JIGAWA STATE COLLEGE OF NURSING SCIENCES HADEJIA CAMPUS

PHARMACOLOGY LECTURE NOTE FOR SET FIVE STUDENT NURSES

TOPIC: DRUGS USED IN THE TREATMENT MUSCULOR SKELETAL DISORDERS

NON-STEROIDAL ANTI INFLAMMATORY DRUGS (NSAIDs)

Non-steroidal anti-inflammatory drugs or NSAIDs are a group of drugs that reduce

inflammation and pain. They are mainly used for arthritic disorders and
musculoskeletal pain.

Aside from their analgesic, antipyretic and anti-inflammatory effects, they also
decrease platelet aggregation which is useful in preventing conditions caused by
thromboembolism such as transient ischemic attacks, myocardial infarction, and
stroke.

NSAIDs work by inhibiting the activity of cyclooxygenase enzymes (the COX-1 and
COX-2 isoenzymes). In cells, these enzymes are involved in the synthesis of key
biological mediators, namely prostaglandins, which are involved in inflammation,
and thromboxane, which are involved in blood clotting.

There are two general types of NSAIDs available: non-selective, and COX-2
selective. Most NSAIDs are non-selective, and inhibit the activity of both COX-1
and COX-2. These NSAIDs, while reducing inflammation, also inhibit platelet
aggregation and increase the risk of gastrointestinal ulcers and bleeds. COX-2
selective inhibitors have fewer gastrointestinal side effects, but promote
thrombosis, and some of these agents substantially increase the risk of heart
attack.

Actions of NSAIDs
The inhibition of prostaglandin biosynthesis is the main mechanism for the anti-
inflammatory and analgesic effect of NSAIDs. They block the cyclooxygenase thus
preventing arachidonic acid from synthesizing prostaglandins. Arachidonic acid is
liberated when there is cell membrane damage during inflammation.

They are classified based on their chemical structures with each category having
slightly different characteristics.

Gastrointestinal

NSAID the acidic molecules directly irritate the gastric mucosa, and inhibition of
COX-1 and COX-2 reduces the levels of protective prostaglandins. Inhibition of
prostaglandin synthesis in the GI tract causes increased gastric acid secretion,
diminished bicarbonate secretion, diminished mucus secretion and diminished
trophic effects on the epithelial mucosa.

Renal

NSAIDs are also associated with a fairly high incidence of adverse drug reactions
(ADRs) on the kidney and over time can lead to chronic kidney disease. The
mechanism of these kidney ADRs is due to changes in kidney blood flow.
Prostaglandins normally dilate the afferent arterioles of the glomeruli. This helps
maintain normal glomerular perfusion and glomerular filtration rate (GFR), an
indicator of kidney function. This is particularly important in kidney failure where
the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II
levels. At these elevated levels, angiotensin II also constricts the afferent arteriole
into the glomerulus in addition to the efferent arteriole it normally constricts.
Since NSAIDs block this prostaglandin-mediated effect of afferent arteriole
dilation, particularly in kidney failure, NSAIDs cause unopposed constriction of the
afferent arteriole and decreased RPF (renal perfusion flow) and GFR.

There are 2 types of cyclooxygenases, COX1 and COX2. COX1 is inherently and
continuously produced by the body while COX2 is produced only during tissue
injury at the site of damage.

Some drugs inhibit both cyclooxygenases while some selectively inhibit COX2.
The 2 types of cyclooxygenase inhibition:

Non – selective COX inhibitors – These NSAIDs block both the cyclooxygenase 1
and 2 pathways resulting in two effects – arresting inflammation and preventing
platelet aggregation.

Selective COX2 inhibitors – This class of NSAIDs were developed mainly to inhibit
inflammation without the side effects that arise from inhibition of COX-1 which
include gastric and duodenal ulcers and bleeding. As such, these drugs can be
used to treat inflammatory disorders but are not useful for the prevention of
diseases that depend on COX-1 inhibition. Desirable effects of NSAIDs.

Classification

NSAIDs can be classified based on their chemical structure or mechanism of

action.

Salicylates

Aspirin (acetylsalicylic acid)

Diflunisal (Dolobid)

Salicylic acid and its salts

Salsalate (Disalcid)

Propionic acid derivatives

Ibuprofen

Dexibuprofen

Naproxen

Fenoprofen

Ketoprofen

Dexketoprofen
Flurbiprofen

Oxaprozin

Loxoprofen

Pelubiprofen

Zaltoprofen

Acetic acid derivatives

Indomethacin

Tolmetin

Sulindac

Etodolac

Ketorolac

Diclofenac

Aceclofenac

Bromfenac

Nabumetone (drug itself is non-acidic but the active, principal metabolite has a
carboxylic acid group)

Enolic acid (Oxicam) derivatives

Piroxicam

Meloxicam

Tenoxicam

Droxicam

Lornoxicam
Isoxicam

Phenylbutazone (Bute)

Anthranilic acid derivatives (Fenamates)

The following NSAIDs are derived from fenamic acid

Mefenamic acid

Meclofenamic acid

Flufenamic acid

Tolfenamic acid

INDICATIONS

NSAIDs are often suggested for the treatment of acute or chronic conditions
where pain and inflammation are present. NSAIDs are generally used for the
symptomatic relief of the following conditions

For analgesic and anti-inflammatory effects:

Rheumatoid arthritis

Osteoarthritis

Localized musculoskeletal syndromes like sprains, strains, and low back pains

Gouty arthritis

Juvenile rheumatoid arthritis

Systemic lupus erythematous

Psoriatic arthritis

Dysmenorrhea

Metastatic bone pain

Postoperative pain

Muscle stiffness and pain due to Parkinson's disease

Pyrexia (fever)

Renal colic

Macular edema

Traumatic injury

Chronic pain and cancer-related pain

For prevention due to antiplatelet effects:

Transient ischemic attack

Coronary artery disease

Cerebrovascular disease

Angina

Colon cancer

Side Effects and Adverse Effects of NSAIDs

The most common side effects are as follows:

Allergic reactions like Urticaria and wheals

Headaches

Dizziness

Fluid retention and edema

Abdominal pain

Dyspepsia

Nausea
Vomiting

Rashes

Pruritus

Asthma attack

Less common side effects include:

Thrombocytopenia

Neutropenia

Aplastic anemia

Abnormal liver function test results

Liver failure

Renal insufficiency

Renal failure

Hyperkalemia

Proteinuria

Congestive heart failure

Myocardial infarction

Gastric and duodenal ulcers

Gastrointestinal bleeding

Contraindications and cautions for NSAIDs

 NSAIDs are contraindicated in patients with the following conditions:

 Patients with hemophilia – NSAIDs have anti-platelet effects that can

exacerbate the bleeding tendencies and may be fatal for these patients.
  Previous NSAID or salicylate hypersensitivity – any previous hypersensitivity
to medication is a contraindication for repeated use of the said medication.

 Asthma attack after ingestion of NSAIDS – such events should be noted as

subsequent attacks may be severe and can be life-threatening.

 Patients who have recently undergone coronary artery bypass graft surgery
– studies have shown an increased risk of myocardial infarction for some
NSAIDs for these patients.

NSAIDs should be used with caution in patients with the following conditions:

Chronic kidney disease

Medication allergy

Hypertension

Diabetes mellitus

Bronchial asthma

Systemic lupus erythematous

Gastric and duodenal ulcers

History of gastrointestinal bleeding

History of bleeding disorders other than hemophilia

Concurrent condition that has bleeding tendencies like dengue and chikungunya
fevers

Recent viral infections like chickenpox and flu. Studies have associated NSAID use
with the development of Reye syndrome, a condition that causes swelling in the
liver and brain.
Drug Interactions with NSAIDs

NSAID metabolism is mainly through the liver by way of the cytochrome P450
system and eliminated through the kidneys. Therefore, all drugs that are
metabolized by these similar enzymes and pathways will have interactions with
NSAIDs to varying extents.

Their effect on the arachidonic acid – prostaglandin pathways of reducing

inflammation and decreasing platelet aggregation crosses with the mechanisms of
actions of several other drugs as well. The following drugs should be used with
caution when taken with NSAIDs.

Drugs that act on the hematopoietic system such as anti-thrombotic and other
anti-platelets increase the risk of bleeding. Examples of these drugs are warfarin,
heparin, novel anti-coagulants, and other anti-platelets.

NSAIDs attenuate the effect of most anti-hypertensive drugs. Taking NSAIDs with
these drugs may decrease their effectiveness and cause increased blood pressure.
Such drugs include ace-inhibitors, angiotensin receptor blockers, thiazide diuretics
and loop diuretics.

NSAIDs may affect the kidney through the regulation of the renal artery’s blood
flow. Drugs that act on the kidneys may precipitate damage when used with
NSAIDs. Drugs that are eliminated through the kidneys may show decreased renal
clearance and increased toxicity. These drugs include the mood disorder drugs,
anti-cancer drugs, cardiac drugs, and nephrotoxic anti-bacterial drugs like
aminoglycosides.

Some drugs interact with NSAIDs through their metabolism in the liver. Anti-
epileptic drugs may show decreased hepatic clearance and displacement from
protein binding since NSAIDs are also highly protein-bound.

Oral anti-diabetic drugs may induce further hypoglycemia when taken with
NSAIDs
Drugs that affect the gastrointestinal tract like corticosteroids may increase the
risk of ulceration and bleeding. Antacids may interfere with the absorption of
NSAIDs.

Nursing Care Plan for Patients on NSAIDs

 Possible Nursing Diagnoses

Nausea and Vomiting due to the gastrointestinal side effects of NSAIDs

 Acute Pain (gastric)

 Risk for Hypoglycemia related to drug interactions between NSAIDs and

anti-diabetic agents

 Risk for Impaired Urinary Elimination related to the effects of NSAIDs on the
kidneys

 Risk for Bleeding (Gastrointestinal) related to drug interactions between

NSAIDs and antacids or corticosteroids

 Deficient Knowledge related to new drug prescription

Nursing Interventions for NSAID

1. Verify the patient’s diagnosis and the need for administering NSAIDs. To
confirm the indication for administering NSAIDs.

2. Check the patient’s allergy status. Previous allergic reaction to NSAIDs may
render the patient unable to take them. Alternatives to NSAIDs should therefore
be considered in case of allergy.

3. Assess if the patient is pregnant. NSAIDs should not be prescribed to a pregnant

woman who is at 20 weeks or above as these drugs can potentially harm the
kidney function of the developing fetus.
4. Assess the patient’s mucous membranes and his/her ability to swallow. If giving
intravenously, assess the suitability of the vein or the status of the central venous
access device or CVAD. To check for any potential problems with administration,
hydration, and absorption. To ensure that the right form of NSAIDs is given
through the right route.

5. Check for current medication history. Taking corticosteroids, anticoagulants,

antacids, cholinergic agonists with NSAIDs may increase the risk for internal
gastrointestinal upset or bleeding.

6. Check the patient’s serum blood sugar levels if taking anti-diabetics alongside
NSAIDs. Patients on NSAIDs and oral anti-diabetics may experience hypoglycemic
episodes.

7. Ask the patient for any medical or family history of hemophilia, gastrointestinal
ulcers, or bleeding disorders. NSAIDs have anti-platelet effects that can
exacerbate the bleeding tendencies and may be fatal for these patients.

8. Administer NSAIDs with or after meals and on time as prescribed.

9. NSAIDs are best taken on full stomach to reduce the occurrence of stomach
upset.

10. NSAIDs should always be taken on time to prevent any delays and errors
during treatment.

11. Educate the patient about the action, indication, common side effects, and
adverse reactions to note when taking NSAIDs. Instruct the patient on how to self-
administer oral NSAIDs. Monitor the patient’s input and output. NSAIDs may
cause impaired urinary elimination.

 ASPIRIN (Ecotrin and buffering)

Group: it is non-steroidal, anti-inflammatory, anti-rheumatic and anti-pyretic

analgesic.

MODE OF ACTION: it inhibits prostaglandins synthesis thereby reducing pain

impulses produced by prostaglandin and also act on the heat regulation in the
hypothalamus to send a sympathetic impulse to the body of the sweat gland
under to the skin to produce more sweat evaporates and producing cooling effect
and lowering the body temperature.

INDICATIONS: rheumatoid arthritis, minor aches and pain, feverish condition,

headache, neuritis, myalgia, toothache, poly arthritis, osteoarthritis and soft
tissue inflammation.

DOSAGE: adult 300mg- 900 mg tree times daily

ROUTES OF ADMINISTRATION: Orally and suppository.

CONTRAINDICATION: As discuss above

 VASOPRIN

GROUP: its analgesic, anticoagulant and antipyretic drug.

MODE OF ACTION: As discussed on aspirin.

INDICATION: For the prophylaxis against thromboembolism, primary and

secondary prevention of heart attack and stroke, toothaches headache and
muscular pain etc.

DOSAGE: For cardio vascular treatment 1-2 tablet daily, for pain 4-8 tablet of
75mg every 4hours daily.

SIDE EFFECT AND CONTRAINDICATION: AS Above.

 KETOPROFEN (Oruvail and Orudis)

Group: It is a potent Non-steroidal, anti- gout, anti- inflammatory, anal- gesic,

anti-rheumatic and anti -dysmenorrheal drug.

MODE OF ACTION: it inhibits prostaglandin synthesis there by reducing and and

inflammation.

Indications: as mentioned above

Dosage: for rheumatoid arthritis100- 200mg in 2-4 divided doses with food, for
Dysmenorrhea 50mg tds daily.by rectum in suppository 100mg at bed time. For
injection 50-100mg every 4 hours.

Routes of administration: orally, rectally and intramuscularly.

Side effect: as above

Contraindication: as above.

NURSINGN INTERVENTION: AS above

IBUPROFEN (ESPEN-400, BRUFEN)

GROUP: It is non -steroidal anti- inflammatory, analgesic, anti -pyretic, anti-

rheumatic and anti- dysmenorrheal drug.

MODE OF ACTION: AS discussed under aspirin

Indications: as above

Dosage: one or two tablet b.d or 1’2-1.8g initially for adult daily. For juvenile
rheumatoid arthritis 30-40mg per kg bodyweight in 3-4 divided doses. For fever
and pain in children 20-30mg daily in divided doses.1-3yrs 100mg tds daily,4-6yrs
150mg tds daily,7-9yrs 200mg tds and 10-12yrs 300mg tds daily.

Route of administration: orally.

Side effect: as discussed above

Contraindication: as above

 PIROXICAM (FELDENE)

GROUP: It is non- steroidal anti- inflammatory, analgesic, and anti-gout, anti-

rheumatic and antipyretic drug.

Mode of action: as discussed above

Indications: same as above

Dosage: for arthritis and post- operative pains 20mg once daily. For
dysmenorrhea 40mg daily for 2 days. For acute muscular- skeletal disorder 40mg
daily for 2 days. Then 20mg once daily for 7-14 days. For gout 40mg on first day as
single dose the 40mg daily for 4-6 days in single divided doses. For juvenile
arthritis under 15kg 5mg per kg or 5-20mg base on body weight.

Routes of administration: orally, topically, suppository and intramuscularly.

Side effect: as mentioned above

Nursing responsibility: as above.

 MELOXICAM

Group: it is a non- steroidal anti-inflammatory, anti-rheumatic and analgesic drug

Mode of action: As discussed above

Indication: as mentioned above

Dosage: for osteoarthritis 7.5-15mg daily. For rheumatoid arthritis and ankylosing
spondylitis 15mg once daily for elderly people 7.5mg daily.

Routes of administration: orally and suppository.

Side effect as mentioned above

Contraindication: as discussed above

Nursing responsibility: as above also.

 MEFENEMIC ACID

GROUP: it is a non-steroidal anti-inflammatory, myometrial relaxant, anti-

rheumatic, anti-dysmenorrheal, anti-hemorrhagic and analgesic drug

Mode of action: As discussed above

Indication: As mentioned above

Dosage: initial dose is 500mg then 250mg every 6 hours with onset of menses not
exceed one week. For children over 6month 25mg/kg body weight daily in divided
doses for not longer than 7 days.

Route of administration: orally in tablet or capsule and suspension forms.

Side effect: As discussed above

Contraindication: as discussed above

Nursing responsibility: as discussed above.

 CATAFLAM (Diclofenac potassium)

Group: it is anti-inflammatory, analgesic and anti-pyretic drug

Mode of action: as discussed above.

Indication: sprains, pharyngo-tonsilitis, otitis media, post dental or orthopedic

surgery, primary dysmenorrhea, adenitis, painful syndrome of vertebral column,
post traumatic and post- operative pains.

Dosage: adult and children over 14 yrs 75-150mg in 2-3 divided doses daily. For
primary dysmenorrhea 50mg-150mg daily

Routes of administration: orally

Side effect: as above

Contraindication: As above

Nursing responsibility: as above.

 ACECLOFENAC

Group: it is non-steroidal anti-inflammatory, anti-rheumatic and analgesic drug

Mode of action: as discussed above

Indications: as discussed above

Dosage: 100mg twice daily

Routes of administration: orally

Side effect: As mentioned above

Contraindication and Nursing responsibility as discussed above.

PARACETAMOL (Acetaminophen)

Group: anti-pyretic and analgesic drug.

Mode of action: act on the heat regulation center in the hypothalamus to send a
sympathetic impulse to the body of the sweat gland under to the skin to produce
more sweat evaporates and producing cooling effect and lowering the body
temperature.

Indication: pyrexia of unknown origin, prevention of febrile convulsion, fever and

pain in tonsillitis, upper respiratory tract infection, post immunization reaction
etc.

Dosage: intramuscular or intravenous injection for adult and children of 10 yrs

and above 2-3mls.children of below 10 yrs 1-2ml.

Tablet for adult 500mg-1g 4-6 hours, up to a maximum of 4g daily. Children

between 5-12 yrs 250-500mg 4hours.the syrup for 125mg per 5ml,for age 1-5 yrs
125-250mg.

Routes of administration: intramuscularly, intravenously and orally.

Side effect: liver damage due prolong use of paracetamol.

Contraindication: Hepatic and renal impairment.

Nursing responsibility:

Give intravenous injection slowly

Do not administer to patient with liver disease.

Patient should not exceed maximum recommended dose of 4grm (8 tablets) daily.

XANAP FORTE (PARACETEMOL AND DICLOFENAC SODIUM)

GROUP: IT IS NON STEROIDAL ANTI INFLAMMATORY, ANALGESIC AND ANTI-

PYRETIC DRUG

Mode of action: as discussed under aspirin

Indications; Painful inflammatory condition and fever

Dosage: one tablet two or three times daily

Side effects: As discussed above

Contraindications: As mentioned above

Nursing responsibility: as mentioned above.