Drugs For Pain And Inflammation

Front 1

What kind of pain are NSAIDS and Acetaminophen used for?

Back 1

Mild-Moderate pain

Front 2

What kind of pain are opioids used for?

Back 2

Moderate - Very severe pain

Front 3

What's the difference between acute and chronic pain?

Back 3

Acute
-Doesn't outlast the noiceptive sitmulus
-Arises from tissue injury/inflammation

Chronic:
-Outlasts initial stimulus

Front 4

Where do opioids act?

Back 4

PAG
C afferent fibers

Front 5

What's released by the Raphe nucleus to mediate pain signals?

Back 5

5HT

Front 6

What is released by mast cells? What's the effect?

Back 6

Histamine

Edema, vasodilation, sensitization, chemotaxis

Front 7

What's released by platelets in the blood? What's the effect?

Back 7

Serotonin

Sensitizes, directly activates noiceptors

Front 8

How is bradykinin formed? What's the effect?

Back 8

Formed by the breakdown of an inactive plasma precursor

Potently produces pain
-Direct noiceptor activation
-Vasodilation
-Edema
-Chemotaxis

Front 9

How are the prostaglandins formed? What is their activity?

Back 9

Compounds formed from long chain fatty acids by COX

-Sensitize noiceptors to histamine, bradykinin
-Facilitate histamine and bradykinin to produce inflammatory injury

Front 10

What is the role of prostaglandings in inflammation?

Back 10

Promote blood flow to the injured tissues-->leukocyte infiltration

Front 11

What prostaglandin has an effect on temperature? What does it do? Where does it do it?

Back 11

E2

Increases in temperature

Hypothalamus

Front 12

What is the activity of corticosteroids in the synthesis of prostagalndins?

Back 12

Blocks the cascade higher up

Stops phospholipase A2

Front 13

PGG2 is the precursor to what types of molecules?

Back 13

Thromboxane
Prostacyclin
Prostaglandins

Front 14

What fatty acid is the precursor to prostaglandins?

Back 14

Aracidonic acid

Front 15

What molecule is the precursor to leukotrienes?

Back 15

HPETE

Front 16

What is the activity of thromboxane?

Back 16

Platelet aggregation

Front 17

What is the activity of prostacyclin/PGI2?

Back 17

Vasodilation
Gastric protection
Inhibition of platelet aggregation

Front 18

What are the activities of prostaglandins?

Back 18

Pain
Inflammation
Vasodilation
Gastric protection

Front 19

What are the different types of COX? How are they expressed?

Back 19

COX-1: constituitive

COX-2: constitutive and inducible

Front 20

What are the functions of COX-1?

Back 20

Housekeeping:
-GI cytoprotection
-Platelet aggregation
-Renal electorlyte homeostasis
-Renal blood flow maintenance
-Gestation, parturition

Front 21

What is the function of constitutive COX2?

Back 21

Renal electrolyte homeostasis
Renal blood flow maintenance

Front 22

What is the function of inducible COX2?

Back 22

Pain
Fever
Inflammation

Front 23

Where do NSAIDs act?

Back 23

They nonselectively irreversibly inhibit the COX enzymes

Front 24

What's the dosing of asprin for pain?

Back 24

325-650 mg orally every 4 hrs

Higher doses doesn't improve pain relief it only causes toxicity.

Front 25

What is the role of asprin in CV disease? What's the dose?

Back 25

Blocks platelet adhesion/aggregation by binding irreversibly to COX enzymes

Front 26

What's the absorption of asprin?

Back 26

Low pKa - absorbed well in stomach, duodenum

Front 27

What happens to asprin whil it's in the blood?

Back 27

Binds to plasma proteins

Rapid hydrolysis to salycilic acid

Then, conjugated to glycine, after which it's excreted.

Front 28

What are the side effects of asprin?

Back 28

GI
Clotting
Reye's syndrome
Hyperuricemia
Asprin toxicity

Front 29

What are the effects of asprin on the GI system?

Back 29

Epigastric distress: nausa, dyspepsia, heartburn
Ulcers (after long-term use)

Front 30

How does asprin cause GI damage?

Back 30

Direct physical irritation combined with the inhibition of the protective effects of COX01.

Front 31

What substance taken with asprin can cause additional GI problems?

Back 31

Alcohol

Front 32

What are ways to handle the GI side effects of asprin?

Back 32

Enteric coated tablets
Use other PG analogs
H2 blockers
PPIs

Front 33

What is the effect of asprin on blood clotting?

Back 33

1 650 mg dose can DOUBLE CLOTTING TIME
-Blocking synthesis of thromboxane A2
-Reduction in synthesis of factor VII-->prolonged prothrombin time
-Displacement of anticoagulents (warfarin) from plasma protein binding sites

Front 34

What is Reye's syndrome? When does it happen, and who does it happen to?

Back 34

A fatal syndrome associated with many internal organs
-Liver
-Brain

If you don't get this early, the kids' going to die!

It's caused when a kid takes asprin when he has a viral illness

Front 35

What's the effect of asprin on urate excretion?

Back 35

It depends!
Low doses (2-3 g/day) decreases urate elimination
High doses (3-5 g/day) increases urate elimination

Front 36

What is the impact of asprin on pregnancy?

Back 36

1st trimester: low, but finite risk

3rd trimester: delayed, prolonged labor, increased bleeding at birth, premature closure of fetal shunt

Front 37

What are contraindications to aspirin?

Back 37

Gastric ulcers
Asthma
DM
Gout
Flu - kids
Hypocoagulation states
Pregnancy

Front 38

What are the DDIs of asprin?

Back 38

Warfarin
Methotrexate
Lithium
ACEis
SSRIs
BOOZE

Many others!

Front 39

What are the side effects of aspirin toxicity?

Back 39

Tinitus
Headaches
Dizzines
Paresthesias
Nausa/vomiting
Blurred vision
HYPERVENTILATILN (too much CO2 going out-->respiratory alkalosis)

Front 40

How much aspirin is necessary for a lethal dose in adults? Kids?

Back 40

Adults: 10-30 g
Kids: 5-8 g

Front 41

What are the stages of aspirin toxicity?

Back 41

Stage 1: ventilatory stimulation; decreased arterial pCO2 (respiratory alkalosis)
Stage 2: increased renal HCO3 excretion (compensated respiratory alkalosis)
Stage 3: Respiratory acidosis + metabolic acidosis
Stage 4: fever, acidotisc, dehydrated, ventilatory collapse-->death

Front 42

What's the treatment of aspirin poisoning?

Back 42

NO ANTIDOTE!
Reduce absorption
Decrease temperature by physical means
Replace base, electrolytes, base
Maintain urine output

Front 43

What are some of the other types of NSAIDs?

Back 43

Proprionic acids (ibuproen, naproxen)
Indoles (indomethacin, etodolac)
Fenamates (diclofenac, mefenamic acid)
Pyrroles (ketorolac)

Front 44

What type of an NSAID is naproxen?

Back 44

Proprionic acid

Front 45

What's the dosing of naproxen?

Back 45

500 mg initially, then 250 mg every 6-8 hrs.

Don't exceed 1375 mg initially, 1100 thereafter

Front 46

What type fo naproxen is given for rapid absorption?

Back 46

Sodium salt

Front 47

What is the dosing of ibuprofen?

Back 47

1200-3200 mg daily

Front 48

What are the uses of ketorolac?

Back 48

Severe pain!

Front 49

How do you administer ketoralac?

Back 49

IM first, then use oral as a continuation

Front 50

What's the dosing of ketoralac?

Back 50

20 mg PO (less in older, renally impaired)

10 mg q4-6 hrs.

Max: 40 mg/day

Front 51

What specific population shouldn't get ketoralac?

Back 51

KIDS

Front 52

What are some of the specific COX-2 inhibitors?

Back 52

Celecoxib
Refecoxib

Front 53

What are hte uses of acetaminophen?

Back 53

Analgesic
Antipyretic

Front 54

Is acetaminophen an antiinflammtory drug?

Back 54

NO!

It's not an NSAID!

Front 55

What's the dosing of acetaminophen?

Back 55

325-1000 mg every 4-6 hrs.

MAX 4 g/day

Front 56

How/where is acetaminophen absorbed?

Back 56

Rapidly absorbed from the GI tract.

Front 57

What complications from NSAIDS AREN'T found in acetaminophen use?

Back 57

Reye's
Uric acid secretion
Asthma contraindication
GI irritation
Platelet activity

Front 58

What's the mechanism of acetamiophen?

Back 58

We don't know!

It doesn't inhibit COX-1 or COX-2.

Front 59

What are the side effects of acetamionphen?

Back 59

Hepatotoxicity!!

Front 60

What are the stages of hepatotoxicity from hepatotoxicity?

Back 60

1st 24 hrs:
-Anorexia
-Nausea/vomiting
-Relief at the end of the 1st day!!!!

24-48 hrs.
-Continued formation of hepatotoxic metabolite: enzymre release, bleeding, pain, hypoglycemia
-Irreversible!

3rd-5th day:
Full blown liver failure

Front 61

What are some signs of liver failure?

Back 61

Vomiting
Jaundice
AST, ALT, bilirubin, INRpeak
Hemorrhage
Hypoglycemic coma

Front 62

How much acetaminophen is needed to cause hepatotoxiciyt?

Back 62

10-15 g causes liver damage

20-25 g is fatal

Front 63

How do most cases of acetaminophen overdose happen?

Back 63

UNINTENTIONALLY!!
-Lots of things have acetaminophen in it!
-People take more than the recommended dose

Front 64

How is acetaminophen toxic to the liver?

Back 64

You consume the glutathione (an important detoxifying agent)

As a result a molecule called N-acetyl-benzoquinone reacts with the liver proteins-->cell injury

Front 65

How is acetaminophen conjugated in the liver?

Back 65

Phase 1: N-hydroxylation by P450's-->conjugation by glutathione (main mechanism)

Phase 2: conjugation to give water soluble solutes and glucuronides (minor mechanism)

Front 66

What's the treatment for acetamiophen overdose?

Back 66

Replace the glutathione supply by giving oral N-acetyl-cysteine

Front 67

What are the side effects of giving N-acetyl-cysteine?

Back 67

Rashes
Nausea/vomiting
Diarrhea
Anaphylaxis

Front 68

What's the timeframe for preventing acetaminophen toxicity?

Back 68

WITHIN 36 HOURS OF INGESTION: OTHERWISE THE LIVER IS IRREVERSIBLY DAMAGED!

Front 69

What are contraindications to acetaminmophen use?

Back 69

Liver disease
Alcoholics
Isoniazie

Front 70

What substances can cause hepatotoxicity when used with acetamionophne?

Back 70

Alcohol
Isoniazid

Front 71

What are side effects of systemic corticosteroid use?

Back 71

Renal Na, H2O retention
Hyperglycemia
Ulcerogenic
Suppression of HPA axis
Immunosuppression

Front 72

What disease is methotreate used for?

Back 72

RA

Front 73

What's the mechanism of methotrexate?

Back 73

Decreased proliferation, increased apoptosis of immune cells

Decreased activation of pro-inflammatory cytokines/cells

Front 74

What are the toxicities of methotrexate?

Back 74

Nausea
Mucosl ulcers

Front 75

What is the mechanism of azathioprine?

Back 75

Decreased B and T cell function

Decreased Ig production

Decreased IL-2 secretion

Front 76

What are the side effects of azathioprine?

Back 76

Bone marrow suppression
GI problems
Increased infection risk

Front 77

What is the mechanism of cyclosporine?

Back 77

Decreased IL-2, -2 receptor synthesis

Front 78

What is the side effect of cyclosporine?

Back 78

Nephrotoxicity

Front 79

What is the mechanism of cyclophosphamide?

Back 79

Cross links DNA--> decreased T, B cell function

Front 80

Wht are some of the anti TNF alpha drugs?

Back 80

Adalimumab
Infliximab
Etanercept

Front 81

What is the mechanism of adalimumab?

Back 81

IgG1; anti-TNF antibody

Downstream, downregulates macrophage, T cell function

Front 82

What are the side effects of adalimumab?

Back 82

Increased risks of infection