Foundations Final Exam

**Provider

A person or place that is licensed to provide health care; doctor or medical professional (ex: hospital, clinic)

**Payor

Entity that assumes the risk of paying for medical treatment; insurance company or government

Top 5 payors in US healthcare system

1. UnitedHealth Group

2. CVS Health (Aetna)

3. Centene Corporation

4. Humana

5. Elevance (Anthem BCBS)

**Beveridge Healthcare Model

• "Socialized Medicine" - every citizen has health insurance

• Provider: government

• Payor: government

• Financed: income taxes

  • costs are low

  • gov controls which services physicians offer and how much they charge

  • most hospitals and clinics are gov-owned

  • some physicians are gov employees

• Ex: UK, Cuba

• Ex in US: Veterans Administration (VA)

**Bismarck Healthcare Model

• "Social Health Insurance"

• Provider: multiple

  • most providers are private but tightly regulated

  • private health insurers are nonprofit and tightly regulated

  • costs are low

• Payor: multiple

• Financed: payroll taxes

• Ex: Germany, Japan, France, The Netherlands

• Ex in US: Affordable Care Act (Obamacare)

**National Health Insurance Model

• Combination of Beveridge and Bismarck models

• Provider: multiple - private but tightly regulated

• Payor: government

• Financed: income taxes and payroll deductions

  • low costs

  • gov regulates prices

  • limited services

  • long patient wait times

• Ex: Canada, South Korea

• Ex in US: Medicare and portions of Medicaid

**Out-of-Pocket

• No insurance

• Ex: rural areas of India, China, South America

• Ex in US: people between jobs, self-employed, earn too much money for Medicaid but not enough to afford commercial insurance

• 8.3% of Americans are uninsured

• US (and Mexico) is the only industrialized nation without universal healthcare

**US Healthcare System (combines all 4 models)

• Combines all 4 models based on socioeconomic status

• Veterans - VA healthcare - Beveridge Model

• over age 65 - Medicare - National Health Insurance Model

• Employer Health Insurance - Horizon BCBSNJ - Bismarck Model

• uninsured - 8.3% of Americans - Out-of-Pocket

Underinsured Americans

• Out of pocket costs (excl premiums) >/= 10% annual household income

• out of pocket costs (excl premiums) >/= 5% annual household income for individuals living under 200% of FPL ($29,160 individual; $60,000 family of 4)

• individual or family deductible >/= 5% annual household income

Impact of being underinsured

• Problems accessing care

• skipping a doctor appt

• can't afford to fill a prescription

**What does the US spend on for healthcare?

• From $6 trillion

• 1. Hospital care (supplies, beds) - 31%

• 2. Physician and clinical services (salaries) - 21%

• 3. Retail sales of medical products (crutches, toilet covers, walkers) - 13.3%

• 4. Prescription drugs - 9.3%

• 5. Nursing homes and assisted living - 4.1%

Who pays for healthcare costs?

1. Private health insurance (employer) - 31.4%

2. Medicare (age > 65 yrs) - 21.8%

3. Medicaid (age 19-64 w income </= 138% FPL) - 17.6%

4. Out of pocket (uninsured, copays, rejected claims) - 10.4%

Private health insurance

• Most often provided by employer

• 160 million - employer-provided health insurance

• 15 million - purchase their own health insurance

**HMOs and PPOs

• Health Maintenance Organizations (HMOs):

  • lower premiums, fewer choices - must choose an "in-network" PCP, any non-emergency out-of-network care is an out of pocket expense

• Preferred Provider Organizations (PPOs):

  • pay higher premiums, more flexibility to see out-of-network providers (esp for specialists)

Government-sponsored (taxpayer-funded) insurance

• Medicaid

• Medicare

• State Children's Health Insurance Program (SCHIP)

• Indian Health Service (IHS)

• Veterans Health Administration (VA)

**Medicaid

• Patients on limited income (age 19-64 w income </= 138% FPL)

• payments made directly to healthcare providers

• patient co-pay required for certain services

**Medicare

• Patients age >/= 65 years

• patients with certain disabilities

• patients w end-stage renal disease

State Children's Health Insurance Program (SCHIP)

Uninsured children from families that earn too much for Medicaid but too little to afford private insurance

Indian Health Service (IHS)

• American Indians and Alaska Natives who:

  • are members of a federally-recognized tribe or group under federal supervision

  • live on tax-exempt land or own restricted property

Veterans Health Administration (VA)

• Military veterans who served 24 consecutive months or the full period of call-up to active duty

• largest healthcare system in the US (170 medical centers and 1704 outpatient clinics)

• routine visits, appts with specialists, home health and elder care, medical equipment, prosthetics, prescription drugs

**Affordable Care Act of 2010 (Obamacare)

• Reduced the number of uninsured Americans by expanding government and private insurance + increasing percentage of those who qualified for insurance

• expanded Medicaid coverage to most adults w incomes below 138% of the FPL

• only 41 states have expanded their Medicaid coverage to meet this goal

• NOT: Wyoming, Texas, Wisconsin, Kansas, Tennessee, Mississippi, Alabama, Georgia, South Carolina, Florida

**US healthcare system performs against OECD

• OECD: Organization for Economic Co-operation and Development

• healthcare expenditures as %GDP -> US spends the highest and more than OECD avg

• expenditures for prescription drugs -> US spends more than OECD avg

• skip needed care due to cost -> US skips most treatment

• PCPs per 1,000 population -> US has less than OECD avg

• total hospital beds per 1,000 population -> US has less than OECD avg

• rate of obesity -> US has higher rate than OECD avg

• adults with multiple chronic diseases -> US has higher rate than OECD avg

• average life expectancy -> US has lower than OECD avg

• maternal death rate per 100,000 live births -> US has higher rate than OECD avg

  • US black women have triple the death rate

**Why does the US perform so poorly?

• Rising cost of new tech and prescription drugs

• rising incidence of chronic diseases esp obesity

• high administrative healthcare costs - US has highest administrative costs of any industrialized nation, up to 50% of US healthcare expenditures are wasteful

• healthcare disparities based on race, ethnicity, socioeconomic status, age, gender, disability, and sexual orientation

Social determinants of health

• Economic stability (employment, income, expenses, debt, medical bills, support)

• neighborhood and physical environment (housing, transportation, safety, parks, playgrounds, walkability, zip code)

• education (literacy, language, early childhood education, vocational training, higher education)

• food (hunger, access to healthy options)

• community and social context (social integration, support systems, community engagement, discrimination, stress)

• healthcare system (health coverage, provider availability, linguistic and cultural competency, quality of care)

• health outcomes (mortality, morbidity, life expectancy, health care expenditures, health status, functional limitations)

Addressing healthcare disparities

• Improve the capacity and number of providers in underserved communities

• invest in our underserved communities

**Medication error

Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of the healthcare professional, patient, or consumer; about 50% of all ADEs

**Adverse drug event (ADE)

Patient harm from drug exposure; medication errors + ADR (50-50 split)

**Preventable ADE

Medication error that reaches the patient and causes harm (about 50% of all ADEs)

**Potential ADE

Medication error that does not cause harm (didn't reach patient or just good luck)

**Adverse drug reaction (ADR)

Side effect; non-preventable ADE; no medication error but patient still experienced harm from drug exposure; (50% of ADEs)

**Pharmacist medication errors

• Medication selection or procurement error:

  • confusion w subs during shortages or recalls, expired or adulterated drug, pulled wrong bottle, improper drug storage, fail to refrigerate or protect from light

• transcription error (approx 25%):

  • med order interpreted incorrectly

  • SOLUTION: CPOE, call prescriber if not sure

• preparation or dispensing error:

  • failure to select, package, label, or dispense the correct drug, dose, or dilution

  • SOLUTION: Tall man lettering to minimize LASA meds

**Prescriber medication errors

• Wrong drug, dose, frequency, or duration prescribed (18.5%)

• missed drug allergy

• missed drug-drug interaction

  • SOLUTION: computerized orders (CPOE); use brand and generic name; avoid abbreviations

**Healthcare Team errors

• Nurse errors

  • administration at bedside (approx 25%):

    • failure to administer med, discrepancy in administration from prescriber's directions or hospital guidelines

    • SOLUTION: barcode beside med administration and Smart infusion pumps

• healthcare team errors:

  • not ensuring proper follow-up for therapeutic effect and potential ADEs

**Medical abbreviations

• ISMP (Institute for Safe Medical Practices) publishes a list of error-prone abbreviations, symbols, and dose designations

• micrograms → mcg

• NEVER use trailing zeroes

• ALWAYS use leading zeroes

US Drug Approval process

Avg 10-15 yrs | $1.3-2.6 billion | avg approval rate: 4%

Step 1: Discovery & Development

• To identify new drug candidates and optimize drug action

• target-based drug discovery

• phenotype-based drug discovery

• 5000-10000 compounds

• 4.5 years; $196 million

Step 2: Preclinical Studies

• To assess drug safety, efficacy, and PK/PD before being tested in humans

• 250 compounds

• 1 year; $122 million

• submit IND at end

Step 3: Clinical Trials

• To evaluate drug safety, efficacy, and optimal use in humans

• phase I -> safety in humans

• phase II -> effectiveness at treating disease

• phase III -> larger scale safety and effectiveness; complete 2 trials

• 5 compounds

• 6.5 years; $169 million, $402 million, $536 million

• submit NDA/BLA at end

Step 4: Review & Approval

• To review and examine data before granting approval

• 1 compound

• 1.5 years

Target-based

Drug or biologic designed to bind specific enzyme, protein, etc

Phenotype-based

Compounds screened for activity based on specific disease phenotype

Lead compounds

Hundreds or thousands of modifications may be tested for safety and efficacy to identify the optimal compound; 20 years of patent protection

**Pharmacodynamics

• What the drug does to the body

  • dose response: relationship between drug concentration and its biological effect (therapeutic and toxic)

  • therapeutic index/window: ratio of the min therapeutic concentration and min toxic concentration

**Pharmacokinetics

• What the body does to the drug

• absorption, distribution, metabolism, excretion

• drug effect is a function of drug concentration at the target site in the body

Absorption

• Unless administered IV, drug must be absorbed

• if administered orally, absorbed across duodenal wall (metabolism) into portal vein, then to liver (1st pass metabolism), then to inferior vena cava (systemic circulation) - bioavailability

Distribution

• Transported to various tissues depending on affinity for plasma proteins, molecular weight and polarity, and how well various tissues are vascularized - measured by apparent volume of distribution

Metabolism

• May activate the drug (active drug metabolite), but usually inactivates it and makes it easier to eliminate

Excretion

• Most drugs are eliminated by the kidneys (glomerular filtration or renal tubular secretion) or liver (biliary excretion of water-soluble drug or metabolite, which ends up in the feces)

Toxicology

• Determine the drug dose and regimen that causes the least amt of toxicity (starting dose for human phase I trials)

• identify biomarkers

• carcinogenicity, genotoxicity, and reproductive toxicity

• min of 6 months drug exposure is required

Mechanism of action and therapeutic effect

• In vitro studies (cell, tissue, organ cultures, or cellular components such as proteins) -> used to identify and confirm mechanism of action

• in vivo (1 rodent and 1 non-rodent animal species) -> needed to evaluate efficacy; commonly mice, rats, and dogs

**Investigational New Drug (IND) application

• Filed at the end of preclinical testing before any human trials begin (end of phase 2)

• FDA reviews the IND to determine whether the investigational drug is being developed based on sound science, and whether it appears to be safe enough to take into human testing

• can start human testing 30 days after IND submission date unless FDA places a hold on the application

**New Drug Application (NDA) or Biologic License Application (BLA)

• Filed at end of Phase III testing

• NDA - small molecule drugs

• BLA - vaccines, monoclonal antibodies and other biologics

• process takes about 6 months to 2 years

• proof of safety and efficacy

**Priority review

• Accelerated approval track: evidence of improved efficacy in disease treatment, prevention, or diagnosis

• substantial dec of treatment-limiting adverse drug rxn

• inc patient compliance that is expected to improve serious disease outcomes

• evidence of safety and efficacy in a new patient population

• applies at end of Phase III clinical trials

• speeds up FDA approval process

**Breakthrough therapy

• Accelerated approval track: used to treat a serious disease and evidence suggests that the drug is a substantial improvement over any drugs currently approved to treat the disease

• drugs given Breakthrough Therapy status earn Fast Track review status

• applied for right after Phase II clinical trials; req human testing

• Performs very very well compared to market drugs

**Fast track

• Facilitate development and hasten review of a drug that meets an unmet medical need

• fast track drugs qualify for breakthrough therapy and accelerated approval status

• used for unmet clinical need

• does not need clinical evidence (human trials)

• rolling review

**Accelerated approval track

• Allows drugs under development for serious conditions that fill an unmet medical need to be approved based on a surrogate endpoint

**Clinical trials (phases overview)

• Early Phase I (Phase 0)

• Phase I

  • 1b (cancer trials) -> preliminary tumor effect at RP2D

• Phase II

  • 2b (cancer trials) -> preliminary tumor effect at RP2D (double-blind, controlled, may be compared to standard of care)

  • Go-No go decision

• Phase III

• Phase IV

Phase I

• Initial human trial

• safe, ethical, efficient

• determine PK profile and PD effects

• open-label, ascending dose

• "two-stage" design:

  • stage 1 - establish drug concentration-time profile in each subject

  • stage 2 - avg the results (mean +/- SD) from each subject at each time point

**Cancer trials

• Approx 5% of investigational cancer drugs gain FDA approval

• most fail during late-phase testing due to lack of efficacy

• focus has shifted to increasing efficiency (identify failures as early as possible)

• Phase 1:

  • 1a - dose escalation to establish MTD, RP2D

  • 1b - preliminary tumor effect and tolerability at RP2D; open label

• Phase 2:

  • more patients and under controlled, blinded conditions

  • 2b - RP2D to cancer patients to determine preliminary tumor efficacy and tolerability; double-blind

  • Go, No-Go decision

• Phase 3:

  • have to statistically prove safety and efficacy

ABT-888

• First Phase 0 oncology trial conducted under exploratory IND

• single oral dose in 13 patients

• 9 patients had paired tumor biopsies

  • 2nd biopsy showed significant PARP inhibition in PBMCs or plasma Cmax

• PK profile achieved plasma Cmax >/= 0.21 micromol/L at each dose

• PARP inhibition (surrogate endpoint) statistically significant in tumor biopsies

• Phase 1a: 3+3 dose escalation, MTD not reached, most common grade 3-4 toxicities were neutropenia, anemia, and thrombocytopenia

• Phase 1b: 5 new patients at 300 mg BID (RP2D), well tolerated and had an encouraging response rate

• Phase II goal: objective tumor response; overall survival should never be primary outcome; continuous enrollment adjustments during randomization based on individual patient outcomes

• Phase III: randomized, double-blind, placebo-controlled trial at 145 centers; adults with newly diagnosed triple-negative breast cancer; primary outcome: pathological complete response in breast and lymph nodes following completion of neoadjuvant chemotherapy

**3+3 dose escalation

• 0 of 3 DLTs: escalate to the next higher dose level with three new patients

• 1 of 3 DLTs: add three more patients at the same dose level to total six

• 1 of 6 DLTs: escalate to the next higher dose level after expanding

• 2+ of 3 DLTs: stop the trial immediately because the dose is too toxic

• 2+ of 6 DLTs: stop the trial because the expanded dose is too toxic

• used to find MTD (max tolerated dose) and RP2D (phase 2 dose)

Blood pressure

• Pressure of circulating blood against walls of blood vessels

• determined by volume and amount of space

• blood pressure = CO x SVR

  • CO: cardiac output (tot amt of blood pumped out of heart per unit of time)

  • SVR: systemic vascular resistance (squeeze of vessels)

• CO = HR x SV

  • HR: heart rate (number of times the heart beats per minute)

  • SV: stroke volume (amt of blood leaving the heart per beat)

• blood pressure = volume x squeeze

Common locations of smooth muscles

• GI tract (stomach, intestines) -> propels and mixes contents

• blood vessels -> regulates vessel diameter and blood flow

• urinary bladder -> expels urine by contracting bladder wall

• airways (trachea, bronchioles) -> constricts or dilates airways to regulate air flow

Blood vessels

• Artery -> thick outer wall; high pressure

• vein -> thin layer of muscle and elastic fibers

• capillary -> single layer of cell

**Mechanism of calcium channel blockers (CCBs); + ending

• “-dipines”

• Bind and block L-type Ca2+ channels in smooth muscle

• calcium cannot enter muscle cells

• vasodilation (relaxing)

• dec SVR -> dec BP

**Dihydropyridine (DHP)

• Targets blood vessels

• primarily peripheral vasodilators

• minimal effect on heart rate

• dec SVR —> LOWERS BP

• "-dipines"

**Non-dihydropyridine (non-DHP)

• Targets heart

• exerts inhibitory effects on SA + AV nodes

• LOWERS HR (by acting on SA node) -> dec CO -> dec BP

**CCB Indications

• hypertension

• DHP:

  • hypertension

  • coronary artery disease

  • chronic stable angina

• non-DHP:

  • atrial fibrillation/flutter

  • vasospastic angina

  • chronic stable angina

  • paroxysmal supraventricular tachycardia (PSVT)

• off-label:

  • migraine prophylaxis

  • Raynaud's phenomenon

  • hypertrophic cardiomyopathy

  • pulmonary hypertension

**CCB side effects

• Peripheral edema - most common; too much volume that leaks from veins causing swollen ankles

• orthostasis

• reflex tachycardia

• headaches

• constipation - slowdown of smooth muscle in intestines of GI tract

• bradycardia (non-DHPs)

• heart block (non-DHPs)

**Available dipines (CCBs)

• Verapamil HCl (Calan, Isoptin) - non-DHP

• diltiazem HCl (Cardizem) - non-DHP

• nifedipine (Adalat)

• nimodipine (Nimotop)

• nicardipine HCl (Cardene)

• isradipine (DynaCirc)

• felodipine (Plendil)

• amlodipine besylate (Norvasc)

• nisoldipine (Sular)

• clevidipine butyrate (Cleviprex)

CCB combos

• Caduet - amlodipine + atorvastatin (lipid-lowering agent)

• Tribenzor - amlodipine + olmesartan + hydrochlorothiazide

• Exforge HCT - amlodipine + valsartan + hydrochlorothiazide

• Azor - amlodipine + olmesartan

• Twynsta - amlodipine + telmisartan

• Prestalia - amlodipine + perindopril arginine

RAAS pathway

Helps increase BP via increasing blood volume and peripheral squeeze; acts on renin-angiotensin-aldosterone system

**ACEi mechanism of action; + ending

• “-pril”

• Block ACE enzyme

• prevent angiotensin I converting into angiotensin II

• prevents vasoconstriction

**RAAS drugs

• Dilate efferent arteriole -> dec pressure and dec resistance and dec GFR

• nephroprotective, prevents strain on kidneys

• comes at the cost of short term bump in SCr + K

• big holes for filtration in patients w HTN + diabetes

• damaged kidney has albumin in urine

-pril vs -prilat

• Prilat is the active metabolite of oral prodrug; poor oral absorption, IV

• -pril has better bioavailability, oral prodrug

**ACEi indications

• hypertension

• heart failure w reduced ejection fraction

• coronary artery disease

• post myocardial infarction

• recurrent stroke prevention

• left ventricular dysfunction

• glomerular disease + nephropathy

• chronic kidney disease

• off-label:

  • stroke prevention

  • Barter syndrome

  • migraines

**ACEi contraindications

DO NOT USE IF:

• bilateral renal artery stenosis

• pregnancy - dec levels of amniotic fluid

• angioedema history - severe swelling of lips and tongue and eyes, allergic reaction type

**ACEi side effects

• Serum creatinine bump

• hyperkalemia - can cause cardiac effects

• angioedema

• dry cough

  • warning signs to discontinue med

**ACEi monitoring & interactions

• Reassess SCr and K within 1-2 weeks after initiation and dose adjustments

• more frequent renal monitoring

• avoid concomitant use of ACEi, ARB, and/or renin inhibitor

• interactions: lithium, triamterene + HCTZ, NSAIDs, foods, potassium supplements

Available -prils

• Captopril (Capoten)

• lisinopril (Prinivil)

• enalapril maleate (Vasotec)

• enalaprilat

• ramipril (Altace)

• fosinopril sodium (Monopril)

• quinapril HCl (Accupril)

• benazepril HCl (Lotensin)

• perindopril HCl (Aceon)

• moexipril HCl (Univasc)

• trandolapril (Mavik)

ACEi combos

• Capozide - HCTZ + captopril

• Lotensin HCT - HCTZ + benazepril

• Vaseretic - HCTZ + enalapril maleate

• Lotrel - amlodipine + benazepril

• Prestalia - amlodipine + perindopril arginine

• combos preferred for HTN patients

**Angiotensin-2 receptor blockers (ARB) mechanism of action; + ending

• “-sartan”

• Inhibits binding of angiotensin II to receptors

• angiotensin II cannot exert vasoconstrictor effects

• vasodilation

**ARB indications

• Hypertension

• heart failure w reduced ejection fraction

• coronary artery disease

• post myocardial infarction

• recurrent stroke prevention

• left ventricular dysfunction

• glomerular disease + nephropathy

• chronic kidney disease

• preventing bradykinin side effects

• off-label:

  • stroke prevention

  • Raynaud phenomenon

  • migraines

**ARB contraindications

• Bilateral renal artery stenosis

• pregnancy - dec levels of amniotic fluid

• angioedema history - lower risk than ACEi but still avoid

**ARB side effects

• Serum creatinine bump

• hyperkalemia

• angioedema (less than ACEi)

• dry cough (less than ACEi)

**ARB monitoring & drug interactions

• Reassess SCr and K within 1-2 weeks after initiation and dose adjustments

• more frequent monitoring in renal impairment

• avoid concomitant use of ACEi, ARB, and/or renin inhibitor

• interactions:

  • potassium supplements

Available ARBs (-sartans)

• Losartan (Cozaar)

• valsartan (Diovan)

• irbesartan (Avapro)

• telmisartan (Micardis)

• candesartan cilexetil (Atacand)

• eprosartan mesylate (Teveten)

• olmesartan medoxomil (Benicar)

• azilsartan medoxomil (Edarbi)

ARB combos

• Hyzaar - HCTZ + losartan

• Diovan HCT - HCTZ + valsartan

• Avalide - HCTZ + irbesartan

• Benicar HCT - HCTZ + olmesartan

• Micardis HCT - HCTZ + telmisartan

• Atacand HCT - HCTZ + candesartan

• Azor - amlodipine + olmesartan

• Exforge - amlodipine + valsartan

• Tribenzor - amlodipine + olmesartan + HCTZ

• Edarbyclor - chlorthalidone + azilsartan

• Entresto - sacubitril + valsartan (first line for patients w heart failure)

• Byvalson - nebivolol + valsartan

**renin inhibitor mechanism; + ending

• “-kiren”

• Directly inhibits renin

• reduces renin activity

• prevents conversion of angiotensinogen to angiotensin I

• no vasoconstriction

Available -kiren

• Tekturna HCT - aliskiren + HCTZ

• Tekamlo - aliskiren + amlodipine

• Amturnide - aliskiren + amlodipine + HCTZ

**renin inhibitor indication

Hypertension

**Renin inhibitor contraindications

• Pregnancy

• combination w ACEi or ARBs

• concomitant use of cyclosporine or itraconazole (CYP3A4 inhibitor, itraconazole is an incredibly potent inhibitor of CYP3A4)

**Renin inhibitor side effects & monitoring

• Risk of angioedema

• hyperkalemia (when used w ACEi)

• Avoid taking w high-fat meals (dec absorption)

• avoid in renal insufficiency

**chemical nomenclature category

• based on chemical structure common to all drugs within the class

• structural similarity ensures the pharmacologic mechanism of action will be the same

• drugs within same chemical class may differ in properties based on differences in functional groups

  • ex: bioavailability, potency based on weight dosing (mg/kg), pharmacokinetics, solubility, onset of action/duration of activity, chemical stability, adverse drug reaction profile, patient adherence

**chemical drug classes examples

• benzodiazepines → anxiety

• thiazolidinediones → type 2 diabetes

• beta-lactams → infection

  • ex: penicillin, cephalospoin, monobactam, carbapenem

  • 4 classes but all work the same

• corticosteroids → inflammation/immunosuppression

• aminoglycosides → infection

• opioids → pain

• statins → dyslipidemia

**pharmacologic nomenclature category

• drugs w same pharmacologic class all have same MOA

• usually same chemical class but not always

ways to express MOA

• anatomical → where it works in the body

• physiological → what action it exerts; stimulate or depresses

• biochemical → effect on enzymes or channels in body

• genetic → expression or protein synthesis changes

**diminished effect

• biochemical → blocker or inhibitor

• physiological → depressant

• general/mixed → antagonist

• ex: alcohol

**enhanced effect

• biochemical → inducer or activator

• physiological → stimulant

• general/mixed → agonist

• ex: adderral, cocaine

pharmacologic drug class examples

• ACE inhibitors → hypertension

• beta-blockers → hypertension

• proton pump inhibitors → acid reflux

• histamine receptor antagonists → acid reflu

• vitamin K antagonists → anticoagulation

• neuromuscular blocking agents → paralysis

• HMG CoA reductase inhibitors → dyslipidemia

• calcium channel blockers → hypertension