Term
| Non-specific COX-I and II inhibitors: |
|
Definition
Salicylates
Indole acetic acids
Propionic acid
Anthranilic acid
Phenyl acetate
Pyrazolone
Oxicam |
|
|
Term
|
Definition
Valdecoxib
Celecoxib
Meloxicam
These are moderate COX-II inhibitors, the better ones were taken off the market. |
|
|
Term
| Salicylates aka __ ___ __ aka ___ are non-selective cox I and II inhibitors. |
|
Definition
| Aceytl salicylic acid aka Aspirin |
|
|
Term
| Propionic acids include __, __, __, and __, and are nonselective cox I and II inhibitors. |
|
Definition
- Ibuprofen
- Naproxen
- Ketoprofen
- Ketorolac |
|
|
Term
| acetaminophen may be a __ __ inhibitor. |
|
Definition
|
|
Term
|
Definition
- Aspirin
- Ibuprofen (Advil, Motrin, Nuprin)
- Naproxen (Aleve, Naprosyn)
- Ketoprofen (orudis)
- Indomethacin (Indocin)
- Etodolac (Lodine)
- Ketorolac (Toradol)
- Meloxicam (Mobic) |
|
|
Term
| Selective COX-II inhibitors: |
|
Definition
- Celexocib
(Refocoxib and Valdecoxib withdrawn) |
|
|
Term
| Non-NSAID antipyretic/ non-narcotic analgesic: |
|
Definition
|
|
Term
| NSAIDs major actions (3): |
|
Definition
- Analgesia
- Antipyretic
- Anti-inflammatory
Note: acetominphen (tylenol) does not have antiinflammatory action |
|
|
Term
| All NSAIDs inhibit ___ which inhibits synthesis of ___, which normally leads to inflammatory processes. |
|
Definition
- cyclooxygenase (COX)
- prostaglandins |
|
|
Term
| COX-1 is expressed in __ ___ and is ___ active, meaning they are always working and making prostaglandins. |
|
Definition
- most tissues
- constituitively active |
|
|
Term
| COX-2 is ___ and its products are associated with __. It is induced by cytokines and inflammatory mediators. This enzyme is target of NSAIDs. |
|
Definition
|
|
Term
| Traditional NSAIDs nonselectively inhibit both COX-1 and 2. |
|
Definition
|
|
Term
| Aspirin __ and ___ inhibits COX-1 and 2. |
|
Definition
- covalently and irreversibly
recovery of COX in most tissues is by synthesis of new enzyme.
Platelets cannot synthesize new COX, so inhibition is irreversible.
other NSAIDs produce reversible inhibition of COX. |
|
|
Term
| Celecoxib characteristics: |
|
Definition
- selective for COX-2
- less GI ulcers
- do NOT effect platelets and bleeding time
- originally approved for dysmenorrhea, osteoarthritis, rheumatoid arthritis, and acute post-op pain |
|
|
Term
| Celecoxib contraindications: |
|
Definition
- Aspirin allergy
- 3rd trimester of pregnancy |
|
|
Term
| Rofecoxib (Vioxx) was taken off market b/c increased risk for CV events. Now all NSAIDs have box warning of cardiovascular risk. |
|
Definition
|
|
Term
The COX-2 selective NSAIDs are associated with an increased risk of serious adverse CV events compared to placebo.
Until other data are available – increased risk of serious CV events is a “class effect”, i.e., both selective and non-selective NSAIDs increase risk |
|
Definition
|
|
Term
| Proposed mechanisms for how NSAIDs may cause CV events: |
|
Definition
1. COX-2 inhibition inhibits PGI2 synhesis of vascular endothelium but does not effect prothrombotic platelet thromboxane A2
2. COX inhibition in general is associated with increases in blood pressure |
|
|
Term
| Advantages of NSAIDs over Aspirin: |
|
Definition
NSAIDS are:
- more potent
- more efficacious at tolerated doses
- cause less GI problems and other side effects
- have longer duration so taken less frequently |
|
|
Term
| Disadvantages of NSAIDs compared to Aspirin: |
|
Definition
- new NSAIDs are more expensive than Aspirin
- some NSAIDs more toxic than Aspirin |
|
|
Term
| Normally ___ sensitizes pain nerve endings to bradykinin, histamine, and substance P. ___ blocks __ formation. |
|
Definition
|
|
Term
| NSAIDs are __ analgesics effective against mild to moderate pain. |
|
Definition
|
|
Term
| NSAIDs can be superior to intermediate efficacy opioids for relief of some forms of post-operative pain and pain associated with inflammation. |
|
Definition
|
|
Term
| NSAIDS+opioids provide greater pain relief than intermediate opioids alone |
|
Definition
|
|
Term
| NSAIDs lack opioid effects of (2): |
|
Definition
- respiratory depression
- physical tolerance/dependence |
|
|
Term
| With NSAIDs Pain from integumental structures is relieved but not pain from hollow viscera |
|
Definition
|
|
Term
| Pyrogens from lymphocytes act on the hypothalamus to cause fever. Heat generation (metabolism) increases and heat loss (vasodilation) decreases. ___ that cross the BBB effectively suppress this response. |
|
Definition
|
|
Term
| PGE2 and PGI2 normally important causes of erythema and edema in inflammation. ___ inhibit PG formation. |
|
Definition
|
|
Term
| NSAIDs inhibit activation and function of __ __, may stabilize ___ membranes, and inhibit ___. Corticosteroids are better at this though |
|
Definition
- inflammatory cells
- lysosomal
- phagocytosis |
|
|
Term
| Normally, prostaglandins are responsible for inhibiting __ secretion and stimulating __ and __ secretion in the stomach. They also promote __ blood flow. NSAIDs inhibit all these actions leading to irritation. |
|
Definition
- acid
- bicarbonate and mucus
- mucosal blood flow |
|
|
Term
| GI side effects of NSAIDs: |
|
Definition
- epigastric distress
- nausea
- vomitting
- microhemorrhage
- ulceration
- anemia |
|
|
Term
| Platelets make __ __, a potent ___ and activator of __ __ and release. Endothelial cells make ___ an inhibitor of __ __ and a ___. Low doses of aspirin irreversibly inhibit COX and platelet aggregation for the life of the platelet (8-11 days). |
|
Definition
- thromboxane A2 (TXA2)
- vasoconstrictor and activator of platelet aggregation
- PGI2
- inhibitor of platelet aggregation and a vasodilator |
|
|
Term
| Low doses of aspirin together with diet and exercise is useful for prophylaxis of: |
|
Definition
- coronary artery disease
- deep vein thrombosis
- unstable angina
- MI and stroke |
|
|
Term
| In situations where there are high levels of circulating vasoconstrictors, e.g., compensated congestive heart failure, chronic renal disease, NSAIDs can reduce renal blood flow. |
|
Definition
|
|
Term
| NSAIDs can cause retention of __ and _, which is not good for hypertension patients. |
|
Definition
|
|
Term
| NSAIDs and COX-2 inhibitors should be used with caution in the following groups of patients: |
|
Definition
- reduced renal function
- heart failure
- liver dysfunction
- patients on ACEI or diuretics |
|
|
Term
| Reye's Syndrome is a rare but often fatal consequence of infection with __ __, ___, and ___ viruses. It results in __ __ and ___. The development of this condition is associated with taking __ and __ while having one of these viruses. |
|
Definition
- chicken pox
- varicella
- influenza
- liver damage
- encephalopathy
- aspirin and salicylates |
|
|
Term
| Aspirin and salicylates are contraindicated in children with: |
|
Definition
chicken pox
varicella
influenza |
|
|
Term
| NSAID uses for pain and fever, pain relief of low to moderate intensity: |
|
Definition
Headache
Dysmenorrhea
Arthralgia
Myalgia
Neuralgia
Arthritis |
|
|
Term
| NSAID uses for antiinflammatory acions: |
|
Definition
Rheumatoid Arthritis
Osteoarthritis
Gout and Crystal Arthritis
Systemic Lupus Erythematosus
Seronegative Spondyloarthropathy
Arthralgia
Myalgia
Bursitis, Tendonitis |
|
|
Term
| Aspirin typically not used for chronic treatments, __ or __ are more likely to be used chronically. |
|
Definition
- ibuprofen or naproxen
COX-2 selective agents were preferred for chronic use, but now its controversial |
|
|
Term
NSAIDs suppress the clinical signs in rheumatic disease, but subsequent tissue damage is not halted.
NSAIDs do not induce remission. |
|
Definition
|
|
Term
| With Patent Ductus Arteriosus ___ keeps the ductus arteriosus open after birth. This is treated with the NSAID ___ to stimulate closure. |
|
Definition
|
|
Term
| NSAID used to treat patent ductus arteriosus: |
|
Definition
|
|
Term
| For patients with Familial Adenomatous Polyposis (FAP) ___ inhibitors reduce numbers of polyps. |
|
Definition
COX-2
COX-2 is overexpressed in several human cancers
Increasing evidence suggest that COX-2 inhibitors may be effective for prevention or treatment, especially for colorectal cancer
Large clinical trials have investigated but recent CV risk controversy has halted one large study |
|
|
Term
| patients scheduled for surgery should be taken off aspirin one week prior b/c it will cause prolonged bleeding time due to anti-platelet effect. |
|
Definition
|
|
Term
| Hypersensitivity to Aspirin/NSAIDs; |
|
Definition
asthma, nasal polyps, chronic urticaria predisposed
progresses from hives, nasal secretion and edema to acute asthma attack, severe dyspnea, hypotension, and shock
Hypersensitivity to aspirin is a contraindication to therapy with any NSAID. |
|
|
Term
| Drug-drug interactions of NSAIDs: |
|
Definition
antacids
Protein binding displacement; phenytoin, thyroxine, thiopental
risk of bleeding for patients on anticoagulants
uricosuric effect in gout patients |
|
|
Term
| Salicylism is __ __ of Aspirin/NSAID. Symptoms include: |
|
Definition
- mild intoxication
- nausea
- vomiting
- TINNITUS
- hyperventilaion
- headache
- mental confusion
- dizziness |
|
|
Term
| Overdose with NSAID or aspirin: |
|
Definition
- acute medical emergency
- fever
- dehyrdation
- delirium
- hallucination
- convulsions
- coma
- respiratory and metabolic acidosis
- death
kids very vulnerable |
|
|
Term
| NSAID/aspirin adverse effects in pregnancy: |
|
Definition
Avoid use during third trimester unless absolutely necessary
low birth weight
increased perinatal mortality
anemia
antepartum and postpartum hemorrhage
prolonged gestation
premature closure of ductus arteriosus |
|
|
Term
| ___ is more efficacious than Aspirin, but more toxic so use is limited. NOT used for routine analgesia. Can be used in resistant __ __ and __. Used for __ of __ __ in __ __ and to promote __ of __ __ __. |
|
Definition
- Indomethacin
- rheumatoid arthritis and gout
- suppression of uterine contractions in preterm labor
- promote closure of patent ductus arteriosus |
|
|
Term
| Ketorolac is a potent ___ but weak ___ agent. Can be given orally, IM, or IV. Used for __ __ pain as an alternative to opioids. Unlike opioids it is not associated with respiratory depression, tolerance, or withdrawal effects. |
|
Definition
- analgesic
- weak antiinflammatory agent
- post-op pain
One of only a few NSAIDs that can be given parenterally
not used in obstetrics |
|
|
Term
|
Definition
Selective for COX-2.
Significantly less GI ulcers by endoscopy
No effect on platelets and bleeding time.
But caution with patients on warfarin.
Approved for osteoarthritis and RA.
Menstrual pain and acute post-operative pain
Expensive |
|
|
Term
|
Definition
Non-narcotic analgesic & antipyretic
Very weak anti-inflammatory activity
Thus, not an NSAID; not used for inflammation
equivalent analgesic efficacy to aspirin
used for mild to moderate pain, but aspirin is preferred if due to inflammatory process
Well tolerated, lacks GI and platelet side effects
Useful analgesic, antipyretic for children and those with contraindications to aspirin. Not associated with Reyes syndrome |
|
|
Term
| Acetaminophen is conjugated in the liver to as the inactive glucuronide and sulphate. This forms oxidation products and __. __ is highly reaction and usually inactivated by conjugation with a thiol of glutathione. But in acetaminophen overdose ___ is exhausted so __ causes cell death. |
|
Definition
NABQI
NABQI
glutathione
NABQI |
|
|
Term
| Acetaminophen adverse effects: |
|
Definition
rare in therapeutic usage
occasional skin rash and allergy
Overdose can result in fulminant hepatic necrosis and liver failure |
|
|
Term
Acetaminophen overdose
Ingestion of >10g of Acetaminophen may be fatal
may be lower in chronic alcoholics or subjects with underlying liver disease.
Clinical features
In severe poisoning
up to 24 hours - none or nausea and vomiting
> 24 hours - nausea and vomiting, right upper quadrant pain, jaundice, encephalopathy |
|
Definition
|
|
Term
|
Definition
Consider-acetylcysteine infusion ( if in doubt of severe poisoning, don’t delay)
Check prothrombin time and plasma creatinine, pH
acute renal (due to acute tubular necrosis) and hepatic failure and occur at 36-72 hours after ingestion
Indications for referral to liver unit are
- rapid development of Grade 2 encephalopathy
- PTT >45 secs at 48 hours or >50 secs at 72 hours
- rising plasma creatinine
- Arterial pH <7.3 more than 24 hours after ingestion |
|
|
