Hospice care - Pain Management:

What's regimen is recommended? Most common agent?

IR doses should be ____ of total daily opioid dose

How do you calculate opioid dose increases?

When switching opioid doses, how does the dose change?

What opioid is avoided in elderly patients and why?

Recommended: Use ATC dosing - Morphine ER q12hr

- Try using same ER and IR medicine (Morphine = gold standard)

IR doses should be 10-15% of total daily opioid dose

Dose increases: Add total daily dose of ER + IR / 2

- That calculated # = new ER dose (Must recalc IR dose)

Switching: reduce dose by 25% to account for cross tolerance

Meperidine = avoided due to active metabolites in elderly

Hospice - Methadone:Morphine comparison

Characteristics which differentiate these two agents

What doses are equal potency between these two?

Methadone = higher bioavailability, longer t 1/2 (30h), takes longer to reach ss (3-7 days), NO active metabolites and fecally eliminated

Morphine = lower bioavailability, shorter 1/2 (3-4h), shorter time to reach ss (12-20hr), active metabolites and renal elimination

**Both are hepatically eliminated

3-5 mg of methadone = 30 mg morphine

Hospice - Methadone:

How often is it usually dosed?  Elderly patients dose?

What is the MOA?

How is it eliminated?

Usually dosed every 8-12 hrs --> long t 1/2 (3-7d for ss)

- Elderly patients may require 24h dosing (active metabolites)

Combined with breakthrough-pain med

MOA: NDMA receptor antagonist and 5-HT3/NE reuptake (x)or

Fecal elimination

Hospice - Treatment of N/V

What are the four drug classes used?

Examples of each and AEs with each

Dopamine antags - Haloperidol, prochlorperazine, metoclopramide

- AEs = sedation and EPS

5-HT3 antags - ondansetron (-setron suffix for all)

- AEs = HA and N

Antihistamines - promethazine, benadryl, hydroxyzine

- AE = sedation

Anticholinergics - transderm scopolamine patches

-AEs = xerostomia, constipation, confusion and blurred vision

Hospice - Dyspnea (subjective symptom):

What is the first line therapy for dyspnea?  How does it work?

What are other possible options (not as commonly used)?

Opioids = first line for treatment of dyspnea (safe/effective)

- has effects on cardiopulmonary system, reduce pain/ax, decreases brain stem responsiveness to CO2 (mechanism in resp. depression) and **proposed to act locally on opioid receptors on alveolar walls

Can be given either po or via nebulizer

- Neb morphine (in NS) - low AEs;

          -  can cause histamine release (problematic for asthma pts)

Other options: CS, benzos and phenothiazines (chlorpromazine)

Hospice - Constipation:

What is the goal of bowel movements in terminally ill patients?

What are the common causes?

What type of treatment should every patient recieve?

What other classes can be used to help relieve constipation?

Goal: 1 bowel movement every 3 days

Causes = low fiber, dehydrated, disease state (e.g. colon cancer) and medications (opioids and TCA's)

Every patient should recieve stimulant laxatives prophylactically**

Ex: Senna or bisacodyl always given at bedtime

Other classes: Stool softener (docusate), bulk forming (well hydrated), osmotic laxatives (lactulose, sorbitol), prokinetics (metoclopramide) and methylnaltrexone (sq; mu-R antag)

Hospice - Delerium:

What are the two distinct types of delirium and Sxs of each?

What are the common causes?

Treament goal? Options?

Hyperactive - agitated, aggresive and combative

Hypoactive - mistaken for depression; sluggish and lethargic

(Can have mixed delirium (combo) --> difficult to treat)

Causes: hypoxia, infxns, fever, dehydrated, stroke and abrupt medication withdrawal (opioids, benzos; should be titrated down)

Symptomatic treatment goal = comfort and safety

-- Can use antipsychotics (haloperidol; lower dose for elderly); atypicals (risperidone) and benzos (lorazepam)

Hospice - Anorexia/Cachexia:

What non-pharm treatment is used?

What are the pharm treatment options?

Non-pharm: Educate family (difficult for them to see), eliminate dietary restrictions and reduce portion size (more meals)

**Treat the symptom preventing patients from eating

- pain, GI motility problems, reflux esophagitis and mouth conditions (dryness, candidiasis and mucositis from chemo)

Pharm treament options:

-- Dexamethasone, mirtazipine, megesterol and dronabinol

Hospice - Fatigue

What non-pharm treatment options are used?

What pharm treatment is used? 

Which is specifically used for opioid induced fatigue?

Non-pharm = permission to be tired and rest (MD write rx for sleep and gives to pt), structure activity to conserve energy and eliminate medications that are not needed that cause fatigue

Pharm treamtent = dexamethasone and antidepressants

-- Methylphenidate (BID) is very effective for opioid induced fatigue**

Hospice - Anxiety and Depression

Non-pharm and pharm treatment for anxiety

Depression pharm treatment options

Anxiety: Non-pharm = relaxation techniques, spirituality

- Pharm: benzos (lorazepam used 1st) and haloperidol (neuroleptics)

Depression - pain is a major risk factor for depression and suicide

- Pharm treatment: SSRIs (sertraline, paroxetine and citalopram), TCAs (amitriptyline, nortriptyline), methylphenidate and mirtazipine

  **Methylphenidate not LT treatment (only in pts w/ few days to live)

Pharmacogenomics: 6-MP (purine antimetabolite)

Genetic variations in what gene effect bioavailability and

toxicity of 6-MP? 

How is this deficiency obtained in patients?

What complications arise in individuals with this polymorphism?

Variations in TMPT gene effect bioavailability and toxicity of 6-MP

- TMPT catalyzes S-methylation of 6-MP to form inactive metabs

The TPMT deficiency = inherited autosomal recessive trait

Patients with TPMT polymorphisms are at risk for severe toxicities when treated with 6-MP b/c of decrease rate of 6-MP metabolism

Allele changes = TMPT*2, TPMT*3A and TPMT*3C

- seen in 95% of observed cases

Pharmacogenomics - Irinotecan

Gene variations in what enzyme lead to severe toxicity?

What specific genotype changes are risk factors? What happens?

Irinotecan inactivated by UGT-1A1

Genotypes UGT1A1*28 and UGT1A1*6 are risk factors for severe tox

Pts have larger than expected dose b/c drug not cleared effectively

UGT1A1*28 found in 35% of whites/blacks --> these patients are at higher risk of grade 4 neutropenia (no clinical adjustments yet)

Pharmacogenomics - Tamoxifen

What enzyme breaks down this drug?

What patients are associated with higher cancer recurrence rates?

Tamoxifen = pro-drug

Metabolized to active forms by CYP-2D6

Poor and intermediate metabolizers have been associated with higher cancer recurrence rates

- b/c less exposure to active drug

        (increase dose to achieve proper concentration)

Pharmacogenomics - 5-FU

What enzyme is responsible for 5-FU metabolism?

DPD (dihydropyrimidine dehydrogenase) catalyzes the rate-limiting step in 5-FU metabolism

- Variability in DPD activity = increase incidence of AEs

Deficiency of DPD = severe toxicity and fatal outcomes w/ 5-FU tx

-- Appears to be genetic disorder in DPYD gene resulting in decreased enzyme activity

Pharmacogenomics

Difference between 3 types of genetic testing:

Predictive genetic testing

Prognostic genetic testing

Genetic Diagnostic testing

Predictive = predict risk status of an individual for contracting disease or condition based on genetics

Prognostic = predict efficacy of particular drug based on genetics

Diagnostic = diagnosing an exisiting disease state or condition based on genetics

Pharmacogenomics - Predictive tests

Hereditary Breast and Ovarian Cancer (HBOC) syndrome increases risk of ______ , often before ________.

What is usually the cause?

HBOC increases risk for developing breast and ovarian cancer, often before the age of 50 (Inc RISK only --> not everyone will get cancer)

Mutation or alteration in BRCA1 or BRCA2 (inherit from either parent)

- Testing reduces risk, pt makes proactive steps and informed choices

If no BRCA1 or BRCA2 mutations are detected then change of ovarian/breast cancer is significantly reduced

- BUT, only looks for mutations in these genes; other causes can lead to cancer

Pharmacogenomics - Prognostic tests

Oncotype DX BC Assay - what are benefits of this test?

What specific patient is this test intended for?

Oncotype DX - examines tumor tissue at molecular level and helps plan or tailor cancer treatment options

Clinical evidence of it's ability to predict the likelihood of chemotherapy benefit and recurrence in early-stage breast cancer

Intended to be used by women with early-stage (Stage 1 or 2), node-negative, estrogen-R positive (ER+) invasive BC who will be treated with hormone therapy

Pharmacogenomics - Prognostic test

Prolaris use?

What does it measure?

Prostate cancer = highly variable/slow growing/nonaggresive

Helps predict cancer aggresiveness w/ other clinical parameter

Test measure the expression level of genes involved with cell cycle progression to predict disease outcome

Pharmacogenomics - Predictive test

Theraguide 5-FU tests for what two genes?

Using this predictive tests helps _____?

Theraguide 5-FU detects variations in two genes, DPYD or TYMS which will inc risk of dose-limiting AEs related to 5-FU therapy

Predictive testing helps:

- Prevent toxicity in high-risk patients

- Individualize treatment for optimal therapeutic response

- Better determine alternate therapies for at-risk patients

- Implement dose reduction and monitoring strategies when appropriate

Adverse Effects:

What are the chemotherapy agents that do not cause myelosuppression?

What two drugs caused prolonged and delayed myelosuppresion?

Vincristine, MTX (only with Leucovorine rescue*), Bleomycin

(also, Corticosteroids, interferons, L-asparaginase and hormones)

Busulfan and carmustine cause prolonged & delayed myelosuppression

- These agents work closer to the stem cell

Adverse Effects:

What factors put a patient at an increased risk for myelosuppression?

List agents that cause impaired drug elimination via

renal/hepatic routes

Risk factors = poor marrow reserve (inc age), type of chemo, prior pelvis radiation, prior chemo and concurrent radiation therapy

Meds w/ impaired drug elimination:

- Renal = cisplatin, carboplatin, MTX and toptecan

- Hepatic = anthracyclines, vincas, taxanes and irinotecan

(Not always b/c of toxicity to region; could be elimination route ex: adriamycin and anthracyclines eliminated hepatic; not toxic to liver)

Adverse Effects:

Febrile neutropenia defined as ___

Antibiotics must cover ____

Examples of antibiotic regimens? What if G+ is suspected?

What class of meds are not recommended to treat neutropenic fever?

Febrile neutropenia accompanied by temp > 101 or 100 for > 1 hr

- neutropenia = ANC < 500 or ANC < 1000 w/ expected drop < 500

Antibiotic regimens must cover Pseudomonas

Examples:

- Mono = ceftazidime (?), Cefepem, Imipenem and Meropenem

- Dual = Pip/Tazo or Mono agent + aminoglycoside

- If G+ suspected = either of above + Vanc

CSFs not recommended for treatment of neutropenic fever

** Used in prevention

Adverse Effects - Neutropenia Prevention:

Agents for primary prevention?

When are these drugs deemed cost-effective for primary prevention?

What agents are used in secondary prevention?

Primary prevention - prophylactic CSFs or treatment at reduced dose

**CSFs deemed cost-effective if neutropenia incidence > 17%

Secondary prevention = either dose reduction of chemo or CSFs

- CSFs are commonly used when dose intensity is correlated with response

Adverse Effects - CSFs:

What is the dose for G-CSF?

Common AE between all CSFs?

When should you stop: G-CSF and pegfilgrastim?

Clinical trial data supports the use of CSF when _____

In what specific cancer is CSF prophylaxis very imp?

G-CSF dose = 5 mg/kg/d sq until ANC > 10,000/mm3

- Start > 24 hrs but < 72 hrs after start of chemo

AE among CSFs = Medullary bone pain

Stop G-CSF w/n 1-2 days of chemo; Pegfilgrastim stop w/in 14 days

Data supports use of CSFs when FN risk > 20%

- < 20% weigh risk vs benefit (complete cure or palliative care)

CSF prophylaxis is very important breast cancer patients

Adverse Effects - Pegfilgrastim:

Prophylactic use of pegfilgrastim results in what?

What is the dose of pegfilgrastim?

When pegfilgrastim be administered and stopped before next chemo?

How is pegfilgrastim cleared in the body?

Pegfilgrastim prophylaxis results in reduced neutropenia duration, fewer hospital days and fewer days of IV antibiotics

Dose: 6 mg subcutaneously every 21 days

- Administered 24hr after cytotoxic chemo and must be > 14 days till next chemo dose (< 14 days do not use)

Pegfilgrastim - slow clearance of protein portion (extended t 1/2) and is primarily cleared by neutrophils

-- Neutrophil count low then drug conc stay high; once neutrophil counts return to normal drug is eliminated more effectively

Adverse Effects - Thrombocytopenia:

What are the four meds commonly associated with thrombocytopenia?

Broad treatment strategy used ______

What agent is used for prevention?  When is it used?

Topotecan, carboplatin (not cisplatin), gemcitabine and bortezomib

Treatment: platelet infusions when counts < 10-20,000 or

                    < 50,000 with active bleeding

Prevention: IL-11 (Oprevelkin)

- Used in high risk patients where dose reduction may compromise outcomes

Adverse Effects - Oprevelkin (IL-11)

MOA, Dose

AEs

When should this agent be initiated and d/c?

This med should be continued until platelet count is _____ for ____

IL-11 stimulates platelet production through stimulation of megakaryocytpoeisis and thrombopoiesis (used to prevent; not tx)

- Dose = 50 ug/kg SC qd

- AEs: fluid retention, pleural effusion, tachy, Afib, Aflutter, **conjunctival redness w/ injection

- Caution in pts with: CHF, cardiac arrhythmias, preexisting visual disturbances, leukemia or multiple myeloma

Dose initiated w/in 6-24hr after completion of chemo; continued until post-nadir platelets is 100,000 for 21 days; treatment should be d/c at least two days before start of next chemo cycle

Adverse Effects - Anemia:

Can occur with any marrow toxic agent.  What agents are common?

When are transfusions of packed RBCs used?

What is the RBC count decreased to in cancer patients?

Common agents = cisplatin and carboplatin

-- most common AE; but Hgb counts not as important w/ chemo tx

Transfusions of pack RBCs for Hgb < 8 or higher if severe symptoms

RBC count decreased to ~ 90 days with cancer

- Anemia inducing substance (AIS) causes reduced EPO production, suppressed BFU-e and CFU-e and impaired iron utilization

- Cancer patients kidneys cannot compensate enough to make up diff

Adverse Effects - EPO and Darbepoetin alfa

Differences between these agents

Dose schedule, structure differences and when to add these agents?

Recombinant EPO - given either 3x/wk or once a week

Darbepoetin - only given every 3 weeks (longer t 1/2)

EPO = 3 N-linked CHO chains w/ 14 sialic acids

Darbo = 5 N-linked CHO chains w/ 22 sialic acids

These agents should be added when Hgb < 10 (D/c if Hgb > 12)

-- No longer indicated for myelosuppresive anticipated treatment

GI Toxicity - Mucositis:

What is mucositis? Direct vs indirect stomatoxicity

Time course of mucositis parallels ____

Risk factors for mucositis

Mucositis = GI tract lining has rapid turnover rate and high tox risk

- Direct stomatotox = due to cytotoxic agents

- Indirect = due to concurrent neutropenia and thrombocytopenia

Time course usually parallels myelosuppression

- Neutropenic = severe mucositis; Improved neutrohils = muco better

RFs: poor oral hygiene; leukemia/lymphoma; young age; radiation; poor nutritional status and high dose therapy

Adverse Effects - Mucositis:

What agents are commonly associated with mucositis?

Prevention strategies?

Treatment?

What is palifermin? Who's it approved for?

Agents: 5-FU, MTX, Doxorubicin, Bleomycin & Cont. infused taxanes

Prevention: hygiene, leucovorin rescue for MTX

**Amifostine for radiation for head/neck cancers = 200 mg/m2 IV over 3 mins once daily starting 15-30 min before radiation tx

All treatments should be given IV (antimicrobials, antifungals, antivirals, antibiotics, hydration and nutritional support)

Palifermin: stims keratinocytes; approved for BMT pts

- Decreased severity of mucositis only NOT incidence

Adverse Effects - Diarrhea:

What agents are common causes?

Irinotecan causes _____ and is treated with?

Important mutation with irinotecan therapy?

Agents: 5-FU, IL-2, irinotecan and EGFR (x)ors (erlotinib, gefitinib and cetuximab)

Irinotecan causes both early and late diarrhea

- Treat early w/ anticholinergics

- Treat late w/ loperamide <-- NO MAX DOSE IN CANCER PATIENTS

Dose = 4 mg stat and then 2 mg q2hr until diarrhea stops

** UGT-1A1 mutation = more diarrhea/neutropenia; do not use if irinotecan mutation is present

- If diarrhea > 1 day while taking loperamide start levoflox after 24h

Adverse Effects - Constipation:

What agents are associated with constipation?

Prevention strategies?

Treatment?

Agents = constipation and pain medications

- consequences: ab cramps, ileus and bowel obstruction

Prevention: stool softeners, stimulant/hyperosmotic laxatives

- stimulant laxatives: 1 bowel movement q48hrs

Treatment: Increased laxatives, fluids and fiber (not w/ pain meds)

- Methylnatrexone (1 time dose - selective opiod antag periph; does not cross the BBB)

Adverse Effects - Renal toxicity:

What agents are known to cause direct renal toxicity?

How do you prevent and treat these agents?

Cisplatin: tubular necrosis and electrolyte wasting (Mg+ and K+)

- Prevent w/ pre and post hydration = 1 L NS + 20 mEq KCl + 8 mEq Mg-SO4 over 1-2hrs to obtain urine flow rate of > 100 mL/hr

         (same for post-hydration)

- Dose adjust for CrCL < 50 mL/min; use mannitol not diarrhea

- Amifostine - modest protection; give 15-30 mins before

High-dose MTX (precipitates in renal tubules); major DI w/ NSAIDs

- Prevent: alkanize urine pH > 7 (12hr prior and cont 24 hrs after)

- Leucovorine doesn't help w/ water solubility (not given to protect against nephrotoxicity)

Adverse Effects - Bladder Toxicity:

Agents known to cause this and why?

What agent is used to prevent this and what dose regimens are used?

Agents: cyclophosphamide and ifosfamide

- inactive metab acrolein binds to and irritates BV --> bleeding

- can result in hemorrhage, loss of fxn and bladder cancer

Prevention = vigorous hydration and MESNA (binds acrolein)

- Mesna IV-IV-IV: IV bolus 20% ifosfamide dose at the time of administration and 4 and 8 hrs after each dose of ifosfamide

(TDD = 60%)

- Mesna IV-oral-oral: IV bolus 20% ifosfamide dose at time of admin; then 40% ifosfamide dose at 2 and 6 hrs after each ifosfamide dose (TDD = 100%

Adverse Effects - Cardiac toxicity:

What agents are known to cause this?

Doxorubicin (anthracyclines in general)

Mitoxantrone (less cardiotoxic b/c no oxygen free radical formation)

5-FU (angina and MI)

High dose Cyclophosphamide

Trastuzumab (EGFR-2) --> DONT EVER GIVE W/ ANTHRACYCLINES

Imatinib, Dasatinib and Nilotinib (TKI of BCR-abl 1 and 2)

Sunitinib and Sorafenib (TK VEGFR); Bevacizumab (VEGF (x)or)

Adverse Effects - Anthracyclines:

What types of cardiac toxicities do anthracyclines cause?

What is the life-time dose of doxorubicin?

MOA?

Prevention? (Scan/antidote)

Cause any type of cardiotoxicity (acute = arrhytmias, pericarditis)

- Chronic = CHF and Late = ventricular dysfunction

Life-time Doxorubicin dose > 450-550 mg/m2

MOA: metabolize reactive intermediates that gen O2 free radicals

All pts need baseline MUGA scan to evaluate potential cardiotoxicity

- Ejection fraction should be > 50% (< 50% no anthracyclines)

** Dexrazoxane (antidote) - prevent cardiotoxic by stop binding of the reactive intermediate to iron (metal chelator); peds pts high use

Adverse Effects - Pulmonary toxicity:

What agents cause this?

How do you prevent pulmonary toxicity?

What treatment strategies are used?

Bleomycin (need baseline PFTs and mucositis), Busulfan, Carmustine, Mitomycin C, All trans-retinoic acid, cyclophosph and MTX

Prevent by limiting cumulative doses:

- Bleomycin = < 400 units total of bleomycin

- Busulfan = < 500 mg

- Carmustine = < 1000/m2

Treatment = no antidote; steroids for symptomatic relief

Adverse Effects - Neurotoxicity

What agents are associated and type of toxicity of each?

Vinca (esp vincristine): periph, autonomic & cranial NN neuropathy

- progress neuropathy; ask pt 2 or 3 dose about ting/numb feet

Cisplatin: periph neuropathy and ototoxicity

Oxaliplatin: acute and chronic neuropathies (diff swallowing)

Taxanes: peripheral neuropathy

Intrathecal chemo: Direct CNS tox, seizures and coma

Ifosfamide: confusion, somnolence, seizures and coma (cloudy feel)

Adverse Effects:

What medications always cause alopecia?

What medications have photosensitivity risks?

What meds cause Hand-Foot syndrome?

What med class typically causes rash? What does it look like?

Alopecia: Anthracycline and Paclitaxel (grow back when chemo d/c)

Photosensitivity: 5-FU, MTX, ATRA and EGFR (x)ors

Hand-foot syndrome: Capecitabine, continuous IV infusion 5-FU, sunitinib and sorafenib [VEGFR TK (x)ors]; also lapatanib (EGFR-2)

Rash = EGFR (x)ors --> all drugs cause acne-like rash

-- if EGFRs are working then rash shows it's working (no prob till sev)

EGFR ex = cetuximab, erlotinib and gefitinib

Adverse Effects - Vesicants:

What are known vesicants?

Treatment?

Specific antidotes?

Anthracyclines, vincas, N mustards, mitomycin and dactinomycin

Treatment: stop infusion and attempt to withdraw fluid

-- Ice packs used for all drugs except vincas (Heat for vincas)

Antidotes:

- N mustard = sodium thiosulfate sq around extravasation site

- Vincas = hyaluronidase sq

- Anthracycilnes = DMSO topical or Dexrazoxane IV (repackaged)

--- Dexrazoxane dose on BSA for 3 days of IV soln

         (Max single dose = 2000 mg)

Adverse Effects - Hypersensitivity Reactions:

Agents known allergic reactions?

Prevention strategies?

What agents always has a premedication cocktail?

L-asparaginase, Pacitaxel, bleomycin (rare), cisplatin, anthracyclines (hives at site) and mAbs (more w/ mouse antibodies)

Prevention: L-asparginase and bleomycin = give test doses

** Paclitaxel always given as premedication cocktail: Corticosteroids, Diphenhydramine and H2-blockers

mAbs (more w/ -ximab) --> premed cetuximab w/ diphenhydramine

What is the most important risk factor for CINV?

Do males or females have worse N/V?

Emetogenicity of chemo regimen = most imp CINV RF

Females have worse N/V than males

Increased RFs for N/V:

- Prior exposure to chemo and history of N/V (worse)

- Younger people have worse N/V

- People who don't drink alcohol or smoke have worse N/V

CINV - Antineoplastic agents

What are the three highly emetogenic drugs?

What medications are moderate emetognic drugs?

What medications are listed in low-minimal emetogenic drugs?

High emetogenic = cisplatin, mechlorethamine and dacarbaine

(**cisplatin only platinum high; carbo and anthracyclines = mod)

Moderate = carboplatin, cyclophosphamide, anthracylines and oxaliplatin (2 moderate agents = highly emetogenic regimen)

Low-minimal = Paclitaxel, doxetaxel and vincas;

-- oral target agents = chlorambucil, erlotinib, sorafenib and sunitinib

What are the three most important NTs in CINV?

How do these NTs work in the body?

Serotonin, Substance P (binds NK-1 receptors) and Dopamine

5-HT3: released from enterochromaffin cells in GI tract and activates serotonin receptors that stimulate the CTZ

- Chemo cause cytotoxic damage to GI mucosa --> release of 5-HT3

- works in the periph (gut) and centrally (CTZ)

Dopamine: stimulates the CTZ

Substance P (binds to NK cells): GI tract and vomitting center

Delayed emesis is common with cisplatin, carboplatin,

doxorubicin and cyclophosphamide

** Cisplatin has biphasic pattern of CINV

- Max intense w/in 24h post dose

- 2nd phase = 2-4d post dose

In CINV, what is always added to a regimen of 5-HT3 antagonists?

5-HT3 antagonists activity is based on ______?

What is ondansetron IV and PO dose?

What are the most prominent AEs?

What is unique about Palonosetron?

Always add corticosteroids to 5-HT3 chemo regimens!! Increases the efficacy by 15-30%

Serotonin antagonist activity is based on receptor binding, not kinetic parameters.  Once 5-HT3 receptors are saturated, higher do not increase effect

Ondansetron IV = 8-16 mg IV bolus infusion 30 min prior to chemo and q4h x 2 dose (16 mg IV is max dose)

Ondansetron PO = 16-24 mg 30 min prior to chemo (24 mg = max and common dose)

Prominent AEs = HA and GI; constipation

(Granisetron not for PONV; dalosetron = QT prolongation caution)

Palonosetron = inc t1/2 (40hrs) and only given IV; no po dose

Aprepitant (Emend)

MOA, IV dose and indication

What is an important change in regimen that must be made?

Drug interactions

Aprepitant - NK-1 receptor antagonist (blocks substance P binding)

- IV dose = 150 mg IV for 1 day only!!

Indicated for acute, highly emetogenic chemo w/ 5-HT3 antags and CS

** DECREASE DEXAMETHASONE BY APPROX 50%

Drug interactions = 3A4 (x)or (why cut DXM dose by 50%) so need to decrease effectiveness of oral contraceptives, ketoconazole, clarithromycin, diltiazem and verapamil

Metoclopramide:

MOA, important AEs and place in therapy

MOA: Dopamine and 5-HT3 antagonist that increases GI motility

AEs = EPS and diarrhea (dystonic rxns and CNS)

Used in DELAYED N/V and moderate-highly emetogenic chemotherapy

Benzodiazepines

AEs = sedation --> reason it's used in CINV

Also used as adjuvant treatment in highly emetogenic chemo!