Practical Pharmacology[PRINT VERSION]

from a (mostly) practical internist

Disclosures

• No disclosures, financial or otherwise

Objectives

• Review an internist’s strategies (or lack thereof) for choosing medications to treat frequently-encountered diagnoses

• Review the ocular implications (e.g., side effects, drug interactions, etc.) of systemic drugs

• Antibiotics, antibiotics, antibiotics

Objectives• Clinical vignettes (where applicable) to illustrate the

strategies and / or concepts being addressed– topics that will not be addressed: chemotherapy, antivirals,

immunosuppressants• Exploration of basic* pharmacologic / physiologic principles

for each topic– *basic - because (a) I don’t want to bore you and (b) I admittedly

don’t know - or care - about much beyond the basics • Current evidence-based guidelines where applicable. The

gaps will be filled in, for better or for worse, with opinions crafted from my personal experience

Background (from whence these opinions were concocted)

• Practicing as a hospitalist* and, occasionally, outpatient urgent care physician - all within the largest healthcare network in the greater Memphis area.

• Bulk of hospitalist duties at a large teaching hospital, rounding with a team of internal medicine residents as well as pharmacy specialists.

*Hospitalist = inpatient physician

Practical pharmacology in internal medicine - topics

• Diabetes mellitus• Hypertension• Cardiovascular disease• Dyslipidemia• COPD / asthma• Autoimmune disease• Anticoagulation• Neurologic disorders

DiabetesA 47 year old male diabetic presents to his internist’s office for routine followup. He is no new symptoms. He denies excessive thirst or frequent urination. He denies visual complaints or foot ulcers. Vital signs are as follows: weight 102.3 kg, heart rate 88, blood pressure 145/78, temperature 36.6, respirations 16. Accucheck is 216 in your office. Basic labs reveal creatinine 1.3, indicating mild renal dysfunction. Hemoglobin A1c is 7.5. Current medications are lisinopril 10 mg daily, atorvastatin 20 mg daily, metformin 1000 mg twice daily, and glipizide XL 10 mg daily, and you have no reason to suspect nonadherence. Which of the following is the least acceptable next step in the management of this patient’s diabetes?

Diabetes

A. Add sitagliptin 50 mg daily, continue all other medications.

B. Add glargine 30 units daily, provide education on appropriate use of insulin, continue all other medications.

C. Add glargine 30 units daily, provide education on appropriate use of insulin, discontinue glipizide.

D. Add canagliflozin 100 mg daily, continue all other medications.

Diabetes

• [video – Stef]

Diabetes

• Goal A1c < 6.5*– (7.0 for general internists)

• Non-insulin vs. insulin– Type I diabetics: insulin only**– Type 2 diabetics: non-insulin, insulin, or both

• Most, but not all, non-insulin medications are oral; some are subcutaneous

*American Academy of Clinical Endocrinolgists (AACE) goal**exception: pramlintide

Diabetes

• Decreased renal function is a major limiting factor– Some medications (e.g., metformin) excluded

entirely– Some medications (e.g., sulfonylureas, insulin)

have prolonged duration of action – Some medications (e.g., DPP-4 inhibitors) can

worsen renal function

Diabetes• Type 2 diabetes - Start with metformin

– Most effective at A1c lowering (~2 A1c %-points)– Cheap (on all $4 lists)– Decreases insulin resistance - cannot cause hypoglycemia.– Should be held for hospitalizable illness, iodinated

contrast, or surgery– Monotherapy for early diabetes or “pre-diabetes”– Warn patients: “upset stomach, temporary”

• Gradually increase dose, usually to goal 1000mg BID

– *Cannot be used in patients with chronic kidney disease • severe lactic acidosis - can be fatal

DiabetesAfter Metformin, pick your poison (up to 3 total)• Sulfonylureas (glyburide, glipizide*, glimepiride)

– Stimulate pancreas to secrete more insulin– Cheap, most commonly used, but most likely to cause

hypoglycemia• DPP-4 inhibitors (sitigliptin, saxagliptin) - oral

GLP-1 agonists (exenatide, liraglutide) - subcutaneous– Glucose-dependent response; i.e., very low risk of hypoglycemia– Causes increased insulin, decreased glucagon, and early satiety[1] – Relatively expensive but relatively safe

*glipizide least likely sulfonylurea to cause severe hypoglycemia

DiabetesPick your poison (up to 3 total), continued• Meglitinides (nateglinide, repaglinide) – like safer

sulfonylureas• Alpha glucosidase inhibitors (acarbose) – lowers glucose

absorption from gut• Thiazolidinediones (pioglitazone, rosiglitazone)

– May cause heart failure(?)– *Can accelerate diabetic macular edema

• SLGT2 Inhibitors (canagliflozin, dapagliflozin) – new & expensive; increase urinary glucose excretion– *Canagliflozin lowers A1c but increases yeast infections [2]

Diabetes

• [picture with all names of SLGT2 inhibitors]

Diabetes - insulin

• Insulin – brief summary of recommended strategies from AACE[3]:– If A1c>6.5 after 3 drug regimen, add insulin– When adding insulin, can start with single dose

basal insulin (can continue oral meds other than sulfonylurea)

– If better control needed, add short-acting / mealtime insulin (at which point oral meds can be discontinued)

Diabetes - insulin

Diabetes - insulin

Basal/bolus insulin approximates normal insulin

Normal endogenous insulin release

glargine or levemir

aspart,lispro, orglulisiline

aspart,lispro, orglulisiline

aspart,lispro, orglulisiline

Diabetes - insulin

Combination (“70/30”) insulin• Pro: only 2 shots• Cons: harder to titrate, harder to control A1c, requires strict

mealtimes, more likely to cause hypoglycemia

HypertensionA 67 year old female presents to her primary care provider’s office for a screening physical exam. Medical history is significant for hyperlipidemia, for which she takes cholesterol-lowering medication. She exercises regularly and reports no new symptoms. Vital signs are as follows: weight 72.2 kg, heart rate 68, blood pressure 142/82, temperature 36.8, respirations 14. The rest of the physical exam is unremarkable. What is your next step in management?

Hypertension

A. Add metoprolol 25 mg twice-a-dayB. Add lisinopril 10 mg dailyC. Add clonidine 0.1 mg twice-a-dayD. Add amlodipine 10 mg dailyE. Add hydrochlorothiazide 25 mg dailyF. Do not add any new medications

Hypertension• LOTS of different strategies and recommendations• JNC 8 guidelines are largely expert-based rather

than evidence-based.– Best evidence is for new guidelines loosening BP goals– Recommendations for initial treatment address

general population as well as some specific populations, although evidence for specific populations (e.g., based on race) is weak

– Side effects profiles and cost of medications are not strongly considered

Date of download: 1/2/2015 Copyright © 2015 American Medical Association. All rights reserved.

From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults:  Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)

JAMA. 2014;311(5):507-520. doi:10.1001/jama.2013.284427

Hypertension• ARB or ACEi – usually best first-line agent

– All help preserve renal function; all once-daily dosing– ARB is preferable (less angioedema, no cough, no risk of

pancreatitis) but slightly more expensive– Losartan has “bonus” uricosuric (i.e., anti-gout) properties– Kidney disease is NOT a contraindication but patients must have

adequate follow up, for potassium monitoring– Should be titrated up to max dose as tolerated– Only true contraindication is prior angioedema with ACEi

• *ARB can still be used cautiously despite prior angioedema[4]

*ARB = angiotensin receptor blocker; ACEi = angiotensin converting enzyme inhibitor

Hypertension• Thiazides (hydrochlorothiazide, chlorthalidone)

– Diuretics; generally well tolerated; once daily dosing

– Excellent adjunct medications to ACEi, ARB, and CCB

– HCTZ often used in combination pills with ACEi or ARB

– As with ACEi / ARB, must have adequate follow up for electrolyte monitoring

– Side effects: low sodium (sometimes dangerously so); low potassium; high calcium (sometimes symptomatic); gout flare; pancreatitis (rare)

– **Titrating up dose does not result in any significant BP lowering

– **HCTZ often used in a combination pill with triamterene, a weak potassium-sparing diuretic

HCTZ = hydrochlorothiazide; CCB = calcium channel blocker

Hypertension• Calcium Channel Blockers

– DHP* (amlodipine, nifedipine): BP lowering >> HR lowering– Non-DHP (verapamil, diltiazem): HR lowering >>> BP lowering

• Beta blockers (metoprolol, carvedilol, labetalol, atenolol, propranolol, nadolol, nebivolol) – Used VERY frequently for hypertension as first-line agents (despite JNC-8

not listing as first-line agents)– Other than labetalol and carvedilol, which additionally block alpha

receptors, beta blockers don’t lower BP much– Can cause bronchospasm, but those more selective for β1 receptors

(atenolol, metoprolol, nebivolol) less likely to do so– Can cause bradycardia

*DHP = dihydropyridine

HypertensionThe problem children of hypertension medicines:• Alpha blockers (doxazosin) – decrease in sympathetic tone

– Cause orthostasis (fainting when standing)– Also used for urinary problems from prostate enlargement

• Hydralazine – direct vasodilator– Quick onset of action causes reflex tachycardia– Can cause drug-induced lupus[5]

• Minoxidil – direct vasodilator / infamous hair-grower– Increased risk of pericardial effusion (up to 20% of dialysis patients)[6]

• Clonidine – acts on central nervous system– Difficult to tolerate (dry mouth, headache, somnolence, bradycardia)– Requires 3-4 time/day dosing to be effective (although it is often dosed

inappropriately)– SIGNIFICANT rebound hypertension if stopped suddenly

Hypertension

• [video – Don]

HypertensionThe great-grandfathers of hypertension medicines:• Reserpine – blocks norepinephrine and dopamine

– VERY effective at lowering BP– Side effects (depression, anxiety, glaucoma, Parkinson-

like symptoms) limit use• Methyldopa, Guanfacine

– Stimulate a2 receptors in brainstem (like clonidine)– Rebound hypertension– Methyldopa often used in pregnant patients with

hypertension

Hypertension

HypertensionDrugs specific to secondary hypertension• Spironolactone, eplerenone

– Aldosterone antagonists– Used to treat primary hyperaldosteronism, a relatively

common condition (up to 10% of hypertensive patients)• Phenoxybenzamine

– Alpha blocker– Used to treat pheochromocytoma (RARE) pending tumor

resection– Doxazosin can be used for longer-term control if surgery

needs to be delayed

Hypertension - Ocular Implications

• Beta blockers: dry eyes, decreased IOP– Use caution when adding topical beta blockers;

can cause symptomatic bradycardia / syncope• ACEi: conjunctivitis, lid discoloration, • CCB: chemosis, irritation, rotatory nystagmus• Hydralazine: ocular symptoms of lupus

(anterior uveitis, scleritis, optic neuritis, etc.)

Cardiac meds –Coronary Artery Disease

A 59 year old male without past medical history is admitted from the emergency room with chest pain after being found to have had a myocardial infarction. He undergoes cardiac catheterization and coronary artery stent placement during the hospitalization. At discharge, assuming no contraindications, what is the most appropriate discharge medication regimen listed?

Cardiac meds –Coronary Artery Disease

A. Aspirin and metoprololB. Aspirin, clopidogrel, and metoprololC. Aspirin, atorvastatin, and lisinoprilD. Aspirin, clopidogrel, metoprolol, and

atorvastatinE. Clopidogrel, metoprolol, atorvastatin, and

lisinopril

Cardiac meds –Coronary Artery Disease

Patients with a diagnosis of coronary artery disease should be on an antiplatelet, a beta blocker, and a statin, assuming no contraindications.• Aspirin: essentially no long-term contraindication other than

allergic reaction to salicylates.• *2nd antiplatelet (Thienopyridines: Clopidogrel, Ticagrelor,

Ticlopidine, Prasugrel) to maintain stent patency– 2nd antiplatelet can be discontinued one year after last stent [7] but

some cardiologists will continue it longer if bleeding risk is low [8]– 2nd antiplatelet MUST be continued at least one month for “non

drug-eluting stent” (large artery) and at least 3 months for “drug eluting stent” (smaller artery)

Cardiac meds –Coronary Artery Disease

• Beta blockers – decrease mortality• Statins – decrease mortality (regardless of lipid

levels) • Nitrates (nitroglycerin, isosorbide mononitrate,

etc.) are used for symptom management (chronic, stable angina) but do not confer mortality benefit

• *Some evidence that addition of ACEi early after myocardial infarction may improve long-term outcome

Cardiac meds –Congestive Heart Failure

• An 87 year old female is hospitalized for shortness of breath. Exam reveals a blood pressure of 184/92, heart rate 88, respiratory rate 22, and temperature 36.2; she has bilateral leg swelling and lung auscultation reveals diffuse fine crackles bilaterally. Ophthalmoscopic exam reveals hypertensive retinopathy but no optic nerve head edema or flame hemorrhages. She is given diuretics with improvement in her leg edema and shortness of breath. Echocardiogram reveals an ejection fraction of 30-35%. She has been diagnosed with congestive heart failure in the past but admits she stopped taking her medicine around 6 months ago. Assuming no contraindications, medicines initiated during hospitalization should include which of the following?

Cardiac meds -Congestive Heart Failure

A. Carvedilol, lisinopril, and furosemideB. Furosemide and digoxinC. Furosemide, digoxin, and losartanD. Digoxin and carvedilolE. Carvedilol and furosemide

Cardiac meds –Congestive Heart Failure

Not all congestive heart failure is the same!• Systolic congestive heart failure (defined by low ejection fraction)

requires the following, assuming no contraindications:– ACEi or ARB [9,10]

• Reduces afterload on heart and helps to prevent “cardiac remodeling”• No benefit was shown when adding ARB to ACEi

– Beta Blocker [11,12]• Reduces cardiac oxygen demand

– Aldosterone antagonists (spironolactone, eplerenone)• Decreases mortality in “severe” heart failure

• Diuretics are used for symptom management and acute decompensation but long term use does not affect mortality

• Digoxin is frequently used for symptom management but long term use dos not affect mortality [13]

Cardiac meds – Arrhythmias

• [video – Elaine]

Cardiac meds –Arrhythmias

• Digoxin– Use in atrial fibrillation is falling out of favor [14]

• Amiodarone / dronedarone– Atrial fibrillation (AF), ventricular tachycardia (VT) - rate

and rhythm control– Very toxic (liver, kidney, thyroid, lung, skin, eye [15])– Dronedarone has reduced toxicity, but is less effective

and should not be used in patients with significant heart failure

Cardiac meds –Arhythmias

• Sotalol– powerful beta blocker for arrhythmia conversion and

prevention; requires 2-day hospitalization for initiation to monitor for QT prolongation

• Propafenone– prevention of arrhythmia recurrence (AF & VT); not a rate

control agent– generally well-tolerated

• Flecainide– prevention of arrhythmia recurrence (AF & VT); not a rate

control agent– more efficacious; less tolerable (side effects)

Cardiac meds -Ocular Implications

• For retinal hemorrhage: one or both antiplatelets may need to be held depending on how recently stents were placed

• Nitrates: IOP variability, retinal vasodilation, “halo vision,” pseudotumor cerebri

• Amiodarone: optic neuropathy, thyroid eye disease (hypo- OR hyper-thyroidism)

• Digoxin: decreased IOP, corneal edema, blue-yellow vision disturbance, “halo vision”

Dyslipidemia• A 48 year old female with type 2 diabetes and hereditary

dyslipidemia (i.e., persistently high LDL) presents for routine diabetic eye exam. Hemoglobin A1c measured in the office is 6.4 and she reports that her glycemic control has been excellent for the past year on metformin alone since voluntarily losing around 30 lbs. However, she complains of worsening vision and believes she may need a new Rx for her glasses. Visual acuity is decreased bilaterally and retinal exam reveals cystoid macular edema without exudates. Which of the following is most likely implicated in her retinal exam findings?

Dyslipidemia

A. AtorvastatinB. NiacinC. HyperlipidemiaD. MetforminE. Type 2 Diabetes

Dyslipidemia• Statins (lovastatin, simvastatin, atorvastatin, rosuvastatin) –

lower LDL– LDL goal depends on age and coronary risk– Patients with coronary artery disease, noncoronary

atherosclerosis, or diabetes have lowest goal (<100)– Major risks: liver disease, rhabdomyolysis– Ocular implications: increased IOP, retinal hemorrhages

• Fibrates (fenofibrate, gemfibrozil) – lower triglycerides– For use in patients with triglycerides > 500 who do not respond to

other forms of therapy (e.g., diabetes control, exercise)– Adverse effects: liver disease, rhabdomyolysis – esp when used

with statins

Dyslipidemia• Niacin

– For use in patients who do not reach goal LDL with max dose statin

– Intolerance, due to flushing and diaphoresis, is common; must be titrated up slowly

• Aspirin 30 minutes prior to niacin attenuates flushing

– Adverse effects: gout flare, decreased diabetic control, liver disease, cystoid macular edema

• Ezetimibe– Makes numbers better, but not patients (no survival

benefit shown)

COPD & asthma• A 10 year old visits his pediatrician’s office one week

after going to the ER for wheezing and shortness of breath; it was his 3rd such emergency visit since he moved to Memphis 6 months ago. His mother reports that he “coughs himself to sleep” almost nightly. He was prescribed an albuterol inhaler during one of the ER visits but is on no other medications at present. The internist prescribes inhaled fluticasone. The patient’s mother inquires about potential long-term adverse effects. Which of the following is NOT an adverse effect of inhaled corticosteroids?

COPD & asthma

A. Increased incidence of cataractsB. Increased incidence of osteoporosisC. Decreased ultimate heightD. Increased incidence of pneumoniaE. Increased incidence of oral thrush

COPD & asthma• Short acting inhaled bronchodilators

– Albuterol – should only be used as needed– Ipratropium – for COPD only (not asthma!)

• Inhaled corticosteroids (usually in combination with long acting beta-agonist)– Fluticasone/salmeterol, budesonide/formoterol,

fluticasone/vilanterol– Indicated for persistent asthma or COPD symptoms– *Long acting beta agonist rarely used as solo agent (slight

increased mortality, no proven benefit)• Tiotropium (inhaled long acting anticholinergic)

– COPD only

COPD & asthma• Montelukast (oral leukotriene inhibitor)

– Asthma only– Not first line agent for persistent asthma (although often used that

way)

• Theophylline (oral methylxanthine, i.e., caffeine analog)– Decreases inflammation in airways– No proven benefit, lots of side effects (seizures, arrhythmias, low

BP)

• Roflumilast (oral phosphodiesterase inhibitor)– COPD only– What theophylline should be (targets inflammatory cells in airways)– Side effects same as theophylline but much less common / severe

COPD & asthma - Ocular Implications

• Glaucoma screening for patients on ipratropium, tiotropium, inhaled corticosteroids– Macular edema also seen in association with

inhaled corticosteroid use• Cataract screening for patients on inhaled

corticosteroids

Autoimmune disease• Methotrexate

– Folate antagonist (requires folate supplementation) – Multiple uses: rheumatoid arthritis (RA), psoriasis, adjunct to

chemotherapy in various forms of cancer– Multiple toxicities limit use [18]: bone marrow suppression, hepatic

fibrosis / cirrhosis, kidney damage, pulmonary fibrosis, infection, neurotoxicity…

– **Drug interaction: sulfamethoxazone / trimethoprim• TNF antagonists (etanercept, adalimumab, infliximab)

– Increased risk of lymphoma / leukemia and infection but are effective and relatively safe

• Other “biologic” agents (abatacept, rituximab, balimumab, tofacitinib)

Autoimmune disease• Other Immunosuppressants:

– Azathioprine – T cell inhibitor• Severe rheumatoid arthritis and inflammatory bowel disease

– Mycophenolate – B & T cell inhibitor• Lupus nephritis; moderate toxicity

– Cyclophosphamide – alkylating agent• Severe RA; massively toxic (multiple organs + bone marrow)

– Cyclosporine – T cell inhibitor• Severe RA & psoriasis; massively toxic (multiple organs)

• Hydroxychloroquine – antiinflammatory• Lupus and RA

Autoimmune disease –Ocular implications

• All drugs: Increased opportunistic infection risk (tuberculosis, histoplasmosis, coccidioidomycosis, blastomycosis), including ocular involvement

• Increased risk of progressive multifocal leukoencephalopathy (PML) (due to reactivation of JC virus, which is ubiquitous)

• Rituxan: associated with visual loss, sometimes permanent• Cyclosporine: cortical blindness, HSV keratitis reactivation• *Patients on chronic hydroxychloroquine or prednisone

should have biannual vision screening, for retinopathy and glaucoma, respectively [18]

Anticoagulation• A hospitalist is called to admit a 29 year old female

who presented to the ER with sudden onset shortness of breath and sharp chest pain. Vital signs are as follows: T 36.5, HR 110, RR 20, BP 108/58, weight 80 kg, oxygen saturation 95% on room air. CT of the chest reveals a left sided pulmonary embolus. Risk factors are cigarette smoking and oral contraceptive use. Which of the following strategies may be employed to treat this patient’s pulmonary embolus?

Anticoagulation

A. Dabigatran 150mg twice a day for 9 monthsB. Rivaroxaban 15mg twice a day for 3 weeks

followed by 20mg daily for 6 monthsC. Apixaban 5mg twice a day for 6 monthsD. Warfarin 5 mg daily + enoxaparin 80mg

injected subcutaneously twice-a-day + close outpatient followup; total 12 months therapy.

E. Any of the above are acceptable

Anticoagulation• Dabigatran, rivaroxaban, and apixaban are the new oral

anticoagulants– All are approved for use in atrial fibrillation (stroke prophylaxis),

venous thrombo-embolism prevention, and deep vein thrombosis / pulmonary embolus treatment

– In cases of bleeding, there is no way to reverse anticoagulation (such as giving vitamin K for warfarin) other than letting the drug “wear off” (~12 hr)

• Warfarin is still around, for:– Patients (and doctors) concerned about the irreversibility of the

newer agents– Anticoagulation in patients with artificial heart valves– Anticoagulation in patients with severe renal disease

Neuropsychiatric medications

• [video – Homer]

Neuropsychiatric medications

Antiepileptics• *Most antiepileptics carry the following statement

under the pharmacology section drug references: “exact mechanism of action unknown.”

• Stabilization of neuron membranes by modulating voltage-dependent ion channels

• All antiepileptics can cause low sodium, Steven-Johnson syndrome, depression, and bone marrow disorders; most have potential liver toxicity

Neuropsychiatric medicationsCommon antiepileptics• Phenytoin

– Requires monitoring; other drugs can affect level– Causes nystagmus in even mild overdoses

• Topiramate– LOTS of side effects, esp. kidney stones– Decreased visual acuity (common); angle-closure glaucoma

(rare) [19]• Valproic acid

– Can raise ammonia levels which can cause confusion– Ocular side effects are rare [19]

Neuropsychiatric medications

Common antiepileptics• Lamotrigine

– Diplopia is main ocular side effect [19]• Carbamazepine

– Can cause rhythm disturbances including heart block– Can cause nystagmus and ocular disturbances [19]

• Levetiracetam– Best side effect profile (including no liver toxicity)– Ocular side effects are rare [19]

Neuropsychiatric medicationsOther diseases• Myasthenia gravis: pyridostigmine

– Irreversible acetylcholinesterase inhibitor– MANY side effects: heart block, wheezing, diarrhea, urinary retention– Ocular disturbances common (esp. miosis)

• Parkinson disease: dopaminergics (carbidopa / levodopa, etc)– Rare side effects– Benztropine is an anticholinergic used to counteract parkinsonianism

caused by antipsychotics• Alzheimer disease: reversible acetylcholinesterase inhibitors

(donepezil, rivastigmine)– Frequent side effects (urinary retention, heart block, weight loss)– Ocular disturbances common (blurry vision) but mild

Neuropsychiatric medications• Antidepressants

– tricyclic antidepressants (amitryptiline, nortryptiline) & selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, sertraline, paroxetine) can all cause angle closure glaucoma (rare) and frequently cause blurry vision

• Antipsychotics (many)– “Typical” (e.g., haloperidol) vs. “atypical” (e.g.,

quetiapine)– All can cause QT prolongation / sudden cardiac death– Angle closure glaucoma (rare), cataracts (long term use)

Antibiotics• Stewardship & responsibility: Antibiotic overuse

is causing rapid drug resistance, creating super-bacteria that will take over the world.

• Personal injury: Antibiotics are not benign drugs!– Cardiac arrhythmias – sometimes fatal– Bone marrow suppression – sometimes fatal– Acute liver injury – sometimes fatal– Acute kidney injury – sometimes permanent– Drug rash – always unsightly

Systemic Antibiotics• Fluoroquinolones

– Good soft-tissue coverage for gram-negatives and anaerobes

– Can cause QT prolongation• Especially if given with other QT prolongers

– Can cause tendon rupture• Macrolides (erythromycin, azithromycin)

– Good coverage for streptococcus but not much else– Can cause QT prolongation

• Especially if given with other QT prolongers

Systemic Antibiotics - MRSA• Cephalexin: no coverage• Clindamycin: coverage is poor; difficult to take (3-4 time / day dosing)• Sulfamethoxazole / trimethoprim: decent coverage

– Poor coverage for streptococcal disease– Must be weight-based– Can raise potassium and creatinine in patients with underlying kidney disease– Can cause bone marrow suppression

• Doxycyline and minocycline: decent coverage– Good streptococcal coverage as well– Frequently cause nausea– Increase risk of sunburn– Minocycline is slightly better coverage and slightly less nausea, but can cause drug-

induced lupus• Linezolid: great coverage, but prohibitively expensive

– Can cause serotonin syndrome; SSRI’s must be discontinued

Systemic Antibiotics• Check allergies

– *Penicillin allergy does NOT preclude cephalosporin use as long as the allergy is not anaphylactic shock

• Check to see if on warfarin– If they are, instruct them to call whoever adjusts their warfarin dose

for follow up and dosing instructions• Check renal function if possible; dose-adjust if necessary• Avoid sulfamethoxazole/trimethoprim if any history of kidney

disease or bone marrow disorder• Check for concurrent QT prolongation meds if you are

considering macrolide or fluoroquinolone• Always warn about main side effects

Drugs are bad. They can make you sick or cause your death, even if used correctly.Example: Blood thinners can make you bleed

Commonly used drugs with unfavorable side effects

• metoclopramide: parkinsonism, seizures[20]• olmesartan: gastrointestinal disease[21]• amlodipine, nifedipine: leg swelling• donepezil: weight loss, vomiting, anorexia, urinary

retention, low heart rate• megesterol: adrenal insufficiency, hypoglycemia,

blood clots• tramadol: seizures, hypoglycemia[22]• methadone: sudden cardiac death[23]• SSRIs (sertraline, citalopram, fluoxetine): low sodium• antipsychotics (e.g., quetiapine, aripiprazole,

risperidone): sudden cardiac death• nitrofurantoin: pulmonary and liver disease[24]• fluoroquinolones (levofloxacin), macrolides

(erythromycin, azithromycin): sudden cardiac death[25]

Practical pharmacology in internal medicine

• Cost matters!!– Uninsured patients– Copays, prior authorizations– Medicare / Medicaid constraints

• Adherence matters!!– Can the patient demonstrate ability to understand how to

administer the medication?– Is the dosing schedule compatible with the patient’s daily

activities?• Drug interactions matter!!

– Use your electronic resources

References1. John R. White, Jr., PA, PharmD; Clinical Diabetes 2008 Apr; 26 (2) 53-572. Neal B, Perkovic V, de Zeeuw D, et al. Efficacy and Safety of Canagliflozin, an Inhibitor of Sodium Glucose

Cotransporter 2, When Used in Conjunction With Insulin Therapy in Patients With Type 2 Diabetes. Diabetes Care. 2014 Dec 2. pii: DC_141237.

3. https://www.aace.com/files/aace_algorithm.pdf 4. Cicardi M, Zingale LC, Bergamaschini L, Agostoni A. Angioedema associated with angiotensin-converting

enzyme inhibitor use: outcome after switching to a different treatment. Arch Intern Med. 2004 Apr 26;164(8):910-3.

5. Finks SW, Finks AL, Self, TH. Hydralazine-induced lupus: maintaining vigilance with increased use in patients with heart failure. South Med J. 2006 Jan;99(1):18-22.

6. Marquez-Julio A, From GL, Uldall PR. Minoxidil in refractory hypertension: benefits, risks. Proc Eur Dial Transplant Assoc. 1977;14:501-8.

7. Collet JP, Silvain J, Barthelemy O, et al. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. The Lancet. 2014 Nov1; 384(9954): 1577-85.

8. Mauri L, Kereiakes DJ, Yeh RW, et al. Twelve or 30 months of dual antiplatelet therapy after drug-eluting stents. N Engl J Med. 2014 Dec 4;371(23):2155-66.

9. The SOLVD investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med. 1991;325(5):293.

References10. Velazquez EJ, Pfeffer MA, McMurray JV, et al. VALsartan In Acute myocardial iNfarcTion (VALIANT) trial. Eur J

Heart Fail. 2003 Aug;5(4):537-4411. Fowler MB. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Am J Cardiol. 2004

May 6;93(9A):35B-9B.12. [No authors listed]. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised

Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999 Jun 12;353(9169):2001-713. Digitalis Ivestigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl

J Med. 1997 Feb 20;336(8):525-33.14. Turakhia MP, Santangeli P, Winkelmayer WC, et al. Increased mortality associated with digoxin in contemporary

patients with atrial fibrillation: findings from the TREAT-AF study. J Am Coll Cardiol. 2014 Aug 19;64(7):660-8.15. Johnson LN1, Krohel GB, Thomas ER. The clinical spectrum of amiodarone-associated optic neuropathy. J Natl

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