Learning objectives

1.be able to describe action mechanisms and side

effects of glucocorticoids and nonsteroiadal anti-
inflammatory drugs and enumerate complications
and contraindications of local glucocorticoid
administration.
2. be able to describe muscle relaxants
classification according to their action mechanisms
(define antispastic and spasmolytic drugs), and
describe clinical usage and side effects.
Non- Streoidal Anti-Inflammatory
Drugs (NSAIIDs)
Benefical effects:
Analgesia
Antipyresis (inhibits PGs in CNS)
Antiinflammatory
Antiplatelet (prevents thromboxane A2
production)
 Mechanism
Inhibiton of the cyclo-oxygenase (COX)
Decrease in prostoglandin production
 Cox-1: stomach, intestine, platelet, kidney
 Cox-2: involved in inflammation
Inhibition of lipoxygenase (sulindac,
diclofenac)
Inhibiton of neutrophil adhesion (aspirin,
indomethacin)
Inhibition of cytokine production
 Classification
Salicylates Anthranilic acid
 Aspirin Mefenamic acid
 Diflunisal Sulfananilides
Para-aminopheno Nimesulid
 Acetaminophen
Heteroaryl acetic acid
Diclofenac
Acetic acids
Ketolorac
 Indomethacin
Arylpropionic acid
 Sulindac
Ibuprofen
 Etodolac
Naproxen
Ketoprofen
 Classification
Enolic acid Cox-2 selective
 Piroxicam Etodolac
 Meloxicam Diclofenac
Alkanones Nabumetone
 Nabumetone
Meloxicam
Coxib
 Celecoxib
 Etoricoxib
 Lumiracoxib
 Side effects
Hepatotoxicity Nephrotoxicity
 İdiosynchratic hepatit  Papillary necrosis

(indomethacin,  İncreased sodium

diclofenac) retantion
 Cholestasis  Decreasing GFR

GİS  Acute tubular necrosis

 Dyspepsia  Acute intersititial

 GOR nephritis
 Peptic ulcer

 Hemorrhage
 Who is at risk for GD ulcers
Elderly
History of PU
Higher dosage
Chronic diseases
Anticoagulant therapy
Corticosteroid use
Tobacco and alcohol
 Protection
Misoprostol (PGE1 analog)
Proton Pump inhibitors
 Glucocorticoids(GC)
GC are widely used for the suppression of
inflammation in chronic inflammatory
diseases such as asthma, RA,
inflammatory bowel disease and
autoimmune diseases.
GC inhibit the expression of multiple
inflammatory genes
 Glucocorticoids(GC)
GC increase the syntesis of lipocortin-1,
that has inhibitory effect on phospholipas
A2 and therefore inhibit the production of
lipid mediators as well as inhbit genes
coding for COX-2.
 Some commonly used
glucocoticoids
Equivalent oral dose(mg)
Cortisol 20
Prednisolone 5
Methylprednisolone 4
Triamcinolone 4
Dexamethasone 0.75
 Dosing (EULAR)
Low dose up to 7.5 mg/d
Medium dose > 7.5 but ≤ 30 mg/d
High dose >30 but ≤ 100 mg/d
 Advers Effects
Bone and muscle:
Osteoporosis
Mean first- year loss of bone ranging from
1.5-20% at the dose range ≤ 10 mg/d
prednisolone.
Addition to GC theraphy Ca and vit D or
bisphosphonate should recieve to patient.
Osteonecrosis
Myopathy
 Advers Effects
Cardiovascular:
Fluid retention (Hypertension)
Affect lipid profile
Premature atherosclerotic vascular
disease
Cardiac arrythmias
 Advers Effects
Dermatologic and appearance
Skin thinning
Ecchymoses
Cushingoid appearance
Hirsutism
Stria
Impair wound healing
Weight gain
 Advers Effects
Gastrointestinal Metabolic and
Gastritis endocrine
Ulcers DM
Gastrointestinal HPA insufficiency
bleeding Neuropsychiatric
Infectious diseases Imsomnia
Ophtalmologic Memory impairment
Cataracts Depression
Increased intra-ocular Psychosis
pressure
 Injections of steroids

These more invasive therapeutic methods

are recognized for the treatment of many
disorders of the musculoskeletal system.
However, except in certain rare cases,
their use over a prolonged period is not
recommended.
Complications The physician should
Hemarthrosis, also recommend that
Exacerbation of the the patient not put
inflammation and pain, any undue tension on
Infection, tendons close to the
Soft tissue atrophy injection site so
Thinning of the skin as to prevent their
Changes in skin possible rupture
pigmentation.


Contraindications
 Any localized or generalized infectious
process,
 Fracture, the wearing of a joint brace,
 Coagulation problems,
 No relief after the first injection.
 Muscle relaxants

The effectiveness of these medications is

much debated.
But it is particularly important to show
prudence when the subjectis elderly, and
to write prescriptions that take into
account the following adverse side effects:
drowsiness, confusion, anticholinergic
effects
 Classification

Peripherally acting (Neuromuscular

blockers)
Centrally acting
Baclofen -Diazepam
Direct acting
Dantrolene
 Spasmolytic agents

Spasticity-characteristics
Increased tonic stretch reflexes
Increased flexor muscle spasm
Muscle weakness
Clinical conditions of spasticity:
Cerebral palsy, Multiple sclerosis, Stroke
Clinical spasticity:
Reflex arc involvement
Higher center affects descending pathways leading to alpha
motoneurons hyperexcitability
Mechanisms (↓ spasticity)
– Alteration in stretch reflex arc
– Attenuation of excitation-contraction coupling
 SPASMOLYTIC DRUGS

(Central effect)
Diazepam
Baclofen
Tizanidine
Dantrolene
Carisoprodol (Soma, Rela)
chlorphenesin (Maolate)
chlorzoxazone (Paraflex)
cyclobenzaprine (Flexeril)
metaxalone (Skelaxin)
methocarbamol (Robaxin)
orphenadrine (Norflex)
Skeletal
There are 2 main categories of skeletal muscle
relaxants: antispastic (such as baclofen or
dantrolene) for conditions such as cerebral palsy
and multiple sclerosis and antispasmodic agents
for musculoskeletal conditions.
The most commonly prescribed antispasmodic
agents are carisoprodol, cyclobenzaprine,
metaxalone, and methocarbamol.
In comparison trials, no single skeletal muscle
relaxant has been proven to be superior to
another
The most widely studied agent is
cyclobenzaprine, with demonstrated efficacy for
various musculoskeletal conditions but with
significant sedation
Tizanidine, which also causes marked sedation,
or cyclobenzaprine may be useful in patients with
insomnia because of severe muscle spasms.
All skeletal muscle relaxants are
associated with adverse effects including
dizziness and drowsiness,

Although methocarbamol and metaxalone

are less sedating than tizanidine and
cyclobenzaprine, evidence is limited for
their efficacy.
A specific skeletal muscle relaxant should
be chosen according to consideration of
adverse effect profile, patient preference,
potential for abuse, and possible
interactions with other prescribed
medications because comparable efficacy
data are limited.
Despite their popularity, skeletal muscle
relaxants should not be the primary drug class of
choice for musculoskeletal conditions,"
The American Pain Society and the American
College of Physicians recommend using
acetaminophen and...NSAIDs as first-line agents
for acute low back pain and reserving skeletal
muscle relaxants as an alternative treatment
option.
Skeletal muscle relaxants are better than
placebo, but not more effective than NSAIDs in
patients with acute back pain.