Zyprexa (olanzapine), Midodrine, Tamsulosin, and Melatonin

Zyprexa (olanzapine), Midodrine, Tamsulosin, and Melatonin — covering mechanism of action (MOA), indication, side effects, and target cells/receptors:

1. Zyprexa (Olanzapine) 2.5 mg

Class: Atypical (second-generation) antipsychotic

Mechanism of Action (MOA):

• Antagonist at multiple receptors:

  • D₂ receptors → decreases dopamine activity in mesolimbic pathway (↓ psychotic symptoms)

  • 5-HT₂A receptors → balances dopamine in mesocortical pathway (↓ negative symptoms and EPS)

  • Also blocks H₁, M₁, and α₁ receptors

Target Cells/Receptors:

• Dopaminergic neurons (D₂ receptors)

• Serotonergic neurons (5-HT₂A receptors)

• Histaminergic, cholinergic, and adrenergic cells

Indications:

• Schizophrenia

• Bipolar disorder (mania or mixed episodes)

• Adjunct for treatment-resistant depression

Common Side Effects:

• Weight gain (↑ appetite via H₁ and 5-HT₂C blockade)

• Sedation (H₁ blockade)

• Orthostatic hypotension (α₁ blockade)

• Anticholinergic effects: dry mouth, constipation, urinary retention

• Metabolic syndrome (↑ glucose, lipids)

2. Midodrine 2.5 mg

Class: Alpha-1 adrenergic agonist (prodrug → desglymidodrine active form)

Mechanism of Action (MOA):

• Stimulates α₁-adrenergic receptors on vascular smooth muscle → vasoconstriction → ↑ peripheral resistance → ↑ blood pressure

Target Cells/Receptors:

• Vascular smooth muscle cells (α₁ receptors on arterioles and veins)

Indications:

• Symptomatic orthostatic hypotension (neurogenic or autonomic failure)

Common Side Effects:

• Supine hypertension

• Piloerection (“goosebumps”)

• Urinary retention (due to bladder neck contraction)

• Pruritus (mainly scalp)

• Paresthesia

3. Tamsulosin 0.4 mg

Class: Selective α₁A-adrenergic receptor antagonist

Mechanism of Action (MOA):

• Blocks α₁A receptors in prostate, bladder neck, and urethra → relaxes smooth muscle → improved urinary flow

Target Cells/Receptors:

• Smooth muscle cells of prostate and bladder neck (α₁A receptors)

Indications:

• Benign Prostatic Hyperplasia (BPH) — relieves lower urinary tract symptoms

Common Side Effects:

• Orthostatic hypotension

• Dizziness

• Retrograde ejaculation

• Nasal congestion

• Fatigue

• “Floppy iris syndrome” (during cataract surgery)

4. Melatonin 3 mg

Class: Endogenous hormone; sleep–wake cycle regulator

Mechanism of Action (MOA):

• Binds MT₁ and MT₂ receptors in the suprachiasmatic nucleus (SCN) of the hypothalamus → synchronizes circadian rhythm → promotes sleep onset

Target Cells/Receptors:

• Neurons in the SCN (MT₁ and MT₂ melatonin receptors)

Indications:

• Insomnia (especially in older adults)

• Jet lag or circadian rhythm sleep disorders

• Shift-work sleep disorder

Common Side Effects:

• Drowsiness

• Headache

• Dizziness

• Vivid dreams

Summary Table

Drug	MOA	Target Cells/Receptors	Indication	Common Side Effects
Olanzapine (Zyprexa)	D₂, 5-HT₂A, H₁, M₁, α₁ antagonist	Dopaminergic, serotonergic, histaminergic neurons	Schizophrenia, bipolar disorder	Weight gain, sedation, orthostatic hypotension
Midodrine	α₁-agonist (vasoconstriction)	Vascular smooth muscle	Orthostatic hypotension	Supine HTN, urinary retention, goosebumps
Tamsulosin	α₁A-antagonist (smooth muscle relaxation)	Prostate & bladder neck smooth muscle	BPH	Dizziness, hypotension, retrograde ejaculation
Melatonin	MT₁/MT₂ receptor agonist KETOROLAC (15 mg IVP) Class Nonsteroidal Anti-inflammatory Drug (NSAID) – Pyrrolo-pyrrole derivative Mechanism of Action (MOA) Inhibits cyclooxygenase (COX-1 and COX-2) enzymes. This blocks the conversion of arachidonic acid → prostaglandins, which are mediators of: Pain Inflammation Fever Platelet aggregation The result is analgesic, anti-inflammatory, and antipyretic effects. Primary Receptor/Target COX-1 and COX-2 enzymes (cytosolic receptors in inflammatory and endothelial cells) Prostaglandin synthesis inhibition decreases sensitization of peripheral nociceptors and central pain signaling. Indications Short-term moderate to severe pain (post-operative, musculoskeletal, or renal colic) Alternative to opioids for acute pain relief (Note: Not for chronic pain or >5 days of use) Side Effects System Common / Serious Effects GI Gastric irritation, peptic ulcers, GI bleeding, nausea, vomiting Renal Decreased renal perfusion → ↑Creatinine, acute kidney injury Hematologic Inhibition of platelet aggregation → ↑Bleeding risk CV Hypertension, fluid retention, edema CNS Dizziness, headache, drowsiness Hypersensitivity Rash, bronchospasm (esp. in aspirin-sensitive asthma) Contraindications Active peptic ulcer or GI bleed Renal impairment Concurrent NSAID use Labor/delivery (can cause premature ductus arteriosus closure) METOLAZONE Class Thiazide-like diuretic Mechanism of Action (MOA) Acts in the distal convoluted tubule of the nephron. Inhibits the Na⁺/Cl⁻ symporter (co-transporter) → blocks sodium and chloride reabsorption. This causes increased excretion of Na⁺, Cl⁻, and water, with mild K⁺ and H⁺ loss. Has some proximal tubular action—effective even in renal impairment or when combined with loop diuretics (e.g., Bumetanide, Furosemide). Primary Receptor/Target Na⁺/Cl⁻ cotransporter (NCC) in distal convoluted tubule epithelial cells. Indirectly affects volume and electrolyte-sensitive baroreceptors → reduces preload and blood pressure. Indications Edema due to CHF, renal disease, or hepatic cirrhosis (esp. refractory edema with loop diuretic) Hypertension (adjunctive therapy) Side Effects System Common / Serious Effects Electrolytes Hypokalemia, hyponatremia, hypomagnesemia, hypochloremia, metabolic alkalosis Renal Azotemia, dehydration (esp. with loop diuretic combo) Cardiac Orthostatic hypotension, arrhythmias (due to K⁺ loss) Endocrine/Metabolic Hyperuricemia (gout), hyperglycemia GI Nausea, vomiting, cramps Other Dizziness, weakness, muscle cramps Special Note Synergistic with loop diuretics (e.g., Bumex) → “Sequential nephron blockade.” Must monitor BMP (Na⁺, K⁺, Cr, BUN) closely due to risk of profound volume and electrolyte depletion. Summary Table Drug Target / Receptor MOA Major Risks Ketorolac COX-1, COX-2 enzymes Inhibits prostaglandin synthesis → analgesia GI bleeding, renal failure, ↑bleeding risk Metolazone Na⁺/Cl⁻ cotransporter (NCC) Blocks Na⁺/Cl⁻ reabsorption in DCT → diuresis Hypokalemia, dehydration, metabolic alkalosis	SCN neurons (hypothalamus)	Insomnia, jet lag	Drowsiness, headache, vivid dreams