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302. Topiramate (Topamax)
Topiramate is a sulfamate-substituted monosaccharide anticonvulsant. Known in the medical community as a "broad-spectrum" agent, it is unique for its multiple mechanisms of action and its famous side effect of weight loss, earning it the nickname "Stupimax" due to its potential for cognitive slowing.

Uses:
🔹 Epilepsy: Monotherapy or adjunctive therapy for focal-onset or primary generalized tonic-clonic seizures.
🔹 Migraine Prophylaxis: One of the most effective FDA-approved medications for preventing chronic migraines in adults and adolescents.
🔹 Lennox-Gastaut Syndrome: Adjunctive treatment for seizures associated with this severe form of childhood epilepsy.
🔹 Weight Management: Used off-label (or in combination with Phentermine as Qsymia) for chronic weight management.
🔹 Alcohol Use Disorder: Used off-label to reduce heavy drinking days and cravings.
🔹 Binge-Eating Disorder: Sometimes used to reduce the frequency of binge episodes.

Dose:
🔹 Migraine Prophylaxis:
Week 1: 25 mg nightly.
Titration: Increase by 25 mg/week.
Target: 50 mg twice daily (100 mg/day).
🔹 Epilepsy:
Target: 200–400 mg/day (divided into two doses).
🔹 Note: "Start low and go slow" to minimize cognitive side effects.

Presentation:
🔹 Tablets: 25 mg, 50 mg, 100 mg, 200 mg.
🔹 Sprinkle Capsules: 15 mg, 25 mg (can be opened and placed on soft food).
🔹 Extended-Release (Trokendi XR / Qudexy XR): 25 mg to 200 mg once daily.

Notes:
🔹 Drug Class: Anticonvulsant.
🔹 Mechanism of Action:
Sodium Channels: Blocks voltage-dependent sodium channels, limiting repetitive neuronal firing.
GABA Enhancement: Acts as a positive allosteric modulator at GABA_A receptors (increases inhibitory tone).
Glutamate Antagonism: Antagonizes the AMPA/kainate glutamate receptors (decreases excitatory tone).
Carbonic Anhydrase Inhibition: Weakly inhibits carbonic anhydrase (isoenzymes II and IV), which contributes to some of its side effects.
🔹 Pharmacokinetics:
Excretion: Primarily renal (70% eliminated unchanged).
Half-Life: 21 hours (long enough for once or twice daily dosing).
🔹 Adverse Effects:
Cognitive: "Word-finding" difficulties, slowed thinking, and memory impairment (the "Stupimax" effect).
Sensory: Paresthesia (tingling in fingers and toes) is very common due to carbonic anhydrase inhibition.
Metabolic: Metabolic acidosis (lowers serum bicarbonate) and increased risk of Kidney Stones (nephrolithiasis).
Ocular: Rare but serious Secondary Angle-Closure Glaucoma (medical emergency).
🔹 Contraindications:
Recent alcohol use (within 6 hours) specifically for the Trokendi XR formulation.
History of metabolic acidosis or kidney stones (relative contraindication).
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303. Levetiracetam (Keppra)
Levetiracetam is one of the most commonly prescribed "broad-spectrum" anticonvulsants in modern medicine. It is favored by neurologists because it has a very low risk of drug-drug interactions and does not require blood-level monitoring, unlike older drugs like Phenytoin or Valproate.

Uses:
🔹 Focal Seizures: Used as both monotherapy and adjunctive therapy for partial-onset seizures.
🔹 Myoclonic Seizures: Adjunctive therapy for patients with juvenile myoclonic epilepsy.
🔹 Primary Generalized Tonic-Clonic Seizures: Adjunctive therapy for idiopathic generalized epilepsy.
🔹 Status Epilepticus: Often used intravenously in emergency settings because it can be administered rapidly without the cardiac risks of Phenytoin.

Dose:
🔹 Standard Adult Dose:
Initial: 500 mg twice daily.
Titration: Increase by 500 mg twice daily every 2 weeks.
Maintenance: 1,000–1,500 mg twice daily.
Maximum: 3,000 mg/day.
🔹 Renal Adjustment: Dosage reduction is mandatory for patients with impaired renal function (CrCl < 80 mL/min).

Presentation:
🔹 Tablets: 250 mg, 500 mg, 750 mg, 1,000 mg.
🔹 Extended-Release (Keppra XR): 500 mg, 750 mg.
🔹 Oral Solution: 100 mg/mL.
🔹 Injection: 100 mg/mL for IV infusion.

Notes:
🔹 Drug Class: Anticonvulsant (Pyrrolidine derivative).
🔹 Mechanism of Action:
SV2A Binding: Unlike most anticonvulsants that act on ion channels, Levetiracetam binds to the Synaptic Vesicle Protein 2A (SV2A).
Vesicle Modulation: This binding is thought to modulate the release of neurotransmitters (like glutamate and GABA) by stabilizing the vesicle fusion process, thereby inhibiting hypersynchronous neuronal firing.
🔹 Pharmacokinetics:
Absorption: Rapid and nearly 100% bioavailable. Food does not affect the extent of absorption.
Metabolism: It is not metabolized by the Cytochrome P450 system. It undergoes enzymatic hydrolysis in the blood.
Excretion: 66% excreted unchanged via the kidneys.
🔹 Adverse Effects:
Behavioral: "Keppra-rage"—irritability, agitation, and aggression are the most notable side effects.
CNS: Somnolence (sleepiness), dizziness, and asthenia (weakness).
Hematologic: Rare cases of pancytopenia (low blood cell counts).
🔹 Contraindications:
Hypersensitivity to levetiracetam.

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Hypersensitivity Reactions - Types I to IV Simplified

Lamotrigine (Lamictal)
‎
‎Lamotrigine is unique among mood stabilizers. While Valproate and Lithium are "top-down" stabilizers (better at treating mania), Lamotrigine is a "bottom-up" stabilizer, it is specifically effective for preventing and treating the depressive phase of Bipolar Disorder.
‎
‎Uses:
‎🔹 Bipolar Maintenance: First-line for preventing Bipolar Depression.
‎🔹 Epilepsy: Used for focal seizures, generalized tonic-clonic seizures, and   Lennox-Gastaut syndrome.
‎🔹 ipolarBipolar Depression: Used off-label for acute depressive episodes.
‎🔹 Off-label: Often used as an augmenting agent in treatment-resistant Unipolar Depression.
‎
‎Dose:
‎Standard Titration (Crucial):
‎Weeks 1–2: 25 mg daily.
‎Weeks 3–4: 50 mg daily.
‎Week 5: 100 mg daily.
‎Target: 200 mg daily (can go up to 400 mg).
‎Note: If the patient stops the medication for more than 3–5 days, they must restart the titration from 25 mg to avoid life-threatening skin reactions.
‎
‎Presentation:
‎🔹 Tablets: 25 mg, 100 mg, 150 mg, 200 mg.
‎Chewable/Dispersible Tablets: 2 mg, 5 mg, 25 mg.
‎🔹 Starter Kits: Color-coded (Blue, Green, Orange) to guide the titration based on other meds the patient is taking.
‎
‎Notes:
‎🔹 Drug Class: Anticonvulsant / Phenyltriazine.
‎🔹 Mechanism of Action:
‎Sodium Channel Blockade: It stabilizes neuronal membranes by inhibiting voltage-gated sodium channels.
‎Glutamate Inhibition: By stabilizing these channels, it inhibits the release of Glutamate (the brain's primary excitatory neurotransmitter). Excessive glutamate is linked to both seizures and mood instability.
‎🔹 Pharmacokinetics:
‎Metabolism: Hepatic via glucuronidation (UGT enzymes).
‎Half-Life: ~25 hours.
‎🔹 Adverse Effects:
‎Common: Dizziness, headache, blurred vision, and mild "brain fog."
‎The "Rash": Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).
‎🔹 Contraindications:
‎Known hypersensitivity to the drug.
‎
‎⚡ Clinical Pearls & High-Yield Additions
‎1. "The Rash" (SJS Warning)
‎Warning: About 10% of patients get a benign rash, but 0.1% develop Stevens-Johnson Syndrome, which is a medical emergency.
‎Pearl: If a patient develops a rash plus a fever, sore throat, or mucosal involvement (blisters in the mouth/eyes), they must stop the drug immediately and go to the ER.
‎2. The Valproate Interaction (The "Blue" Kit)
‎Warning: Valproate doubles the level of Lamotrigine in the blood.
‎Action: If a patient is on Valproate, the Lamotrigine starting dose must be halved (12.5 mg or 25 mg every other day) to prevent SJS.
‎3. The Carbamazepine Interaction (The "Green" Kit)
‎Warning: Carbamazepine and Phenytoin decrease Lamotrigine levels by about 50%.
‎Action: In these cases, the dose of Lamotrigine must be increased more aggressively.
‎4. Oral Contraceptives
‎Pearl: Estrogen-containing birth control pills can reduce Lamotrigine levels by half. Patients may notice their mood dipping during the "active pill" weeks and returning to normal during the placebo week.
‎5. Cognitive Profile
‎Clinical Tip: Unlike Valproate or Lithium, Lamotrigine is generally weight-neutral and does not cause sedation or significant cognitive "dulling," making it a favorite for high-functioning patients.
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300. Gabapentin (Neurontin)

Gabapentin is a structural analogue of the neurotransmitter GABA, originally developed as an anticonvulsant. In modern clinical practice, its primary utility is in the management of neuropathic pain and as an off-label treatment for various anxiety disorders.

Uses:
🔹 Postherpetic Neuralgia: First-line treatment for pain following a shingles (herpes zoster) infection.
🔹 Diabetic Peripheral Neuropathy: Management of nerve pain in the extremities.
🔹 Partial Seizures: Adjunctive therapy for patients 3 years and older with focal-onset seizures.
🔹 Restless Legs Syndrome (RLS): Effective for both idiopathic and secondary RLS.
🔹 Generalized Anxiety Disorder (GAD): Often used off-label when SSRIs/SNRIs are insufficient or not tolerated.
🔹 Alcohol Use Disorder: Used to reduce cravings and as an adjunct for mild withdrawal.

Dose:
🔹 Neuropathic Pain/Anxiety:
Initial: 300 mg once daily on Day 1, 300 mg twice daily on Day 2, and 300 mg three times daily (TID) on Day 3.
Titration: Increase by 300 mg/day every 3–7 days.
Target: 900–1,800 mg/day (divided TID).
Maximum: 3,600 mg/day.
🔹 Renal Adjustment: Mandatory for CrCl < 60 mL/min.

Presentation:
🔹 Capsules: 100 mg, 300 mg, 400 mg.
🔹 Tablets: 600 mg, 800 mg.
🔹 Oral Solution: 250 mg/5 mL.

Notes:
🔹 Drug Class: Gabapentinoid.
🔹 Mechanism of Action:
Binding Site: It binds with high affinity to the \alpha_2\delta subunit of voltage-gated calcium channels (VGCCs) in the CNS.
Synaptic Inhibition: This binding reduces calcium influx into the presynaptic nerve terminal, which subsequently inhibits the release of excitatory neurotransmitters, including glutamate, norepinephrine, and substance P.
Misconception: Despite its name and structure, it does not bind to GABA receptors, nor does it affect GABA uptake or metabolism.
🔹 Pharmacokinetics:
Absorption: Mediated by the L-amino acid transporter in the small intestine. This process is saturable (zero-order kinetics), meaning the bioavailability decreases as the dose increases.
Metabolism: None; it is not metabolized by liver enzymes.
Excretion: 100% eliminated unchanged via the kidneys.
🔹 Adverse Effects:
CNS: Somnolence, dizziness, ataxia, and fatigue.
Peripheral: Significant peripheral edema (swelling of lower extremities).
Neuropsychiatric: "Brain fog," confusion, and in some cases, paradoxical aggressive behavior.
🔹 Contraindications:
Hypersensitivity to gabapentin.

⚡ Clinical Pearls & High-Yield Additions
1. The "Ceiling Effect" of Absorption
Pearl: Because the intestinal transporters become saturated, taking 900 mg at once is much less effective than taking 300 mg three times a day. If a patient isn't responding, check if they are dividing their doses properly.
2. The "Renal Red Flag"
Warning: In patients with renal failure or elderly patients with low GFR, the half-life can jump from 6 hours to over 50 hours.
Action: Always calculate the Creatinine Clearance before prescribing. Overdose in renal patients leads to severe myoclonus and sedation.
3. "The Gabapentin Hangover"
Clinical Tip: To improve adherence, start the entire dose at night. Once the patient tolerates the sedation, you can begin adding daytime doses.
4. Withdrawal Syndrome
Warning: Abrupt discontinuation can trigger seizures (even in non-epileptic patients) or a withdrawal syndrome similar to alcohol or benzodiazepine withdrawal (anxiety, insomnia, sweating). Always taper over at least 7 days.
5. Potentiation of Opioids
Pearl: Gabapentin can increase the respiratory depressant effects of opioids. This combination is a high-risk factor for fatal overdose in chronic pain management.

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301. Pregabalin (Lyrica)

Pregabalin is the more potent, pharmacokinetically "refined" successor to Gabapentin. While they share the same target, Pregabalin offers more predictable absorption and higher bioavailability, making it a staple in the management of neuropathic pain and anxiety disorders.

Uses:
🔹 Neuropathic Pain: Effective for diabetic peripheral neuropathy and postherpetic neuralgia.
🔹 Fibromyalgia: One of the few drugs FDA-approved specifically for the widespread pain and fatigue of fibromyalgia.
🔹 Generalized Anxiety Disorder (GAD): Approved in Europe (not FDA) as a first-line treatment; highly effective for somatic symptoms of anxiety.
🔹 Partial Seizures: Used as adjunctive therapy in adults and pediatric patients (1 month and older).
🔹 Spinal Cord Injury Pain: Management of neuropathic pain associated with spinal cord trauma.

Dose:
🔹 Neuropathic Pain/Anxiety:
Initial: 75 mg twice daily (150 mg/day) or 50 mg three times daily.
Titration: May increase to 300 mg/day within one week based on tolerability.
Maximum: 600 mg/day (doses above this rarely show extra benefit but increase side effects).
🔹 Fibromyalgia:
Target: 300–450 mg/day.
🔹 Renal Adjustment: Essential for patients with CrCl < 60 mL/min.

Presentation:
🔹 Capsules: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg, 200 mg, 225 mg, 300 mg.
🔹 Oral Solution: 20 mg/mL.
🔹 Extended-Release (Lyrica CR): 82.5 mg, 165 mg, 330 mg (once-daily dosing).

Notes:
🔹 Drug Class: Gabapentinoid.
🔹 Mechanism of Action:
High-Affinity Binding: Like Gabapentin, it binds to the \alpha_2\delta subunit of voltage-gated calcium channels.
Neurotransmitter Modulation: It reduces the calcium-dependent release of pro-nociceptive neurotransmitters (Glutamate, Substance P, and Norepinephrine) in "hyperexcited" neurons.
Selectivity: It does not block the channel itself but modifies its function, meaning it only affects "overactive" nerves, leaving normal neurotransmission relatively untouched.
🔹 Pharmacokinetics:
Linear Absorption: Unlike Gabapentin, its absorption is not saturable. If you double the dose, you double the blood level. Bioavailability is >90\%.
Onset: Reaches peak plasma levels within 1 hour.
Metabolism: Negligible; excreted 90% unchanged in urine.
🔹 Adverse Effects:
Common: Dizziness, somnolence, dry mouth, and blurred vision.
Weight Gain: More common and often more significant than with Gabapentin.
Peripheral Edema: Significant leg swelling, especially when combined with Thiazolidinediones.
Euphoria: Can cause a sense of "well-being," leading to its classification as a Schedule V controlled substance.
🔹 Contraindications:
Hypersensitivity to pregabalin.
History of Angioedema (rare but reported).

⚡ Clinical Pearls & High-Yield Additions
1. The "Linear" Advantage
Pearl: Because Pregabalin has linear pharmacokinetics, it is much easier to titrate than Gabapentin. If a patient is on a high dose of Gabapentin with no result, switching to Pregabalin often works because you can actually achieve the necessary therapeutic blood levels.
2. Fast-Acting Anxiolytic
Clinical Tip: In GAD, Pregabalin works much faster than SSRIs. While an SSRI may take 4–6 weeks to work, Pregabalin can reduce anxiety symptoms within one week. This makes it an excellent "bridge" while waiting for an antidepressant to kick in.
3. The "Lyrica Bloom" (Edema)
Warning: Be cautious in patients with Congestive Heart Failure (CHF). The peripheral edema caused by Pregabalin can exacerbate fluid overload and heart failure symptoms.
4. Withdrawal & Dependence
Warning: Abruptly stopping Pregabalin can cause insomnia, nausea, headache, and diarrhea. In seizure patients, it can trigger status epilepticus. Always taper over at least one week.
5. Cognitive "Dullness"
Pearl: Patients often describe a "thick-headed" feeling or word-finding difficulties. If this happens, try a slower titration or a lower bedtime-only dose.

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Pregabalin
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295. Tranylcypromine (Parnate)
Tranylcypromine is a non-hydrazine, irreversible, non-selective MAOI. While Phenelzine is known for being sedating and anxiolytic, Tranylcypromine is famously stimulating. It is often considered the most "potent" of the antidepressants for patients with severe, "paralyzing" depression.

Uses
🔹 Major Depressive Disorder (MDD): Specifically for treatment-resistant cases where the patient has failed multiple other classes.
🔹 Treatment-Resistant Depression (TRD): Often used when a patient has "given up" and shows no response to traditional meds.
🔹 Atypical Depression: Effective for mood reactivity and hypersomnia, though Phenelzine is usually first-line for this subtype.

Dose
🔹 Start: 10 mg twice daily (morning and noon).
🔹 Titration: Increase by 10 mg per day at 1–3 week intervals.
🔹 Target: 30–60 mg per day.
🔹 Max: 60 mg/day (though some specialists go higher in inpatient settings).
🔹 Note: Avoid dosing after 3:00 PM to prevent severe insomnia.

Presentation
🔹 Tablets: 10 mg.

Notes
🔹 Drug Class: Irreversible, Non-selective MAOI (Monoamine Oxidase Inhibitor).
🔹 Mechanism of Action:
Enzyme Inhibition: Like Phenelzine, it permanently disables MAO-A and MAO-B.
Structural Mimicry: Its chemical structure is similar to Amphetamine. This allows it to act as a mild catecholamine releasing agent, providing an immediate "spark" of energy and alertness that other MAOIs lack.
🔹 Pharmacokinetics:
Metabolism: Hepatic.
Onset: While the enzyme inhibition is immediate, the clinical antidepressant effect still takes 2–4 weeks.
Duration: Because it is irreversible, you must wait 14 days after stopping before starting a conflicting drug (the "washout" period).
🔹 Adverse Effects:
Insomnia: The most common side effect due to its stimulating nature.
Orthostatic Hypotension: Very common; patients may feel dizzy when standing.
Hypertensive Crisis: Risk with Tyramine-rich foods (the "Cheese Effect").
Restlessness/Agitation: Can sometimes feel "too pushy" for anxious patients.

⚡ Clinical Pearls & High-Yield Additions
1. The "Stimulating" MAOI
Pearl: Tranylcypromine is structurally related to amphetamine. For a patient who is "bedded" by depression—unable to move, speak, or get out of bed—this drug provides the "engine start" they need.
2. The "Parnate" vs. "Nardil" Choice
Clinical Tip: * If the patient is Anxious/Agitated/Thin \rightarrow Choose Phenelzine (Nardil) (Sedating/Weight gain).
If the patient is Lethargic/Sleeping too much/Overweight \rightarrow Choose Tranylcypromine (Parnate) (Stimulating/Weight neutral).
3. Dietary Restrictions are Real but Relaxed
Pearl: Modern medical literature suggests the "MAOI Diet" isn't as restrictive as once thought. Most fresh foods are fine. The main "Danger Foods" are aged cheeses (Stilton, Cheddar), tap beers (yeast), sauerkraut, and soy sauce.
4. Blood Pressure Spikes
Warning: If a patient on Tranylcypromine develops a sudden, "explosive" headache at the back of the head (occipital), they must go to the ER. This is the hallmark sign of a hypertensive crisis.
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