🧭 Module 1 · Introduction to Pharmacology

🧵 Exam traps ⭐ HIGH YIELD

• First-pass effect is a LIVER event, not a stomach event. It is why the same drug needs a bigger oral dose than IV dose.
• Potency is how much you need; efficacy is how much you get. The stem often calls the more potent drug the 'stronger' one to see if you bite.
• Tolerance (needs more for the same effect) is not dependence (withdrawal if stopped) is not addiction (compulsive use despite harm). Questions swap the three.
• A side effect is expected and dose-related; an allergy is immune-mediated and can happen at any dose. 'Nausea with codeine' is a side effect, not an allergy.
• Trough = right before the next dose. Peak = after administration, at the drug's expected peak. Students reverse these and lose easy points.

Absorption (What is it, what regulates the process, what affects the process?)⭐ HIGH YIELD

Absorption is the movement of a drug from where it was given into the bloodstream. It is regulated by the ROUTE and the drug's ability to cross cell membranes; it is affected by blood flow, surface area, pH/ionization, lipid solubility, food, and GI motility.

• IV = 100% absorbed with no absorption phase, so it has the fastest onset.
• Most oral drugs are absorbed in the small intestine (huge surface area from villi).
• Small, lipid-soluble, non-ionized molecules cross membranes best.
• Slowed by food, low blood flow, decreased motility, and enteric coatings.

Absorption = getting IN. IV skips the line entirely.

Distribution (What is it, what regulates the process, what affects the process?)⭐ HIGH YIELD

Distribution is the movement of drug from the blood into tissues and fluids. It is regulated by blood flow to the tissue, membrane permeability (blood-brain and placental barriers), and PROTEIN BINDING; it is affected by cardiac output, albumin level, body fat vs water, and competing drugs.

• Only FREE (unbound) drug is active. Low albumin = more free drug = toxicity.
• Two highly protein-bound drugs compete; one gets displaced and becomes toxic (warfarin is the classic).
• Highly perfused organs get drug first: heart, liver, kidney, brain.
• The blood-brain barrier blocks large/water-soluble drugs; the placenta blocks almost nothing.
• Lipid-soluble drugs store in fat, so effects last longer in obese and older adults.

Bound = benched. Only free drug plays.

Metabolism (What is it, what regulates the process, what affects the process?)⭐ HIGH YIELD

Metabolism (biotransformation) chemically changes the drug, usually into a more water-soluble, inactive form so it can be excreted. It happens mainly in the LIVER via cytochrome P450 enzymes; it is affected by liver function, age, genetics, and CYP inducers and inhibitors.

• INHIBITORS (grapefruit, ketoconazole, erythromycin, cimetidine, fluoxetine) raise drug levels toward toxicity.
• INDUCERS (St John's wort, rifampin, phenytoin, carbamazepine, smoking) lower drug levels toward treatment failure.
• Prodrugs are the reverse: metabolism ACTIVATES them (codeine to morphine, enalapril to enalaprilat).
• Infants and older adults metabolize slowly, so they need lower doses.
• Liver disease means reduce the dose.

InDucers Decrease the drug. InHibitors Heighten it.

Elimination/Excretion (What is it, what regulates the process, what affects the process?)⭐ HIGH YIELD

Excretion is removal of drug and metabolites from the body. The primary route is the KIDNEY (glomerular filtration, tubular secretion and reabsorption); it is affected by renal function/GFR, age, hydration, urine pH, and competition at the tubules.

• Other routes: bile and feces, lungs (anesthetics, alcohol), breast milk, sweat, saliva.
• Renal impairment causes accumulation: reduce the dose or lengthen the interval. Check creatinine and GFR.
• Older adults have a lower GFR even when serum creatinine looks normal (less muscle mass).
• Enterohepatic recirculation prolongs some drugs by sending them back through the gut.

The kidney is the exit door. Broken door = drug piles up.

First Pass Metabolism / First Pass Effect (What is it? Which dosage forms are affected?)⭐ HIGH YIELD

First-pass effect: a drug absorbed from the GI tract travels through the portal vein to the liver and is partly metabolized BEFORE it ever reaches systemic circulation, so less active drug arrives. ORAL dosage forms are the ones affected.

• This is why the oral dose of a drug is much larger than its IV dose (morphine, propranolol).
• Nitroglycerin is almost entirely destroyed on first pass, which is why it is given sublingually.
• Rectal is only partially affected: the lower rectal veins bypass the liver, the upper ones do not.

The liver takes its cut first. SL and IV don't pay the toll.

Bioavailability⭐ HIGH YIELD

Bioavailability is the fraction of an administered dose that actually reaches systemic circulation in active form. IV is 100% by definition; oral is lower and more variable because of incomplete absorption plus first-pass metabolism.

• Rough order: IV (100%) > IM/subQ > sublingual, inhaled, transdermal > oral > rectal (variable).
• Anything that reduces absorption or increases first-pass metabolism reduces bioavailability.
• Formulation matters: brand-to-generic switches can matter for narrow-therapeutic-index drugs like levothyroxine, warfarin, and phenytoin.
• Food, gastric pH, and other drugs change oral bioavailability; IV has none of those variables.

Bioavailability = how much made it to the party, not how much left the house.

Enteral vs Parenteral Routes⭐ HIGH YIELD

Enteral routes deliver drug through the GI tract (oral, sublingual, buccal, NG/PEG tube, rectal). Parenteral routes deliver drug by injection, bypassing the GI tract entirely (IV, IM, subQ, intradermal, epidural, intrathecal).

'Enteral' has ENTER in it, it enters through the gut. 'Par-enteral' means PAST the gut.

Half-Life (What is it? How do I calculate the time it takes for a drug to reach a certain serum⭐ HIGH YIELD

Half-life (t1/2) is the time it takes for the serum drug concentration to fall by 50%. It takes about 4 to 5 half-lives to reach steady state on repeated dosing, and about 4 to 5 half-lives to clear a drug after it is stopped.

• Solve the classic question by halving: a drug at 200 mg/L with a 6-hour half-life is 100 at 6 h, 50 at 12 h, 25 at 18 h.
• Half-life determines dosing FREQUENCY. The dose size determines the level.
• Liver or kidney impairment lengthens half-life, so the drug accumulates.
• A loading dose is what you use when you cannot wait 4 to 5 half-lives.

Cut it in half, then in half again. Five cuts and it is basically gone (or basically full).

Loading Dose⭐ HIGH YIELD

A loading dose is a large initial dose given to reach a therapeutic serum level FAST, instead of waiting 4 to 5 half-lives. Smaller maintenance doses then keep the level there.

• Used for long half-life drugs when you cannot wait: digoxin, amiodarone, phenytoin, vancomycin, heparin bolus.
• The loading dose is based on volume of distribution; the maintenance dose is based on clearance.
• A loading dose does not change the drug's half-life.
• Watch closely after a loading dose: this is when toxicity shows up.

The loading dose fills the tank. Maintenance doses keep topping it off.

Potency vs efficacy⭐ HIGH YIELD

Potency is how MUCH drug it takes to produce an effect. Efficacy is how BIG an effect the drug can produce at its maximum, its ceiling. Efficacy matters more clinically.

• A more potent drug is not a better drug, it just takes fewer milligrams.
• Graphically: potency shifts the dose-response curve left or right; efficacy raises or lowers its ceiling.

Potency = how much. Efficacy = how good. You would rather have the drug that works better than the one you need less of.

Agonist vs antagonist⭐ HIGH YIELD

An agonist binds a receptor and ACTIVATES it, producing a response. An antagonist binds the receptor and BLOCKS it, producing no response and preventing the body's own chemical or an agonist from acting.

• Partial agonist: binds and activates, but with a lower ceiling than a full agonist (buprenorphine).
• A competitive antagonist can be overcome by giving more agonist; a noncompetitive one cannot.
• Antidotes are usually antagonists: naloxone, flumazenil, atropine, protamine.

Agonist = the key that turns the lock. Antagonist = the key that fits but won't turn, and now nobody else can get in.

Therapeutic index⭐ HIGH YIELD

Therapeutic index (TI) = TD50 divided by ED50 (the toxic dose in 50% of subjects over the effective dose in 50%). A HIGH/wide TI means a large safety margin; a LOW/narrow TI means toxic and therapeutic doses are close together and the drug needs serum level monitoring.

• The therapeutic range or window is the concentration between the minimum effective level and the toxic level.
• For narrow-TI drugs also watch renal and hepatic function, drug interactions, and brand-to-generic switches.
• Practical example: a digoxin level of 2.5 ng/mL is already toxic while the target is roughly 0.5 to 2 ng/mL.

Narrow index = narrow ledge. One step and the patient falls into toxicity.

Peak and trough⭐ HIGH YIELD

Peak is the HIGHEST serum level, drawn shortly after a dose, and it tells you about toxicity. Trough is the LOWEST level, drawn immediately BEFORE the next dose, and it tells you whether the drug is staying therapeutic and clearing properly.

• Classic peak and trough drugs: vancomycin, gentamicin, tobramycin, amikacin.
• Document the exact time the level was drawn AND the time the last dose was given, or the result is meaningless.
• Follow the order: some protocols hold the next dose until the trough result returns.

TROUGH is the low spot in the road, and it comes right before you climb (the next dose).

Tolerance vs dependence⭐ HIGH YIELD

Tolerance means the body needs MORE drug over time to get the same effect. Dependence means the body has adapted so that stopping the drug causes WITHDRAWAL. Neither one is the same as addiction.

• Addiction (substance use disorder) is compulsive use, craving, and continued use despite harm. It is behavioral, not a lab value.
• Cross-tolerance: tolerance to one drug in a class carries over to others in that class.
• Tachyphylaxis is rapid tolerance after only a few doses, classically with nitrates.
• Physical dependence is expected and normal in a patient on long-term opioids and does not mean they are addicted.

Tolerance = 'need more.' Dependence = 'can't stop without withdrawal.' Addiction = 'can't stop and it's wrecking my life.'

Allergic Responses⭐ HIGH YIELD

An allergic (hypersensitivity) response is an IMMUNE-mediated reaction to a drug. It requires a prior sensitizing exposure, is not dose-related, and ranges from a mild rash to fatal anaphylaxis.

• Type I (IgE, immediate): urticaria, angiedema, anaphylaxis, within minutes to an hour.
• Type II and III (cytotoxic and immune complex): hemolytic anemia, thrombocytopenia, serum sickness, drug fever.
• Type IV (delayed, T-cell): contact dermatitis, morbilliform rash, and SJS/TEN, appearing days to weeks later.
• An allergy is NOT a side effect or intolerance. GI upset from erythromycin is not an allergy. Always ask WHAT happened, not just 'are you allergic,' and document the actual reaction.
• Top offenders: penicillins and cephalosporins, sulfonamides, NSAIDs, contrast media, neuromuscular blockers.

First exposure sensitizes, second exposure reacts. That is why 'I've taken it before' does not protect the patient.

Mild allergy⭐ HIGH YIELD

A mild allergic reaction involves the SKIN AND MUCOUS MEMBRANES ONLY: itching, hives (urticaria), flushing, localized rash, mild swelling, watery eyes, runny nose, with NO airway, breathing, or blood pressure involvement.

• Treatment: stop the drug, antihistamine (diphenhydramine or cetirizine), sometimes a topical or oral corticosteroid, and keep monitoring.
• Add it to the allergy list with a description of what happened.
• A mild reaction can become severe on re-exposure, so never dismiss one.

Skin only = mild. Skin plus breathing or blood pressure = epinephrine.

Nephrotoxicity (What is it? What groups of drugs are nephrotoxic?)⭐ HIGH YIELD

Nephrotoxicity is drug-induced kidney injury: rising creatinine and BUN with falling urine output and GFR. Monitor renal function, keep the patient hydrated, and avoid stacking nephrotoxic drugs.

• Nephrotoxic groups to know: aminoglycosides (gentamicin, tobramycin, amikacin), vancomycin, amphotericin B, NSAIDs, IV contrast media, cisplatin, cyclosporine and tacrolimus, IV acyclovir, lithium, sulfonamides, and ACE inhibitors/ARBs in low-flow states.
• Signs: rising serum creatinine and BUN, urine output under 30 mL/hr, edema, weight gain, electrolyte derangement.
• Nursing: baseline and serial BUN/creatinine, strict intake and output, daily weights, hydration, trough levels, and do not combine nephrotoxins.
• Many nephrotoxic drugs are also OTOTOXIC: aminoglycosides, vancomycin, loop diuretics, cisplatin, high-dose aspirin. Ask about tinnitus, vertigo, and hearing loss.

The kidney killers travel together: Aminoglycosides, Vancomycin, Amphotericin ('ampho-terrible'), NSAIDs, Contrast, Cisplatin.

Cardiotoxicity⭐ HIGH YIELD

Cardiotoxicity is drug-induced damage to heart muscle or conduction. It shows up three ways: cardiomyopathy and heart failure, arrhythmias and conduction block, or QT prolongation leading to torsades de pointes.

• Cardiomyopathy/HF: anthracyclines (doxorubicin, with a lifetime cumulative dose limit), trastuzumab, cyclophosphamide, some tyrosine kinase inhibitors.
• QT prolongation and torsades: amiodarone, sotalol, haloperidol, droperidol, methadone, macrolides, fluoroquinolones, ondansetron, TCAs, citalopram.
• Rate and conduction: digoxin toxicity, beta blockers, and non-dihydropyridine calcium channel blockers (verapamil, diltiazem) cause bradycardia and heart block.
• Monitoring: baseline and serial echocardiogram/ejection fraction for anthracyclines; ECG with QTc plus potassium and magnesium for QT drugs.
• Teach the patient to report new dyspnea, orthopnea, swelling, weight gain over 2 to 3 lb in a day, palpitations, or syncope.

Doxorubicin is 'the red devil': cardiotoxic, and dose-limited for life.

Drug Interactions⭐ HIGH YIELD

A drug interaction occurs when one drug, food, or herb changes another drug's effect. Interactions can be additive/synergistic, antagonistic, or pharmacokinetic (altered absorption, protein binding, CYP metabolism, or excretion). Under the torsade de pointes heading on this handout: combining two QT-prolonging drugs, or adding a CYP3A4 inhibitor to a QT drug, is a classic cause of torsades.

• Torsades combinations to know: macrolide or fluoroquinolone plus amiodarone or sotalol; haloperidol or methadone plus ondansetron; any QT drug plus HYPOKALEMIA or HYPOMAGNESEMIA.
• A QTc over 500 ms is the danger threshold. Treat torsades with IV magnesium sulfate, and defibrillate if the patient is pulseless.
• Pharmacokinetic: CYP inhibitors (grapefruit, ketoconazole, erythromycin, cimetidine, fluoxetine) raise levels; CYP inducers (St John's wort, rifampin, phenytoin, carbamazepine) lower them.
• Pharmacodynamic: warfarin plus an NSAID causes bleeding; opioid plus benzodiazepine causes respiratory depression; two serotonergic drugs cause serotonin syndrome.
• Correct potassium and magnesium before blaming the drug alone.

Two QT drugs plus a low potassium equals twisting ribbons on the monitor.

Medication Errors (What are common causes? What are some prevention strategies?)⭐ HIGH YIELD

Medication errors are preventable events that lead to inappropriate medication use or patient harm. The most common causes are communication failures, look-alike/sound-alike drugs, illegible or verbal orders, distraction and interruption, and heavy workload. Prevention centers on the rights of medication administration, barcode scanning, and independent double checks.

• Common causes: decimal and dose miscalculations, unapproved abbreviations, LASA drugs (hydralazine/hydroxyzine, celecoxib/citalopram), verbal or telephone orders, interruptions during administration, and incomplete medication reconciliation at transitions of care.
• Prevention: the rights (patient, drug, dose, route, time, documentation, reason, response), two identifiers, barcode scanning, read-back of verbal orders, the 'do not use' abbreviation list, a leading zero (0.5 mg) and never a trailing zero (never 5.0 mg).
• High-alert drugs (insulin, heparin, opioids, chemotherapy, concentrated electrolytes) require an INDEPENDENT double check by a second nurse.
• Report every error and near-miss. Non-punitive reporting is what fixes the system.
• After an error: assess and stabilize the PATIENT first, then notify the provider, then complete the incident report. Do not chart 'incident report filed' in the medical record.

Patient first, provider second, paperwork third.

Physiological changes of the elderly⭐ HIGH YIELD

Aging changes all four pharmacokinetic phases: absorption slows, distribution shifts (less body water, more fat, less albumin), hepatic metabolism declines, and renal excretion declines. The result is that drugs last longer and accumulate, so you start low and go slow.

• The aging CNS is more sensitive, so benzodiazepines, anticholinergics, and opioids cause more sedation, confusion, and falls.
• Blunted baroreceptor response means more orthostatic hypotension. Thinner skin changes topical and transdermal absorption.
• Practical nursing: use renally adjusted dosing, review the whole med list at every visit, and treat new confusion or falls as a drug side effect until proven otherwise.

Less water, less albumin, less liver, less kidney: the same dose hits harder and stays longer.

Groups of medications to avoid in the elderly (i.e., Beers criteria)⭐ HIGH YIELD

The Beers Criteria (American Geriatrics Society) is a list of potentially inappropriate medications for adults 65 and older, where the risk outweighs the benefit. The biggest categories are anticholinergics, benzodiazepines and Z-drugs, antipsychotics, NSAIDs, and certain cardiac and endocrine drugs.

• First-generation antihistamines (diphenhydramine, hydroxyzine) and other strong anticholinergics (oxybutynin, amitriptyline and other TCAs, cyclobenzaprine, muscle relaxants): confusion, dry mouth, urinary retention, constipation, falls.
• Benzodiazepines (lorazepam, diazepam) and Z-drugs (zolpidem): falls, fractures, delirium.
• Antipsychotics used for behavioral symptoms of dementia: increased stroke risk and mortality.
• Chronic NSAIDs: GI bleeding, kidney injury, worsening heart failure and hypertension.
• Others: meperidine (neurotoxic metabolite), sliding-scale insulin as the only regimen, long-acting sulfonylureas like glyburide and chlorpropamide (prolonged hypoglycemia), digoxin above 0.125 mg/day, PPIs beyond 8 weeks without indication. Beers is a caution and review list, not an absolute ban. It prompts you to find a safer alternative.

Anticholinergics in the elderly: blind as a bat, dry as a bone, red as a beet, mad as a hatter, and then they fall.

Polypharmacy⭐ HIGH YIELD

Polypharmacy is the use of multiple medications, commonly defined as 5 or more at once, or the use of more drugs than are clinically necessary. It multiplies the risk of interactions, adverse effects, nonadherence, falls, and prescribing cascades.

• Prescribing cascade: a drug side effect is mistaken for a new disease and treated with another drug (metoclopramide causes EPS, which gets treated with an anti-Parkinson drug).
• Risk factors: multiple prescribers, multiple pharmacies, OTC and herbal use, several chronic conditions, and no medication reconciliation.
• Nursing role: a 'bring all your bottles' medication review, reconciliation at every transition, and specifically asking about OTCs, supplements, eye drops, and creams, which patients rarely volunteer.
• Deprescribing is legitimate care. Fewer drugs is often better outcomes in older adults.

Every new symptom in an older adult is a drug side effect until proven otherwise.

Echinacea⭐ HIGH YIELD

Echinacea is taken to PREVENT or shorten the common cold and upper respiratory infections by stimulating the immune system. That is exactly why it is CONTRAINDICATED in autoimmune disease and in transplant or immunosuppressed patients.

• Avoid in multiple sclerosis, lupus, rheumatoid arthritis, HIV, tuberculosis, and with cyclosporine, tacrolimus, or corticosteroids: it works against the drugs suppressing the immune system.
• Cross-allergy with ragweed, daisies, chrysanthemums, and marigolds (Asteraceae family).
• Inhibits CYP1A2 and CYP3A4, so it can raise levels of some drugs. Limit continuous use (commonly 8 weeks or less) because of reported hepatotoxicity.
• Evidence for actual benefit is weak and inconsistent.
• Common effects: GI upset, rash, and a temporary tingling of the tongue.

Echinacea REVS the immune system, so never give it to someone whose immune system we are trying to shut down.

Garlic⭐ HIGH YIELD

Garlic is taken to lower cholesterol and blood pressure and for general cardiovascular prevention. The tested problem is BLEEDING: it inhibits platelet aggregation and adds to warfarin, aspirin, clopidogrel, heparin, and NSAIDs.

• Stop about 7 to 10 days before surgery or an invasive procedure.
• May lower blood glucose, which is additive with insulin and oral antidiabetics.
• Reduces levels of saquinavir and other HIV protease inhibitors, risking treatment failure.
• May lower blood pressure, which is additive with antihypertensives.
• Common effects: breath and body odor, heartburn, and GI upset.

The G-herbs that make you bleed: Garlic, Ginger, Ginkgo, Ginseng (plus feverfew, fish oil, and vitamin E).

Gingko Biloba (How does it work?)⭐ HIGH YIELD

Ginkgo biloba is taken for MEMORY and dementia, cognitive decline, and intermittent claudication. It works by increasing blood flow (vasodilation) and inhibiting platelet-activating factor, and that antiplatelet action is exactly why it is dangerous: BLEEDING.

• Serious risk of intracranial and postoperative bleeding with warfarin, aspirin, clopidogrel, heparin, NSAIDs, and vitamin E. Stop 1 to 2 weeks before surgery or any invasive procedure.
• LOWERS THE SEIZURE THRESHOLD. Avoid in seizure disorders and with bupropion, TCAs, and tramadol.
• Avoid with SSRIs and MAOIs (serotonin effects) and in pregnancy.
• Adverse effects: headache, dizziness, GI upset, palpitations.
• Never eat raw or roasted ginkgo SEEDS: they are toxic and can cause seizures.

Ginkgo helps you think and helps you bleed.

Saw Palmetto⭐ HIGH YIELD

Saw palmetto is taken for BENIGN PROSTATIC HYPERPLASIA: urinary frequency, nocturia, and weak stream. It is thought to act like a mild 5-alpha-reductase inhibitor, blocking conversion of testosterone to DHT.

• Contraindicated in pregnancy and in women who could become pregnant. The hormonal effect can harm a male fetus, and pregnant women should not even handle the capsules.
• Can LOWER the PSA level and mask or delay a prostate cancer diagnosis. Tell the provider before PSA testing.
• Mild antiplatelet effect: caution with anticoagulants and antiplatelets, and hold before surgery.
• May add to finasteride, dutasteride, and alpha blockers, and may interact with hormonal contraceptives and estrogen therapy.
• Never let it delay evaluation of urinary retention or hematuria.

Saw palmetto saves the stream and saws down the PSA number.