Pharm Test 2 Spring 09

Front 1

these agents inhibit cyclooxygenases (COX), enzymes responsible for formation of prostaglandins (PGs), prostacyclin, and thromboxane from arachidonic acid (see Prostaglandin lecture).

Back 1

NSAIDS

Front 2

Celecoxib

Back 2

Non-steroidal
antiinflammatory
Cyclooxygenase 2 inhibitor

Front 3

Acetaminophen

Back 3

Non-steroidal
antiinflammatory
Cyclooxygenase inhibitor

Front 4

Indomethacin

Back 4

Non-steroidal
antiinflammatory
Cyclooxygenase inhibitor

Front 5

Nambumetone

Back 5

Non-steroidal
antiinflammatory
Cyclooxygenase inhibitor

Front 6

ubiquitous expression produces PGs that protect the stomach from gastric acid, and mediates production of TXA2 in platelets.

Back 6

cox 1

Front 7

is induced in inflammation by cytokines (induction is blocked by corticosteroids). Cox-2 also protects renal blood flow and cardiac blood flow. PGs are released by the kidney in response to reduced blood flow and protect the kidneys during hypovolemia or in the presence of pressors. Cox-2 selective agents are currently under fire for increased risk of myocardial infarctions.

Back 7

cox 2

Front 8

3 uses of NSAIDS

Back 8

1. Analgesic-these agents reduce mild to moderate pain peripherally by blocking synthesis of prostaglandins that potentiate pain transduction in nociceptive neurons by activating dormant nociceptors or increasing nocicepter sensitivity. NSAIDS are especially useful if inflammation is a significant component of pain.
2. Antipyretic-PGE1 acts on the hypothalamus and results in increase in the set point of body temperature. NOTE: fever is not the same as hyperthermia!

a. Fever: produced by a pyrogen-infectious process
• Lipopolysaccharide triggers release of IL-1, IL-6 and tumor necrosis factor (TNF).
• Prostaglandins released and travel to hypothalamus to increase body temp.
• Fever is a regulated rise in temperature-the thermostat is set higher, but temp is still regulated-increase outside heat and body will work to cool to the new higher set point.
• Antipyrogens work to reduce fever by blocking prostaglandin synthesis.

b. Hyperthermia: no pyrogen, not regulated by prostaglandins
• No thermoregulation
• Drug-induced-malignant hyperthermia - Serotonin syndrome
• Antipyretics have no effect-use tepid water sponging or bath

3. Anti-inflammatory [Not shared by acetaminophen]
Higher doses required than for analgesic or antipyretic effects.

Front 9

kin of NSAIDS

Back 9

1. Highly bound to plasma proteins: DISPLACEMENT INTERACTION could temporarily enhance potency of other protein-bound drugs (important with drugs with small Vd, narrow therapeutic index and rapid onset of action, e.g. warfarin).

2. Excreted via proximal organic acid pump in the kidney.

3. Potential for GI toxicity, tinnitus, salt and water retention, acute renal insufficiency, headache, rash.

Front 10

SALICYLATE

Back 10

aspirin

Front 11

aspirin works by

Back 11

acetylsalicylic acid or ASA) is rapidly metabolized to salicylic acid

Front 12

aspirin irreversable or reversable?

Back 12

aspirin irreversibly acetylates cycloxygenase

Front 13

asa analgesic

Back 13

used for less severe pain than opioids; no development of tolerance or physical dependence. Blocks production of PGs that sensitize peripheral pain neurons to stimuli.

Front 14

asa antipyuretic

Back 14

eliminates low-grade fevers by preventing production of PGs. (consider that temperatures below 102 °F are generally not considered harmful and allow one to follow the course of the disease)

Front 15

antiinflamatory asa

Back 15

Anti-inflammatory effects: the same individual doses are taken as for analgesia or antipyresis, but chronic ingestion leads to accumulation and higher plasma concentrations owing to zero order kinetics of ASA.

Front 16

what order is asa? 1 or 0

Back 16

o

Front 17

overdose asa

Back 17

HYPERVENTILATE
DEHYDRATE
• Acute: vomiting, abdominal pain, hyperventilation, acid-base disturbances: respiratory alkalosis (any age); metabolic acidosis (usually in infants); respiratory acidosis if really severe-CNS depression and exhaustion, dehydration (sweating, vomiting, hyperventilation), tinnitus, confusion
Note: respiratory alkalosis is protective-increases fraction of drug charged in plasma (can’t cross BBB)
Treatment-charcoal, gastric lavage

Front 18

treat overdose asa

Back 18

bicarb isotonic fluids

Front 19

PARA-AMINOPHENOL DERIVATIVE

Back 19

tylenon acetamenophen

Front 20

is it useful with as an anti-inflammatory agent or antiplatelet

Back 20

no

Front 21

can Opioids and an NSAID act synergistically and are a useful combination but combinations of NSAIDS are not.

Back 21

t..

Front 22

non-selective COX inhibitor-may also inhibit PLA2 - an older drug used to close patent ductus arteriosus (Ibuprofen has replaced this--as effective and less toxic)

Back 22

indomethathin

Front 23

Propionic Acids: considered to have less GI toxicity than salicylates, safer in overdose; those listed below are available OTC and are approved as antipyretics
pediatric prep OTC

Back 23

ibprofin

Front 24

F. Nabumetone:

Back 24

non-acidic prodrug –gentle on stomach-very expensive. Long half-life (24 hours—48 hours in renal compromised patients).

Front 25

G. Cox-2-Specific Agents -expensive! ($1.60/day) Not more effective, but fewer bleeding side effects. Appropriate for patients at high risk of GI or bleeding disorders. MUST BE USED WITH CAUTION due to risk of MI!

Back 25

celecoxib celebrex

Front 26

do DMARDS have analgesic or antipyretic activity. These drugs are generally very toxic!

Back 26

NO

Front 27

immunosupressant-thought to induce release of adenosine that inhibits production of AICAR (5-Aminoimidazole-4-carboxamide ribonucleoside, an activator of AMP-activated protein kinase (AMPK), modulating monocyte function. At higher doses methotrexate blocks DHFR, reducing levels of active foliate affecting DNA synthesis in immune cells. Efficacious with low dropout rate at low doses. Slows progression of the disease. 10-25 mg/week (anti-inflammatory doses) are effective. Nausea and mucosal ulcers are common side effects.

Back 27

methotrexate

Front 28

humanized monoclonal antibody to tumor necrosis factor reduces plasma TNF levels.

Back 28

infliximab

Front 29

a fusion protein composed of the TNF receptor ligand binding domain with IgG Fc.

Back 29

enteracept

Front 30

nucleic acid synthesis inhibitor. Metabolized into 6-mercaptopurine. Metabolism is bimodal in human populations with fast and slow metabolizers. Toxicities include bone marrow suppression and increased risk of infections and malignancies

Back 30

azathiopprine

Front 31

how do tri[tans work

Back 31

serotonin 5-HT1B/1D agonists, known as the triptans, cause vasoconstriction of cerebral vessels and represent a major advance in the treatment of acute migraine.

Front 32

triptan

Back 32

sumatriptan

Front 33

tx migranes with

Back 33

sumatriptan
PROPHYLAXIS - propranolol, amytriptiline, verapamil

Front 34

which is not useful in other types of inflammation, is quite specific for treatment of acute gouty attacks and is thought to decrease neutrophil migration into the joint and to prevent release of a glycoprotein

Back 34

colchicine

Front 35

was originally used to prolong the action of penicillin by decreasing active tubular secretion of the antibiotic
decrease reabsorption at tubulr level

Back 35

probenesid

Front 36

uricosuric agents

Back 36

probenecid

Front 37

xanthine oxidase. This enzyme is inhibited by a metabolite

prevent formation of uric acid

Back 37

allopurinol

Front 38

opium, heroin (dust, H, horse, junk, smack), morphine, methadone, meperidine, codeine,

Back 38

opioids

Front 39

opiiods coming off life threat?

Back 39

no

Early (8 12 hr): rhinorrhea, salivation, lacrimation, yawning/stretching
b. Later: restless sleep (yen), piloerection, mydriasis, anorexia, tremor
c. Peak (48 72 hr): constant movement, insomnia, chills, sweating, gut pain with retching, vomiting
d. Recovery: psychological craving, insomnia, muscle aches, weakness
e. Not life threatening, but very unpleasant

Front 40

alcohol, barbiturates, benzodiazepines, other sedatives

Back 40

cns depressant

Front 41

abstinance syndr of cns depressants life threat?

Back 41

yes

16 hr: increasing restlessness, anxiety, tremor, weakness, nausea, vomiting, cramping
b. 24 hr: too weak to get up, coarse tremor, hyperreflexic, and purposive behavior
c. 2 3 days: peak for short acting drugs; convulsions
d. 4 days: delirium, hallucinations; agitation, hyperthermia exhaustion, cardiovascular collapse
e. Alcohol withdrawal similar but shorter course; hallucinations, seizures within 24 hr, peak in 24 48 hr with confusion, disorientation, delusions and gross tremulousness (DTs)

Front 42

amphetamines, cocaine cafeine, nicotine

Back 42

cns stimulants

Front 43

LSD PCP MDMA mescaline anicholinergics THC

Back 43

hallucinogens

Front 44

gas, touline, nO

Back 44

inhalants

Front 45

abcde drug abuse

Back 45

A – airway
2. B – breathing
3. C – cardiovascular (I.V. fluids maintain blood pressure)
4. D – drugs (i.e., identify cause, initiate drug screen)
5. E – environment (put the patient in a calm non-threatening environment)

Front 46

BBB of morphone codeine heroin

Back 46

> > >

Front 47

classical usage: acute parenteral administration by medical personnel when patient complained of pain. This is BAD because the patient associates drugs with relief of pain and euphoria. Modern usage: PCA (post-op patient-controlled analgesia), or regular dose schedule to block pain before it arises. Also, chronic ingestion by patients with terminal

Back 47

morphine

Front 48

almost always oral, usually mixed with an NSAID.

Back 48

cdeine

Front 49

insoluble in water) + atropine (Lomotil) to decrease abuse

Back 49

antidiarrheal diphenoxylate

Front 50

OTC, poorly absorbed, low abuse potential

Back 50

looperamide