Advanced Pharm exam 2

bacteriocidal classes

aminoglycosides

beta-lactams

daptomycin

fluoroquinolones

metronidazole

vancomycin

**need to use in immunocompromised patients

bacteriostatic classes

clindamycin

linezolid

macrolides

nitrofurantoin

tetracyclines

concentration-dependent bacteriocidal

aminoglycosides

daptomycin

fluoroquinolones

metronidazole

** also have post-antibiotic effect

time-dependent bacteriocidal drugs

beta-lactams

vancomycin

beta-lactams

• beta-lactam ring—>breaking down ring by beta lactamases halts antimicrobial activity

• structural analogs of d-ala substrate—>interfere with transpeptidation of bacterial cell wall synthesis

  • bactericidal; time-dependent

penicillins general

1. G/VK

2. dicloxacillin, nafcillin, oxacillin—cover MSSA

3. amoxicillin/ampicillin, amoxicillin + clavulanate/sulbactam—drug of choice for enterococci, enhanced gram neg, anaerobe coverage with inhibitors

4. piperacillin-tazobactam—very broad, pseudomonas, anaerobes

penicillins AE and prescribing considerations

common: n/v/d, rashes

less common: hypersensitivity, blood dyscrasias, interstitial nephritis

• allergy history

• all require renal adjustment except: nafcillin, oxacillin, dicloxacillin

• dosed multiple times per day

• take on empty stomach or after meal

• safe in pregnancy

Cephalosporins overview

• similar structure and mechanism to penicillins

• differ in R1/R2 groups

• increased spectrum of activity

• no enterococci coverage

  • increase in spectrum activity (especially gram negative) with successive generations

cephaloporins cross-reactivity

ampicillin—>cephalexin and cefactor

amoxicillin—>cefadroxil

which cephalosporins cover pseudomonas

cetazidime and cefepime

which cephalosporins cover MRSA

ceftaroline

cephalosporins prescribing considerations

• allergy history

• all require renal adjustment except ceftriaxone

• less frequent dosing

• similar AE to penicillins

  • cefotetan: disulfiram rxn, hypoprothrombinemia

  • ceftriaxione: NO NEONATES (biliary sludging)

Monobactams

aztreonam

only covers gram neg, including pseudomonas—needs additional agents for gram pos + anaerobes

available as inhalation for CF patients

**no cross reactivity with penicillins—>can prescribe for true allergies

carbapenems

-penem

very broad coverage, gram pos and neg, anaerobes

1. ertapenem, imipenem/cilastatin, doripenem, meropenem

**reserve for penicillin resistant

avoid monotherapy for pseudomonas

significant drug interaction—>decrease valproic acid levels

extended infusion preferable for time-dependent killing

what abx have gram pos only coverage

clindamycin

linezolid

vancomycin

daptomycin

clindamycin

• inhibits protein synth by interfering with formation of initiation complexes and with aminoacyl translocation rxn

• gram pos, inlcuidng MRSA

• does not cover gram neg

• not for brain infections

• major AE: C DIFF

linezolid and tedizolid

MOA: inhibits protein synth by preventing formation of ribosome complex

no cross-resistance with other drugs

gram + aerobes and anaerobes: MRSA, VRE, nocardia, mycobacterium

bacteriostatic (except bactericidal against strep)

AE

hematological (reversible) >10 days of therapy: decrease platelets, RBC, WBC

peripheral neuropathy > 4 weeks: may be irreversible

risk for serotonin syndrome (linezolid) if combined with SSIR/SNRI >10 days

*tyramine restricted diet for linezolid, monitor CBC

vancomycin

MOA: inhibits cell wall synth by preventing PG elongation and cross-linking

gram pos only, including MRSA, + cdiff (PO)

requires monitoring—>target trough 10-20 mcg/mL, >15 increases nephrotoxic risk

AE: vancomycin infusion reaction—>Not an allergy, just slow infusion; nephrotoxic at high doses

dosing interval dependent on kidney fx

administer after dialysis

daptomycin

MOA: binds to cell membrane via Ca2+ dependent insertion of lipid tail, causes depolarization of membrane and cell death

ONLY GRAM POS, including MRSA and VRE

bactericidal

AE: dose-dependent increases in CPK, myopathy, eosinophilic pneumonitis

renal adjustment required, monitor INR and CPK

do not use for pulmonary infections, surfactant inactivates

tetracyclines

MOA: bacteriostatic, block protein synth

-cycline

broad-spectrum coverage

AE: GI, liver dysfx, new teeth/bone staining, photosensitivity

consider: age and pregnancy status, good oral bioavailable

macrolides

MOA: inihibt protein synth, prevents peptide elongation

-thromycin

gram + and neg coverage, atypicals

AE: GI upset and QTC prolongation (erythromycin worst for both)

cyp3a4 drug interactions esp erythro

increasing resistance d/t overuse

aminoglycosides

MOA: bactericidal, irreversible inhibitors of protein synth

amikacin, gentamicin, tobramycin

gram pos and neg, inhaled for CF

AE: ototoxicity (high peaks, repeated doses), nephrotoxicity (high troughs)—>risks increase with prolonged dosing, high doses, reduced renal fx

requires monitoring, renal adjustment, hearing test

aminoglycoside pharmacokinetics

bactericidal

concentration-dependent

post-antibiotic effect

drug monitoring required

synergistic killing with beta-lactams and vancomycin

amikacin: peak 20-35, trough <5

gentamicin/tobramycin: peak 3-10, trough <1

TMP-SMX

MPA: blocks folate acid synth—>blocks DNA synth

broad spectrum except anaerobes

AE: sulfonamide allergy (rash, dermatitis, SJS), photosensitivity, heme (pancytopenia)

consider: allergy history, renal adjustment, interaction with warfarin/other meds, false elevation in SCr

fluoroquinolones

MOA: prevents relaxation of supercoiled DNA required for normal transcription and translation

-floxacin

** all good gram neg, all good gram pos except cipro

AE: QTC prolongation, tendonitis/tendon rupture, avoid in peds, maybe CNS toxic

**do not use moxi for UTIS

separate from di and tri valent ions, 2 hours before, 4 hours after

includes atypical coverage

FDA warning for fluoroquinolones

harms outweigh benefits for acute sinusitis, acute bronchitis, and uncomplicated UTIs when other treatment options exist

metronidazole

MOA: converted to products toxic to anaerobes

anaerobes only

indicated: anaerobic infections, vaginitis, c diff

AE: GI, neuropathy, disulfiram reaction

Fosfomycin

MOA: inhibtis early stage of cell wall synth

gram pos and neg

for uncomplicated UTIs

1 dose only

Nitrofurantoin

MOA: unknown, metabolites may disrupt protein synth by reacting with ribosomes

indication: UTI, no systemic absorption

AE: pulmonary fibrosis

contraindicated in patients with CrCl <30

anti-herpes agents

MOA: nucleoside analogs that require phosphorylation by virus and host enzymes—inhibits DNA synth

• competitively inhibit viral DNA polymerase

  • causes chain termination by incorporating into viral DNAH

HSV and VZV antivirals

nucleoside (guanosine) analogs phosphorylated by viral thymidine kinase—resistance can develop

more potent for HSV than VZV

considerations when treating HSV and VZV

HSV: more effective for genital, reduces symptom duration, time to healing and duration of viral shedding

can also be used for LT suppression: decreases recurrences, reduces shedding and transmission

VZV: decrease lesion number, symptom duration, and viral shedding within 24 hours for varicella and 72 hours for zoster

Nirmatrelvir (+ ritonavir)

MOA: protease inhibitor preventing COVID replication

boosted with ritonavir—cyp3a4 inhibitor

initiation within 5 days of symptom onset

renal adjustment required

avoid in sever kidney/liver impairment

AE: elevated LFTs, dysgeusia, metallic taste, diarrhea

COVID rebound reported

Remdesivir

IV infusion on multiple days

adenosine nucleotide incorporated into RNA chains—>chain termination

AE: hypersensitivity, elevated LFTs, nausea, bradycardia, hypotension

contraindicated with hydroxychloroquine

toclizumab and vilobelimab

target spike protein of COVID

IV admin, limited availability, need to be used early

flu antivirals

oseltamavir, zanamivir, peramivir—neuraminidase inhibitors, reduce viral release from infected cells

baloxavir—polymerase inihbitor, inhibit viral replication

start within 48 hours of symptoms

can be used as post-exposure prophylaxis (Oseltamivir and Zanamivir)

baloxavir resistance is possible—avoid in immunocompromised

baloxavir should not be administered with Ca, Mg, Fe, dairy

peramivir requires kidney adjustment

Ribavirin

for RSV

aerosolized nebulizer 12-18 hours continuously per day

for hospitalized patients with severe sx

nirsevimab

mAB to prevent RSV in all infants and children < 8mo

can be used in those 8-19 mo with increased risk

one dose

can be used in second season for those at high risk

no ADE

amphotericin B

bind to ergosterol and alters permeability of cell by forming pores in membrane

AE: infusion reaction, pretreat with diphenhydramine and acetaminophen; nephrotoxicity—give with fluid bolus and avoid nephrotoxic drugs

azoles

MOA: reduce ergosteral synthesis by inhibiting fungal cyp450 enzymes

significant drug interactions—inhibit cyp450 and 3a4

AE: GI, hepatotoxic, rash, QT changes

echinocandins

-fungin

MOA: inhibit synthesis of beta 1-3 glucan disrupting cell wall—cell death

hepatic clearance—can’t use for kidney infections

AE: GI and flushing

Oral antihistamines

• diphenhydramine (first gen, most sedating; most anticholinergic);

  • -tadine/tirizine (second gen)

• daily dosing

• fenofexadine is least sedating

intranasal antihistamines

• seasonal, perennial, or episodic AR

• better efficacy over oral, faster onset

• olapatadine, azelastine

• AE: same as INCS, headache/nosebleed

intranasal corticosteroids

-sonide/solide-sone

• when sx affect QOL

• most effective tx for sx control

• daily or PRN

• AE: epistaxis and headache

oxymetazoline

MOA: alpha-adrenergic agonist—>nasal arteriole vasoconstriction

• most effective in combination with INCS

  • development of rebound nasal congestion with use > 3 days

opthalmic agents for allergic rhinitis

• naphazoline—OTC vasoconstrictor

• ketotifen—OTC antihistamine

• ketorolac—Rx NSAID

• loteprednol—Rx corticosteroid

AE: opthalmic irritation, mydriasis, photophobia

remove contacts before use

leukotriene receptor antagonists for allergic rhinitis

not first line agent—similar or less efficacy

LDL

bad cholesterol, increased by cholesterol/sat/trans fat

primary target of rx therapy

VLDL

secreted by liver, converted to LDL

sucrose, fructose, excess calories increase VLDL

exports TG to peripheral tissues

triglycerides

associated with pancreatitis

may be drug-induced or caused by fat intake, alcohol, excess calories

HDL

good cholesterol—retrieves cholesterol from artery wall

secondary drug target

who is considered high risk for ASCVD for lipid therapy

2 major events (ACS, MI, stroke, PAD

OR 1 major event and 2 or more high-risk conditions (>65years, CABG/PCI, smoker, diabetes, CHF, HTN, resistant high LDL)

high dose statins

atorvastatin 40/80

rosuvastatin 20/40

moderate intensity statins

atorvastatin 10/20

rosuvastatin 5/10

simvastatin 20-40

pravastatin 40/80

lovastatin 40/80

fluvastatin 40 BID

low intensity statins

pravastatin 10-20

lovastatin 20

risk outweight statin benefit

class 2-4 heart failure

hemodialysis

LDL-C <70

initial eval for statin therapy

• fasting lipid panel

  • LDL>190 check for family hyperlipidemia or secondary cause

  • treat TG>500

  • repeat at 4-12 weeks, then every 3 months

• ALT: >3x ULN contraindication to statins

• CK

• HbA1C

  • hx of muscle symptoms

Statins

MOA: Inhibit HMG-COA reductase—>reduce cholesterol synth, increase LDL receptors

AE: confusion/memory issues, liver dysfx, myopathy/rhabdo, diabetes

Contraindicated: pregnancy, lactation, severe liver dysfx

some more effective given in PM

statin muscle adverse effects management

high risk: comorbidites (liver/kidney), hx of statin intolerance/myopathy, ALT> 3xULN, age >75, genes/drugs that decrease statin metabolism/clearance

• obtain hx of muscle symptoms at baseline and every visit

• if muscle symptoms—>discontinue, evaluate predisposing factors, rule out other causes

• severe sx—>check CK, creatinine, myoglobinuria

lipophilic statins (atorv, simva, lova) worse than hydrophilic (rosuva/prava)

statin myopathy pathway

mild-moderate symptoms

• if they resolve after stopping, no contraindications—>restart same statin at same/lower dose

• if resolve and statin established as cause—>use low dose of diff statin and titrate up

• if unresolved after 2 months—>consider other causes, if other cause identified, restart original statin at original dose

Fibrates

gemfibrozil/fenofibrate

MOA: PPAR alpha agonist—> decrease VLDL secretion, increase lipoprotein lipase activity, increase HDL

AE: dyspepsia, rash, hypokalemia, myopathy, liver dysfx, gallstones, rhabdo

caution in obesity bc of gallstones

avoid in: liver/kidney dysfx, concurrent statins

*may add fenofbirate to low-moderate intensity statin if TG >500

ezetimibe

MOA: in bile inhibits resorption of cholesterol, decreases LDL

AE: liver dysfx, myositis

monitor: LFTs, d/c if ALT>3 ULN

used in combo with statins

Contraindicated in pregnancy/lactation

bile acid sequestrants

cole/chole

MOA: prevent bile acid reabsorption by binding in GI tract, increase cholesterol breakdown, increase LDL receptors

AE: GI effects

monitor: fasting lipid at baseline, 3 mo, every 6-12mo

avoid in: diverticulitis, TG>250

decreases vit k/folic acid absorption

must take with food and administer other meds 1 hour before or 2 hours after

Nicotinin acid

vitamin B3

MOA: decrease VLDL secretion and catabolism of apoAI; increases HDL, decreases LDL and TG

start low and titrate up

monitor: fasting BG/A1C, LFT, uric acid (baseline and when increasing dose)

AE: flushing, pruritis, rash, dry skin, hyperuricemia—>can prevent flushing with aspirin 30 mins before dose

contraindicated pregnancy and lactation

discontinue: persistent cutaneous sx, persistent hyperglycemia, gout, abd pain/GI, a-fib, weight loss

omega 3 ethyl esters

lovaza or OTC fish oil—>3-4gm DHA and EPA

MOA: reduce synth of TG, increase lipoprotein lipase activity

AE: pruritis, rash, dysgeusia, dyspepsia, constipation, LFTs

monitor: GI

may use when TG >500

PCSK9 inhibitors

alirocumab and evolocumab

adjunct treatment or nonresponding patients

MOA: inhibits PCSK9

injection q 2-4 weeks

very effective in lowering LDL

peds lipid therapy

over 8 years old with LDL persistent over 160—>start statins

pregnancy and lactation lipid therapy

most are contraindicated

bile acid sequestrants and omega 3s okay

HTN classification

elevated: 120-129 systolic and <80 diastolic

stage 1: 130-139 sys or 80-89 dia

stage 2: >140 sys or >90 stage 2

important considerations of HTN med flow chart

if none of the risk criteria met—counsel on diet/lifestyle changes and recheck in 3-6 months, if unresponsive, start meds

if meds started initially, reassess BP in 1 mo

first-line therapy for HTN

meds: thiazides, DHP CCB, ACE/ARB

if stage 1: use 1 med

if stage 2: use 2 meds

goal BP of <130 systolic

thiazide and thiazide like diuretics

hydrochlorothiazide, chlorthalidone, indapamide, metolazone

early MOA: blocks Na/Cl transporter in renal DCT—>decreases blood volume and CO

late MOA: CO normalizes, SVR decreases

AE: hyponatremia, hypokalemia, metabolic alkalosis, photosensitivity, hyper uricemia, hyperglycemia, weakness

monitor: electrolytes, BP, fluid status

can give with loop

all sulfa drugs

avoid taking in PM

higher doses—>increased natriuresis without anti-HTN benefit

ACE inhibitors

-pril

MOA: prevent conversion of AT1 to AT2—inhibits AT2 effects

AE: hyperkalemia, dry cough, angioedema, rash, dysgeusia

teratogenic

if cough occurs—>trial another ACE or switch to ARB

if angioedema—swith to ARB

hold in AKI (but good for CKD lol)

ARBs

-sartan

MOA: block AT receptor—>block vasoconstriction and aldosterone secretion

AE: fatigue, diarrhea, hyperkalemia, angioedema (no cough)

teratogenic

do not use with ACE/renin inhibitor

ACE/ARB side effects and management

• hypotension—monitor BP

• dry cough—rule out pulm. congestion or fluid overload, consider ARBs or alternative

• angioedema—>stop immediately, consider ARB/CCB/thiazide

• renal failure—>monitor BUN/Scr, Scr increase up to 50% above baseline or 3.0 above is ok; avoid nephrotoxic drugs, consider alternative

• hyperkalemia—>monitor K 1-2 weeks after starting and after each titration, caution with elevated K/Scr, okay to increase K up to 5.5, advise about salt substitutes

Dihydropyridine calcium channel blocker

-dipine

MOA: relax arterial smooth muscle—vasodilation without cardiac effects

AE: edema, flushing, headache, dizziness

avoid immediate release nifedipine for HTN crisis

non DHP calcium channel blockers

diltiazem and verapamil

MOA: nonselective antagonism of l-type calcium channels—>arterial relaxation and vasodilation; depression of myocardial contractility, slows conduction

AE: bradycardia, heart block, constipation, edema

inhibits pgp and cyp3a4

avoid in patients with systolic HF

increased risk of heart block w beta blockers

loop diuretics

furosemide, bumetanide, torsemide

MOA: block Na/K pump in loop of Henle

AE: decrease Na, K, Mg, increase uric acid, dehydration, ototoxic, photosensitivity

all are sulfa drugs except ethacrynic acid

avoid PM dosing

potassium sparing diuretics

amiloride, triamterene

MOA: sodium channel blocker

AE: hyponatremia, hyperkalemia, metabolic acidosis, dehydration, kidney stones (triamterene)

aldosterone antagonist

spironolactone and eplerenone

MOA: block aldosterone receptor

AE: hyponatremia, hyperkalemia, gynecomastia (spirono)

renin inhibitor

aliskiren

AE: hyperkalemia, diarrhea

don’t use with ACE or ARB

avoid in renal impairment, diabetes, or pregnancy

clonidine

MOA: central alpha 2 agonist—>decreases SNS and increases PNS—>reduced SVR, bradycardia, reduced CO

AE: sedation/depression/cognitive changes

abrupt withdrawal cause HTN crisis

methyldopa

central acting, reduces SVR

AE: sedation/depression/cognitive changes

used in pregnancy

beta-blockers

-olol

MOA: beta 1 antagonists, reduce HR, contractility, SVR, renin release, some are also alpha blockers

AE: bradycardia, bronchoconstriction (beta-2), hypoglycemia unawareness, depression, sexual dysfx

most effective w diuretic

abrupt discontinuation results in rebound tachycardia

avoid in patients w depression/asthma

Naming: A-N: b1 selctive, o-z beta 1 and 2 nonselective

alpha blockers

-zosin

MOA: alpha 1 receptor antagonists—>vasodilation of arteries and veins, decreases SVR

AE: orthostatic hypotension, dizziness fatigue, headache, priapism

avoid in elderly, titrate slowly, PM dosing, get out of bed slow

also effective for BPH

nitrates

nitro-

MOA: vasodilation of veins and arteries—>increase CO by decreasing afterload

AE: flushing, tachycardia/palpitations/dizziness, methemoglobinemia and hypothyroidisim for nitroprusside

contraindicated with PDE5 inhibitors (sildenafil)

not appropriate for LT management

hydralazine

MOA: direct vasodilation of arterioles through NO release—decreases SVR

AE: flushing/headache/dizziness/reflex tachycardia

tachyphylaxis develops rapidly, more effective in combo

minoxidil

moa: direct vasodilation of arterioles—decrease SVR

AE: flushing/headache/dizziness/edema

must administer with diuretic to prevent edema, may exacerbate HF

key HTN med contraindications

angioedema: ACE

bronchospastic disease: BB

depression: reserpine

liver disease: methyldopa

pregnancy: ACE/ARB

heart block: BB, non DHP CCB

main anti-HTN meds for pregnancy

labetalol, ER nifedipine, low dose aspirin

may also consider methyldopa or HCTZ (second-third)

peds anti-HTN meds

same recommendation as adults

DHP CCB, thiazide, ACE/ARB