B/1D agonists) are the DOC for abortive therapy, not prophylaxis.

Central Nervous System Pharmacology Indian Medical PG Question 5: Which of the following acts as an antagonist to the NMDA receptor?

• A. Ketamine (Correct Answer)
• B. Spermine
• C. Muscimol
• D. Baclofen

Central Nervous System Pharmacology Explanation: **Explanation:** The **NMDA (N-methyl-D-aspartate) receptor** is an ionotropic glutamate receptor that plays a critical role in synaptic plasticity and memory. It is unique because it requires both glutamate binding and glycine as a co-agonist, along with the removal of a magnesium (Mg²⁺) plug via depolarization. **Ketamine** (Option A) is a dissociative anesthetic that acts as a **non-competitive antagonist** at the NMDA receptor. It binds to the phencyclidine (PCP) site inside the ion channel, effectively blocking the flow of cations. This blockade results in "dissociative anesthesia," characterized by profound analgesia, amnesia, and a cataleptic state. **Analysis of Incorrect Options:** * **Spermine (Option B):** This is a polyamine that acts as a **positive allosteric modulator** (agonist-like effect) at the NMDA receptor, facilitating its function rather than inhibiting it. * **Muscimol (Option C):** This is a potent, selective **GABA-A receptor agonist** derived from the mushroom *Amanita muscaria*. * **Baclofen (Option D):** This is a selective **GABA-B receptor agonist** used clinically as a centrally acting muscle relaxant to treat spasticity. **High-Yield Clinical Pearls for NEET-PG:** * **Other NMDA Antagonists:** Memantine (used in Alzheimer’s), Amantadine (Parkinson’s), Dextromethorphan (antitussive), and Phencyclidine (PCP). * **Ketamine Side Effects:** It is notorious for causing **emergence delirium** and hallucinations. It is also the anesthetic of choice in patients with **asthma** (due to bronchodilation) and **hypovolemic shock** (due to sympathetic stimulation). * **Contraindication:** Ketamine should be avoided in patients with increased intracranial pressure (ICP).

Central Nervous System Pharmacology Flashcard 1 of 5

Question: Mechanism of action of sodium valproate: No answer _____

Answer: :)

Central Nervous System Pharmacology Flashcard 2 of 5

Question: The given plant is? _____

Answer: Erythroxylum cocca

Central Nervous System Pharmacology Flashcard 3 of 5

Question: tetanospasmin blocks _____

Answer: presynaptic inhibitory neurotransmitter release

Extra Information: 

Central Nervous System Pharmacology Flashcard 4 of 5

Question: The three nonbenzodiazepine hypnotics are _____, Zaleplon, and esZopiclone

Answer: Zolpidem

Central Nervous System Pharmacology Flashcard 5 of 5

Question: _____ and duetetrabenazine are VMAT-2 inhibitors used in the treatment of Tardive Dyskinesia

Answer: Valbenazine