Aspirin, Nsaids, Acetaminophen, Local Anes,cyp450

Front 1

4 therapeutic uses for aspirin

Back 1

analgesic, antipyretic, anti-inflammatory, anti-thrombotic

Front 2

Difference between half life of salicylic acid and acetylsalicylic acid? (aspirin)

Back 2

Salicylic acid: half life = hours
Aspirin: half life = 20-30 minutes

Front 3

What's the basic rxn by which aspirin is inactivated?

Back 3

ASA + HOH --> SA + acetic acid

Hydrolysis/ Deactylation

Front 4

t/f ASA acetylates some proteins, but SA does not, therefore no platelet effect

Back 4

T

Front 5

How does the pH of urine affect aspirin excretion?

Back 5

It is a weak acid, so less will be reabsorbed after filtration in ionized state. Can excrete MUCH MORE with basic urine

Front 6

Basic mechanism for production of anti-inflammatory activity

Back 6

likely due to ASA's acetylation of cyclooxygenase, the enzyme necessary for the synthesis of prostaglandins (PGs) and thromboxanes.; at high doses also inhibits induction of NFκB, a pro-inflammatory molecule

Front 7

T/F Aspirin but NOT SA inhibits induction of NFκB (a pro-inflammatory molecule)

Back 7

F. ASA and SA both do this

Front 8

Basic mechanism for production of anti-pyretic activity

Back 8

1) resetting hypothalamic temp. reg. center
2) competing with pyrogens for receptor sites
3) inhibition of synthesis of pyrogenic prostaglandins

Front 9

Basic mechanism for production of analgesic activity

Back 9

Central: via SA(?)
Peripheral:May include inhibition of PGs which sensitize pain receptors to cause hyperalgesia

Front 10

Basic mechanism for production of anti-thrombotic activity

Back 10

Decreases platelet aggregability, inactivates platelet cyclooxygenase to prevent formation of thromboxane

Front 11

T/F Aspirin's Antiplatelet Effect Is Antagonized by Ibuprofen

Back 11

T

Front 12

Metabolic effects of low dose ASA

Back 12

Uncouple OX-PHOS leading to incr O2 use, incr CO2 production, therefore <b>increased ventilation depth</b>.

Front 13

Metabolic effects of high dose ASA

Back 13

Metabolic acidosis due to decreased renal function, increased production of organic acids, and salicylic acid itself

Front 14

Most predominant side effect of salicyclates

Back 14

GI upset (epigastric distress). ASA can cause gastric ulcers due to decreased formation of cytoprotective PGs

Front 15

What is Reye's syndrome?

Back 15

sudden (acute) brain damage (encephalopathy) and liver function problems. can occur when aspirin is given to chidlren with viral illnesses

Front 16

Salicylism: defn

Back 16

Mild, CHRONIC salicylate intoxication. Headache, dizziness, hearing problems, mental confusion, lassitude, drowsiness, sweating, thirst, hyperventilation, nausea, vomiting and occasionally diarrhea.

These symptoms subside upon stopping or lowering salicylate dose.

Front 17

Aspirin hypersensitivity

Back 17

Treat with epinephrine, Uncommon but can be severe/fatal.

Front 18

Diflunisal: what is it used for and what is it?

Back 18

Derivative of SA(another salicylate). Used for sprains, arthritis. NO ANTIPYRETIC EFFECTS, less GI upset

Front 19

Sulfasalazine:what is it used for and what is it?

Back 19

antimicrobial, used for ulcerative colitis and regional enteritis. 

sulfapyridine, an active sulfonamide, and 5-aminosalicylate, which is thought to be the effective anti-inflammatory agent when used to treat inflammatory bowel disease.

Front 20

How do NSAIDS differ from aspirin in mechanism?

Back 20

They reversibly inhibit COX1 and COX 2 (aspirin is permanent)

Front 21

How do NSAIDS differ from aspirin in function?

Back 21

1. produce fewer or more side effects,
2. have greater tissue distribution,
3. be more potent and
4. have a longer duration.

Front 22

T/F Individuals who are allergic to aspirin will be allergic to other NSAIDs that inhibit cyclooxygenase.

Back 22

T

Front 23

NSAIDs can decrease GFR in those with what 3 conditinos?

Back 23

renal failure, congestive heart disease or cirrhosis of the liver.

Front 24

NSAIDs can produce interstitial nephritis in what population?

Back 24

a small %age who are hypersensitive

Front 25

How can NSAIDs complicate antihypertensive therapy?

Back 25

They can decrease renal functino and excretion (lead to excess fluid), which tends to increase BP

Front 26

Additional concerns for NSAID use in the elderly

Back 26

1) Fluid retention - may exacerbate heart disease
2) Higher rate of GI bleeding
3) Can quickly develop impaired renal fxn from NSAIDS

Front 27

What are the indoles?

Back 27

indoleacetic acid derivatives.

Include indomethacin, sulindac, diclofenac.

Front 28

Major side effects of the indomethacin

Back 28

GI bleeding and ulceration; frontal headaches

Front 29

Why does sulindac have duration of action longer than expected from half-life?

Back 29

Accumulates in synovial fluid

Front 30

In what conditions is diclofenac used?

Back 30

RA, osteoarthritis, anklyosing spondylitis

Front 31

What are the Propionic Acid Derivatives?

Back 31

Naproxen, ibuprofen

Front 32

Which are more potent, Propionic Acid Derivatives or indoles?

Back 32

indoles

Front 33

What are the oxicams?

Back 33

Piroxicam

Front 34

Naproxen absorption decreased by _____.

Back 34

NaHCO3, by Al(OH)3 and antacids.

Front 35

WHat type of drug is ketorolac?

Back 35

Cox inhibitor with strong analgesic props. Can replace morphine/opioids. NOT for chronic pain. ACute pain only

Front 36

Side effects of ketorolac?

Back 36

Excessive bleeding, renal failure. Do not use longer than 24-48 hours, and definitely not longer than2 weeks

Front 37

How is celecoxib different from other NSAIDS?

Back 37

Cox2 selective inhibitor. less GI ulcers and little/no effect on bleeding time

Front 38

T/F Acetaminophen is a cox inhibitor

Back 38

F

Front 39

T/F Acetaminophen is anti-inflammatory and anti-thrombotic

Back 39

F

Front 40

T/F Acetaminophen is equal to aspirin in analgesic and antipyretic properties

Back 40

T

Front 41

_______ is chemically related to acetaminophen and once prevalent in many OTC agents. Its use is no longer advised since ______is believed to cause analgesic nephropathy.

Back 41

phenacetin

Front 42

What drug causes analgesic nephropathy?

Back 42

phenacetin

Front 43

80% of acetaminophen is excreted in urine after liver conjugation with what?

Back 43

glucuronic acid

Front 44

an oxygen free radical scavenger and promotes formation of glutathione. Glutathione promotes detoxification and elimination of P450 metabolite

Back 44

N acetylcysteine

Front 45

How does drinking alcohol affect acetaminophen metabolism?

Back 45

Drinking may lower threshold for damage because it induces enzymes that catalyze oxidative metabolism of acetaminophen and thus may more readily form the toxic metabolite. People who drink more may have less glutathione

Front 46

Acetaminophen normally (not in overdose) is metabolized to what?

Back 46

Glucuronide or sulfate metabolite

Front 47

Acetaminophen in overdose is metabolized to what?

Back 47

Metabolized by P450 mixed fxn oxidase; a toxic intermediate that bonds covalently to hepatic protein

Front 48

Acetaminophen in overdose but after administration of N-acetyl cysteine, is metabolized to what?

Back 48

Glutathione intermediate --> mercapturic acid

Front 49

drug class that block conduction when applied locally to tissue

Back 49

local anesthetics

Front 50

What are the 3 parts of a local anesthetic?

Back 50

1) Lipophilic
2) Ester/amide linkage
3) Hydrophilic end

Front 51

Part of the anesthetic that allows it to pass to site of action. Determinant of intrinsic anesthetic potency.

Back 51

Lipophilic part

Front 52

What part of local anesthetic determines the route of metabolism, hypersensitivity rxns, and chemical stability of the compound?

Back 52

Ester/amide linkage

Front 53

Would an ester or amide linkage be expected to have longer duration of action ?Why?

Back 53

Amide linkage. This is because esters are metabolized by esterases in the PLASMA, and amidases are in the liver, so the drug will have to stay around long enough to get to liver.

Front 54

When someone has a hypersensitivity reaction, they're reacting to (amide or ester) linkage

Back 54

ester. (PABA can be formed)

Front 55

Local anesthetics block ____ potential without affecting _____ potential

Back 55

action ; resting

Front 56

Sites/Mechanisms by which compounds can produce anesthetic effect (3)

Back 56

1) Bind to receptor at surface of membrane, blocking nerve conduction (less important bc too toxic)
2) Within the axonal membrane
3) At a receptor associated with Na+ channel on the interior surface of the membrane

Front 57

What is most important site of action for local anesthetics?

Back 57

Action at the internal membrane receptor.

Front 58

In order to bind to internal membrane receptor, anesthetic must be in ___________ form but to get into site of action it must be __________

Back 58

ionized; non-ionized

Front 59

How is action of local anesthetics frequency dependent?

Back 59

They bind more tightly and can get better access to internal Na+ membrane receptor in the inactivated (ie, following channel opening) state than in the resting state.

Therefore, the most active neurons are the ones blocked the fastest.

Front 60

A)Drugs with a pKa closer to ________ will have more rapid onset of action.

B)Why?

Back 60

A) Physiological pH

B) Because more will be in unprotonated form

Front 61

Local Anesthetics: Effect of Fiber Diameter

Back 61

Smaller fibers anesthetized faster

Front 62

Local Anesthetics: Effect of Myelination.

Back 62

Myelinated nerves blocked before unmyelinated (of the same diameter).

This is because myelinated fibers have fewer Na+ channels

Front 63

Nerves on (outside,inside) of a nerve bundle are blocked before those on (outside,inside)

Back 63

Outside;inside

Front 64

What are first kind of neurons to be inactivated?

Back 64

Autonomic (smallest myelinated), then pain (smallest unmyelinated)

Front 65

Major cause of systemic toxicity is high blood concentration of local anesthetics. How to prevent?

Back 65

1) Use smallest amount needed
2) Include a vasoconstrictor (like EPI) to keep it out of neighboring tissues as much as possible
3) Remember topical use isn't necessary "safer" as it can lead to high blood levels too

Front 66

CNS toxicity of local anesthetics

Back 66

Stage of stimulation then depression. Death is usually from respiratory depression, a central effect.

Front 67

CV toxicity of local anesthetics

Back 67

1) Central depression
2) Direct vasodilation
3) Direct depressant effect on heart

All these result in profound hypotension

Front 68

Cocaine: properties as local anesthetic

Back 68

Only local that doesn't require vasoconstrictor to be added because it also acts as a vasoconstrictor due to catecholamine reuptake inhibition.

Front 69

Short-acting, esteratic local anesthetic (produces PABA) and can be associated with hypersensitivity

Back 69

Procaine (aka novocaine)

Front 70

Intermediate acting amide local anesthetic with high intrinsic vasodilation activity (used with EPI), rapid onset of action.

Back 70

Lidocaine

Front 71

Long acting amide local anesthetic. Racemic mix

Back 71

Bupivacaine

Front 72

S-enantiomer of bupivicane, Long acting amide local anesthetic.

Back 72

Levobupivicane

Front 73

Less cardiotoxic than bupivacaine, but less potent. Long acting local anesthetic. Mainly used for epidural anesthesia.

Back 73

Ropivacaine

Front 74

What is EMLA?

Back 74

Eutectic Mix of Local Anesthetics. A combo of equal portions lidocaine and prilocaine that forms oil at room temp. Applied topically 45-60 min prior to a procedure. Especially good for kids.

Front 75

Where is spinal anesthesia injected?

Back 75

Injected into lumbar subarachnoid space below termination of spinal cord.

Front 76

Disadvantages to spinal anesthesia

Back 76

Potential for hypotension (due to sympathetic denervation), respiratory arrest (from hypotension-associated decrease in brain perfusion), neurological complications including headaches

Front 77

Advntages to spinal anesthesia

Back 77

Low probability of systemic toxicity
Less potential for physiological perturbations (due to smaller dose given)

Front 78

Advantage of epidural anesthesia

Back 78

Fewer headaches

Front 79

Disadvantages to epidural anesthesia

Back 79

A larger amount of drug required. Using epinephrine helps avoid problem of systemic uptake

Front 80

Grapefruit: effects

Back 80

Inhibits CYP3A4

Front 81

Tizanidine (&alpha;2 agonist) substrate for ________

Back 81

CYP1A2

Front 82

Fluvoxamine inhibits

Back 82

CYP1A2

Front 83

ciprofloxacin inhibits

Back 83

CYP1A2

Front 84

metronidazole inhibits

Back 84

CYP2C9

Front 85

Tizanidine should not be given with _________ or ___________

Back 85

ciprofloxacin; fluvoxamine (all inhibit CYP1A2)

Front 86

Metronidazole should not be given with ____________

Back 86

trimethoprim-sulfamethoxazole (bactrim)

Front 87

trimethoprim-sulfamethoxazole (bactrim) inhibits __________

Back 87

CYP2C9

Front 88

Absent in 15-30% of Asians and 3-5% of
Caucasians

Back 88

CYP2C19

Front 89

Absent in ~ 1% of Caucasians and African-Americans

Back 89

CYP2C9

Front 90

Absent in ~ 7% of Caucasians, 1-2% non-Caucasians

Back 90

CYP2D6

Front 91

30% of East Africans have multiple copies

Back 91

CYP2D6

Front 92

Large phenotypic variability in which CYP?

Back 92

CYP2D6 - range from ultra-fast to poor metabolizers

Front 93

Metabolizes S-warfarin

Back 93

CYP2C9

Front 94

Metabolizes R-warfarin

Back 94

CYP1A2, 3A4

Front 95

Codeine metabolized by _____ to morphine?

Back 95

CYP2D6

Front 96

Inhibitors of this enzyme include cimedtidine and fluvoxamine

Back 96

CYP1A2

Front 97

Inhibitors of this enzyme include metronidazole, trimethoprim-sulfamethoxazole

Back 97

2C9

Front 98

Inhibitors of this enzyme include Grapefruit, ritonavir

Back 98

3A4

Front 99

Inducers of this enzyme include alcohol

Back 99

CYP2E1

Front 100

Carbamazepine induces which enzymes?

Back 100

1A2, 2C9, 2C19, 3A4

Front 101

Substrates of this enzyme include tizanidine and r-warfarin

Back 101

1A2

Front 102

Substrates of this enzyme include acetaminophen

Back 102

2E1

Front 103

Substrates of this enzyme include omeprazole, clopidogrel

Back 103

2C19

Front 104

Substrates of this enzyme include CCBs, statins, and amiodarone

Back 104

3A4

Front 105

CYP3A4
A) Inhibitors
B) Inducers
C) Substrates

Back 105

A) Grapefruit, ritonavir
B) Carbamazepine
C) CCBs, Statins, Amiodarone

Front 106

CYP2C19
A) Inhibitors
B) Inducers
C) Substrates

Back 106

A) (don't need to know)
B) Carbamazepine
C) Omeprazole, Clopidogrel (plavix)

Front 107

CYP2C9
A) Inhibitors
B) Inducers
C) Substrates

Back 107

A) Metronidazole, Trimethoprim/sulfameth.
B) Carbamazepine
C) Warfarin

Front 108

CYP1A2
A) Inhibitors
B) Inducers
C) Substrates

Back 108

A) Cimetidine, Fluvoxamine
B) Carbamazepine
C) Tizanidine

Front 109

Simvastatin and amiodarone: what kind of interaction?

Back 109

Both are CYP3A4 substrates

Front 110

Carbamazepine can cause (increased, decreased) levels of warfarin.

Back 110

Decreased, This is because carbamazepine induces 3A4, 2C9, and 1A2, all of which warfarin is substrate.