4 medical claims of fiber

if applicable, what type of fiber dose each

1.  Laxation (insoluble fiber)

2.  Serum lipid reduction (whole grain)

3.  Serum glucose reduction (cereal grain)

4.  Wt loss (inconclusive b/c people eating more fiber tend to be healthier anyway)

Prebiotics (Support)

1.  Function

2.  What they help with (3)

1.  Maintain healthy bacteria (Are in fact, Bifidobacteria and Lactobacilli)

2.  Bulk forming; Mg and Ca absorption; Dec TGs

Probiotics (Restore)

1.  What are they?

2.  Strains

3.  Medical claims (5)

4.  Added to what in diet?

1.  Living organisms with beneficial effects on host

2.  Lactobacillus, Streptococcus, Bifidobacterium

3.  Shorten diarrhea; Improve lactose intolerance; decrease IBS; help tx H. Pylori; helps reduce incidence of necratizing infanitis

4.  Dairy products

*min of 10^7-10^10 daily

CHO Sports Nutrition

1.  What do CHOs do in sports?

2.  Define "bonking or hitting the wall"

3.  How many g cabs per hour of exercise according to FDA

1.  First, immediate energy source

2.  Depletion of carbs to the point where it is difficult to finish the workout

3.  30-60 g/hr

1.  Poor motility

2.  Dec absorption (hydrolyzed fats and carbs)

3.  Dysfagia (refer for medical)

4.  Bariatric surgery (med supervision required)

Sports Nutrition-Fat and TGs

1.  What is considered aggressive restriction which should be avoided

Sports Nutrition-Protein

1.  ADA recommendations for highly active people

2.  Define a highly active person according to ADA

1.  1.2-1.7 g/kg/d

2.  Vigorous exercise > 1 hr daily

Pre-exercise 

1.  Fluid recommendations

2. CHO recommendations

1.  5-7 mL/kg at least 4 hrs before exercise

2.  200-300g at least 3 hrs before exercise

Post-Exercise

1.  Rehydration recommendation

2.  CHO recommendation

3.  Protein REcommendation

1.  16-24 oz of sports drink for every 0.5 kg body wt lost during exercise

2.  Within 30 min post-work out, consume 1.5 g/kg

3.  Only use if planning to work out again in next 18 hrs

Caffeine and Exercise:

1.  Doseand when to consume

Creatine

1.  Type of exercise for which it is beneficial

2.  Loading dose

3.  MD

4.  Lasting improvement?

1.  Anaerobic requiring short bursts of high activity

2.  20 gm days 1-5 dosed QID

3.  5 gm/d broken into QID

4.  No

1.  Ephedra

2.  Steroidal precursors

1.  Infant Catch-Up Calories Calculation

2.  What % of calories from CHOs

3.  What is the primary source and primary CHO in the infant diet

1.  Take total calories and multiply by 1.25-1.5 

2.  40-50%

3.  Lactose from human milk and milk based formulas

Protein and AAs in Infants

1.  What does Taurine do that is so importatn?

Taurine is NOT energy source

Cell membrane protector

Deficiency causes retinal dysfunction and slow development of auditory brain stem

Infant Fatty Acids

1.  What % of non-protein calories should be essential FAs?

2.  What are the essential PUFAs

3.  What are the long chain PUFAs

1.  50%

2.  Linoleic acid (omega-6); Linolenic acid (omega-3)

3.  DHA, Arachidoinc acid

WHO and AAP Breast Feeding Recommendations

1.  Minimum amt of time recommended

2.  Why is breast feeding good?

3.  3 diseases that are contraindicaitons for breast feeding

1.  6 months

2.  Optimal nutrition for infant, mother-infant bonding; decreased diarrhea, respiratory tract infections, otitis media, bacteremia, bacterial meningitis

*Premies:  dec nectrotizing enterocolitis, UTIs, late-onset sepsis

3.  HIV, T cell disease (lymphoma), herpes

1.  Cipro, 2. Cytoxan, 3.  Cyclosporine, 4. Doxepin, 5. Doxorubicin, 6. Ergotamine, 7. Leflunomide, 8. MTX

*If unavoidable, feed baby during trough

1.  Amphetamine

2.  Cocaine

3.  Heroin

4.  Marijuana

5.  Phencyclidine

1.  20 kcal/mL

2.  200-300 mOsm/mL

Tooth Decay with Bottle Feeding

1.  When does it happen (2)

1.  Kids sleeping with bottle in mouth

2.  Kids sipping constantly throughout the day

1.  Ready to use:  do NOT dilute

2.  Liquid:  dilute

3.  Powdered

1.  Meropenem (risk for superinfection)

2.  Piperacillin/tazobactam

3.  Cefepime and Metronidazole

4.  Aztreonam + Vanc + metronidazole

1.  Main causes of acute pancreatitis (2)

2.  What happens to pancreas during pancreatitis

3.  Other common causes of pancreatitis (4)

1.  EtOH and gallstones

2.  Early activation of zymogen pancreatic enzymes causes inflammation

3.  A)  Hypertriglyceridemia (>500); B)  Endoscopic retrograde chol-angiopancreatography (ERCP); C) Pregnancy; D) Autodigestion d/t early pancrfeatic enzyme activation

1.  Pancreatic pseudocyst (may require drainage)

2.  Pancreatic nectrosis (Gm -)

3.  Pancreatic abscess (E.coli, enterobacteriacease, S. aureus, Viridans strep, anaerobes)

Dx of Pancreatitis

1.  2 of these 3 S/S

2.  What enzymes are the Gold standard

1.  Pain; Increased enzymes (3X upper normal); CT scan

2.  Lipase and colipase because they remain elevated for days...amylase can fall within 24 hrs

1.  Resoluation of N/V, abdominal pain, fevere

2.  Ability to tolerate oral intake

3.  Normalization of serum amylase, lipase, and WBCs

4.  Resoluation of absess, pseudocyst, or collection of fluid as measured by CT

1.  IV fluids

2.  D/C oral feedings unless jasojujunal tube that bypasses duodenum

3.  Pancreatic necrosis:  surgical debridement or you die

1.  Analgesics (Meperidine cases less sphincter of Oddi contraction, but lacks clinical evidence; most pts get fentanyl and hydromorphone)

2.  ABX:  Empiric not necessary if pt has mild disease or noninfectious etiology of acute pancreatitis

1.  Somatostatin or atropine to reduce pancreatic secretions

2.  Reducing gastric acidity with H2RAs

3.  Inhibition of pancreatic enzymes with aprotinin (protease inhibitors)

4.  Probiotics

5.  Immunomodulation

6.  NG suction only if pt doesn't ileus or persistant vomiting

1.  Pancreatic cancer

2.  Diabetes

1.  Dietary malabsorption

2.  Impaired glucose tolerance

3.  Cholangitis

4.  Potential addiction to opioid analgesics

Chronic inflammatory process damaging enzyme-producing cells in the pancreas and destroying the endocrine function of the pancrease through scarring and fibrosis

*Same incidence b/t binge and social drinkers

1.  Dec lipid and protein absorption

2.  Wt loss, steatorrhea

3.  CHO absorption usually not altered 

**Does not appear to alter ADEK

1.  Presentation similar to acute pancreatitis

2.  CT and scarring more important b/c amylase and lipase can both be normal...CT or ERCP allow visualization of calcified regions

1.  Prevention and resolution of chronic abdominal pain

2.  Correction of dietary malabsorption with exogenous pancreatic enzymes

1.  Lifestyle mod:  No EtOH and dec fat

2.  Surgical (Whipple; not often used/recommended d/t lack of proven efficacy)

1.  Analgesics (tramadol or opioids)

2.  Pancreatic enzyme supplementation:  dose based on lipase

1.  Ultresa

2.  Viokase

3.  Creon

4.  Zenpep

5.  Pancreaze

Viral Hepatitis

____ Interferons have extended t1/2 so they can be given subQ once weekly

Viral Hepatitis

G-CSF can be used for ___  ___ neutropenia

Viral hepatitis

A ____ in platelet count of 25-30% usually occurs within 6-8 wks after initiation of tx

Viral Hepatitis

____ syndrome can be caused by taking EXPIRED tetracyclines and also by the antiviral drug tenofavir when taken by pts coinfected with HIV and HBV

Viral Hepatitis

Hep A and E has only been documented/occurs as an ___ ___

Viral Hepatitis

____ _____ response is defined as having an undetectable viral load or HCV RNA level at 6 months post-tx

Viral Hepatitis

A group recommended for pre-exposure hepatitis B vaccination includes ___ individuals who hav/had multiple sexual partners in the last 6 months

Viral Hepatitis

FDA-approved ___ treatments are not recommended d/t significant ADRs

Viral Hepatitis

The ideal chronic hepatitis C tx is ___ pegylated interferon + oral ribavirin

Viral Hepatitis

___ usually occurs within the first 2 weeks after initiating tx with either formulation of interferon

Viral Hepatitis

Lamivudine is no longer indicated as first-line therapy for chronic hepatitis B d/t a high rate of ___

Viral Hepatitis Basics

1.  S/S

2.  Typical transaminase levels

3.  What 2 types of the hep can be chronic?

1.  N/V; fatigue; abdominal pain; anorexia; erythematous rash; urticaria; arthralgia; fever; dark urine; pale stool; pruritus; jaundice; lymphadenopathy; slenomegally

2.  Aminotransferases in thousands

3.  B and C

Hepatitis A

1.  Transmission/incubation

2.  Dx

3.  What % is positive for diagnostic feature in US

4.  What indicates acute or recent infection

1.  Fecal-oral; 3-5 wks

2.  Anti-HA which is detectable at onset and declines within 6-12 months

3.  30-40%

4.  IgM Anti-HAV

Hepatitis A Prophylaxis

1.  Preexposure

2.  Post-exposure

1.  IGIM: passive immunity

HAV IM takes several weeks to become protective and may last 8 yrs (VAQTA and Havrix)

2.  Give IGIM and vaccine within 2 weeks

*Vaccine is in 2 doses

Hepatitis B

1.  Transmission/Incubation

2.  % that become chronic

3.  Dx with what 2 things and time frame

4.  Complications with chronic

1.  Parenteral, sexual, vertical transmission; 2-4 months

2.  10%; 33% of pts have no identifiable risk factors

3.  HBsAG (4-12 wks); then Anti-HBc

4.  Cirrhosis; hepatic failure; hepatocellular carcinoma

Hep B Prophylaxis

1.  Preexposure

2.  Postexposure

1.  HBV IM (may need to check titers)

2.  HBIG IM for passive

HBV:  series or booster

1.  Twinrix

2.  >18 yrs old

Hep B Tx-Chronic Infection

1.  Drug of choice

2.  Early (within hrs) S/E

3.  Late (>2 wks) S/E

4.  Monitoring what tests and when

1.  Interferon

2.  Fever; chills; anorexia; nausea; myalgias; fatigue; HA 

*Tx with APAP 2g/d

3.  Worsening of flu-like ADE; ALT flare +/-

4.  CBC w diff; TSH; LFTs after 1 and 2 wks, then montly therafter

1.  Interferon/pegylated interferon

2.  Entecavir (Baraclude):  do not use if co-HIV infection

3.  Tenofovir disoproxil fumarate (Viread):  Fanconi's syndrome

4.  Adefovir dipivoxil (Hepsera

5.  Lamivudine (Epivir-HBV):  no longer first-line

6.  Telbivudine (Tyzeka)

*  Monitor liver and kidneys with all tx

Hep C

1.  Transmission

2.  Aminotransferases

3.  Dx with what short term and long-term (>6 months)

4.  Long-term sequelae 

1.  Parenteral; sexual; vertical transmission

2.  May or may not be elevated although cirrhosis is common

3.  Early:  HCV RNA; Late:  Anti-HC

4.  20-30% cirrhosis; 1-5% carcinoma

*10% of cases have no identifiable risk factors

Sexual Trasmission of HCV

1.  Likelihood?

2.  What can increase the liklihood (4)

1.  Very low

2.  Coinfection with HIV; High viral load; Multiple partners; Rough sex

Hepatitis C

1.  Vaccine or post exposure prophylaxis?

2.  First line treatment once infected (2)

1.  No

2.  Pegylated interferon + ribavirin

*Peg-IFN SQ

a-2a (Pegasys):  weekly

a-2b (PEG-Intron):  weekly

Hepatitis C

1.  What happens after interferon tx ends?

2.  Define:  response; Nonresponse; relapse

1.  Relapse

2.  Response:  normalization of ALT and dec HCV RNA to undetectable levels

Nonresponse:  ALT fails to normalize or HCV RNA still detectable

Relapse:  normalization of ALT and dec HCV RNA to undetectable levels than either reemerge in 6 months after tx

1.  Fever, chills, rigors, myalgias (APAP/NSAID and take dose HS)

2.  Irritability, depression, suicidal ideation (Antidepressants/anxiolytics; D/C if suicidal)

3.  Thrombocytopenia (DO NOT recommend tx)

4.  Neutropenia (G-CSF)

1.  Hemolytic anemia or mixxed anemia within 4 wks

*Dose reduction or D/C; or use transfusion or EPO

2.  Teratogenic/embryocidal effects:  women and men should use 2 forms contraception during AND until 6 months post-tx

1.  Current/past psychosis, severe depression

2.  Neutropenia, thrombocytopenia

3.  Organ transplant, excpet liver

4.  Symptomatic heart disease

5.  Decompensated cirrhosis

6,  Uncontrolled seizures

Hepatitis D

1.  Tramsisson and requirements/incubation

2.  Early and late Dx

3.  Interaction with other type of hep

4.  What % of superinfections with D become chronic often leadin to cirrhosis?

1.  Parenteral and recuires Hep B also; 3-13 wk incubation

2.  Early:  HDAg (10d), then Anti-HD

3.  Type D can lower Type B but worsen acuity

4.  75%

Hepatitis E

1.  Transmission/Age preference

2.  Particularly significant mortality risk with? (20%)

3.  Dx

1.  Fecal-oral; 15-40 YO in developing countries

2.  Pregnancy

3.  Tests not widely available 

Liver Function Tests

LFTs vs Function Tests

1.  LFTs:  AST, ALT, Alk phos, GGT, Other enzymes

2.  Bilirubin, Albumin, INR

Cirrhosis

1.  Definition

2.  Most common decade of life it occurs in

3.  __th leading cause of death in US

1.  Progressive replacement of normal hepatic cells with fibrous scar tissue

2.  4th decade

3.  12th leading cause of death

1.  Alcohol use:  women quicker than men d/t slow metabolism

2.  Hepatitis:  C in US; B worldwide

3.  Genetics

4.  Metabolic risk factors:  diabetes, dyslipidemia, obesity

5.  Medications:  APAP, Ibuprofen/NSAIDs

1.  Ascites

2.  Portal HTN

3.  Varices

4.  Spontaneous bacterial peritonitis

5.  Hepatic Encephalopathy

6.  Hepatorenal syndrome

7.  Bleeding abnormalities 

1.  Elevated:  Aminotransferase; Alk phos; GGT (LFT levels do NOT correlate with liver damage)

2.  Inc total, direct, and indirect bilirubin

3.  Elevation of LDH

4.  Thrombocytopenia

5.  Anemia

6.  Elevated PT/INR

7.  Dec albumin and protein

8.  Inc ammonia

9.  Inc SCr

1.  Class A:  1-6 pts

2.  Class B:  7-9 pts

3.  Class C:  10-15 pts

Portal Hypertension

1.  Aim/goal of therapy

2.  First line therapy

3.  What to NEVER give alone, but can be an add-on

1.  Dec portal pressure; Dec HR by 25% or a goal of 50-60 bpm

2.  Nonselective B-blockers

3.  Nitrates

Ascites

1.  Definition

2.  Surgical procedure employed

3.  Mechanism by which it occurs

1.  Accumulatio nof fluid in peritoneal space

2.  Paracentesis:  if >5L removed, give 6-8 g/L albumin to prevent hepatorenal syndrome

3.  Dec albumin decreases oncotic pressur ein plasma allowing third spacing

Intravascular volume is decreased activating RAAS which increases intravascular volume and increasing ascites

Diuretic use in Cirrhosis

1.  What class combination used

2.  Dose and daily fluid loss target

Aldosterone antagonist used with loop 

*Up to 400 mg spironolacton/d with a target fluid loss of 0.5 L/d

Bleeding abnormalities cirrhosis

1.  Why do they occur?

2.  What do you give to reverse?

3.  Even though pts may have therapeutic INR...what can they develop?

1.  Lack of clotting factor production

2.  Vitamin K

3.  Thrombosis 

Cirrhosis Spontaneous Bacterial Peritonitis

1.  Definition

2.  Common pathogens

3.  Propylactic ABX

4.  Tx ABX

1.  Acute bacterial infection of peritoneal fluid

2.  E. Coli, Klebsiella, Strep pneumo

3.  3rd gen cephalosporin; FQN; bactrim

4.  IV 3rd gen Cephalosporin; IV extended spectrum PCN; FQN

Esophageal Varices

1.  Definition

2.  What % of all upper GI bleeds ar evariceal?

3.  % mortality from first bleed

4.  Nonpharm

5.  Pharm

1.  Swelling and expansion of collateral vessels d/t portal hypertension; they divert blood from hepatic to systemic circulation

2.  20-30%

3.  55%

4.  Band ligation (1st); balloon tamponade; transjugular intrahepatic portal-systemic shunt (TIPS)

5.  Octreotide selective vasoconstriction of splanchnic bed

*50-100 mcg IV load followed by 25-50 mcg/hr

**Continue 24-72 hrs after bleeding stops

Hepatic Encephalopathy

1.  S/S

2.  Drug Threapy (3)

1.  Asterixis:  flapping of hands upon extension of arms with wrist flexion

*Ammonia is proposed toxicant

2.  Lactulose:  15-30 mL 2-3 X per day titrate to 2-4 soft bowel movements daily

ABX:  Neomycin, Rifaximin (preferred d/t less abosprtion)

Flumazenil (short term only b/c long term benefit unclear)

Hepatorenal Syndrome (HRS)

1.  What is a potential trigger?

2.  What happens

3.  How do you treat it?

1.  SBP

2.  Renal artery vasoconstriction and decreased MAP which precipitates renal failure

3.  Increase volume within CVS to inc renal perfusion

Albumin:  1 g/kg on day 1 followed by 20-40 g daily thereafer

Midodrine:  7.5 mg TID

Octreotide:  100 mcg SubQ TID

Terlipressin:  Vasopressin analog in Europe

1.  Avoid hepatic insult (no EtOH)

2.  Restrict sodium

3.  If acute encephalopahy, restrict protein

4.  Vaccines:  Hep A/B; Pneumococcal; Influenza

1.  Carbamazepine

2.  Lamotrigine

3.  Levetiracetam

4.  Oxcarbazepine

5.  Phenobarbital

6.  Phenytoin

7.  Topiramate

8.  Valproate

9.  Zonisamide

1.  Ethosximide

2.  Lamotrigine

3.  Valproate

4.  Zonisamide

1.  Lamotrigine

2.  Levetiracetam

3.  Topiramate

4.  Valproate

5.  Zonisamide

1.  Lamotrigine

2.  Valproate

3.  Zonisamide 

1.  Carbamazepine

2.  Gabapentin

3.  Lamotrigine

4.  Levetiracetam

5.  Oxcarbazepine

6.  Phenobarbital

7.  Phenytoin

8.  Topiramate

9.  Valproate 

Tendency to have seizures on a chronic, recurrent basis

*Affects 2 million in US alone

**8% of people seize in lifetime

***Most common age <1YO and >55YO

1.  Tonic-clonic

2.  Absence

3.  Myoclonic

4.  Atonic

1.  Simple

2.  Complex

3.  Secondarily generalized

Sudden and brief (several sec) losses of consciousness without muscle movements-daydreaming or blanking out episodes

"petit mal"

Single and very brief jerks of all major muscle groups, may not lose consciousness d/t seizure lasting only 3-4 sec

*may cluster and build into tonic-clonic

Loss of consciousness and muscle tone.  No muscle movement is noted and the pt may fall 

"falling out"

1.  Idiopathic

2.  Symptomatic

3.  Cryptogenic

1.  Juvenile myocloinc epilepsy (JME)

2.  Lennox-Gastaut Syndrome (LGS)

3.  Mesial Temporal Lobe Epilepsy (MTLE)

4.  Infantile Spasms

Primary generalized epilepsy, early to middle teenage yrs, strong familial component

Myoclonic jerks and tonic-clonic seizures, may have absence seizures

1.  Surgery

2.  Vagal Nerve Stimulation

3.  Ketogenic Diet

1.  Definite dx of epilepsy

2.  Failure of adeuqte drug therapies

3.  Definion of electroclnical syndrome (localization to region of the brain)

Protein Binding Antiepileptic Drugs

1.  2 of the most highly protein bound

2.  Pts with naturally altered protein binding (6)

1.  Phenytoin (88-92%); Valproate

2.  Kidney failure

Hypoalbuminemia

Neonates

Pregnant women

Pts on highly protein bound drugs

Pts in critical care

1.  Valproic acid

2.  Felbamate

3.  Zonisamide

1.  Carbamazepine

2.  Phenytoin

3.  Phenobarbital

4.  Lamotrigine

Carbamazepine

*Start at 24-30% of MD (15 mg/kg/d) and increase dose weekly until MD reached in 3-4 wks

Michaelis-Menten (non-linear)

*Normal dosage range, max clearance capacity is reached

1.  Gradually uptitrate new med

2.  Once new med is at goal, down-titrate old med

3.  Watch for drug interactions

4.  Caution pts about possibility of increased seizure activity and possible new ADRs

1.  Seizure free post surgery can titrate down over 1-2 yrs

2.  5 criteria to stop:

No seizures 2-5 yrs

Normal neuro exam

Normal IQ

Single type of partial or generalized seizure

Normal EEG w/ treatment

*61% success if these 5 criteria met...taper over 1-3 months

Control quickly to avoid interference with development of brain cognition...

Be cautious though, b/c AEDs can cause cognitive delays in kids and you must monitor serum levels much more frequently

Women of Child-Bearing Age AED Use (4)

**Avoid what 3 drugs?

1.  Use OC with at least 50 mcg estrogen

2.  Folic acid supplementation (1-4 mg daily)

3.  Use monotherapy if possible

4.  Continue regimen that best controls seizures prior to preg

5.  Avoid:  Phenytoin, valproate, carbamazepin (neural tube, cleft palate)

1.  Monitor AED at start of pregnancy and monthly

2.  Monitor postopartum AED conc

3.  Adjust AED to maintain baseline level

4.  Administered supplemental Vitamin K during 8th month if on an enzyme inducer

5.  Many AEDs are excreted in breast milk

1.  Aplastic anemia (blood dyscriasis)

2.  Hyponatremia

3.  Leucopenia

4.  Osteoporosis

5.  Rash

1.  Hepatotoxicity

2.  Neutropenia

3.  Rash

1.  Anorexia

2.  Aplastic anemia

3.  HA

4.  Hepatotoxicity

5.  Wt loss

1.  Peripheral edema

2.  Wt gain

1.  Hyponatremia

2.  25-30% cross sensitivity with H/S to carbamazepine with dec blood counts

1.  Attention deficit

2.  Cognitive impairment

3.  Hyperactivity

4.  Osteoporosis

5.  Passive-aggressive behavior

1.  Anemia

2.  Gingival hyperplasia

3.  Hirsutism

4.  Lymphadenopathy

5.  Osteoporosis

6.  Rash

1.  Edema

2.  Wt gain

1.  Acute glaucoma

2.  Metabolic acidosis

3.  Oligohidrosis

4.  Paresthesia

5.  Renal calculi

6.  Wt loss

1.  Hepatotoxicity

2.  Osteoporosis

3.  Pancreatitis

4.  Wt gain

1.  Metabolic acidosis

2.  Oligohidrosis

3.  Parasthesia

4.  Renal calculi

1.  Any seizure lasting > 2 min

2.  Continuous seizures > 5 min

3.  >2 seizures w/o complete recovery of consciousness

Status Basics

1.  Do you have to convulse?

2.  Most fequent groups it occurs in (3)

3.  2 types of SE

1.  No

2.  African Am; Children; Elderly

3.  Nonconvulsive SE (NCSE): need EEG to determine

Generalized Convulsive SE (GCSE):  full body with greatest risk fo neurologic and physical damage

Phase I:  increased metabolic demand with increased cerebral blood flow:  compensated

Phase II:  continued increased metabolic demand, but loss of the compensatory increase in cerebral blood flood

*Hypoglycemia, hyperthermia, decreased motor activity even though brain seizing

1.  Cause of seizure if known

2.  EEG

3.  EKG

4.  Complete chemistry profile

5.  Toxicology panel

1.  Metabolic disturbances

2.  CNS disorders

3.  Infections

4.  Injuries

5.  Hypoxia

6.  Toxicity

7.  Acute illness

1.  Pre-existing epilepsy

2.  Chronic EtOH abuse

3.  CNS tumors

4.  Strokes

1.  Glucose for increased energy demands

2.  Thiamine 100 mg IV-If alcoholic

*Give thiamine before glucose to prevent encephalopathy

Start AEDs after 1st dose of benzodiazepine

Most common agents:  phenytoin/fosphenytoin

Valproat sodium not approved for SE, but may work for NCSE

*Other agents:  phenobarbital, levetiracetam

Fosphenytoin:  Water-soluble prodrug of phenytoin

1.  Route

2.  How is dose calculated (units)

3.  Given at what rate...and what is phenytoin rate

1.  IM

2.  Phenytoin equivalents (PE)

3.  Fosphenytoin:  150 mg/min

PHenytoin:  50 mg/min

Treating Refractory Status Epilepticus

1.  When is it considered refractory?

2.  Mortality?

3.  Last ditch drugs to try (6)

1.  Pts not responding to benzos or antiepileptics or seizures over 60 mins

2.  50%

3.  Midazolam; Propofol; Pentobarbital; Levetiracetam; Ketamine; Topiramate

Wt-based and higher than adults d/t higher clearance

*Similar approach to adults

1.  Look at drug-disease state induced seizures

2.  May have more pronounced depressive effects of other medications

1.  Signal from Substance P, Cholecystokinin, Prostaglandin, Bradykinin, or other neurotransmitters on the afferent nerves

2.  Primary afferent transmits signal to doral horn and activation of excitatory (Glutamate) or inhibitor (GABA; NE/SE?) transmitters take over

Neuropathic Pain Trasnmission

1.  Defect is in primary afferent nerve itself unlike nociceptive where the signal stimulates the primary afferent to fire...primary afferent is damaged

Ectopic Impulses:  Nerve impingement; Metabolic destruction; Chemical destruction

1.  Somatic (musculoskeletal)

2.  Visceral (organ)

1.  Physical

2.  Psychological

3.  Immunological

4.  Sociological

1.  Increased catabolic demands:  poor wound healing, asthenia, fatigue

2.  Respiratory:  shallow breathing; tachypnea; atelectasis; pneumonia

3.  GI:  Dec motility; constipation; N/V

4.  Cardio-Renal:  Tachycardia; HTN; Inc Na and H2O retention

1.  Mood disorders (anxiety, depression)

2. Sleep disorders

3.  Existential suffering

1.  Inc health care utilization:  increased ED visits, Increased us of pharmacotherapy

2.  Dec productivity:  dec performance, lost work days

3.  Societal Interaction:  lack of family involvement; decreaed ability to interact in society

1.  Lack of training

2.  Lack of pain-assessment skills

3.  Insufficient attention to pts

4.  Difficulty in assessing pain

5.  Rigidity or timidity in prescribing practices

6.  Regulatory oversight

1.  Reluctance to report pain:  get labeled as a pain seeker

2.  Reluctance to take certain analgesics:  social stigma; ADEs

3.  Poor adherence:  must educate on S/E, frequency of F/U, involvement of family caregivers to promote compliance

1.  Low priority given to symptom control historically

2.  Medicaiton availability (opioids; cost)

3.  Inaccessibility of speacialized care (too few clinicians with pain expertise)

1)  Pain type (nociceptive v neuropathic)

2)  Pain intensity (numeric)

3)  Pain source (if known...tumor, arthritis, etc)

4)  Pain location (body map)

5)  Pain duration

6)  Time course (persistent, intermittent, fluctuating)

7)  Alleviating factors (meds, position, hot/cold)

8)  Aggravating factors (walking, sitting, lysing on back)

9)Pain affect (depression/anxiety)

10)  Effects on ADLs (unable to bathe)

11)  Effects on QOL

12)  Effects on functional capacity (Tasks unable to perform)

13)  Presence of common barriers

14)  Patient's goal

The WHO Pain Tx Ladder

1.  Step 1; Pain Intensity?

2.  Step 2; Pain Intensity?

3.  Step 3; Pain Intensity?

1.  Nonopioid +/- adjuvant; Pain 1-3

2.  Opioid for mild to moderate pain + Nonopioid +/- Adjuvant

Pain 4-6

3.  Opioid for moderate to severe pain +/- Nonopioid +/- Adjuvant

Pain 7-10

1.  Codeine

2.  Hydrocodone

3.  Oxycodone

1.  Morphine

2.  Oxycodone

3.  Hydromorphone

4.  Fentanyl

5.  Methadone

6.  Levorphanol

1.  TCAs

2.  Anticonvulsants (Gabapentin)

3.  Bisphosphonates

4.  Calcitonin

5.  Radiopharmaceuticals

6.  Steroids

7.  Psycho-stimulants (methylphenidate)

1.  What % do you increase dose by in opioids for severe to uncontrolled pain?

2.  What about mild to moderate pain?

1.  50-100%

2.  25-50%

1.  How do you calculate the dose for breakthrough pain with opioids?

2.  What are dose intervals for breakthrough pain?

1)  5-15% (10% is what he seems to like) of the total 24 hr daily dose

* This is per dose

2)  Dose intervals should be appropriate for the agent being used for breakthrough pain

*Short-acting opioids Q4H but can be as short as Q2H

What phenomenon do we have to take into consideration and make allowances for when using equianalgesic dose conversions?

1.  What % of new opioid do you use when completing equianalgesic dose conversion for pt with GOOD pain control?

What is the exception?

2.  What about POOR pain control?

1.  50-75% of calculated dose

Methadone is exception:  higher than expected potency during chronic dosing compared with published equianalgesic doses for acute dosing

2.  75-100% of calculated dose

1.  Pts who don't have the cognitive ability to understand how to use the PCA device

2.  Pts who physically cannot use the device

3.  Anticipated need for opioids is less than 24 hrs

4.   Hx of substance abuse

5.  Pt chooses not to be responsible for analgesia administration

1.  Drug and con'c

2.  Route

3.  Loading dose

4.  Demand or PCA dose (mg)

5.  Basal or Continuous Rate (mg/hr)

6.  Demand Dose Lockout or Delay (min)

7.  1 or 4 hr dose limit

PCA Pearls

1.  Titration:  What is target pain score at rest or with activity

2.  How many successful demand doses per hour is target?

3.  What has good correlation with pain control and what is poorly correlated?

1.  Rest:  <3/10; Activity:  <5/10

2.  2-3

3.  Correlates with gender and age, not with height and weight

1.  >100,000 hospitalizations

2.  >15,000 deaths

Low:  < 60 YO

Moderate:  60-64 YO

High:  > 65 YO

High:  < 1 month

Moderate:  1-3 months

Low:  > 3 months

1.  Ibuprofen (<1200 mg/d)

2.  Diclofenac

1.  Piroxicam

2.  Ketoprofen

3.  Ketorlac

1.  Low-dose ASA

2.  Anticoagulants

3.  Corticosteroids

4.  Other NSAIDs

Consensus NSAID Tx Strategies GI Risk Factors 

1.  No risk factors

2.  Low

3.  Moderate (advanced age or 1-2 risk factors)

4.  High, or previous ulcer complications or >2 risk factors

5.  Previous lower GI bleed

1.  Monotherapy with lowest ulcerogenic agent at lowered dose for shortest duration

2.  Mono thearpy with least ulcerogenic nonselective NSAID at lowest dose for shortest duration

3.  Nonselective NSAID + PPI/Misoprostol or COX-2

4.  COX-2 at lowest dose or nonselective with PPI or H. Pylori eradication

5.  COX-2 lowest effective dose

1.  Constipation:  Tx with stimulant and stool softener

2.  N/V

3.  Sedation and/or mental clouding

4.  Agitation, confusion, excessive sedation, hallucinations, myoclonus, nightmares, seizures

1.  Do pts often become tolerant to opioid-induced constipation?

2.  What drugs are good/bad

1.  No, tolerance is rare so must manage proactively

2.  Stimlant (senna, bisacodyl) +/- stool softener

Avoid bulk-forming

Encourage proper hydration

1.  Too much opioid

2.  Toxic metabolite build-up

1.  Sedating so may be good with insomina pts

2.  Can exacerbate cognitive problems in elderly

3.  Almost entirely renally excreted so must monitor renal function

4.  Titration may require 3-8 wks

1.  Patch not desirable for face and should NEVER be used on nonintact skin

2.  Use caution with Class I antiarrhythmic drugs (tocainide and mexiletine) although titration not necessary

1.  DDIs with SSRI or MAOIs (Serotonin syncrome)

2.  Increased risk of seizure with seizure PMH or concurrant:  opioids, TCAs, neuroleptics

3.  Cognitive impairment elderly

4.  Adjust with renal/hepatic dysfunction

5.  Must titrate over 2-7 wks

1.  Elderly cognitive impairment

2.  Hx or CVD, depression, suicidality

3.  DDIs:  antihypertensives (clonidine, guanethidine) and drugs metabolized by 2D6 (cimetidine, phenothiazine, class IC antiarrhytmics) and drugs inhibiting 2D6 (SSRIs)

4.  Titration over 2-6 wks

They may show an improvement of 1.7ish in the numerical pain scale, but their use is very common

**Makes sense to use multiple drugs for neuropathic pain b/c 2-4 drugs may help control pain better

Gabapentin

1.  Starting dose

2.  Titration

3.  Max

4.  Duration for adequate trial

1.  100-300 mg QHS or 100-300 mg TID

2.  Inc by 100-300 mg TID every 1-7 days as tolerated

3.  3600 mg/; reduce if low CrCl

4.  3-8 wks plus 1-2 wks at max tolerated dose

5% Lidocaine

1.  Beginning Dose

2.  Titration

3.  Max

4.  Duration for adequate trail

1.  Max 3 patched daily for max of 12 hr

2.  None needed

3.  Max 3 patches daily for max of 12 hr

4.  2 wks

Opioid analgesics (morphine sulfate is reference)

1.  Beginning dose

2.  Titration

3.  Max dose

4.  Duration of adequate trial

1.  5-15 mg Q4H PRN

2.  AFter 1-2 wks covert total daily doseto long-acting and continue short acting PRN

3.  No max with careful titraation but consult pain specialist for 120-180 mg/d

4. 4-6 wks

Tramadol HCl

1.  Beginning dose

2.  Titration

3.  Max dose

4.  Duration of adquate trial

1.  50 mg daily or BID

2.  Inc by 50-100 mg/d in divided doses every 3-7 days as tolerated

3.  400 mg/d; if older than 75, 300 mg/d divided

4.  4 wks

TCAs

1.  Beginning Dose

2.  Titration

3.  Max dose

4.  Duration of adequate trial

1.  10-25 mg QHS

2.  Inc by 10-25 mg/d every 3-7 d as tolerated

3.  75-150 mg/d; if blood level of drug and active metabolite < 100 ng/mL, titrate with caution

4.  6-8 wks; 1-2 wks at max tolerated dose

1.  How many annual deaths does substance abuse account for annually?

2.  What is the most likely source of painkillers for those who abuse?

1.  ~15,000

2.  Obtained free from friend or relative

1.  Prevention

2.  Education

3.  Assistence

Narcotic

1.  Historical use

2.  Modern use

1.  Used to describe opium and its derivatives

2.  Legal term encompassing wide range of sedating and potentially abused substances, no longer limited to opioid analgesics

1.  Define addiction

2.  In the context of opioid use it means

1.  Compulsive use of a substance resulting in physical, psychological, or social harm to the user

AND

continued use despite of that harm

2.  Dysfunctional opioid use that may involve:  adverse consequences associated with the use of opioids:  loss of control over use, preoccupation with obtaining opioids despite the presence of adequate analgesia

Physiological phenomenon characterized by:  abstinence/withdrawal syndrome upon:  

1)  Abrupt discontinuation

2)  Substantial dose reduction

3)  Administration of an antagonist

*Can occur with steroids

1.  Define tolerance

2.  What are the types of tolerance?

3.  When is tolerance desirable?

4.  Does tolerance drive dose escalation?

5.  Does tolerance cause addiction?

1.  Form of neuroadaptation to the effects of chronically administered opioids which is indicated by the need for increasing or more frequent doses of the medicaiton to achieve the intial effects of hte drug.  Tolerance is variable in occurrence, but it does not, in and of itself, imply addiction

2.  Varied types:  associative vs pharmacologic

3.  When it is to a S/E

4.  Rarely "drives" dose escalation

5.  Tolerance does not cause addiction

1.  Analgesia:  may occur in first days to weeks of therapy; rare after pain relief achieved with consistent dosing w/o increasing or new pathology

2.  Respiratory Depression/Sedation:  occurs predictably after 5-7 days of consistant opioid administration

3.  Constipation:  dose not occur, must give scheduled stimulant laxatives with opioids

1.  Define pseudo-addiction

2.  How is it relieved?

1.  Pts who have severe, unrelieved pain may become intensely focused on finding relief for their pain.  They can become preocupied with obtaining opioids, but the preoccupation is based on pain relief, rather than opioids, per se.  Pts actually have appropriate drug seeking behavior to relieve their pain

2.  Improved analgesia 

1.  Define pseudo-tolerance

2.  What variables can cause pseudo-tolerance (8)

1.  Situation where opioid dose escalation occurs and appears consistent with pharmacological tolerance.  However, following careful assessment this is better attributed to other variables such as disease progression, new pathology, increased or excessive physical activity

2.  Progressive disease; new pathology; excessive activity; noncompliance; medication changes; drug interactions; drug diversion; addiction

1.  Pt advocacy

2.  ID use of unreported substances

3.  Uncover traffickign or diversion of opioids

4.  Confirm pt using prescribed medication

1.  New  pt to a practice already prescribed a controlled substance

2.  Pt resistant to evaluation of have incomplete Hx

3.  Pt requesting a specific drug

4.  Pt who display aberrant behavior

1.  Considering initiating therapy with a controlled substance

2.  Making substantive changes to a regimen

3.  Support referral when indicated

4.  At random as part of a pt care treatment agreement (pain contract)

1.  Marijuana

2.  Cocaine

3.  Opiates

4.  Phencyclidine

5.  Amphetamine

Opiate Screens and UDT...

1.  What can be detected?

2.  What is rarely detected?

3.  What is never detected by opiate UDT?

1.  Natural opioids:  codeine and morphine

2.  Semi-synthetic agents:  oxycodone

3.  Methadone, must do specific assay to detect

1.  FQNs

2.  Poppy seeds

*Heroin is confirmed with 6-monoacetylmorphine which is a unique heroine metabolite over poppy seeds

1.  Not actually using medication

2.  Timing of last dose in relationship to UDT

3.  Rapid excreter or metabolizer

4.  pH of urine

5.  UDT not sensitive or specific

6.  Clerical errors caused positive UDT to be reported as negative

Risk of addiction

1.  Acute pain

2.  Cancer pain

3.  Chronic, noncancer pain

1.  Very unlikely

2.  Very unlikely

3.  Addiction rare if no Hx of addiction, mixed if Hx of addiction

Chronic Opioids and Substance Abuse Hx as it relates to pt risk

1.  What 3 things have good outcomes

2.  What 3 tend to be poor outcomes in relation to addiction potential

1.  Primarily alcohol abuse; Good family support; Membership in AA or similar group

2.  Polysubstance abuse; poor family support; no membership in suppot groups

*VA study:  good pain relief with appropriate therapy and only 5% abuse rate

1.  Pain relief

2.  Function:  physical and psychosocial

3.  S/E

4.  Drug-related behaviors

1. Selling prescription drugs

2.  Prescription forgery

3.  Stealing or borrowing another pts drugs

4.  Injecting oral formualtion

5.  Obtaining prescription drugs from nonmedical sources

6.  Concurrent abuse of related illicit drugs

7.  Multiple unsanctioned dose escalations

8.  Recurrent prescritpion losses

1.  Aggressive complaining about need for higher doses

2.  Drug hoarding during periods of reduced symptoms

3.  Requesting specific drugs

4.  Acquisition of similar drugs from other medical sources

5.  Unsanctioned dose escalation 1-2 times

6.  Unapproved use of drug to treat another symptom

7.  Reporting psychic effects not intended by the clinician

1.  Addiction vs pseudo-addiciton vs pseudo-tolerance

2.  Psychiatric disorders (personality disorders)

3.  Cognitive disorders

4.  Family issues

5.  Criminal intent

1.  Frequent visits and small quantities

2.  NO replacement or early scripts

3.  Long-acting drugs with no rescue doses

4.  Use of random UDTs

5.  Coordination with sponsor, program, psychotherapist

6.  Consultation with addiciton medicine specailist

7.  Prescription Drug Monitoring Program (PDMP)

8.  Medication agreements

Opioid Abuse Deterrant 

1.  Talwin NX

2.  Lomotil

3.  Partial and Mixed agonist-antagonists (what do they have)

4.  Fentanyl

5.  Subutex and Suboxone

1.  Pentazocine and naloxone

2.  Diphenoxylate and atropine

3.  Ceiling effects

4.  Transdermal?

5.  Buprenorphine +/- naloxone

1.  Antagonists, prodrugs (morphine w/ naltrexone)

2.  Aversion agents (taste/emetics)

3.  Novel dosage forms (Oxycontin)

4.  New packaging/delivery concepts (REMS)

Why is the following statement false:

Dependence and Tolerance Indicate Risk of Addiction

1.  Tolerance to analgesia is uncommon

2.  Dependence is universal after 5-7 days of regularly scheduled opioids and pts can be tapered off opioids in 5-10 days

Why is the following statement false:

Tolerance to opioids occurs predictably

Why is the following statement false:

If used early in progressive disease, opioids may not work later.

No ceiling effect for mu opioids

Tolerance to analgesia rare in chronic, stable pain

Why is the following statement false:

All pain is opioid-responsive

1.  Most nociceptive pain is opioid responsive

2.  Some chronic pain is not:  

Stressor pain

Somatization disorder pain

Learned pain behavior

3.  Cannot treat consipation pain with opioids

Why is the following statement false: 

Pts who demand increasing opioid doses are tolerant or addicted

1.  May just be under treated

2.  May be pseudo-addiction:  such pts are angry and hostile

*Trial 50% dose increase to determine analgesic effect

3.  May be pseudo-tolerance

Why is the following statement false:

Morphine is the most potent opioid

Equivalent mu opioid doses are equianalgesic

*however, duration may vary and time to onset

Tolerance is not the same as activity

Can be influenced by pt belief

NIDA Substance Abuse Screen

1.  Covers what drugs

2.  What do you do if pt has no hx of use

3.  What are 3 risk levels

1.  Cannabis, cocaine, opioids, methamphetamine

2.  Reinforce continued abstinence

3.  Lower/Moderate/High

HTN, tachycardia, tremors, seizures, irritabiliyt

*Long-term:  psychosis

1.  Intensifies the high

2.  Leads to more bizarre, erratic, or violent behavior

3.  May experience tremors, vertigo, muscle twiches, or paranoia

1.  Considerable tolerance to effects of cocaine

2.  Users try to get previously level of pleasure, thereby requiring them to increase use

1.  Users can become sensitized to anesthetic and convulsant effects with repeated use

2.  This can lead to death with a low dose

1.  Cocaine blocks dopamine reuptake

2.  Meth blocks dopamine reuptake, and causes dumping of dopamine from nerve terminals

*Cahnges CNS by damaging nerve terminals and reducing motor speed

**Decreased verbal learning

***Long-term changes in brain associated with emotion and memory disturbances

1.  Modafanila nd topiramate

2.  Baclofen