PHARMACOLOGY

NSAIDs, DMARDs, NON-OPIOID SHIFT 1

REVIEWER 1.1
ANALGESICS AND DRUGS USED IN GOUT
REVIEWER | MAY 2020

OUTLINE → Algesic flare before surgery

I. Introduction → Hyperalgesic states after surgery
A. Pain III. Non-Opioid Analgesics B. PROSTAGLANDINS
B. Pre-Emptive Analgesia A. Paracetamol • Along with thromboxane and leukotrienes, are collectively
C. Prostaglandins IV. Disease Modifying Anti- called eicosanoids. Produced from arachidonic acid that is
D. Therapeutic Strategies Rheumatic Drugs liberated from cell membrane phospholipids.
II. Non-Steroidal Anti- V. Corticosteroids
Inflammatory Drugs VI. Drugs used in gout Prostaglandin Synthesis
A. Common Properties VII. References
B. Clinical Uses VIII. Summary of Drugs
C. Adverse Effects
D. Classification of NSAIDs
LEGEND
MUST KNOW SAMPLEX
 

I. INTRODUCTION
A. PAIN
• An unpleasant emotional and sensory experience, that is
associated with an actual or potential tissue damage
Table 1. Classification of Pain
Types
Duration Acute Pain
• Arachidonic acid -> 𝑃𝐺𝐺2 and 𝑃𝐺𝐻2 via cyclooxygenase (COX)
- Lasts <1 month
pathway
- Pain resolves upon healing of tissue
→ 𝑃𝐺𝐺2 and 𝑃𝐺𝐻2 are unstable compounds, thus, coverted to:
damage ▪ PGE2, PGD2 & PGF2a by isomerase enzyme in tissues
- Serves as protective function ▪ PGI2 by prostacyclin synthase
Chronic Pain ▪ TXA2 by thromboxane synthase
• Two major actions of prostaglandins:
- Lasts ≥ 3-6 months
▪ Mediators of inflammation, stimulates nerve endings and
- Beyond expected period of healing cause pain
- Usually has no protective function, ▪ Allows the movement of other inflammatory mediators (i.e.
degrades health histamine and bradykinins) to the site of inflammation and
Pathophysiology Nociceptive Pain aggravates pain.
- Stimulus outside the nervous
Table 2. Important prostaglandins and their effect
system Products Effects
- Pain is proportional to stimulation of 𝑃𝐺𝐼2 (Prostacyclin) Vasodilation
nociceptor - Seen predominantly Inhibition of platelet
Neuropathic Pain at vascular aggregation
- initiated by primary lesion or endothelium
𝑇𝑋𝐴2 (Thromboxane) Vasoconstriction
dysfunction of nervous system (no
- Found in platelets Platelet aggregation
nociceptor stimulation required)
𝑃𝐺𝐸2 Inhibition of gastric acid
- Disproportionate to stimulation of secretion
receptor Contraction of pregnant uterus
- with other evidence of nerve Contraction of GI smooth
damage muscles
Location Visceral Pain 𝑃𝐺𝐹2𝑎 Contraction of bronchi
- caused by disruption of internal Contraction of myometrium
organs, not localized • Phospholipase-A2 inhibitors (glucocorticoids) & COX
Somatic inhibitors (NSAIDs) inhibit the synthesis of prostaglandins,
- not from viscera, localized thereby, produce anti-inflammatory actions.

B. PRE-EMPTIVE ANALGESIA
• Administration of analgesia before a nociceptive stimulus
reduces the degree of sensitization produced in the nervous
system and facilitates subsequent treatment
• Pre-operative, preventive analgesia
• Along with multimodal analgesia, prevents:
Reviewer 1.1 PREPARED BY: Ramos, Precious 1 of
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Cyclooxygenase Enzymes - Occurs even with complete
sensory nerve block,
Table 3. Comparison of COX-1 & COX-2 Enzymes possibly due to humoral
Properties COX-1 COX-2 signal
Site of Found in many tissues, Induced by
action important for homeostasis inflammatory
(housekeeping enzyme) stimuli at the site Multimodal Analgesia
of inflammation • Achieved by use of multiple drugs to achieve synergistic effect
Effects of • Coverts arachidonic acid • Increases pain, • Use of:
activation to inflammatory inflammation ▪ Non-opioids: NSAIDs, paracetamol, COX-2
prostaglandins • Vasodilatory ▪ Opioids: Codeine, Morphine, Tramadol
• Maintains renal function effects ▪ Adjuvants: Antidepressants, Anticonvulsants,
• Provides integrity to • Blocks platelet Corticosteroids, NMDA, Antagonists
gastric mucosa clumping
(cytoprotective) B. THERAPEUTIC STRATEGIES
• Promotes vascular • Technique in giving analgesics:
homeostasis ▪ 3L’s: Lowest Dose, Longest Duration, with Least Side
• Autocrine effects cause Effects
fever • Primary Goals in the treatment of patients with inflammatory
Effects of Decreased swelling, pain Decreases pain conditions:
blocking and inflammation and inflammation ▪ Relief of symptoms and maintenance of function
Effects of • Damage to renal system Prevents ▪ Slowing or arrest of the tissue damaging process.
blocking (acute tubular necrosis protective
for a may occur) vasodilation; II. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
prolonged • Sodium retention, Allows platelet (NSAIDs)
period edema, increased BP clumping, which A. COMMON PROPERTIES
leads to • GI erosions (ulcer) and can lead to MI and
adverse bleeding cerebrovascular Table 5. NSAIDs and COX selectivity
effects • Decreases fever accidents COX-1 Non-selective COX COX-2
like Selective Inhibitors Selective
Inhibitors Inhibitors
-Acetylsalicylic - Acetylsalicylic acid -Celecoxib
acid (Aspirin) at (Aspirin) at high dosage -Etoricoxib
low doses -Non-acetylated -Valdecoxib
salicylates -Rofecoxib
-Diclofenac
-Ibuprofen
-Ketoprofen
-Ketorolac
-Flurbiprofen
-Indomethacin
-Piroxicam
-Naproxen
-Meclofenamate &
Mefenamic acid
-Sulindac
-Nabumetone
Figure 1. Pharmacotherapy of pain. [A2022 trans]. *withdrawn from the market because of association with increased CV thrombolic
events
• COX1 is expressed as constitutive isoform in gastric epithelial *The following were not extensively discussed during the lecture (see appendix
for summary table)
cells; major source of cytoprotective prostaglandin formation
• Weak organic acids except nabumetone, a ketone prodrug
▪ Inhibition leads to gastric AE that complicate therapy of
• Non-steroidal, have similar eicosanoid-depressing, anti-
NSAIDs, thus, the development of NSAIDs specific for
COX-2 inhibition inflammatory action as steroids
• Most prominent members: aspirin, ibuprofen and naproxen
• COX-3 enzyme is a spliced variant of COX-1
▪ Can cause IgE mediated anaphylaxis
▪ Has COX like enzyme activity, known to be involved in pain
▪ Sometimes not IgE mediated- ibuprofen mediates release
perception and fever but NOT inflammation
of histamine leading to an anaphylactoid reaction
▪ Paracetamol – selective COX-3 inhibitor
(pseudoallergy)
Sensitization to Pain
Pharmacokinetics
Table 4. Types of Sensitization
Table 6. Common pharmacokinetic profile of majority of NSAIDs
Peripheral sensitization Central sensitization Absorption • Well absorbed, Bioavailability
- COX-2 is expressed - Peripheral inflammation unchanged by food; Aspirin has pKa of
following tissue injury leads to induction of COX-s
3.5, best absorbed in the stomach 
- Prostaglandins produced in the CNS
increase nociceptor - Prostaglandins produced
sensitivity to pain by COX-2 in the CNS
cause further sensitization
to pain
 PHARMA REVIEWER 1.1: NSAIDs, DMARDs, Non-Opioid Analgesics and Drugs used in Gout
Distribution Highly protein-bound in plasma (98%)
Usually bound to albumin
Found in synovial fluid after repeated
dosing:
- Drugs with short half lives remain
in the joints longer
- Drugs with longer half lives
disappear at rate proportional to their
half lives
Metabolism Highly metabolized in the liver: Phase I
and Phase II or Phase II alone
Metabolized by CYP3A or CYP2C
Excretion Undergoes biliary excretion and
reabsorption (enterohepatic circulation) *
Final elimination by the kidneys
*amount of enterohepatic circulation undergone by drug correlates
with degree of lower GIT irritation
Pharmacologic actions
• Most NSAIDs inhibit the activity of COX-1 and COX-2, thereby
Table 8. Specific pharmacodynamic effects of NSAIDs
inhibits the synthesis of prostaglandins and thromboxanes.
• Selectivity for COX-1 vs COX-2 is variable and incomplete for
the older NSAIDs,
Table 7. Pharmacologic actions of NSAIDs
Anti- Primary mechanism: 
inflammatory
- Inhibition of biosynthesis of
prostaglandin in inflammatory cells
through inhibition of cyclooxygenase
(COX2) isoform of the arachidonic acid
Other mechanisms of action of NSAIDs:
- Inhibition of chemotaxis
- Down regulation of IL-1 production
- Decreased production of free radicals
and superoxide
- Interference with Ca-mediated
intracellular events
Aspirin irreversibly blocks platelet COX
Non-COX selective reversibly blocks platelet
COX
- When non-selective COX inhibitors
such as Ibuprofen are given
concomitantly with Aspirin, the total
anti-inflammatory effect is
decreased. 
Analgesic NSAIDs, as opposed to opiates, are non-
narcotic and used as non-addictive
alternatives
Primary mechanism: 
- Inhibition of formation of PGs and other
inflammatory mediators, which is
achieved by inhibiting enzymes involved
in their synthesis.
NSAIDs Opiates
Relieves dynamic Relieves static pain
pain Centrally acting in
Peripherally acting the brain and spinal
through COX cord
inhibition
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Antipyretic Fever may reflect infection, from tissue
damage, inflammation, graft rejection or
malignancy. These conditions lead to
enhanced formation of cytokines (i.e. IL-1, IL-
6, interferons and TNF-a)
Cytokine release -> inc. PGE2 -> inc. cyclic
AMP -> hypothalamus elevates body temp.
(FEVER)
Mechanism:
- Inhibition of prostaglandin production
in the hypothalamus; resetting
thermostat (through dilatation of
superficial vessels, sweating -> dec
temp.)
Anti-platelet NOT EXHIBITED by COX-2 selective
aggregation inhibitors and non-acetylated saliclylates
Pharmacodynamics
Respiratory At full therapeutic dose:
- Salicylates increase O2 consumption
and CO2 production (especially in
skeletal muscles); result of uncoupling
oxidative phosphorylation
- Inc. CO2 -> stimulates respiration
- Plasma CO2 tension does not change;
balanced out by inc. alveolar
ventilation
Acid Base and Salicylates at therapeutic dose:
Electrolyte - Definite change in acid base balance
and electrolyte pattern
Low dose:
- Stimulation of resp. center ->
respiratory alkalosis
Moderately high dose:
- Metabolic acidosis
High dose:
- Depresses resp. center ->
accumulation of CO2 -> respiratory
acidosis
Cardiovascular Low dose of Aspirin (<100mg daily)
- Used for cardioprotective effects
High therapeutic dose (>3g daily)
- For acute rheumatic fever
- Salt and water retention-> inc. in
circulating plasma (20%) -> dec.
hematocrit
Uterine NSAIDs
- lower uterine PGs -> relief of
menstrual cramps
- delays and retards labor (do not use at
term)
Uricosuric Markedly dose dependent.
Low dose (1 or 2g/ day)
- decreased urate excretion and elevate
plasma urate levels
Intermediate dose (2 or 3g/day)
- no alteration on urate excretion
Large doses (>5g / day)
- uricosuric and lowers plasma urate
levels
Blood Inhibition of platelet hemostasis can lead
to significant hemorrhage. Thus, aspirin use
is contraindicated in patients with the ff:
- severe hepatic damage
- hypoprothrombinemia
- vit K deficiency
 PHARMA REVIEWER 1.1: NSAIDs, DMARDs, Non-Opioid Analgesics and Drugs used in Gout 4 of
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- hemophilia III. NON-OPIOID ANALGESICS
- G6PD (mild degree of hemolysis)
PARACETAMOL/ACETAMINOPHEN/APAP
B. CLINICAL USES Chemical
structure
• Indications for NSAIDs by FDA:
▪ For symptomatic relief (anti-inflammatory action):
▪ In Rheumatoid arthritis
▪ Osteoarthritis
▪ Gout (except tolmetin) N-acetyl-para- aminophenol
▪ Musculoskeletal Syndromes (e.g. sprains and strains) MOA Inhibits COX-3 in the CNS (effective
▪ Seronegative spondyloarthropathies (e.g.psoriatic arthritis analgesic and antipyretic action).
and arthritis associated with Inflammatory bowel disease)
• Relief of headache, dysmenorrhea, backache, bony
metastasis, post-operative pain (analgesic action) Weak COX-1 and COX-2 inhibitor in
▪ Short term use: aspirin, paracetamol, ibuprofen peripheral tissues
▪ For chronic pain: more potent, long-acting (e.g. naproxen - No anti-inflammatory effect
in combination with - No platelet inhibiting effect
*take note that PARACETAMOL is generally not considered as an
NSAID because of little anti-inflammatory activity. It is a selective
COX-3 inhibitor Indications - For headache, myalgia, post-
B. ADVERSE EFFECTS partum pain
- For patients allergic to ASA, have
Table 9. Specific Organ-system Adverse Effects of NSAIDs
PUD, hemophilia
CNS Headache, tinnitus, dizziness
- For children with viral infection
CVS Fluid retention, edema, hypertension
- Increased incidence with selective Adverse At a dose of 4-6 grams: Liver function
COX-2 use Effects abnormality, dizziness, excitement,
MI and CHF (rare) disorientation
Pulmonary Asthma At a dose of 15 grams: Severe
Skin Rashes, pruritus hepatotoxicity and nephrotoxicity (due to
GIT Ulcers and bleeding formation of active metabolite, N-acetyl-P-
- Greater with use of COX-1 benzoquinone imine).
inhibitors
Toxicity Acetaminophen poisoning
Abdominal pain, dysplasia, nausea, vomiting
- Medical emergency
Hepatic Hepatotoxicity can occur with any NSAID
Renal Nephrotoxicity due to their interference with - Severe liver damage in 90% of
the autoregulation of renal blood flow, which is patients (if plasma conc. Is
modulated by PGs >300g/mL at 4 hrs or 45g/ml at 15
Hematologic Rare: Thrombocytopenia, neutropenia, aplastic hrs post-ingestion).
anemia - Antidote:N-acetylcysteine
*Note: Several NSAIDs (including Aspirin ) reduce incidence of (NAC) 
colon cancer when taken chronically
IV. DISEASE MODIFYING ANTIRHEUMATIC DRUGS
Specific adverse effects associated with some NSAIDs
(DMARDs)
• Reye’s syndrome
▪ Aspirin use should be avoided in pediatric patients on anti- METHOTREXATE (AntI-Metabolite)
viral treatment MOA Inhibition of aminoimidazole
▪ Encephalopathy + Liver damage carboxamide ribonucleotide (AICAR)
• Increased cardiovascular thrombotic events transformylase & thimydylate
▪ Specifically with rofecoxib and valdecoxib (withdrawn from synthase
the market) - ↑ AICAR (intracellular) -> inh.
AMP deaminase-> ↑AMP-> ↑
B. CLASSIFICATION OF NSAIDs adenosine ->potent inhibition of
• Aspirin (ASA) – oldest NSAID; irreversible inhibitor inflammatory process
• Non-acetylated salicylates
• COX-2 Selective Inhibitors Other MOA:
• Non-selective COX Inhibitors- reversible inhibitor - Some effects on
polymorphonuclear chemotaxis
Table 10. Selectivity of COX inhibition - Some effects on dihydrofolate
COX-1 > COX-2 COX-1 = COX-2 COX-1 < COX-2 reductase
- Decreased rate of appearance
Aspirin, Ibuprofen and Celecoxib and
of new erosions
Indomethacin, Meclofenamate Etoricoxib
Piroxicam and Indication First choice of treatment in
Sulindac Rheumatoid arthritis in 60% of
patients
*Note: Please see summary table at the end of this reviewer for specific NSAIDs Drug Interactions With PROBENECID (anti-gout) oral
and their drug information that were lifted from the handouts, but were not - Increases level of Methotrexate
discussed in full during the lecture.
sodium inj. because both
 PHARMA REVIEWER 1.1: NSAIDs, DMARDs, Non-Opioid Analgesics and Drugs used in Gout 5 of
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compete for the same pathway Adverse Effects Ocular toxicity may occur (TOXIC
for excretion OCULAR NEUROPATHY)
- If it must be taken together, - Ophthalmologic monitoring every
decrease the dose of 6-12 months is advised
methotrexate.
Adverse Effects - Nausea and mucosal ulcers
Combination Therapy with DMARDs
(most common)  Table 11. Combination therapy with DMARDs
- Rare: Hepatotoxicity, cirrhosis IMPROVED WITH NO ADDITIONAL
- Pseudolymphomatous reactions METHOTREXATE THERAPEUTIC BENEFITS
- Increased risk for uric acid Cyclosporine Azathioprine
neuropathy as it Increases uric Chloroquine Auranofin
acid production Leflunomide Sulfasalazine
Infliximab
LEUCOVORIN/FOLINIC ACID Adalimumab
- Rescue drug Rituximab
- Used 24h after each weekly Etanercept
dose or by the use of daily folic *were not discussed extensively during the lecture
acid
- Reduces GI and liver function V. CORTICOSTEROIDS
test abnormalities assoc with
Methotrexate use • Capable of slowing the appearance of new bone erosions
Contraindications Pregnancy • Indications:
▪ Serious extra-articular manifestations of RA (i.e.
CYCLOPHOSPHAMIDE (Alkylating agent) pericarditis) or during periods of exacerbation
MOA Cross-links DNA to prevent cell replication. ▪ Prednisone as long term therapy, not exceeding 7.5mg
Alkylations of DNA within the nucleus leads daily
to cell death. ▪ Intraarticular corticosteroids are often helpful to alleviate
Used as an antineoplastic agent painful symptoms.
- Suppress T and B cell function by • Adverse effects:
30-40% ▪ Serious and disabling toxic effects upon prolonged use
- T cell suppression correlates with
clinical response in rheumatic VI. DRUGS USED IN GOUT
disease
COLCHICINE
Indications SLE
Vasculitis Chemistry Alkaloid isolated from autumn crocus
Wegener’s granulomatosis (Colchicum autumnale)
Severe rheumatic diseases MOA Binds to intracellular protein tubulin,
Adverse Effects Bone marrow suppression, Dose-related prevents polymerization leading to
infertility, Alopecia, Hemorrhagic cystitis, inhibition of leukocyte migration and
Bladder carcinoma (rare) phagocytosis
MESNA: Rescue drug
Inhibits formation of leukotriene B4
CYCLOSPORINE
Pharmacokinetics - Absorbed readily after oral
MOA - Immunosuppressant
- Regulation of gene transcription administration
- Inhibits IL-1 and IL-2 receptor - Peak plasma level within 2
production hours
- Inhibits macrophages T cell - Half-life: 9 hrs
interaction and T cell - Excretion of metabolites
responsiveness
through the intestinal tract and
Pharmacokinetics Erratic absorption
Grapefruit juice increases bioavailability urine
Metabolized by CYP3A Indication Primary treatment for acute gout
Indications For RA, retards appearance by new bony Used for prophylaxis of recurrent
erosions episodes of gouty arthritis
Adverse Effects Leukopenia, Thrombocytopenia, Anemia,
Cardiotoxicity, sterility in women - Relieves pain and
CHLOROQUINE AND HYDROXYCHLOROQUINE
inflammation in 12-24 hours
(Antimalarial agents)
MOA Suppression of T lymphocyte responses without altering metabolism of
to mitogens urates and without other
Inhibition of DNA and RNA synthesis analgesic effects

*note: NOT CONSIDERED very efficacious Colchicine and NSAID should be given in
DMARDs the first week of allopurinol therapy to
prevent gout flares.
Adverse Effects Diarrhea (most common SE) 
 PHARMA REVIEWER 1.1: NSAIDs, DMARDs, Non-Opioid Analgesics and Drugs used in Gout 6 of
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Increases bone marrow toxicity if given
IV
Contraindications Patients with severe renal impairment
Do not take with P-glycoprotein or
CYP3A4 Inhibitor
Dosage For prophylaxis:
recommendation - 0.6mg, 1-3x daily
For gouty attack:
- 0.6-1.2 mg followed by 0.6 mg
every 2 hrs until pain is relieved
or nausea and diarrhea appear
Fatal dose (IV) : 8mg in 24 hours

ALLOPURINOL
Chemistry Purine analog (Isomer of hypoxanthine)
MOA Inhibits xanthine oxidase enzyme
Indication Standard care of therapy for gout in
between acute attacks/chronic gout,
reduces uric acid body pool

Not given in acute attacks, can give rise

to gouty flares
Adverse Effect SJS, GI-nausea, vomiting, diarrhea
FEBUXOSTAT
MOA First non-purine inhibitor of xanthine
oxidase, potent and selective
Indication Alternative drug to decrease uric acid
for patients with gouty nephropathy
- Well tolerated by patients with
allopurinol intolerance
Adverse Effect Nausea, diarrhea,headache

NSAIDs in Gout
• MOA: (1) Inhibits prostaglandin synthase and (2) Inhibits urate
crystal phagocytosis
▪ INDOMETHACIN: 50mg 3x daily
▪ Oxaprozin (lowers serum uric acid): not to be given to
patients with uric acid stones because it increases uric acid
excretion in the urine
• NSAIDs contraindicated in gout: Aspirin, Salicylates, and
Tolmetin

Uricosuric Drugs
• PROBENECID and SULFINPYRAZONE
▪ MOA: competitively inhibits uric acid reabsorption in the
proximal tubule of the kidney; increases renal excretion of
uric acid
▪ Probenecid prolongs half-life of indomethacin
▪ Patients are encouraged to increase water intake to
maintain adequate urine volume to avoid nephrotoxicity
and urolithiasis.
▪ Aciduria should be corrected if it occurs.
VII. REFERENCES
Powerpoint and lecture of Dr. Calimag on NSAIDs, DMARDs, Non-
opioid analgesics and Drugs used in gout
Basic and Clinical Pharmacology by Bertram G. Katzung, 14th edition
A2022 Pharmacology Trans
VIII. SUMMARY OF DRUGS
See appendix, after the quiz section.
Highly encouraged to skim this table as it includes the drugs that were
not discussed during the lecture and some common samplex
questions.
END OF REVIEWER
Prepared by: Ramos, Precious
 PHARMACOLOGY
NSAIDs, DMARDs, NON-OPIOID SHIFT 1
REVIEWER 1.1
ANALGESICS AND DRUGS USED IN GOUT
REVIEWER | MAY 2020

UNIVERSITY OF SANTO TOMAS

FACULTY OF MEDICINE AND SURGERY
D2022 Reviewer
Sample EXAMINATION
May 2020

Instructions:
1. There are 20 items in this questionnaire
2. CHOOSE THE BEST ANSWER.
3. Try to answer on your own (without the use of reviewers/trances)
4. Answers are given in a separate document.
5. God bless!

------------------------------------------------------------------------------------------------------------------------------------------------------------------
CHOOSE THE BEST ANSWER

MATCHING TYPE (Mechanism of Action).

A. Celecoxib
B. Probenecid
C. Aspirin
D. Allopurinol
E. Methotrexate

1. Inhibition of xanthine oxidase enzyme

2. Inhibition of aminoimidazole carboxamide ribonucleotide (AICAR) transformylase
3. Selective inhibitor of COX-2 enzyme
4. Inhibits uric acid secretion
5. Acetylation and subsequent inhibition of COX-1 and COX-2

MULTIPLE CHOICE:

6. Which of the following NSAIDs is recommended to be given post-MI in a 50 year old male?
A. Paracetamol B. Indomethacin C. Aspirin Ibuprofen

For questions 7 & 8: A 40 y/o presents with markedly swollen and painful left knee after binged alcohol drinking.
His uric acid was elevated and left knee aspirate revealed monosodium urate crystals.

7. The most appropriate drug that will relieve pain and inflammation within 24 hours is:
A. Allopurinol B. Aspirin C. Colchicine D. Celecoxib

8. The most appropriate drug to give between acute attacks of gout:

A. Indomethacin B. Prednisone C. Allopurinol D. Colchicine

9. A 30 y/o male was diagnosed with Rheumatoid Arthritis. Which of the following is the first line drug for his
condition?
A. Azathioprine B. Chloroquine C. Cyclophosphamide D. Methotrexate

10. Concomitant administration of Ibuprofen and Aspirin may result in:

A. Decreased risk of GI adverse effects
B. Increased incidence of CV thrombotic events
C. Decreased total anti-inflammatory effect
D. Potentiation of platelet aggregation

Reviewer 1.1 PREPARED BY: Ramos, Precious 7 of

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11. This antipyretic-analgesic drug should be avoided in a 5 y/o with varicella infection because of Reye’s syndrome:
A. Celecoxib B. Aspirin C. Paracetamol D. Ibuprofen

12. The most appropriate drug for a 70 y/o male with osteoarthritic pain who presents in your clinic with concomitant
gastritis.
A. Celecoxib B. Paracetamol C. Aspirin D. Ibuprofen

13. Among NSAIDs, aspirin is unique because it

A. Irreversibly inhibits its target enzyme
B. Prevents episodes of gouty arthritis with long-term use
C. Reduces fever
D. Selective inhibits COX-2 enzyme

14. An 18-month-old boy dies from an accidental overdose of paracetamol. Which of the following is the most likely
cause of this patient’s death?
A. Hemorrhagic stroke B. Liver failure C. Pulmonary edema D. Arrhythmia

15. A 4 y/o boy has intermittent low to moderate grade fever and colds for the past 3 days. The most appropriate
antipyretic with the best safety profile is:
A. Paracetamol B. Aspirin C. Ibuprofen D. Celecoxib

PRESCRIPTION
ERASURES MAY BE ALLOWED “BUT” COMPLAINTS ON THE ERASED ANSWER WILL NOT BE ENTERTAINED

16-20: A 52-year-old woman presented with intense pain, warmth, and redness in the first toe on her left foot. Examination
of fluid withdrawn from the inflamed joint revealed crystals of uric acid. She was given a medication to control the acute
attack. Over the next 7 months, the patient had 2 more attacks of acute gout. Her serum concentration of uric acid was
elevated. The decision was made to put her on chronic drug therapy to try to prevent subsequent attacks. Which of the
following drugs could be used to decrease this woman’s rate of uric acid production?
A. Allopurinol Preparation: 100 mg tablet
Recommended dose: 100 mg PO OD for two weeks

B. Colchicine Preparation: 500 mcg tablet

Recommended dose: 0.5 mg PO BID for for 1 week

PPCR2020

- END OF QUIZ-
 PHARMA REVIEWER 1.1: NSAIDs, DMARDs, Non-Opioid Analgesics and Drugs used in Gout 9 of
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GUIDE: Drugs that are in cells highlighted in orange are the ones that appear on the 2012-2018 samplexes. The information on other drugs
were taken from the handout, however, these were not thoroughly discussed during the lecture.
SUMMARY OF DRUGS
Subclass, Drug Mechanism of Effects Clinical Application Adverse Effects,
Action Interactions,
Contraindications
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS
Aspirin Acetylation of COX-1 Decreased PG Low dose assoc. with AE:
and COX-2, synthesis low incidence of colon GI upset, bleeding; Large
inhibition of enzymes cancer dose: salicylism (tinnitus,
Analgesic, Antipyretic, deafness, dizziness); Toxic
Anti-inflammatory Angina, coronary artery dose: Uncompensated
(rarely used) and thrombosis with MI and metabolic acidosis; Reyes
Antithrombotic after CABG Syndrome
Interactions:
Anti-inflammatory action
decreased with concomitant
use of non-selective COX
Contraindications:
Pediatric patients on antiviral
Tx
NSAID- Selective COX-2 Inhibitors
Celecoxib Selective, reversible Decreased PG COX-2 selective AE:
inhibition of COX-2 synthesis inhibitors are the Less risk of GI toxicity
*COX2:COX1 appropriate choice in compared to nonselective
inhibition Analgesic patients with gastric NSAIDs; Greater risk of
(10-20:1) Antipyretic assoc. problems thrombosis compared to non-
Anti-inflammatory (gastritis, PUD)  selective NSAIDs
Interaction:
CELECOXIB: Occasional
interaction with warfarin
(CYP2C9)

Etoricoxib COX-2 selective

inhibitor
*COX2:COX1
inhibition (106:1)
Meloxicam Inhibition of COX-2
over COX-1 (2:1)

Inhibits synthesis of
TXA2
Valdecoxib/Rofecoxib Withdrawn from the market
NSAID- Non-Selective COX Inhibitors
Ibuprofen Non-selective COX Dec. PG synthesis: Effective in closing AE:
inhibitor Less fluid retention and patent ductus arteriosus RARE:Agranulocytosis,
dec in urine output in preterm infants aplastic anemia

Interactions:
Decreases total anti-
inflammatory effect of Aspirin
when concomitantly given
CI:
Nasal polyps; Angioedema;
Bronchospastic reactivity to
aspirin
Indomethacin Potent nonselective Decreased Treatment of Patent AE:
COX inhibitor prostaglandin in Ductus Arteriosus; Abdominal pain; Diarrhea; GI
kidneys, leading to NSAID for gout and hemorrhage
Hyperkalemia ankylosing spondylitis
Interaction:
Inhibits With Probenecid:
phospholipase A and Reduced neutrophil Prolongs half-life of
C migration, dec. T cell indomethacin by inh. both
and B cell proliferation renal and biliary clearance
 PHARMA REVIEWER 1.1: NSAIDs, DMARDs, Non-Opioid Analgesics and Drugs used in Gout 10 of
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Naproxen Non-selective COX Decreased PG Effective for usual AE:
(the only NSAID marketed inhibitor synthesis rheumatologic Rare cases of allergic
as a single enantiomer) (free fraction is indications pneumonitis, leukocytoclastic
significantly higher in vasculitis, pseudoporphyria
women than in men)
Others: Diclofenac, Ketoprofen, Ketorolac, Meclofenamate & Mefenamic acid, Piroxicam, Sulindac, Nabumetone, Oxaprozin, Tenoxicam,
Tolmetin, Diflunisal, Etodolac, Fenoprofen, Flurbiprofen, Tiaprofen, Phenylbutazone,
DISEASE MODIFYING ANTI-RHEUMATIC DRUGS (DMARDs)
DMARDS- Non-Biologicals
Methotrexate Inhibition of Potent inhibition of First choice of treatment AE:
aminoimidazole inflammatory process in Rheumatoid Nausea and mucosal ulcers
carboxamide arthritis (most common)
ribonucleotide Rare: Hepatotoxicity, cirrhosis
(AICAR) Pseudolymphomatous
transformylase & reactions
thimydylate synthase Leucovorin: rescue drug
Interactions:
With PROBENECID (anti-
gout) oral : Increases level of
Methotrexate sodium inj.
CI: Pregnancy

Chloroquine, Suppression of T Not considered as a Tx of skin AE:

Hydroxychloroquine lymphocyte very efficacious manifestations, Ocular toxicity (Toxic ocular
responses to DMARDs serositis, joint pains of neuropathy)
mitogens SLE

Cyclophosphamide Cross-links DNA to Alkylations of DNA SLE; Vasculitis; AE:

prevent cell within the nucleus Wegener’s Bone marrow suppression,
replication. leads to cell death. granulomatosis; Severe Dose-related infertility,
*T cell suppression rheumatic diseases Alopecia, Hemorrhagic
correlates with clinical cystitis, Bladder carcinoma
response in rheumatic (rare)
disease
MESNA (rescue drug)
Cyclosporine Inhibits IL-1 and IL-2 Suppresses the For RA, retards AE:
receptor production; immune system appearance by new Leukopenia,
Inhibits bony erosions Thrombocytopenia, Anemia,
macrophages T cell Cardiotoxicity, sterility in
interaction and T cell women
responsiveness
Leflunomide Inhibits Decrease in RNA For RA AE:
dihydroorotate synthesis and arrest of Diarrhea, inc liver enzymes,
dehydrogenase stimulated cells in the mild alopecia, weight gain
G1 phase

Inhibits T-cell
proliferation
Others: Azathioprine, Sulfasalazine, Mycophenolate Mofetil
DMARDs- Biologicals (Mechanism of Action)
(1) Targets TNF-alpha: Adalimumab, Etanercept, Galimumab, Infliximab, Certolizumab
(2) T cell modulator: Abatacept
(3) B cell cytotoxic: Rituximide
(4) Anti IL-6 antibody: Tecilizumab
NON-OPIOID ANALGESICS
Paracetamol Inhibits COX-3 in the Effective analgesic and For headache, myalgia, AE:
CNS antipyretic; post-partum pain Hepatotoxicity in overdose
For patients allergic to (toxic metabolite: N-acetyl-P-
Weak COX-1 and No anti-inflammatory benzoquinone) (antidote: N-
ASA, have PUD,
COX-2 inhibitor in  and no anti-platelet acetylcysteine);
peripheral tissues inhibiting effect hemophilia Nephrotoxic
Antipyretic for children
with viral infection
(instead of Aspirin)
DRUGS USED IN GOUT
Allopurinol Active metabolite Lowers production of For chronic gout, in AE:GI upset, hypersensitivity,
irreversibly inhibits uric acid between acute SJS, bone marrow
xanthine oxidase Reduced uric acid pool attacks suppression
in the body Interactions:
 PHARMA REVIEWER 1.1: NSAIDs, DMARDs, Non-Opioid Analgesics and Drugs used in Gout 11 of
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Increased effect of
cyclophosphamide
Inhibits metab. of probenecid
and oral anticoagulants;
increase hepatic iron conc.

Febuxostat Potent and selective Reduces formation of Alternative drug (for AE:
inhibitor of xanthine xanthine and uric acid patients with Liver function abnormalities;
oxidase without affecting other allopurinol nausea; diarrhea; headache
enzymes in the purine intolerance) to
and pyrimidine pathway
decrease uric acid for
patients with gouty
nephropathy

URICOSURIC Competitively Increase renal For patients in whom AE:

Probenecid, Sulfinpyrazone
Colchicine
inhibits uric acid excretion of uric acid febuxostat and GI irritation
reabsorption in the allopurinol are
proximal tubule of contraindicated; for
the kidney tophaceous gout
Binds to Decreased Primary treatment for AE:
intracellular protein macrophage migration acute gout Diarrhea (most common) 
tubulin, prevents and phagocytosis Prophylaxis of recurrent Bone marrow toxicity (IV)
polymerization
episodes of gouty
arthritis

NSAIDs Inhibits PG synthase See common properties of NSAIDs

(except ASA, Salicylates Inhibits urate crystal
and Tolmetin) phagocytosis

Preferrably: Indomethacin
Glucocorticoids For severe symptomatic gout
Prednisone
Others: Pegloticase and Interleukin