Chapter 9: Drugs To Treat Inflammation - Steroidal And Nonsteroidal Anti-Inflammatories Flashcards
(93 cards)
1
Q
What is the generic name for corticosteroid?
A
Prednisone
2
Q
What are other names for Bayer and Bufferin? What drug class are they in?
A
- aspirin or acetylsalicylic acid (ASA)
- salicylate, non selective irreversible COX-1 and COX-2 inhibitor
3
Q
What is the generic name for Aleve and Naprosyn?What drug class are they in?
A
- Naproxen
- nonsteroidal, nonselective COX-1 and COX-2 inhibitor
4
Q
What is the generic name for Motrin and Advil? What drug class are they in?
A
- ibuprofen
- propionic acid derivative, nonselective COX-1 and COX-2 inhibitor
5
Q
What is the generic name for Celebrex? What drug class are they in?
A
- celecoxib
- nonsteroidal, selective COX-2 inhibitor
6
Q
Define inflammation.
A
A complex response to cell injury that primarily occurs in vascularized connective tissue, with inflammatory mediators functioning to eliminate the cause of cell injury and clear away debris in preparation for tissue repair.
7
Q
The inflammatory response is activated by….
A
Noxious agents, infections, or physical injuries that release damage and pathogen-associated molecules, which are then recognized by immune system cells.
8
Q
When can inflammatory response be bad?
A
When the intensity and duration is inappropriate and destructive, resulting in chronic inflammatory conditions.
9
Q
What are the 2 major classes of anti-inflammatory medications?
A
- corticosteroids (specifically glucocorticoids)
- nonsteroidal anti-inflammatory drugs (NSAIDs)
10
Q
Name the local chemical mediators (cytokines) that bring on vascular changes in the inflammatory process.
A
- histamine
- bradykinin
- prostaglandins
11
Q
What are the 3 phases of acute inflammation?
A
- Vascular phase
- Cellular phase
- Tissue healing (granular) phase
12
Q
What does chronic inflammation result from?
A
- continuous or repeated exposure to the offending element or process
- can result from continued tissue damage, persistence of pathogens, autoimmune diseases, cancers
13
Q
What is the hallmark of chronic inflammation?
A
Accumulation and activation of macrophages and lymphocytes, as well as fibroblasts that replace the original, damaged, or necrotic tissue.
14
Q
Define fibrosis.
A
An excessive deposition of fibrous tissue that can interfere with normal tissue function due to excessive amounts of growth factors and angiogenic factors.
15
Q
Define granulomas.
A
- chronic inflammation can lead to the formation of this.
- a mass of cells consisting of activated macrophages surrounded by activated lymphocytes.
16
Q
Nonselective NSAIDs target ______, which is…
A
- cyclooxygenase (COX)
- the rate-limiting enzyme in the production of prostaglandins
17
Q
What part of the arachidonic acid cascade do corticosteroids effect?
A
Corticosteroids prevent the liberation of arachidonic acid from plasma-membrane phospholipids and thus reduce the synthesis of the eicosanoids (prostaglandins, thromboxanes, leukotrienes)
18
Q
What are the eicosanoids?
A
- prostaglandins
- thromboxanes
- leukotrienes
19
Q
Corticosteroids are ______ hormones, such as the glucocorticoid ______, that are secreted naturally by the cortex of the ________ ______.
A
- endogenous
- cortisol
- adrenal glands
20
Q
Cortisol is released in response to _______.
A
Stress
21
Q
Corticosteroid medications are a synthetic version of _______, such as ______, _______, or _______, that are very effective at reducing _______ and ______ the immune system.
A
- cortisol
- cortisone, prednisone, hydrocortisone
- inflammation
- suppressing
22
Q
Why are corticosteroids among the most frequently prescribed classes of drugs?
A
Treats inflammatory and autoimmune diseases
23
Q
Why can you get serious side effects from rapid withdrawal of corticosteroids?
A
Because corticosteroids exert effects on almost every organ system
24
Q
How are corticosteroid medications named?
A
—ones (rhymes with zones)
25
The hypothalamic-pituitary adrenal axis can be suppressed in what kind of patients?
Patients who are receiving corticosteroids for prolonged periods.
26
Large doses of exogenous corticosteroids inhibit _______ release from the pituitary gland, which stimulates the release of ______ from the adrenal cortex.
- adrenocorticotropic hormone (ACTH)
- cortisol
27
Mechanisms of action for corticosteroids.
- suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability
- reduction in the synthesis or release of a variety of inflammatory mediators, including prostaglandins, which are also inhibited by NSAIDs.
28
Corticosteroids inhibit certain aspects of leukocyte function, which accounts largely for their _______ effect.
Immunosuppressant
29
General oral formulations of prednisone, methylprednisolone, and triamcinolone typically last for _____ hours in the body, whereas dexamethasone and betamethasone last for _____ hours.
- 12-36 hours
- 32-72 hours
30
Why is prednisone one of the most commonly used corticosteroids?
- low cost
- only available in oral form
31
All oral corticosteroids undergo _____ _____ _____ during absorption.
First-pass metabolism
32
Discontinuation of corticosteroid therapy that has lasted longer than 7 days may require tapering of the drug to prevent ______ _____.
Adrenal crisis
33
Prednisone onset of action, peak effect, duration, bioavailability, and half life.
- onset of action: depends on drug formulation
- peak effect: IR - 2 hr, delayed release - 6-6.5 hr
- duration: 12-36 hr
- bioavailability: inter individual variability
- half life: 2-3 hr
34
Metabolism and excretion of prednisone.
- metabolism: hepatic to metabolite prednisolone (active)
- excretion: urine
35
Describe the negative immunosuppressive effects of prolonged corticosteroid use:
- secondary infection
- mask acute infection (including fungal infections)
- prolong or exacerbate viral infections
- limit response to killed or inactivated vaccines
36
Describe MSK adverse effects from corticosteroids.
- arthralgia
- osteonecrosis of femoral and humeral heads
- increased risk of #
- loss of muscle mass
- muscle weakness
- myalgias
- osteopenia
- osteoporosis
- pathological # of long bones
- steroid myopathy
- tendon rupture (esp. Achilles tendon)
- vertebral compression #
37
Name the indications for short-term administration (for acute episodes or exacerbations) of corticosteroids:
- acute and subacute bursitis
- acute nonspecific tenosynoviitis
- ankylosing spondylitis
- epicondylitis
- post traumatic osteoarthritis
- several types of arthritis
38
Name some indications for corticosteroid use for an exacerbation or as maintenance therapy.
- acute rheumatic carditis
- systemic dermatomyositis (polymyositis)
- systemic lupus erythematosus
39
High levels of exogenous corticosteroids for a prolonged time cause the hypothalamus to secrete less ______, which reduces ______, thereby causing the adrenal glands to stop making ______.
- corticotropin-releasing hormone (CRH)
- ACTH
- cortisol
40
What is acute adrenal insufficiency?
- corticosteroid medication suddenly stopped, and the adrenal cortex does not immediately begin producing corticosteroids again
- aka Addison’s disease
41
Symptoms of acute adrenal insufficiency (Addison’s disease):
- irritability
- nausea
- joint pain
- dizziness
- low blood pressure
42
Why is corticosteroid use preferred for pregnant women with MSK inflammation late in pregnancy?
NSAIDs are contraindicated during the third trimester
43
Name another time that corticosteroids can be used during pregnancy (other than for MSK).
Treat an autoimmune disorder of the mother that could be more harmful to fetal health than high doses of the medication.
44
Name some corticosteroid risks during pregnancy.
- cleft lip
- preeclampsia
- low birth weight
- preterm birth
- potential hyperglycemia and ketoacidosis for patients with gestational diabetes
45
Adult patients receiving ______ mg per day of prednisone may be most susceptible for side effects.
> 20 mg
46
Name some side effects of corticosteroids:
- agitation and irritability
- blurred vision
- difficulty concentrating
- dizziness
- facial hair growth in females
- fast or irregular heartbeat
- fluid retention
- headache
- HBP
- increased blood sugar, cholesterol, or triglycerides
- increased risk of gastric ulcers or gastritis
- loss of potassium
- shortness of breath
- sleeplessness
- weight gain
47
What is Cushing’s syndrome?
- hypercortisolism
- abnormally high cortisol levels
- long term use of exogenous corticosteroid therapy
48
Symptoms of Cushing’s syndrome:
- fatty (buffalo) hump between the shoulders
- round face
- weight gain
- irregular menstrual cycles
- fatigue
- depression
49
What effects do NSAIDs have?
- analgesic
- antipyretic
- anti-inflammatory
50
Traditional (nonselective) NSAIDs have what additional effect?
Antithrombotic
51
NSAIDs relieve pain in joints, muscles, and other soft tissues by inhibiting the ______ enzymes.
COX
52
What are the 2 major categories of NSAIDs?
1. Nonselective (traditional, classic, older) COX inhibitor NSAIDs.
2. Selective (newer) COX-2 inhibitor NSAIDs.
53
How are selective COX-2 inhibitor NSAIDs named?
—coxib
54
What are the advantages of using selective COX-2 inhibitor NSAIDs?
Produces analgesia equivalent to that of the nonselective NSAIDs while decreasing the adverse effects, specifically the GI toxicity associated with chronic NSAID use.
55
What are the disadvantages of using selective COX-2 inhibitor NSAIDs?
- higher incidence of cardiovascular thrombotic events than with nonselective drugs
- increased risk of adverse cardiovascular events at high doses in the elderly
- skin reactions
- only celecoxib is currently available for use in the US despite having similar risks
56
Coadministration of NSAIDs can reduce the ______ dose needed for sufficient pain control and thus, reducing the likelihood of adverse _____ effects.
- opioid
- opioid
57
Give an example of coadministration of NSAIDs and opioids.
Ibuprofen and hydrocodone
58
NSAIDs are particularly effective when ________ has caused sensitization of pain perception, thus making it effective for ______ pain or ______ pain, but not for pain arising from the _____ _____, except for ________ pain.
- inflammation
- postoperative
- arthritic
- hollow viscera
- menstrual
59
NSAIDs are commonly used to treat migraine attacks and can be combined with ______ to aid relief of the associated nausea.
Antiemetics
60
NSAIDs and opioids generally lack efficacy in ______ pain, but _______ 60 mg administered IM has been shown to produce analgesia for this type of pain.
- neuropathic
- Toradol
61
What are the 3 ways that NSAIDs affect pain pathways?
1. Prostaglandins reduce the activation threshold at the peripheral terminals of primary afferent nociceptors neurons.
2. NSAIDs decrease the recruitment of leukocytes, and the production of leukocyte-derived inflammatory mediators.
3. NSAIDs that cross the blood-brain barrier prevent the generation of prostaglandins that act as pain-producing neuromodulators in the spinal cord dorsal horn
62
The primary route of NSAID administration is ______ for both prescription and OTC medicines.
Oral
63
What is the only NSAID routinely administered via the parenteral route?
Ketorolac (Toradol)
64
Why do topical NSAIDs cause less serious side effects than oral and IV forms?
Decreased systemic exposure (ie. lower absorption into the systemic circulation)
65
Name 3 NSAID gels that work well for strains and sprains.
- diclofenac gel
- ketoprofen gel
- piroxicam gel
66
Describe the absorption of NSAIDs.
- peak plasma concentrations reached after 3 hours of oral intake
- oral NSAIDs undergo hepatic first pass metabolism, resulting in reduced bioavailability
- food intake may delay absorption and systemic availability
- antacids delay absorption
67
For distribution, NSAIDs bind to _____ _____, usually _______.
- plasma proteins
- albumin
68
How are NSAIDs metabolized and excreted?
- liver
- urine
69
Why do NSAIDs have risk of stomach ulcers and GI bleeding?
COX-1 plays a role in protecting the stomach lining, and NSAIDs block COX-1
70
NSAIDs should be avoided in patients with …
- renal insufficiency (creatinine clearance < 60 mL/min)
- GI bleeding
- platelet dysfunction
- reduced cardiac output
- difficult to control hypertension
- hypovolemia
- hyponatremia
- aspirin-sensitive asthma
- cirrhosis
71
NSAIDs may have a drug-drug interaction that induces _______ among diabetic patients prescribed other drugs.
Hypoglycaemia
72
What drugs should not be combined with warfarin and other blood thinner medications due to risk of bleeding?
- nonsalicylate, no selective NSAIDs
- acetylsalicylic acid (aspirin)
73
Most common GI symptoms associated with NSAIDs:
- dyspepsia
- abdominal pain
- nausea
- diarrhea
74
Clinical manifestations of NSAID-induced nephrotoxicity include:
- electrolyte abnormalities such as hyperkalemia
- reduced glomerular filtration rate
- nephrotic syndrome related to drug induced minimal change disease
- chronic kidney disease
- acute interstitial nephritis
- sodium retention
- edema
- renal papillary necrosis
75
What is acute kidney injury?
- result of compromised renal hemodynamics, intramuscular volume depletion, and reduction of glomerular capillary pressure
- can lead to chronic kidney disease
- can happen with a single NSAID does, more likely when exceeding recommended daily dose
76
Name some hypersensitivity symptoms to aspirin and NSAIDs.
- vasomotor rhinitis
- generalized urticaria
- bronchial asthma
- laryngeal edema
77
What are the 2 most commonly used NSAID classes in the AT setting?
- salicylates
- propionic acid
78
Aspirin was initially found where?
In the bark of the willow tree. It is considered the original NSAID.
79
What is the major difference between the mechanisms of action of aspirin and those of other NSAIDs?
- Aspirin irreversibly inhibits COX and platelet functioning for the life of the platelet (7-10 days)
- leads to longer duration of its anti platelet effect and the basis for its use as an anti thrombotic drug.
80
What is the dose of a typical aspirin tablet? How should it be dosed?
- 325 mg
- for fever or analgesic: 325-650 mg every 4-6 hours or 1000 mg every 6 hours up to 3x/day
- maximum recommended dose/day = 3000 mg
81
Regular NSAID use should be avoided, if possible, in patients taking low-dose aspirin for _______ ______.
Cardiovascular protection
82
What is the onset of action, peak effect, duration, bioavailability, and half life of aspirin?
- onset of action: within 1 hr (nonenteric coated)
- peak effect: IR ~1-2 hr (nonenteric coated), 3-4 hr (enteric coated), ER 2 hr
- duration: 4-6 hr, but platelet inhibitory effects last ~10 d
- bioavailability: 50-75% reaches systemic circulation
- half life: dose dependent
83
Aspirin is rapidly absorbed in the ______ and _____ _____.
- stomach
- upper intestine
84
Describe the metabolism and excretion of aspirin.
- metabolism: hydrolyzed to salicylate (active) in GI mucosa. Occurs primarily by hepatic conjugation.
- excretion: urine
85
What is Reye’s syndrome?
Rare but serious disorder of rapid liver degeneration and brain damage.
- using aspirin during infection with influenza A or B or varicella increases the risk of Reye’s syndrome by 35x.
86
Why has the incidence of Reye’s syndrome fallen dramatically recently?
Public has been educated not to give aspirin to children
87
What is the most commonly used propionic acid derivative?
Ibuprofen
88
Routes of administration for Ibuprofen:
- tablets
- chewable tablets
- capsules
- caplets
- gel caps containing 50-800 mg
- oral suspension
- injectable
89
Name some drug combinations with ibuprofen.
- antihistamines
- histamine-2 blockers
- decongestants
- hydrocodone
90
What is the usual ibuprofen dose for mild to moderate pain?
400 mg every 4-6 hours
91
Why can naproxen be administered less frequently than other propionic acids?
Longer half life
92
Describe the onset of action, peak effect, duration, bioavailability, and half life of ibuprofen.
- onset of action: analgesic - within 60 min
- peak effect: 1-2 hr
- duration: 6-8 hr
- bioavailability: 80%
- half life: 2 hr
93
Describe the metabolism and excretion of ibuprofen.
- metabolism: hepatic
- excretion: urine (primarily as metabolites: 45-80%), some in feces
