---

🧠 COMPLETE PHARMACOLOGY EXAM GUIDE

Everything Explained Simply - From Zero to Ready

---

PART 1: AUTONOMIC NERVOUS SYSTEM DRUGS

First, understand the two systems (super important foundation)

• Sympathetic = "Fight or Flight" - You see a lion. Your heart pounds, pupils dilate, you sweat, muscles get blood, digestion stops.
• Parasympathetic = "Rest and Digest" - You're relaxing after dinner. Heart slows, digestion works, pupils small, you salivate.

• Sympathetic uses norepinephrine (NE) at the end organ (and epinephrine from adrenal gland)
• Parasympathetic uses acetylcholine (ACh) at the end organ
• Both systems use ACh at the ganglion (the relay station)

---

ADRENERGIC (Sympathetic) DRUGS

The Receptors - Know These Cold

---

GROUP A: DIRECT ADRENERGIC AGONISTS (stimulate receptors directly)

Epinephrine (Adrenaline) - The King of Emergency Drugs

• Acts on: α1, α2, β1, β2 (everything!)
• Uses: Anaphylaxis #1, cardiac arrest, severe asthma (last resort), with local anesthetics (to prolong effect)
• Side effects: Hypertension, tachycardia, arrhythmias, anxiety, tremor, headache
• Contraindications: Narrow-angle glaucoma (relative); hypertension (but in anaphylaxis you give it anyway - life > BP)
• Toxicity: Hypertensive crisis, ventricular arrhythmias, stroke, pulmonary edema
• Treat toxicity with: Alpha-blockers (phentolamine) for the vasospasm; beta-blockers for arrhythmias

Norepinephrine (Levophed)

• Acts on: α1, α2, β1 (very little β2)
• Uses: Septic shock (vasopressor of choice), hypotension
• Side effects: Severe vasoconstriction (can cause limb ischemia!), reflex bradycardia, hypertension
• Contraindications: Extravasation causes tissue necrosis - MUST be given in central line
• Treat extravasation with: Phentolamine injected locally
• Toxicity: Hypertensive crisis, tissue necrosis at IV site

Dopamine

• Dose-dependent effects (this is classic exam material!):
  • Low dose (1-5 mcg/kg/min): D1 receptors - dilates renal vessels, increases urine output
  • Medium dose (5-10 mcg/kg/min): β1 - increases heart rate and contractility
  • High dose (>10 mcg/kg/min): α1 - vasoconstriction, like norepinephrine
• Uses: Cardiogenic shock, septic shock (second-line), heart failure with hypotension
• Side effects: Arrhythmias, hypertension, nausea/vomiting
• Contraindications: Pheochromocytoma, uncontrolled tachyarrhythmias, VF

Dobutamine

• Acts on: β1 mainly (some β2)
• The inotrope: Makes the heart squeeze harder WITHOUT major effect on BP or heart rate
• Uses: Acute decompensated heart failure (with adequate BP), stress testing (dobutamine stress echo)
• Side effects: Tachycardia, arrhythmias, can increase ischemia in CAD patients
• Contraindications: Hypertrophic obstructive cardiomyopathy (HOCM) - making it squeeze harder is bad!

Phenylephrine (Neo-Synephrine)

• Acts on: α1 only (pure alpha agonist)
• Uses: Nasal decongestant, hypotension during anesthesia, SVT (raises BP → reflex bradycardia → breaks SVT)
• Side effects: Reflex bradycardia, hypertension
• Contraindications: Severe hypertension

Albuterol / Salbutamol

• Acts on: β2 (lungs)
• Uses: Asthma (first-line rescue inhaler!), COPD, hyperkalemia (shifts K+ into cells)
• Side effects: Tremor, tachycardia, hypokalemia (long-term), anxiety
• Contraindications: Use with caution in cardiovascular disease (can cause arrhythmias)
• Toxicity: Severe tachycardia, hypokalemia

---

GROUP B: INDIRECT ADRENERGIC AGONISTS

Amphetamines / Cocaine

• Mechanism: Block reuptake of NE (and dopamine, serotonin)
• Side effects: HTN, tachycardia, euphoria, psychosis, addiction, hyperthermia
• Toxicity: Hypertensive crisis, MI, stroke, hyperthermia
• Treat toxicity: Benzodiazepines (first line!), phentolamine for HTN crisis, cooling for hyperthermia. NEVER give pure beta-blockers (causes unopposed alpha stimulation - BP goes dangerously high!)

---

GROUP C: ADRENERGIC ANTAGONISTS (blockers)

Alpha Blockers

• Phentolamine - short acting, used for pheochromocytoma crisis, cocaine-induced HTN crisis, NE extravasation
• Phenoxybenzamine - long acting, used for pheochromocytoma (pre-op preparation)

• Uses: Hypertension, BPH (benign prostate hyperplasia - relaxes smooth muscle in prostate/bladder neck)
• Side effects: "First-dose hypotension" (classic!) - dizziness/syncope after first dose. Tell patients to take it at bedtime!
• Also: reflex tachycardia, nasal congestion, headache
• Contraindications: Caution in patients on PDE5 inhibitors (Viagra) - severe hypotension!

---

CHOLINERGIC DRUGS (Parasympathetic)

The Receptors

---

Direct Cholinergic Agonists (Muscarinic)

Bethanechol

• Uses: Urinary retention (post-op or neurogenic), paralytic ileus
• Never give IV (causes massive vasodilation and CV collapse) - oral or SC only
• Side effects: SLUDGE effects - bradycardia, bronchospasm, diarrhea, sweating

Pilocarpine

• Uses: Glaucoma (eyedrops - constricts pupil, opens canal of Schlemm), dry mouth (Sjogren syndrome)
• Side effects: Sweating, GI cramps

Carbachol

• Uses: Glaucoma, intraocular surgery

---

Cholinesterase Inhibitors (Indirect) - These increase ACh by blocking the enzyme that breaks it down

Reversible:

• Neostigmine: Post-op urinary retention, ileus, reversal of non-depolarizing NMJ blockers
• Pyridostigmine: Myasthenia gravis (doesn't cross BBB)
• Physostigmine: Glaucoma, CROSSES BBB - antidote for anticholinergic poisoning (atropine overdose)
• Donepezil, Rivastigmine, Galantamine: Alzheimer's disease (CNS-acting)
• Edrophonium: Tensilon test for myasthenia gravis (very short acting)

Irreversible:

• Organophosphates (pesticides, nerve agents like Sarin)
• Mechanism: Permanently bind acetylcholinesterase → ACh accumulates everywhere
• Toxicity signs: SLUDGE + seizures + paralysis (too much ACh at NMJ)
• Treatment of organophosphate poisoning:
  1. Atropine (muscarinic antagonist - first and most important) - give HUGE doses until secretions dry
  2. Pralidoxime (2-PAM) - regenerates the enzyme IF given EARLY (before aging occurs)
  3. Benzodiazepines for seizures

---

Muscarinic Antagonists (Anticholinergics) - Block the "rest and digest"

• Hot (no sweating = hyperthermia)
• Dry (dry mouth, dry eyes, dry skin)
• Red (flushing)
• Mad (confusion, delirium - especially in elderly)
• Blind (mydriasis - pupil dilation, blurry vision)

Atropine

• Uses: Bradycardia (first-line!), organophosphate poisoning antidote, pre-anesthesia (dry secretions), eye exams (dilate pupils)
• Side effects: All the anticholinergic effects above
• Toxicity treatment: Physostigmine (crosses BBB to reverse CNS effects)

Scopolamine

• Uses: Motion sickness (patch), nausea
• Side effects: Sedation plus all anticholinergic effects

Ipratropium / Tiotropium

• Uses: COPD (bronchodilator - blocks M3 in airways), asthma
• Tiotropium: Once daily, long-acting for COPD
• Side effects: Dry mouth, urinary retention, constipation (minimal systemic absorption)
• Contraindications: Narrow-angle glaucoma (can precipitate acute attack)

Oxybutynin, Tolterodine, Solifenacin

• Uses: Overactive bladder, urge incontinence
• Side effects: Dry mouth, constipation, blurry vision, confusion (especially elderly)

Benztropine, Trihexyphenidyl

• Uses: Parkinson's disease (reduces tremor), drug-induced extrapyramidal symptoms (from antipsychotics)

---

PART 2: PSYCHIATRIC DRUGS

ANTIPSYCHOTICS

The Big Picture First

• Positive symptoms: Hallucinations, delusions, disorganized speech (something ADDED that shouldn't be there)
• Negative symptoms: Flat affect, social withdrawal, no motivation, no speech (something TAKEN AWAY that should be there)

---

TYPICAL (1st generation) Antipsychotics

Examples:

• High potency: Haloperidol, Fluphenazine, Trifluoperazine
• Low potency: Chlorpromazine, Thioridazine

Indications:

• Schizophrenia (positive symptoms)
• Acute agitation (haloperidol IM is classic in ER)
• Tourette's syndrome (haloperidol)
• Delirium (haloperidol)
• Nausea/vomiting (low potency - chlorpromazine)

Side Effects - The Most Important Part

• What it is: Life-threatening reaction to antipsychotics
• Features: "FALTER" - Fever (HIGH - >38°C), Autonomic instability (BP swings, tachycardia, diaphoresis), Lead-pipe muscle Rigidity (severe!), Tremor, Elevated CPK (muscle breakdown), altered consciousness (confused/stuporous)
• Timing: Can happen any time, usually within first 2 weeks
• Treatment:
  1. STOP the antipsychotic immediately!
  2. Supportive care (cooling, IV fluids)
  3. Dantrolene (muscle relaxant) - relaxes the rigid muscles
  4. Bromocriptine or Amantadine (dopamine agonists) - restore dopamine activity
  5. Benzodiazepines for agitation
• Key differentiator from serotonin syndrome: NMS has LEAD-PIPE rigidity and happens MORE SLOWLY; Serotonin syndrome has CLONUS/HYPERREFLEXIA and happens FASTER (see below)

• Weight gain (huge problem with low potency)
• Hyperglycemia, Type 2 DM
• Dyslipidemia
• QT prolongation → risk of Torsades de Pointes (especially thioridazine!)

• D2 block in pituitary → prolactin goes up
• Results in: Galactorrhea (breast milk when not pregnant), amenorrhea, gynecomastia, sexual dysfunction

• QT prolongation (thioridazine avoided)
• Parkinson's disease (worsens it - they need dopamine!)
• Bone marrow suppression (relative)

---

ATYPICAL (2nd generation) Antipsychotics

Key drugs to know:

• Unique indications: Treatment-resistant schizophrenia, suicidal ideation in schizophrenia
• Lethal side effect: AGRANULOCYTOSIS (drops white blood cells - patient can die from infection)
  • Must monitor CBC (ANC) weekly for first 6 months, then every 2 weeks!
  • If ANC drops below threshold → STOP IMMEDIATELY
• Other bad side effects: Seizures (dose-dependent), weight gain, metabolic syndrome, myocarditis, hypersalivation (sialorrhea), orthostatic hypotension, MINIMAL EPS (advantage), does NOT raise prolactin

• Biggest metabolic effects - worst weight gain of all antipsychotics, diabetes risk highest
• Used for schizophrenia, bipolar, acute agitation (IM), adjunct in depression

• At higher doses → EPS appear (not truly "atypical" at high doses)
• Highest prolactin elevation of all atypicals
• Used for schizophrenia, bipolar, irritability in autism

• Sedating - commonly used for sleep (off-label)
• Least EPS, least prolactin elevation
• Good for bipolar depression
• Significant weight gain and metabolic effects

• Partial D2 agonist (unique mechanism - acts like an agonist when dopamine is low, antagonist when high)
• Least weight gain and metabolic effects
• Used for schizophrenia, bipolar, adjunct in depression, Tourette's, irritability in autism
• Can cause akathisia (restlessness is a problem)

• QT prolongation - cardiac monitoring needed
• Least weight gain

---

ANTIDEPRESSANTS

---

SSRIs (Selective Serotonin Reuptake Inhibitors)

• Major depressive disorder (first-line!)
• Anxiety disorders (GAD, panic disorder, social anxiety, PTSD)
• OCD
• Bulimia nervosa (fluoxetine specifically approved)
• PMDD

• Sexual dysfunction (decreased libido, delayed orgasm) - very common, often why patients stop
• Nausea, diarrhea, headache (especially early on)
• Insomnia or sedation
• Weight gain (paroxetine worst)
• GI bleeding (SSRIs inhibit platelet aggregation - watch if on NSAIDs or anticoagulants)
• Hyponatremia (SIADH - syndrome of inappropriate ADH) - especially in elderly
• Serotonin syndrome (see below)
• QT prolongation - especially citalopram at high doses

• MAOIs (can cause serotonin syndrome - must wait 14 days between)
• Fluoxetine - need 5 weeks washout before MAOI (long half-life!)
• Avoid with other serotonergic drugs (triptans, tramadol, linezolid, dextromethorphan)
• Pregnancy - paroxetine (cardiac defects), but sertraline is relatively safest

---

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Depression (similar to SSRIs, often second-line or if anxiety also present)
• Generalized anxiety disorder (GAD) - duloxetine/venlafaxine excellent
• Neuropathic pain (duloxetine approved for diabetic peripheral neuropathy, fibromyalgia)
• Stress urinary incontinence (duloxetine)
• Chronic pain conditions

• Hypertension (due to NE effect) - monitor BP especially with venlafaxine at higher doses
• Tachycardia
• Sweating
• Worst discontinuation syndrome of all antidepressants (venlafaxine)

---

TCAs (Tricyclic Antidepressants)

• Depression (effective but rarely first-line now due to toxicity)
• Neuropathic pain (excellent!)
• Migraine prophylaxis (amitriptyline)
• Bedwetting in children (imipramine)
• OCD (clomipramine)
• Chronic pain, fibromyalgia

1. Anticholinergic: Dry mouth, urinary retention, constipation, blurry vision, confusion (big problem in elderly)
2. Antihistamine (H1): Sedation, weight gain
3. Alpha-1 blockade: Orthostatic hypotension, dizziness
4. Cardiac: QT prolongation, widening of QRS (most dangerous!)

• Coma (CNS depression)
• Convulsions (seizures)
• Cardiac arrhythmias (wide QRS, ventricular tachycardia/fibrillation)

1. Sodium bicarbonate (NaHCO3) IV - the most important! Alkalinization narrows the QRS, prevents arrhythmias. The sodium load also competes with TCA at Na channels.
2. Intubation/ventilation if unconscious
3. Benzodiazepines for seizures
4. NEVER give physostigmine (can cause cardiac arrest in TCA OD - despite both being "anticholinergic" problems, physostigmine is harmful here)
5. Avoid Class IA antiarrhythmics (quinidine) - they worsen QRS widening

• Recent MI
• QT prolongation
• Narrow-angle glaucoma
• Urinary retention / BPH
• Elderly (high risk of falls, confusion)
• With MAOIs (washout 14 days)

---

MAOIs (Monoamine Oxidase Inhibitors)

• Atypical depression (classic indication)
• Treatment-resistant depression
• Social anxiety disorder (phenelzine)
• Parkinson's (selegiline)

• Orthostatic hypotension (most common)
• Insomnia
• Weight gain
• Sexual dysfunction

• Normally MAO in gut destroys tyramine in food
• On MAOIs, tyramine gets absorbed → massive NE release → BP shoots up dangerously (hemorrhagic stroke risk!)
• Foods to AVOID: Aged cheese ("cheese reaction!"), red wine, cured meats, soy sauce, fermented foods, beer, fava beans
• Treatment: Phentolamine or nitroprusside for the hypertensive crisis

• Must wait 14 days between stopping MAOI and starting any serotonergic drug
• Fluoxetine needs 5 weeks washout before MAOI

---

Other Antidepressants

• Mechanism: Blocks reuptake of dopamine and norepinephrine (NOT serotonin)
• Unique advantages:
  • Does NOT cause sexual dysfunction (patients love this)
  • Does NOT cause weight gain (actually causes weight loss)
  • Smoking cessation (Zyban - same drug, different brand name)
  • Depression + ADHD
• Major contraindications: SEIZURES (lowers seizure threshold - contraindicated in eating disorders like bulimia/anorexia due to electrolyte imbalances that risk seizures, in patients with seizure history, and during alcohol/benzo withdrawal)
• Side effects: Insomnia, dry mouth, headache, agitation

• Mechanism: Blocks α2 auto-receptors (increases NE and serotonin release) and blocks H1 histamine
• Advantages: Sedating (good for insomnia), stimulates appetite (good for underweight or elderly patients), low sexual dysfunction
• Side effects: Sedation, weight gain (significant), increased appetite
• Contraindicated with: MAOIs

• Blocks serotonin reuptake AND some receptors
• Mostly used for insomnia now (low dose)
• Priapism (prolonged painful erection) - rare but famous side effect!

• Multi-modal serotonin drug
• Less sexual dysfunction, may improve cognition
• Used in depression

---

SEROTONIN SYNDROME

• SSRIs + MAOIs (most classic combo)
• SSRIs + other serotonergic drugs (triptan, tramadol, meperidine, linezolid, methylene blue, fentanyl, dextromethorphan/DXM)
• High-dose single serotonergic drug

1. Neuromuscular: Clonus (rhythmic muscle jerking), hyperreflexia (exaggerated reflexes), tremor, myoclonus - THIS IS THE KEY FEATURE
2. Autonomic: Hyperthermia (usually milder than NMS), tachycardia, diaphoresis, diarrhea, BP lability
3. Mental status: Agitation, anxiety, confusion

NMS vs. Serotonin Syndrome - The Exam Classic:

1. STOP the serotonergic drug
2. Supportive care (IV fluids, cool the patient)
3. Benzodiazepines for agitation/seizures
4. Cyproheptadine (serotonin antagonist) - the specific antidote
5. If severe: ICU, sedation, intubation
6. For hyperthermia > 41°C: consider muscle paralysis and intubation

---

LITHIUM

What it does:

• Flattens the mood swings in bipolar disorder - prevents both mania AND depression
• Mechanism: Complex - affects signal transduction (inhibits inositol phosphatase, modulates ion channels)

Indications:

• Bipolar disorder (manic and depressive episodes) - FIRST-LINE
• Augmentation in treatment-resistant depression
• Reduces suicide risk in bipolar disorder (proven!)
• Cluster headache prevention

The Narrow Therapeutic Index (THIS IS EVERYTHING WITH LITHIUM)

• Dehydration / sodium depletion - when Na+ is low, kidneys compensate by holding onto more Na+ (and Li+ follows!) → levels rise. So: diarrhea, vomiting, excessive sweating (exercise, hot weather), low-salt diet ALL RAISE LITHIUM
• NSAIDs (reduce renal prostaglandins → reduce GFR → less lithium cleared)
• ACE inhibitors / ARBs (reduce GFR)
• Thiazide diuretics (cause Na loss → kidneys reabsorb more Li+)
• Renal failure

Side Effects (at therapeutic levels):

• Fine hand tremor (most common - treat with propranolol if bothersome)
• Polyuria and polydipsia (nephrogenic diabetes insipidus - kidney doesn't respond to ADH)
• Weight gain
• Hypothyroidism (blocks thyroid hormone synthesis and release) - check TFTs regularly!
• Acne, psoriasis worsening
• Nausea, diarrhea (take with food)
• Leukocytosis (elevated WBC - benign)
• Edema

Lithium Toxicity Signs (levels >1.5 mEq/L):

Treatment of Lithium Toxicity:

1. Stop lithium immediately
2. IV normal saline - restore sodium/volume → kidney excretes lithium
3. Hemodialysis for severe toxicity (levels >2.5, seizures, coma, renal failure)
4. Monitor levels every 4-6 hours
5. There is NO specific antidote - supportive care

Contraindications:

• Pregnancy (cardiac defect: Ebstein anomaly of tricuspid valve with 1st trimester exposure)
• Severe renal impairment (can't clear it)
• Breastfeeding
• Dehydration states

---

PART 3: CARDIOVASCULAR DRUGS

ACE INHIBITORS (ACEi) and ARBs

ACE Inhibitors

• No Ang II → no vasoconstriction → BP goes down
• No Ang II → no aldosterone → no sodium retention → less volume → BP goes down
• ACE also breaks down bradykinin (a vasodilator) → when you block ACE, bradykinin builds up → causes cough and can cause angioedema!

• Hypertension (first-line)
• Heart failure with reduced EF (one of the best drugs - reduces mortality!)
• Diabetic nephropathy (protects kidneys by dilating efferent arteriole → reduces intraglomerular pressure)
• Post-MI (reduces remodeling, reduces mortality)
• Chronic kidney disease (slows progression)
• Left ventricular dysfunction

1. Dry, persistent cough - most common reason for stopping! Caused by bradykinin buildup. Not allergic - it's a class effect. Switch to ARB if cough occurs.
2. Hyperkalemia - no aldosterone → K+ isn't excreted. DANGEROUS! Monitor K+.
3. Hypotension - especially first dose
4. Renal impairment - dilating efferent arteriole can drop GFR. A small creatinine rise (< 30%) is acceptable. Monitor renal function!
5. Angioedema - rare but life-threatening! Swelling of face, lips, tongue, throat. Bradykinin accumulation. Can be delayed years after starting drug. MEDICAL EMERGENCY - stop drug, give epinephrine/antihistamines. ARBs can also rarely cause this.

• Pregnancy (ABSOLUTE contraindication - causes fetal renal failure, oligohydramnios, limb contractures, skull defects, death in 2nd/3rd trimester. "ABCD" - ACE inhibitors Cause fetal Death)
• Bilateral renal artery stenosis - dilating efferent arteriole when afferent is also narrowed → no perfusion pressure → acute renal failure
• Hyperkalemia (K+ >5.5)
• Angioedema history from ACEi
• Avoid with NSAIDs (reduce renal protective effect)
• Avoid with K+ sparing diuretics or K+ supplements (hyperkalemia risk)

---

ARBs (Angiotensin Receptor Blockers)

• DO NOT build up bradykinin (so NO cough, LOWER angioedema risk)
• Angiotensin II is still made, just can't act on AT1 receptors

• The go-to when ACEi causes cough!
• Heart failure (if ACEi intolerant)
• Hypertension, diabetic nephropathy, post-MI

• Same as ACEi EXCEPT NO cough (or much less common)
• Hyperkalemia, hypotension, renal impairment still occur
• Angioedema (rare, less common than ACEi)

• Pregnancy (absolutely contraindicated!)
• DO NOT combine ACEi + ARB together - doubles the hyperkalemia and renal damage risk without added benefit

---

DIURETICS

Loop Diuretics - The Most Powerful

• Acute heart failure / pulmonary edema (first-line!)
• Chronic heart failure (symptom control)
• Edema (any cause)
• Hypertension (especially if renal disease present)
• Hypercalcemia (increases calcium excretion!)
• Hyperkalemia (increases K loss)
• Ethacrynic acid - the only loop diuretic that can be used if allergic to sulfa drugs (others are sulfonamide-based)

• HYPOKALEMIA (most important - can cause arrhythmias!)
• Hyponatremia
• Metabolic alkalosis (when you lose H+ in urine, blood becomes more alkaline)
• Hypocalcemia (loop diuretics increase Ca excretion - remember "loops lose calcium")
• Hypomagnesemia
• Dehydration, hypotension
• Ototoxicity (especially at high doses IV - hearing loss, tinnitus, vertigo - especially with aminoglycoside antibiotics together!)
• Hyperuricemia (gout)
• Hyperglycemia
• Sulfa allergy (furosemide is sulfa-based)

• Anuria / severe renal failure (no tubular fluid to work on)
• Allergy to sulfonamides (switch to ethacrynic acid)
• Hypokalemia (worsens it further)
• Hepatic encephalopathy (K loss makes it worse)

---

Thiazide Diuretics

• Hypertension (first-line!)
• Mild heart failure
• Hypercalciuria / calcium kidney stones (thiazides actually RETAIN calcium - opposite of loops!)
• Nephrogenic diabetes insipidus (paradoxical - causes mild dehydration → kidney becomes more concentrated → reduces urine volume)
• Osteoporosis prevention (calcium retention)

• HYPOKALEMIA (like loops but milder)
• Hyponatremia (SIADH-like - can be severe!)
• Metabolic alkalosis
• Hypercalcemia (thiazides retain calcium - remember "thiazides save calcium")
• Hyperglycemia / worsens diabetes
• Hyperuricemia (gout)
• Hyperlipidemia (raises LDL and triglycerides mildly)
• Impotence
• Photosensitivity

• Gout
• Hypokalemia
• Diabetes (worsens blood sugar control)
• Sulfa allergy (thiazides are sulfonamide-based)

• Loops = calcium Lost (hypocalcemia)
• Thiazides = calcium Trapped (hypercalcemia)

---

Potassium-Sparing Diuretics

• Mechanism: Block aldosterone receptor in collecting duct → can't reabsorb Na, can't secrete K → K is spared
• Spironolactone indications: Heart failure with reduced EF (reduces mortality!), hypertension, hyperaldosteronism (Conn syndrome), cirrhosis with ascites, resistant hypertension
• Eplerenone: More selective than spironolactone (fewer hormonal side effects), used in heart failure post-MI
• Side effects:
  • HYPERKALEMIA (biggest danger!)
  • Gynecomastia and sexual dysfunction (spironolactone only - blocks testosterone receptors too; eplerenone is selective so avoids this)
  • Menstrual irregularities
  • Metabolic acidosis

• Mechanism: Block epithelial sodium channel (ENaC) directly in collecting duct
• Uses: Adjunct to loop/thiazide to prevent hypokalemia, Liddle syndrome, lithium-induced nephrogenic DI (amiloride)
• Side effects: Hyperkalemia, metabolic acidosis

• Hyperkalemia (K >5.0)
• Renal failure
• Do NOT combine with ACEi/ARB (triple hyperkalemia risk)
• Do NOT combine with NSAIDs

---

Carbonic Anhydrase Inhibitors

---

SGLT2 INHIBITORS

• Type 2 Diabetes (lowers blood sugar)
• Heart failure with reduced EF (reduces hospitalization and death - proven!)
• Chronic kidney disease (slows progression - proven!)
• Cardiovascular risk reduction in T2DM patients with established CV disease

• Causes osmotic diuresis (glucose in urine pulls water) → reduces blood volume → reduces preload → good for heart failure
• Reduces blood pressure
• Weight loss (calories lost in urine)

• Genital mycotic infections (yeast infections!) - most common. Glucose in urine = food for Candida. More common in women, but men get it too (balanitis). Tell patients to maintain good hygiene.
• UTIs (more glucose in urine = more bacterial growth)
• Euglycemic DKA - DKA can happen even with NORMAL blood sugar! (because of altered metabolism). Risk increased with low-carb diet, fasting, surgery, illness. STOP the drug 3-4 days before surgery!
• Polyuria, dehydration, hypotension (especially in elderly)
• Fournier's gangrene (necrotizing fasciitis of genitals) - rare but serious!
• Bone fractures (canagliflozin especially - reduces bone density)
• Lower limb amputations (canagliflozin - diabetic foot complications)
• Hyperkalemia (mild)

• Type 1 diabetes (high DKA risk)
• eGFR <30 (not effective, kidneys not functioning well enough)
• Recurrent UTIs or genital infections
• History of DKA

---

DIGOXIN

1. Positive inotropy (stronger contractions): Inhibits Na+/K+ ATPase pump → Na+ builds up in cell → Na-Ca exchanger reverses → Ca2+ builds up → stronger contractions!
2. Negative chronotropy (slower rate): Increases vagal (parasympathetic) tone → slows AV node conduction → controls ventricular rate in atrial fibrillation

• Atrial fibrillation with rapid ventricular rate (rate control) - especially in heart failure patients
• Heart failure with reduced EF (helps symptoms, does NOT reduce mortality - important exam point!)

• Nausea, vomiting, anorexia
• Visual changes: "Yellow-green vision" (xanthopsia) - classic! Things look yellow or with halos
• Fatigue

DIGOXIN TOXICITY - Super Important!

• Bradycardia (heart block of any degree)
• PVCs (especially bigeminy)
• Atrial tachycardia with block (very specific for dig toxicity!)
• Ventricular tachycardia/fibrillation (most dangerous)

• Hypokalemia (MOST IMPORTANT - low K+ allows digoxin to bind more effectively to the pump!) - loops and thiazides cause hypokalemia → increase digoxin toxicity risk
• Hypomagnesemia (similar mechanism)
• Renal failure (can't clear digoxin)
• Drug interactions that raise digoxin levels: Amiodarone, verapamil, quinidine (all increase digoxin levels dramatically - must halve the digoxin dose when adding these drugs!)
• Hypothyroidism

1. Stop digoxin
2. Correct hypokalemia/hypomagnesemia (give IV K+ and Mg2+)
3. Digoxin-specific Fab antibody fragments (Digibind) - the ANTIDOTE! Binds digoxin and pulls it away from receptors. Use for: severe toxicity, arrhythmias, K+ >5 with acute toxicity.
4. Atropine for bradycardia
5. Pacemaker if needed for severe bradycardia
6. DO NOT give calcium (worsens digoxin toxicity - can cause cardiac arrest - "Stone Heart")

---

CALCIUM CHANNEL BLOCKERS (CCBs)

Dihydropyridines (Amlodipine, Nifedipine)

• Hypertension (amlodipine - first-line for elderly, isolated systolic HTN)
• Angina (especially vasospastic/Prinzmetal angina!)
• Raynaud phenomenon
• Preterm labor (nifedipine - relaxes uterine smooth muscle)

• Peripheral edema (most common - ankle swelling from vasodilation)
• Headache, flushing, dizziness
• Reflex tachycardia (especially nifedipine - rapid acting)
• Gingival hyperplasia (amlodipine)

Non-Dihydropyridines (Verapamil, Diltiazem)

• Hypertension
• Angina (stable)
• Rate control in Afib/Aflutter (slow down ventricular rate)
• SVT (diltiazem IV, verapamil IV)
• Hypertrophic cardiomyopathy (verapamil)

• Bradycardia, AV block (major concern!)
• Negative inotropy (weakens heart contraction)
• Constipation (verapamil - classic! Blocks Ca channels in gut smooth muscle)
• Edema (less than DHPs)

• Heart failure with reduced EF - they depress contractility, can cause acute decompensation!
• WPW (Wolff-Parkinson-White) syndrome with Afib - DANGEROUS! Blocks AV node → all conduction goes down accessory pathway → rapid ventricular rate → VF
• 2nd or 3rd degree AV block
• Sick sinus syndrome
• Do NOT combine with beta-blockers (additive bradycardia/heart block)

---

NITRATES

• Venodilation (main effect at low doses) → decreases preload (less blood returning to heart) → heart does less work → less O2 demand → chest pain relieved!
• Arterial dilation at high doses → decreases afterload too

• Acute angina (sublingual NTG - first line! Works in 1-2 minutes)
• Stable angina prophylaxis (oral long-acting or patch)
• Acute MI (IV nitroglycerin)
• Acute heart failure / pulmonary edema (IV - reduces preload rapidly)
• Hypertensive emergency (IV nitroglycerin)
• Esophageal spasm (off-label)

• Headache (most common! Vasodilation in head - classic "nitroglycerin headache")
• Hypotension (especially with first dose)
• Flushing
• Reflex tachycardia
• Tolerance with continuous use (24-hour patch) - must have an 8-10 hour nitrate-free period each day to prevent tolerance! Usually overnight.

• Hypotension (SBP <90 mmHg)
• PDE5 inhibitor use (within 24-48 hours, or 72h for tadalafil)
• Right ventricular infarction - RV depends on preload; reducing preload with nitrates causes severe hypotension
• Hypertrophic obstructive cardiomyopathy (reduces preload → makes obstruction worse)

---

BETA BLOCKERS

• Non-selective (β1 + β2): Propranolol, Carvedilol (also α1 block), Labetalol (also α1 block), Nadolol, Timolol
• Selective β1 (cardioselective): Metoprolol, Atenolol, Bisoprolol, Esmolol, Acebutolol

• β1 block: ↓ heart rate, ↓ contractility, ↓ renin (less angiotensin production)
• β2 block (non-selective): bronchoconstriction, vasoconstriction, inhibits glycogenolysis

• Hypertension (decrease cardiac output + reduce renin)
• Heart failure with reduced EF (despite being negative inotropes, they prevent adverse remodeling and reduce mortality - use Metoprolol succinate, Carvedilol, Bisoprolol!)
• Post-MI (reduce mortality, prevent arrhythmias, prevent re-infarction)
• Angina (reduce O2 demand - slow rate and reduce contractility)
• Arrhythmias - Afib/flutter rate control, SVT prevention, ventricular arrhythmias
• Migraine prophylaxis (propranolol)
• Essential tremor (propranolol)
• Pheochromocytoma (given AFTER alpha blockers - never give beta first!)
• Hyperthyroidism (propranolol - controls symptoms: tachycardia, tremor, also inhibits T4→T3 conversion)
• Variceal bleeding prophylaxis (propranolol reduces portal pressure)
• Glaucoma (timolol eyedrops)
• Anxiety (propranolol - blocks peripheral symptoms)

• Bradycardia, AV block
• Fatigue (most common complaint)
• Bronchoconstriction (β2 block - why we avoid in asthma/COPD)
• Masking hypoglycemia - β2 mediates tachycardia/tremor as warning signs of low blood sugar → masked in diabetics on beta-blockers! (sweating is NOT masked - adrenergic pathway)
• Cold extremities (peripheral vasoconstriction)
• Sexual dysfunction (impotence)
• Depression (propranolol lipophilic - crosses BBB more)
• Hyperlipidemia (increased TG, decreased HDL)
• Weight gain
• Rebound effects on withdrawal - NEVER STOP ABRUPTLY! Tachycardia, hypertension, angina, MI risk. Taper slowly.

• Asthma / reactive airway disease (β2 block → bronchospasm) - avoid non-selective; cardioselective can sometimes be used cautiously
• Decompensated heart failure (can worsen acutely - but chronic HF is an INDICATION - this is a classic trap!)
• 2nd/3rd degree AV block (worsens block)
• Sick sinus syndrome
• Pheochromocytoma without alpha blockade (unmasked alpha stimulation → severe HTN crisis)
• Prinzmetal (vasospastic) angina (β2 block removes vasodilation → coronary spasm worsens)
• Cocaine intoxication (pure beta blockade leaves alpha stimulation unopposed → severe HTN/coronary spasm)

• Labetalol and Carvedilol = α + β blockers. Used in: hypertensive emergency, heart failure, pheochromocytoma (these are safe because they block both)
• Esmolol = ultra-short acting (half-life ~9 min), IV only. Used for intraoperative tachycardia, acute rate control in SVT/Afib

---

ANTIARRHYTHMICS

Class I - Sodium Channel Blockers

• ALSO prolong action potential and QT interval (also block K channels)
• Quinidine:
  • "Quinidine syncope" - torsades de pointes
  • Causes diarrhea (most common)
  • Cinchonism (tinnitus, headache, blurred vision)
  • Increases digoxin levels (halve digoxin dose!)
  • Thrombocytopenia
• Procainamide:
  • Long-term use → Drug-induced lupus (antinuclear antibodies, especially anti-histone antibodies)
  • Active metabolite (NAPA) prolongs QT
  • Good for WPW with Afib (drug of choice!)
  • Can be used in Afib/Aflutter when adenosine fails
• Disopyramide:
  • Strong anticholinergic effects
  • Used for vagally-mediated arrhythmias
  • Negative inotrope (contraindicated in HF)

• Short duration, SHORTEN action potential
• Work BEST on ischemic tissue (depolarized cells)
• Lidocaine (IV):
  • Used for ventricular arrhythmias (especially post-MI)
  • CNS side effects: Drowsiness, confusion, seizures, tinnitus
  • NOT effective for atrial arrhythmias
• Mexiletine (oral version of lidocaine):
  • Chronic ventricular arrhythmia suppression

• STRONGEST Na channel block
• Flecainide:
  • Very effective for Afib/Aflutter (both conversion and maintenance of sinus rhythm)
  • CONTRAINDICATED in structural heart disease or post-MI (CAST trial showed increased mortality!)
  • Safe in "lone Afib" (structurally normal heart)
  • "Pill in pocket" approach for paroxysmal Afib
• Propafenone:
  • Similar to flecainide
  • Also has mild beta-blocking properties
  • Same contraindications

---

Class II - Beta Blockers

• Used for arrhythmias: Rate control in Afib/Aflutter, SVT, post-MI ventricular arrhythmias
• Key drugs: Metoprolol, Esmolol, Propranolol

---

Class III - Potassium Channel Blockers

• Ventricular tachycardia, ventricular fibrillation (first-line in cardiac arrest with refractory VT/VF!)
• Afib (rate AND rhythm control)
• SVT (second line)
• Often the "last resort" when other drugs fail

1. Pulmonary toxicity (pneumonitis, fibrosis) - check chest X-ray/CT regularly, pulmonary function tests. Can be fatal!
2. Thyroid toxicity - contains HUGE amount of iodine (37% iodine by weight!) → can cause hyperthyroidism OR hypothyroidism! Check TSH regularly.
3. Hepatotoxicity - liver fibrosis. Check LFTs.
4. Corneal microdeposits - yellow-brown deposits visible on slit lamp. Usually benign, but can cause halos around lights.
5. Photosensitivity - skin turns blue-gray (slate-colored skin)
6. Peripheral neuropathy
7. QT prolongation (despite treating arrhythmias, can cause torsades - less commonly than other class III)
8. Raises digoxin levels (halve digoxin dose!)
9. Raises warfarin levels (increase bleeding risk)

• Combined beta-blocker (Class II) + K channel blocker (Class III)
• Used for Afib, ventricular arrhythmias
• QT prolongation → torsades risk (monitor QT, avoid hypokalemia)
• Contraindicated: renal failure (cleared by kidneys), bradycardia, asthma

• Pure Class III, used for Afib
• Significant torsades risk - must be started in hospital with telemetry!

• IV only, used for acute cardioversion of Afib/Aflutter
• Torsades risk - monitor ECG

---

Class IV - Calcium Channel Blockers (Non-DHP)

• Verapamil and Diltiazem
• Used for SVT (AV nodal block), Afib/Aflutter rate control

---

Other Antiarrhythmic Agents

• Not in Vaughan-Williams classification
• Mechanism: Activates potassium channels → hyperpolarizes AV node → briefly blocks AV conduction
• Uses: FIRST-LINE for acute SVT (terminates AV-nodal reentrant tachycardia in seconds!)
• Dose: 6 mg IV rapid push, then 12 mg if no response
• Side effects: VERY brief (half-life 10-15 seconds!): flushing, chest tightness, brief asystole, dyspnea, bronchospasm
• Contraindications: Asthma (causes bronchospasm), 2nd/3rd degree AV block, sick sinus
• Note: Theophylline and caffeine BLOCK adenosine receptors (antagonists) - won't work!
• Note: Dipyridamole BLOCKS adenosine uptake (potentiates effect - use smaller dose)

• Drug of choice for Torsades de Pointes!
• Also used for digoxin-induced arrhythmias
• Eclampsia seizures in pregnancy
• Give 2g IV slowly for torsades

---

QUICK TOXICITY TREATMENT SUMMARY TABLE

---

KEY EXAM MNEMONICS AND MEMORY AIDS

Contraindications to Remember:

• ACEi/ARB: Pregnant, bilateral renal artery stenosis, hyperkalemia
• Beta-blockers: Asthma, 2nd/3rd degree block, decompensated HF, pheochromocytoma (without alpha block)
• Verapamil/Diltiazem: HF with reduced EF, WPW+Afib, AV block
• Nitrates: PDE5 inhibitors, RV infarction, hypotension, HOCM
• Lithium: Pregnancy (Ebstein anomaly), NSAIDs raise level, thiazides raise level

Drug-Drug Interactions to Memorize:

• Digoxin + Amiodarone → digoxin level doubles → HALVE the digoxin dose
• Digoxin + Verapamil/Quinidine → digoxin level rises → reduce dose
• Warfarin + Amiodarone → warfarin level rises → reduce warfarin
• MAOIs + SSRIs/SNRIs → serotonin syndrome (14-day washout)
• MAOIs + Tyramine foods → hypertensive crisis
• Nitrates + Viagra → severe hypotension (NEVER combine)
• Beta-blockers + Verapamil → complete heart block (NEVER combine IV forms)
• SGLT2 + surgery → stop 3-4 days before surgery (DKA risk)

Special Drug Pregnancy Rules:

• ACEi/ARB: Absolutely contraindicated (fetal renal agenesis/failure)
• Lithium: Ebstein's anomaly (1st trimester)
• Tetracyclines: Bone/teeth abnormalities
• Methotrexate: Teratogen
• Warfarin: Fetal warfarin syndrome (CNS defects, nasal hypoplasia)
• Safe in pregnancy for HTN: Methyldopa, Labetalol, Nifedipine, Hydralazine

---

KEY CONCEPT COMPARISONS FOR EXAM

• Both can terminate SVT but NEVER give IV together!
• In stable: try vagal maneuvers first, then adenosine, then verapamil/metoprolol

• ACEi: cough (bradykinin), angioedema (more common)
• ARB: No cough (no bradykinin), but same other risks

• Loop: More powerful, causes hypocalcemia, used in acute situations and renal disease
• Thiazide: Weaker, causes hypercalcemia, first-line for uncomplicated hypertension

• Typical: More EPS, no metabolic, high prolactin
• Atypical: Less EPS, more metabolic (weight gain, DM), variable prolactin; Clozapine = agranulocytosis

---

1. Digoxin toxicity treatment = Digibind + correct K+ and Mg2+
2. TCA OD = Sodium bicarbonate for wide QRS
3. NMS vs Serotonin syndrome distinction (rigidity vs clonus)
4. Lithium + NSAIDs/Thiazides = toxicity
5. ACEi + pregnancy = absolute contraindication
6. Nitrates + PDE5 inhibitors = absolutely contraindicated
7. Clozapine = agranulocytosis, weekly CBC
8. SGLT2i = yeast infections + euglycemic DKA
9. Amiodarone = pulmonary/thyroid/liver toxicity, extremely long half-life
10. Torsades = IV Magnesium

1. Serotonin syndrome vs NMS - almost always on exams, must know cold
2. Digoxin toxicity (treatment = Digibind, triggers = hypokalemia)
3. TCA overdose (treatment = sodium bicarb)
4. Lithium toxicity (causes: NSAIDs, thiazides, dehydration)
5. Antiarrhythmics - memorize Vaughan-Williams classes and one key drug from each
6. ACEi/ARB - contraindications especially pregnancy and bilateral RAS