Pharm 3 Flashcards
MIC
The lowest concentration of an antimicrobial that will inhibit the visible growth of an organism
Post-antibiotic effect
Period of time after complete removal of an antibiotic during which there is no growth of the target organism
Patient specific antibiotic factors
Renal, hepatic function
Age
Size
Drug specific Abx factors
IV vs. PO
Bacteriostatic vs -cidal
Cost
Distribution
Bacterial resistance mechanisms
Inactivation by beta lactamases (+new/other -ases, ex carbapenemase)
New binding proteins w/ decreased affinity for Abx
Decreased permeability of bacterial cell wall
Modification of cell membrane constituents that prevent penetration
G+ aerobes
Staph, Strep, Enterococcus, Listeria
G- aerobes
E. coli, Klebsiella, Proteus, Pseudomonas, Moraxella
G+ anaerobes
Peptococcus, peptostreptococcus, Clostridium
G- anaerobes
Bacteroides, Fusobacterium, Prevotella
PCNs
Cell wall active-disrupt bacterial cell wall formation by inhibiting certain enzymes that create cross-linking –> activation of endogenous autolytic systems causes cell lysis and death (bacteriostatic)
Coverage: mostly G+, some G-
ADEs: hypersensitivity rxn, neutropenia, interstitial nephritis, CNS toxicity (seizures)
Peak concentration in 1-2 hr, most have wide distribution, minimal liver metabolism
Excretion by kidneys
Natural penicillins
Penicillin G, Penicillin V
Active against Strep, Enterococcus, some G+ anaerobes (peptococcus, peptostreptococcus)
Distribute to most tissues: lung, ascites, synovium, pericardium, soft tissues
Dose reduction for GFR <50
Most associated w/ ADEs
Drug of choice for syphilis, strep
Aminopenicillins
Ampicillin
Amoxicillin
Retain activity of naturals (More active against Enterococcus than other PCNs)
+
Extended G- coverage (H. flu, E. coli, K. pneumo)
Distributes to renal tissue, septic joints, ascitic fluid, CSF
Not very beta-lactamase stable
Penicillinase resistant PCNs
Oxacillin
Nafcillin
Dicloxacillin
Activity against: Strep good), Staph (excellent), Peptostrep
Very narrow, mostly just used for staph
No G- activity
Distributes to bone, septic joint effusions, cardiac tissue (endocarditis, septic joints)
Drug of choice for MSSA
Dose adjustment for severe HEPATIC impairment
Nafcillin
Penicillinase resistant PCN
Big sodium load when prepared IV. Caution in ascites/HF
Ureidopenicillins (Anti-pseudomonal penicillins)
Piperacillin
Always given w/ a beta lactamase inhibitor
Significantly improved activity against G- (Psuedomonas, Bacterioides) , some enterococcal activity, good anaerobe activity
No staph activity
Not very beta-lactamase stable
Distribution: pleural fluid, ascitic fluid, wound fluids
Dose adjustment for CrCl <50
Beta-lactam/Beta-lactamase inhibitors
Ampicillin/Sulbactam (Unasyn)
Amoxicillin/Clavulanic acid (Augmentin)
Piperacillin/Tazobactam (Zosyn)
Adds H. flu, M. cat, N. gonorrhea, B. fragilis coverage
Extends G+ and G- activity
Useful in mixed infections or for broad empiric coverage as a single agent
No antibiotic activity of its own
Good concentration throughout the body
Dose adjustment for CrCl < 50
Cephalosporins
Cell wall active: Disrupt bacterial cell wall formation by inhibiting certain enzymes that create cross-linking –> activation of endogenous autolytic systems to cause cell lysis and death
Activity variable across classes. None cover enterococcus
Some have MTT side chain which prolong PT/INR and may cause disulfram rxn w/ alcohol
1-3% cross reactivity w/ PCN allergy (maybe even less)
Rapidly absorbed, short T1/2, most excreted renally (ceftriaxone = liver metabolism)
1st Gen Cephalosporins
Cefazolin (IV)
Cephalexin, Cephadroxil (PO)
Good G+ coverage, limited G-, no anaerobes
Very active against strep and MSSA
Wide distribution throughout body (bone, skin, soft tissue) poor CSF penetration
Dose adjustment for CrCl < 50
Second Gen Cephalosporins: Group 1
Cefuroxime, Cefaclor
Very active against Strep, MSSA
Improved activity against G- (aerobes) BUT no G- anaerobes
variable CSF penetration (Cefuroxime penetrates well into CSF)
Dose adjustment in kidney disease
Second Gen Cephalosporins: Group 2 (Cephamycins)
Cefoxitin, cefotetan
Inferior activity against strep and MSSA BUT enhanced activity against G–
Preferred for “dirty” surgery (GI, GU,)
Dose adjustment in kidney disease
MTT side chain
Third Gen Cephalosporins
Anti-pseudomonal: Ceftazidime
Other: Cefotaxime, Ceftriaxone, Cefiximine, Cefpodixime
Anti-pseudomonals (Ceftazidime): excellent coverage G- aerobes (including pseudomonas), adequate Strep coverage (less than other cephalosporins)
Weak MSSA coverage (all 3rd gen)
Extensive distribution including good CSF penetration
Dose adjustment for decreased renal and hepatic function
Very broad coverage. Great for meningitis.
4th Gen Cephalosporins (Cefepime)
Staph/strep coverage comparable to earlier generation cephalosporins
Superior G- activity (including very good pseudomas aeruginosa coverage)
No MRSA
5th Gen Cephalosporins (Ceftaroline)
Widest spectrum: coverage of G-, G+, aerobic/anaerobic
MRSA coverage
Strep pneumo coverage
NO PSEUDOMONAL coverage
Restricted access because very broad and concerns for resistance if overused. Only for definitive therapy. Must consult ID
Thienamycins (-penems)
Imipenem
Ertapenem
Meropenem
Broadest coverage: G+ an G- aerobe coverage (except MRSA and E. faecium), most G- anaerobes
Meropenem has best pseudomonal coverage
Ertapenem: no pseudomonal but great against ESBLs
MOA: cell wall active, similar MOAs to PCN/Cephs
Pro: Post-Abx effect
ADE: N/V/D (IV)
Imipenem lowers seizure threshold, toxic metabolites. Always given w/ cilastatin to inhibit
Penetrate most tissues, including bone, meninges
Monobactams (aztreonam)
Covers G- aerobes (including pseudomonas)
No G+
No anaerobes
Good substitute for aminoglycosides in pt at risk for toxicity
Widely distributed, often used in combo w/ clindamycin, macrolides
Dose reduce in renal insufficiency
Non Beta-Lactam, Cell Wall Active: Glycopeptides (Vancomycin)
Binds to D-alanyl-D-alanine terminal residue in growing peptidoglycan chain, inhibiting cell wall synth
Bacteriocidal
Activity against G+ aerobes: strep, staph (including MRSA, MRSE), enterococcal spp
No G-, no anaerobes (except oral vanco for C. diff)
ADE: red mans syndrome, neutropenia, nephrotoxicity, ototoxicity
Distributes to CSF and widely to other tissues
Aminoglycosides
Gentamycin
Tobramycin
Amikacin
Streptomycin
Most toxic antibiotic class
MOA: Binds to 30S ribosomal subunit which decreases protein synth. Increases misreading of mRNA
Covers aerobic G- (including pseudomonas)
No anaerobe, no G+
Synergistic w/ cell wall active beta lactams (Vanco) for MRSA, MSSA, Enterococcus, Pseudomonas
Good penetration into urine, CSF, lungs
BBW: nephro/ototoxic. Need drug level monitoring
100% excreted by kidneys
Tetracyclines
Tetracylcine
Doxycycline
Minocycline
MOA: Reversibly binds to 30S subunit on ribosome, preventing protein synth
Bacteriostatic @ therapeutic concentrations
Good coverage of G+ and G- aerobes, except pseudomonas
No G- anaerobes
Doxy: good for MRSA cellulitis
atypical pneumonia pathogens
Penetrates brain/CSF in small amounts
ADE: photosensitivity, decrease skeletal growth in children, GI, hepatotoxicity, vertigo, worsening of renal failure
Separate from milk/antacids by 2-4 hr window
Esophageal irritant: drink lots of water and take sitting upright
Macrolides
Erythromycin
Clarithromycin
Azithromycin
Good coverage G+ aerobes (erythro best)
Good coverage G- aerboes (azithro best)
Good atypical PNA coverage (legionella, mycoplasma, chlamydia) and typical pna (H. flu, M. cat)
H pylori
Clarithro/azithro active agaisnt MAC
No coverage G- anaerbobes
Erthromycin
Macrolide
Best in its class for G+ aerobe coverage, worst for G- aerobes
many drug interactions due to metabolism through the CYP450 enzyme system
ADEs: abd cramps/N/V/D, thrombophlebitis, cholestatic hepatitis
Poor penetration in body tissues
Short T1/2.
Dose adjustment in hepatic/renal failure
Azithromycin/Clarithromycin
Macrolides, best in class for G- aerobes, less coverage of G+ aerobes
No G- anaerobes
Both cover H pylori and MAC
Azithro: long T1/2 (5 days), less QTc prolongation than other macrolides
ADE: less GI side effects than erythro, tinnitus/dizziness
Penetrate well into many tissues, including lungs/alveolar macrophages
Lincosamides (Clindamycin)
Binds to 50S ribosomal subunit, decreases protein synth
Active against staph (MSSA and MRSA), strep, G- anaerobes (B fragilis group), G+ anaerobes, toxoplasmosis
No activity against G- aerobes
Penetrates bone, bile, most body tissues but NOT CSF
ADE: GI intolerance, hepatotoxicity, neutropenia/thrombocytopenia, esophageal irritation (drink w/ lots of water and sitting uprignt)
Fluoroquinolones
Ciprofloxacin (bone/UTI)
Levofloxacin (both)
Moxifloxacin (atypical resp)
Inhibits DNA gyrase (inhibit DNA synthesis and breakage of bacterial DNA)
All active against G- aerobes
Cipro and Levo active against pseudomonas ***only oral agents available to treat pseudomonas
Variable against G+ aerobes: MSSA, Moxi/Levo better coverage of Strep
No G- anaerobes
Also: atypical PNA
ADE: GI, HA/dizziness, phototoxicity, increased LFTs, tendon rupture, QTc prolongation
Renal dose adjustments needed. Contraindicated in peds and pregnancy
Avoid w/ dairy, antacids for 2-4 hr window
Sulfas
Trimethoprim/sulfamethoxazole (Bactrim)
Inhibit bacterial folic acid synth, inhibiting cell growth
*One of only oral drugs for MRSA cellulitis
Good activity G- and G+ aerobes (Except pseudomonas, Group A strep, enterococcus)
No G- anaerobes
Penetrates well into most tissues, CSF levels 40% of serum levels
ADE: crystalluria (hydrate well), increases INR in patients on warfarin, increases phenytoin levels, hyperkalemia, GI intolerance, SJS, anemia, neutropenia
Avoid in HD patients. Dose adjust in renal failure
Nitroimidazoles (Metronidazole)
bacteriocidal: enters cell, reduced to free radicals which damage DNA
covers all anaerobes (including C diff, H pylori)
No aerobe coverage
ADE: disulfram rxn w alcohol, increased INR w/ warfarin, metallic taste, GI disturbance, dark urine, reversible neutropenia
Oxalinediones (Linezolid)
Bacteriostatic: binds to 50S ribosomal subunit, inhibits early phase protein synth
Broad coverage!
G+pathogens (including VRE)
Staph (including MRSA)
Strep (including PCN resistant strains)
ADE: diarrhea, nausea, taste perversion, increased LFTs, thrombocytopenia
No hepatic/renal dose adjustment
Lipopeptides (Daptomycin)
Bacteriocidal: Binds to bacterial cell membranes, causing rapid depolarization of membrane potential –> leads to inhibition of protein, DNA and RNA synthesis
G+ activity including VRE, MRSA
1st bacteriocidal drug against resistant bugs
Widely distributed to tissues except lungs
Dose reduce in renal insufficiency
CURB-65
Each 1 point for determining PNA site of treatment:
Confusion
Uremia/BUN > 20
Resp Rate > 30
BP < 90/60
65 years or older
0-1 = home
>3 = possible ICU
Typical CAP pathogens
H flu
Chlamydia
Strep pneumo
Atypical PNA pathogens
CML:
Chlamydia
Mycoplasma
Legionella
Empiric CAP therapy: non-ICU
Macrolide (ex: azithromycin) + beta-lactam (cephalosporin, PCN, penem, etc)
Ex: Azithro + cephtriaxone
Azithro + ertapenem
OR
Fluoroquinolone alone (levo or moxifloxacin)
Empiric CAP therapy: ICU
Cephalosporin (Ceftriaxone) OR Ampicillin-Sulbactam + Fluoroquinolone
if PCN allergy: moxi or levo + aztreonam
CAP treatment modifying factors
IF structural lung disease: add antipseudomonal agent (Cefipime, pip/tazo, imipenem, meropenem) PLUS macrolide/ FQ(levo/cipro )
BL allergy: FQ +/- vanco
CAP MRSA: Vanco or Linezolid + FQ
HAP common pathogens
E coli, Klebsiella pneumo, Staph, Psueodomonas
Anaerobes (d/t aspiration)
Watch for multi drug resistant organisms
HAP tx (low risk mortality)
No MRSA risk factors
Pip/Tazo (Zosyn) OR
Cefipime OR
FQ (Levofloxacin) OR
Penem (Meropenem/imipenem)
MRSA risk factors
Add vanco or linezolid
VAP empiric tx
Cover MRSA: linezolid, vanco
Cover pseudomonas
-Beta lactam: zosyn OR 3rd gen ceph OR penem OR aztreonam
-Non-beta lactam: FQ(cipro/levo) OR aminoglycosides (amikacin, tobramycin, gentamycin)
Aspiration pneumonia
Primarily anaerobic in nature. Direct therapy towards mouth flora
Lincosamide (Clinadamycin) + FQ
Primary, Type I Osteoporosis
loss of trabecular bone with estrogen loss
Primary, Type II Osteoporosis
loss of trabecular and cortical bone w/ inefficient remodeling (d/t diet, age, physical activity)
Secondary osteoporosis
D/t systemic illness or meds
Calcium products
Dietary preferred
Take supplements <500 mg w/ meals
Eliminated unabsorbed via GI tract
ADE: N/C
Interactions: Binding w/ FQs/Tetracycline Abx
Vitamin D
Dietary, UV exposure preferred
Supplemented w/ cholecalciferol, calcitrol in susceptible pt
ADE: Hypercalcemia: promotes absorption of Ca from SI
Decreases PTH and bone resorption
Bisphosphonates
1st line osteoporosis therapy
Binds to bone, inhibits osteoclast activity
Renally excreted
ADE: nausea, abd discomfort, rare jaw necrosis/femur fx
Interactions: antacids
Avoid in renal impairment, esophageal obstruction
PTH analog (Teriparatide)
Stimulates osteoblasts, increases renal tubular reabsorption of Ca, increasing bone mass/density
SQ for 18-24 months
ADE: HA/LH, hypotension, palpitations, transient hyperca
Avoid in hx skeletal malignancy or bone mets
SERMS (Raloxifene)
Estrogen R agonist in bone and antagonist @ breast/uterus.
Slow rate of bone loss
Highly protein bound
ADE: hot flash, flushing, leg cramps, VTE
Calcitonin
3rd line tx for osteoporosis
inhibits osteoclast
Nasal or SQ
ADE: N/V, flushing, injection site rxns
Avoid in hypocalcemia
Estrogen products
Short term symptom mgmnt of osteoporosis Inhibit osteoclast activity via estrogen receptor
ADE: HA, depression, N/V, cramps, hypertension, VTE, bleeding, breast CA
CKD
Structural (blood/protein in urine) and/or functional (decreased GFR) damage to kidneys over at least 3 months
Causes: hyperglycemia, uncontrolled HTN/HLD
Loss of renal function is slow
Microalbuminuria = high prognostic factor for progression of CKD
GFR <120 = damage
60-90 = modeerate kidney function
<30 = ESRD
Things to watch: Anemia, secondary hyperparathyroidism, hyperkalemia, acidosis, nutrition
Anemia of CKD
Decreased EPO production
Decreased RBC survival
Iron deficiency
Blood loss (via GI or dialyzer)
Target goal Hgb 11-13/Hct 33-36%
EPO products and iron
*Always correct iron prior to or in conjunction w EPO therapy
Secondary hyperparathyroidism of CKD
Decreased renal elimination of phosphate, decreased production of active vitamin D
Increased serum phos = decreased Ca –> increased PTH production in response to decreased Ca and active vitamin D –> PTH increases Ca mobilization from bone
Goals of therapy:
Serum phos 2.7-5.5
Serum Ca 8.4-9.5 (adjust for albumin)
Serum PTH 35-300 (dependent on CKD stage)
Serum vit D >30 ng/mL
Phosphate binders
Binds phosphorus in the gut, complex is subsequently eliminated in the feces
Must be taken with meals to optimize binding effect
Initiate when Phos >4.5
If serum Ca x PO product < 55 –> calcium containing product
If serum Ca x PO product >55 –> nonabsorbable polymer (sevalamer)
Vitamin D products
Inhibits PTH secretion & promotes GI Ca absorption
Calcitriol, Paricalcitol, Doxercalciferol
ADE: Hypercalcemia
Calcimimetic agent
Designed to activate the Ca-SR on the PT glands
Receptors become more sensitive to the binding of extracellular Ca, which then inhibits PTH
Cinacalcet (Sensipar®)
ADE: N/V, hypocalcemia
Can be used in combination with Vit D analogs and phosphate binders
Hyperkalemia in CKD
Diminished renal potassium excretion + Redistribution of K+ into extracellular fluid due to metabolic acidosis
Tx depends on serum K+ level as well as presence of ECG changes
Therapy usually initiated when K+ > 6 mmol/L
Metabolic acidosis in CKD
In normally functioning kidneys H+ ion is
generated to facilitate absorption of filtered
bicarbonate. In the diseased kidney there is a decrease in H+ ion production and subsequently reduced bicarb absorption
Reduced bicarb absorption is responsible for the development of metabolic acidosis
Contributes to osteodystrophy and muscle loss
Tx: dialysis, bicarb replacement
Bicarb replacement
Dose (mmol) = 0.5 L/kg x (22- pt serum bicarb)
Initial replacement = 1/2 total dose daily to prevent excess Na intake
Maintenance = 10-20 mmol daily
Hyperthyroid
Etiology: Graves, pituitary/toxic adenomas, drug induces (amiodarone)
Presentation: weight loss, heat intolerance, tachycardia, warm/moist skin
Dx: high T4, low TSH, radioactive iodine studies, thyroid related Antibodies (Grave’s)
Thioureas (MMI, PTU)
MOA: inhibit iodination and synthesis of thyroid hormones, block T3/T4 conversion in periphery.
MMI more potent than PTU
Both have slow (4-6 week) onset
ADE: hepatotoxicity, arthralgia, fever, rash, agranulocytosis
Teratogenicity: PTU safe in 1st trimester, MMI in 2nd-3rd trimester
Nonselective beta blockers (propranolol)
For symptomatic control of hyperthyroidism. Blocks hyperthyroid manifestations mediated by beta-adrenergic receptors and can block T4/T3 conversion
ADE: bradycardia, hypotension, cardiac ischemia
Iodines/iodides
MOA: inhibit release of stored TH, decreases vascularity of thyroid gland prior to surgery
Indicated before surgery, after ablative therapy, in thyroid storm
ADE: metallic taste, burning mouth
Thyroid storm
Life-threatening decompensated thyrotoxicosis
Causes: Trauma, infections, noncompliance with pharmacotherapy, severe inflammation of thyroid
Tx: thiourea, iodide therapy, beta blockers for tachycardia, tylenol for fever, IV corticosteroids
Hypothyroid
Causes: Hashimotos, iodine deficiency, secondary (pituitary insufficiency), iatrogenic
Presentation: cold intolerance, weight gain, bradycardia, areflexia
Dx: low T4, elevated TSH, thyroid antibodies present
Screen all patients > 60 years
Levothyroxine
Start @ 1.6 mcg/kg/day ideal body weight
Give in AM on empty stomach
Highly protein bound (100%)
4-6 weeks to reach peak effect
Hepatic metabolism to T3, eliminated in urine
ADE: hyperthyroidism, tachyarhthymias, increased risk fx
Myxedema coma
Life threatening decompensated hypothyroidism
Causes: trauma, infection, HF, drug induced
Presentation: AMS, hypoventilation, hypothermia
Tx: IV thyroid hormone replacement, empiric Abx, corticosteroids
Metformin
1-2% Reduction in A1C
1st line for T2DM
MOA: decreases hepatic gluconeogenesis, increases insulin sensitivity and glucose uptake into tissues
ADE: N/V/D, B12 deficiency, BBW for lactic acidosis
Contraindications: renal impairment, metabolic acidosis
Concentrates in liver, kidney, GI
Category B in pregnancy
No weight gain, low risk hypoglycemia as monotherapy, can use as adjunct w/ other agents
Sulfonylureas (Gliperizide, glimepiride, glyburide)
1-2% reduction in A1C
MOA: binds to receptors on pancreatic beta cell, depolarizes membrane and stimulates insulin secretion
ADE: hypoglycemia, weight gain, must take w/ food
Contraindications: poor renal function, hepatic insufficiency
Meglitinide (Repaglinide)
0.5-1.5% reduction in A1C
MOA: similar to sulfas w faster onset of action
ADE: hypoglycemia, weight gain, URI
Contraindications: concomitant use w/ gemfibrozil
TZDs (pioglitazone, rosiglitazone)
0.5-1.4%
MOA: increases insulin sensitivity of adipose tossue
Delayed (1-3 month) onset
ADE: weight gain, edema, bone rx, worsening HF, myalgia, increased LFTs
Contraindications: NYHA Class III/IV HF
DPP4 inhibitors (Sitagliptin, Saxafliptin)
0.5-0.8% reduction in A1C
MOA: inhibits breakdown of GLP 1 secreted during meals which increases insulin secretion, decreases glucagon secretion, and promotes satiety
Monitor s/sx pancreatitis
SGLT2 inhibitors (Canagliflozin, empagliflozin)
0.3-1% reduction A1C
MOA: increases urinary glucose excretion by blocking normal reabsorption in proximal convoluted tubule
ADE: increased urination, UTI hypotension, increased risk bone fx
Contraindicated in renal impairment
Acarbose
MOA: decreases absorption of glucose from intestine to bloodstream by slowing breakdown of large CHO into smaller, easier to absorb sugars
ADE: flatulence, diarrhea, abd pain, LFTs
Contraindications: IBD, colonic ulcerations, intestinal obstructions
Basal insulin dosing
10 units daily or 0.1-0.2 units/kg daily
Titrate by 2 units every day 3 days to target A1C
Prandial insulin dosing
Start w/ 1 dose @ largest meal (if A1C above goal w/ appropriately titrate basal dosse)
increase by 1-2 units twice weekly
Insulin dosing options
2/3 NPH + 1/3 regular
OR
50% basal, 50% prandial divided into 3 meals daily
GLP 1 analogs (injectable) ( Liraglutide, Exanatide)
MOA: analog of human GLP-1 that increases glucose dependent insulin secretion, decreases glucagon secretion, and decreases gastric emptying.
ADE: N/V/D, hypoglycemia, acute renal impairment
Monitor for pancreatitis
Rapid acting insulin
Lispro
Aspart
Glulisine
15 min onset
Short acting insulin
Regular (Humulin)
60 min onset
Intermediate acting insulin
2-4 hr
Long acting insulin
Glargine (Lantus)
4-5 hr onset, 24 hr duration
No pea
GERD:
Decreased basal LES pressure –> LES relaxation
Impaired esophageal clearance
Decreased acid clearance, delayed gastric emptying
Severity r/t amount of time esophagus exposed to acid and pepsin
Tx: avoid aggravating factors: diet, exercise, pregnancy, tight clothing, smoking cessation
OTC antacids, H2 blockers, PPIs
Complications: esophagitis, strictures, Barrett’s esophagus
PUD
Gastric, duodenal ulcers
Common causes: H. pylori, NSAIDs, stress-related
Tx: dietary/lifestyle changes, eradicate H pylori, relieve pain/heal ulcers and erosions
OTC antacids, H2 blockers, PPIs
Misoprostol for NSAID induced
PPI Triple therapy (or alt) for H pylori induced
Antacids
Neutralize acid by increasing gastric pH. Inhibits conversion of pepsinogen to pepsin. May also stimulate production of mucosal prostaglandins
Symptomatic relief only, does not provide healing
Types: aluminum, magnesium, Ca, bismuth
Suspensions superior to capsules/tablets. Thoroughly chew and take w full glass of water
Decreases absorption of H2 antagonists, ampicillin, phenytoin, iron, FQs, tetracycline
Soln: separate from other meds/food by at least 2 hr
Quick onset, short duration. Can mask other issues
Accumulation in renal disease
H2 antagonists
Inhibit histamine receptors on parietal cells, decreased secretion of hydrogen ions.
Indication: DU (4-8 wks), GU/GERD (8 weeks)
1st line for tx of chronic mild-moderate GERD. Intended only for short term use BUT if long term therapy required, H2 antago preferred over PPI
ADE: HA, diarrhea,
Monitor renal function
PPI
Irreversible inhibition of H/K/ATPase pump on parietal cells (the final step of acid secretion)
1st line for moderate-severe GERD, preferred over H2 blockers for H pylori and erosive esophagitis
Take 30-60 min before 1st meal of the day. Do not crush or chew
ADE: risk of fracture, hypomag, C diff diarrhea, CAP, HA
Pantoprazole has fewest drug interactions because not CYP mediated
Reglan (Metoclopramide)
Unclear MOA, stimulates motility in upper GI, prokinetic agent, increases LES tone and peristalsis.
Only for use after confirmed diagnosis
ADE: Galactorrhea, diarrhea, EPS, depression/drowsiness (DA driven ADEs)
Contraindications: Parkinsons, obstruction
Monitor renal function
Interactions: anticholinergics, MAO-I, Levodopa
Sucralfate
Promote mucosal defense, react w/ hydrochloric acid in stomach to form a paste that binds to surface of ulcer. Barrier allows ulcer to heal
No acid reducing capacity
Useful as adjunct therapy, not alone
Misoprostol
PGE1 analog, stimulates production of mucus and bicarb, Cryoprotection.
ADE: abd pain, diarrhea, spontaneous abortions, bleeding in postmenopause
Contraindications: women of childbearing age
H. pylori therapy
Clarithro based triple therapy:
PPI + clarithromycin + amoxicillin //
PPI + clarithromycin + metronidazole
OR
In escalating resistance:
Bismuth quadruple therapy:
Bismuth + metro + tetra + PPI
OR
PPI/Levo/Amoxicillin
–> best in terms of adherence/resistance
Phenothiazines (Prochlorperaine, promethazine)
MOA: DA antag @ CT
ADE: sedation, dry mouth, urinary retention, blurred vision, EPS
Benzamides (Metoclopramide, trimethobenzamide)
MOA: inhibits DA in GI/CTZ, +reglan aids motility in gastric paresis
ADE: sedation/ EPS
5HT3 antagonist (Ondansetron, granisetron)
MOA: inhibits 5-HT in vomiting center
ADE: HA, malaise, constipation, hypotension, EPS (rare), anorexia
Overall well tolerated but prolonged QTc w/ doses >16 mg, now contraindicated.
Correct hypoMag and hyperK
Benzos (Ativan)
prevent limbic input from reaching vomiting center
Anticipatory nausea, anxiety
ADE: sedation, amnesia, akithesia
Corticosteroids (Dexamethasone)
MOA unknown, for chemo-induced vomiting
ADE: mood changes, increased appetite, weight gait
Antihistamines, anticholinergics
Inhibit cholinergic receptors which decreases stimulation of vomiting center
ADE: sedation, dry mouth, blurred vision
Aprepitant (Emend)
Substance P/Neurokinin 1 receptor antagonist in GI tract and CTZ
Primarily for chemo induced N/V
Effective as combo w/ steroid and 5HT3 antag
Antiperistaltic agents (Loperamide, diphenoxylate)
Slow GI motility
Caution in infectious diarrhea, avoid in children
ADE: sedation, CNS effects
Adsorbants (Polycarbophil, Bismuth)
Absorbs water, no systemic absorption
Less effective, but fewer ADEs than anti-motility agents
ADE: fullness, bloating gas
Anti-secretory (Bismuth subsalicylate)
Antisecretory, antimicrbial, and absorbant properties
Toxicity-broken down to salicylate, watch if on ASA or other anticoags
ADE: black stool, tongue darkening, tinnitus
Bulk forming laxatives (polycarbophil, methylcellulose)
1-3 days to onset
Preferred med since not systemically absorbed. Holds water in stool, swells, increases stool bulk which then stimulates intestinal movement
ADE: flatulence
Surfactants -docusate sodium (Colace)
1-3 days to work
Preventative, esp to prevent straining
Facilitates mixture of fats, aqueous materials
Do not give w/ mineral oil–toxicity!
Saline laxatives (Mag citrate, sodium phosphate, milk of magnesia)
1-6 hr onset
Mostly used for evacuation of bowels prior to diagnostic exams
Caution in hypertension, sodium restricted diets, renal dysfunction
Osmotics (lactulose, sorbitol, glycerin)
Metabolized to solutes in GI tract, moves water osmotically and facilitates propulsion and evacuation
Stimulants (Bisacodyl, Senna)
stimulates colonic contractions –> evacuation
Bisacodyl (Dulcolax): 6-12 hr onset
Do not use every day!! risk paralytic ileus
Senna (ExLax): 6-12 hr onset
More gentle/preferable over bisacodyl
