-Barrier defenses

-Cellular defenses
-Inflammatory response
-Immune response
 Acts as a physical
barrier to protect the
internal tissues and
organs of the body.

 Normal bacterial flora

of the skin help to
destroy many disease-
causing pathogens.
 Line the area of the
body that are exposed
to external influences
but do not have the
benefit of the skin
protection.
 Acts as a physical
barrier to invasion.
 Secretes sticky mucus
 The stomach secretes
acid in response to
many stimuli.
 The ability to
distinguish between
self-cells and foreign
cells.
 major
histocompatibility
compplex (MHC)
 Produces
histocompatibility
antigens, or human
leukocyte antigens
(HLAs).s
 Stem cells
in the bone marrow

White Blood Cells or

Leukocytes

Lymphocytes Myelocytes

T cells Neutrophils

B cells Basophils

Natural Killer Cells Eosinophils

Monocytes/
Macrophages
 - called PHAGOCYTES -because neutrophils
are able to engulf and digest foreign material

 polymorphonuclear leukocytes that are

capable of moving outside of the blood
stream and engulfing and digesting foreign
material (phagocytosis).
 Myelocytic leukocytes that are not capable of
phagocytosis.
 Contain chemical substances or mediators
important for initiating and maintaining an
immune or inflammatory response.
 Histamine, heparin, and other chemical used in
the inflammatory response.
 Mast cells
 Basophils that are fixed and do not circulate.
 Circulating myelocytic leukocytes whose
exact function is not understood.
 Often found at the site of allergic reactions.
 They help to remove
foreign material from
the body, including
pathogens, debris from
dead cells, and necrotic
tissue from injury sites,
so the body can heal.
 They can also process
antigens and present
them to active
lymphocytes for
DESTRUCTION.
 Kupffer cells – liver
 Cilia – alveoli of the respiratory tract
 Microglia – CNS, GI, circulatory, and lymph
tissues

 Active phagocytes
 Macrophage release chemicals that are necessary
to elicit a strong inflammatory reaction.
 Lymph nodes, spleen, thymus gland, bone
marrow, and lymphoid tissue found
throughout the respiratory and GI tracts.
 Tissue Injury

Activation of the chemical in

the plasma

Factor XII or Hageman

factor

Plasminogen
Kinin system Clotting cascade
system
Hageman Factor Kallikrein Kininogen

Local Bradykinin ARACHIDONIC

vasodilation ACID
-Blood and WBC -Release of Autacoids
PAIN
- Nerve endings
are stimulated
 Prostaglandins
 Some of which augment the inflammatory
reaction and some of which block it.
 Leukotrienes
 Some of which can cause vasodilation and
increased permeability, and some of which can
block the reactions.
 Thromboxanes
 Which cause local vasoconstriction and facilitate
platelet aggregation and blood coagulation.
 Injury to a cell
↓
Local release of HISTAMINE
↓
Vasodilation
Alters capillary permeability
Stimulates pain perception

Vasodilation and changes capillary permeability bring

neutrophils to the area to engulf and get rid of the invader or to
remove the cell that has been injured.
 Ability to attract neutrophils and to stimulate
them and other macrophages in the area to
be very aggressive.
 Activation of the neutrophils and other
chemicals into the area can lead to cell injury
and destruction.
 When destroyed, the cell releases various
lysosomal enzymes that dissolve or destroy
cell membranes and cellular proteins.
 The lysosomal enzyme are an important part
of biological recycling and the breakdown of
once living tissues after death.

 In the case of an inflammatory reaction, they

can cause local cellular breakdown and
further inflammation which can develop into
vicious cycle leading to cell death.
 Many inflammatory diseases such as
rheumatoid arthritis (RA) and systemic lupus
erythematosus (SLE), are examples of these
uncontrolled cycles.

 Prostaglandins and Leukotrienes are

important to the inflammatory response
because they act to moderate the reaction,
thus preventing this destructive cycle
 Many of the drugs used to affect the
inflammatory and immune system modify or
interfere with these inflammatory reaction.
 Calor or heat
 Occurs because of the increased blood flow to the
area
 Tumor or swelling
 Occurs because of fluid that leaks into the tissues as a
result of the change in capillary permeability
 Rubor or redness
 Related to increase blood flow caused by vasodilation
 Dolor or pain
 Comes from the activation of pain fibers by histamine
and kinin system
 Pyrogen
 Fever- causing substance released by active
neutrophils as it engulf, and digest injured cells or
the invaders
 Resets specific neurons in the hypothalamus to
maintain higher temperature (fever)
 The higher temperature acts as a catalyst to
many body’s chemical reactions, making the
inflammatory and immune responses more
effective.
 Treating fevers remains a controversial
subject because lowering a fever decreases
the efficiency of the immune and
inflammatory response.
 Energy Conservation
 Leukotrienes affect the brain to
induce slow-wave sleep, which is
believed to be an important energy
conservation measure for fighting
the invader.
 Energy Conservation
 They also cause myalgia and arthralgia (muscle
and joint pains)- common signs and symptoms of
various inflammatory diseases which also cause
reduced activity and save energy.

 All these chemical responses make up the total

clinical picture of an inflammatory reaction
T cells
B cells
Complement Proteins
Antibody formation
Other mediators: interferons secreted by cells
that have been invaded by viruses; prevent viral
replication,suppress malignant cell replication
and tumor growth
 Produced in bone marrow as lymphocytes
that can develop into T lymphocytes
 Programmed in the thymus gland and
provide what is called cell-mediated
immunity
 Effector or Cytotoxic T cells
 Aggressive against non-self-cells, releasing cytokines, or
chemicals, that can either directly destroy a foreign cell or
mark it for aggressive destruction by phagocytes in the
area by inflammatory response.
 Helper T cells
 Respond to chemical indicators of immune activity and
stimulate lymphocytes, including B cells, to be more
aggressive and responsive.
 Suppressor T cells
 Respond to the rising levels of chemicals associated with
immune response to suppress or slow the reaction.
 Programmed to identify specific proteins, or
antigens.
 They provide humoral immunity.
 Plasma cell produce antibodies or
immunoglobulins (circulates in the body and react with
this specific antigen) to form a new antigen-
antibody complex.
 This new Ag-Ab complex will activate a series
of plasma proteins called complement
system
 React in a cascade fashion to form a ring
around Ag-Ab complex
 It can destroy the antigen by altering the
membrane and allowing the osmotic inflow
of fluid that causes the cell to burst.
 Induce chemotaxis; increase the activity of
phagocytes and release histamine.
 Histamine release causes vasodilation-
increases blood flow to the area to destroy
the antigen.
 Once activated B cells form memory cells
that will produce antibodies in the form of
immunoglobulins:
 IgM- 10% produced at first exposure to the antigen
 IgG- 75% found in serum
 IgA- 15% found in tears, saliva, sweat, mucus,and
bile.secreted by plasma cells in GI and respi
tract,and in epithelial cells.
 IgE- 0.004related to allergic response and activation
of mast cells
 IgD- 0.2% B lymphocyte differentiation /role not
determined
 The process of antibody formation called
acquired or active immunity, is a lifelong
reactoin.is
 Interferons- are chemicals secreted by cells
that have been invaded by viruses and other
stimuli
 - Prevent viral replication, suppress malignant
cell replication and tumor growth
 Interleukins – are chemicals secreted by
active leukocytes to influence other
leukocytes
 Interleukin I (IL-1)stimulates T and B cell to
initiate an immune response
 Interleukin 2(IL-2) is released from active T
cells to stimulate the production of more T
cells and to increase the activity of B cells,
cytotoxic T cells and natural killer cells.
 Interleukins also cause fever, arthralgia,
myalgia, and slow-wave sleep induction-all
help the body to conserve energy for use in
fighting off the invader.
 Lymphocytes & Basophils release Interleukins
such as:
 B-cell growth factor
 Macrophage-activating factor
 Macrophage-inhibiting factor
 Platelet- activating factor
 Eosinophil chemotactic factor
 Neutrophil chemotactic factor
 Thymus gland- releases Thymosin, hormones
that aid in the maturation of T cells and cell-
mediated immunity.

 Tumor necrosis factor (TNF) a cytokine is a

chemical released by macrophages that
inhibits tumor growth and cause tumor
regression. Also help to make inflammatory
and Immune Response effective.
 -Both work together to protect the body and
to maintain a level of homeostasis within the
body.
 Helper T cells stimulate the activity of B cells
and effector T cells
 Suppressor T cells monitor the chemical
activity in the body and act to suppress B cell
and T cell activity when foreign antigen is
under control.
 Both B cells and T cells ultimately depend on
the effective inflammatory reaction to
achieve the end goal of destruction of the
foreign protein or cell.
 Neoplasms
 Viral invasion of cells
 Autoimmune Disease
 Transplant rejection
 Neoplasms occur when mutant cells escape
the normal surveillance of the immune
system and begin to grow and multiply
-aging lowers immune system
-Location- breast tissue- low blood supply
-tumors- produce blocking antibodies
 Invasion of a cell alters the cell membrane
and the antigenic presentation of the cell
(MHC) – thus activate cellular immunity or
weaken immune system’s response
 Occurs when the body responds to specific
antigen to produce antibodies or cell –
mediated IR against its own cells due to:
-in response to cell that was invaded by a
virus leading to antibody production to
similar cells
-failure of suppressor T cells to suppress
normal production of autoantibodies
-genetic predisposition to develop
autoantibodies
 Self /auto transplantation- no IR

 All other transplantation produce an IR

 Matching a donor’s HLA marker

 More closely matched, the lesser the IR

SALICYLATES
NONSTEROIDAL ANTIINFLAMMATORY AND RELATED AGENTS
ANTIARTHRITIS
AGENTS
 Drug in focus: aspirin
 Treatment of fever, pain, inflammatory
conditions; at low dose to prevent the
risk of death and MI in patients.
 Drug in focus: aspirin
 ACTION:
 Salicylates block prostaglandin activity,
which Inhibits the synthesis of
prostaglandins; blocks the effects of
pyrogens at the hypothalamus; inhibits
platelet aggregation by blocking
thromboxane A2.
Drug in focus: aspirin
 Common Adverse Effects: Salicylates can
cause GI irritation, eighth cranial nerve
stimulation, and salicylism — ringing in the
ears, acidosis, nausea, vomiting, diarrhea ,
mental confusion, and lassitude.
 Contraindication:?______________________
 Nursing Responsibilities:_________________
 Drug class-
 Analgesic: anti- inflammatory drug
 Trade name: ASA, Bayer, Ecotrin
 *Astrin
 Pregnancy category: D
 Dosage:
 Analgesic:
 A:PO:325-650mg q 4h PRN; max 4 g/d
 C:PO: 10-15 mg/kg in 4 to 6 divided doses; max:4 g/d
 TIA and thromboembolic condition
 A:PO:81-325 mg/d
 Arthritis:
 A.PO:3 g/d in divided doses
 TDM: 15-30 mg/dl; 150 to 300 mcg/ml
 Hypersensitivity to salicylates or NSAIDs, flu
or virus symptoms in children, anticoagulant
therapy, GI bleeding , bone marrow
suppression, third trimester of pregnancy

 Caution: renal or hepatic disorders, gout, alcoholism

 Lab: Decrease cholesterol and potassium, T3T4
levels, increase PT , bleeding time , uric acid
 Drug: increase risk of bleeding with
anticoagulants /NSAIDs
 Increase risk of hypoglycaemia with oral
hypoglycemic drugs;
 Increase ulcerogenic effect with
glucocorticoids
 To reduce pain and inflammatory
symptoms
 to decrease body temperature; to inhibit
platelet aggregation
 Mode of Action:
 Inhibition of prostaglandin synthesis,
inhibition of hypothalamic heat-
regulator center
 Anorexia, nausea, vomiting,
diarrhea, dizziness, confusion,
hearing loss, heartburn , rash,
abdominal pain, drowsiness
 Tinnitus, urticarial, ulceration, GI
bleeding,
 Life- threatening: Agranulocytosis,
hemolytic anemia, bronchospasm,
anaphylaxis, thrombocytopenia, Reye’s
syndrome, hepatotoxicity, leukopenia
 Assessment :
 Obtain medical hx- gastric upset/bleeding/ liver
disease
 Aspirin can cause gastric irritation, prolongs
bleeding time by inhibiting platelet
aggregation

 Obtain drug history-report drug-drug

interaction
 Risk for injury r/t vertigo

 Chronic pain r/t tissue swelling of

rheumatoid arthritis
 The patient’s pain will be reduced
within 12 to 24 hrs

 The patient’s inflammation will be

reduced within one week
1. Monitor serum salicylate (aspirin)
for chronic conditions
15-30 mg/dl normal therapeutic range
 >30mg/dl-mild toxicity
 >50mg/dl –severe toxicity
2. Observe for signs of bleeding:(high doses)

Dark tarry stools, bleeding gums,

petechiae, (round red spots)
ecchymosis (excessive bruising)
purpura (large red spots)
 Do not take aspirin with alcohol or drugs that
are highly protein bound such as anticoagulant -
warfarin sodium (Coumadin)
 Inform dentist before dental visit
 Discontinue aspirin 3-7 days prior to surgery
 Keep bottle of aspirin out of reach of children
 -educate parent to call poison control center
in case child has taken unknown amount
(acetaminophen)
 Warn patients: not to administer aspirin for
virus or flu symptoms in children
 Reye’s syndrome: (vomiting, lethargy, delirium
and coma) has been linked with aspirin and
viral infection
 Acetaminophen is usually prescribed for cold
and flu symptoms.
 Inform patient aspirin can cause GI distress
 For dysmenorrhea take
acetaminophen instead of aspirin 2
days before and during the first two
days of the menstrual period.
 Side effects:
 report drowsiness, tinnitus (ringing in the
ears), headaches, flushing, dizziness, GI
symptoms (bleeding, heartburn)visual
changes and seizures.
 Cultural consideration:
 Don’t misunderstand loud voice
 Diet
 Instruct to take aspirin with food, at mealtime
or with plenty of water

 EC (enteric coated) aspirin helps prevent GI

disturbance

 Evaluate effectiveness; if pain persist try

another analgesic like ibuprofen
 Determine side effects to aspirin
 Nonsteroidal anti-inflammatory
drugs (NSAIDs)
 NSAIDs Are: aspirin and aspirin –like drugs
that inhibit the enzyme COX which is needed
for the biosynthesis of prostaglandins-

 Hence they are called prostaglandin inhibitors

with varying degrees of analgesic & antipyretic
effects but are used as anti-inflammatory
agents to relieve inflammation and pain.
 With several exceptions NSAIDs are not
suggested for use in alleviating mild
headache and mildly elevated temperature.

 Preferred drugs for headache and fever are:

 Aspirin , acetaminophen, ibuprofen (high
fever)

 NSAIDs are more appropriate for reducing

swelling, pain and stiffness in joints.
 Other than aspirin the only NSAIDs that
can be purchased OTC (over the counter )
are:
 ibuprofen (Motrin, Advil, ) and
 naproxen (Aleve)

 Ibuprofen is also available in generic

form in 200mg tablets /capsules
 Anaprox, Celebrex,
 Clinoril, Daypro,
 Equagesic, Naprosyn,
 Percodan, Relafen,
 Soma Compound,
 Talwin, and Toradol.
 Salicylates
 Para- chlorobenzoic acid derivatives or
indoles
 Phenylacetic acids
 Propionic acid derivatives
 Fenamates
 Oxicams
 Selective COX-2 inhibitors
 Provide strong anti-inflammatory and
analgesic effects without the adverse
effects associated with corticosteroids

 Drug in Focus:
 Ibuprofen and Acetaminophen
 Drug class-NSAIDs: propionic acid
derivative
 Trade name: Motrin, Advil
 Pregnancy category C (D third trimester)

 Dosage:
 A: PO:200-800mg t.i.d./q.i.d.; max
2400mg/d
 Contraindication: severe renal or
hepatic disease, asthma,peptic
ulcer, anticoagulant therapy
 caution:bleeding dis orders,
pregnancy, lactation, systemic lupus
erythematosus
 Drug –lab-food interactions
 Drug:
 increase bleeding time with oral
anticoagulants;
 increase effects of phenytoin,
sulphonamides, warfarin;
 decrease effect with aspirin,
 may increase severe side effects of lithium
 Pharmacodynamics :
 PO: onset 1 h
 Peak: 2-4 h
 Duration:4-6 h
 Therapeutic effects/ uses:
 To reduce inflammatory process
 To relieve pain, anti-inflammatory effect for
arthritic conditions
 To reduce fever
 Mode of action: inhibition of prostaglandin
synthesis thus relieving pain and
inflammation
 Indication: treatment of pain, arthritis,
dysmenorrhea and juvenile arthritis.

 Actions: Inhibits prostaglandin synthesis

by blocking cyclooxygenase-1 and -2
receptor sites, leading to an anti-
inflammatory effect, analgesia, and
antipyretic effects.
NSAIDs block two enzymes, known as
cyclooxegenase-1 (COX-1) and
cyclooxygenase -2 (COX-2).

 COX-1 protects the stomach lining and

regulates blood platelets

 COX-2 triggers inflammation and pain

 Cyclooxygenase (COX) Is the enzyme
responsible for converting arachidonic
acid into prostaglandins and their
products.

 This synthesis of prostaglandins causes

inflammation and pain at a tissue injury
site.
 Cyclooxygenase - COX-1- is present in all
tissues and seems to be involved in
many body functions including blood
clotting, protecting the stomach lining,
and maintaining sodium and water
balance in the kidney.

-turns arachidonic acid into prostaglandins

as needed in a variety of tissues.
 COX- 2 is active at sites of trauma or injury
when more prostaglandins are needed, but it
does not seem to be involved in other tissue
functions.

 By interfering with this part of inflammatory

reaction, NSAIDs block inflammation before
all the signs and symptoms can develop.
 Most NSAIDs block various other functions of
prostaglandins, including protection of the
stomach lining, regulation of blood clotting,
and water and salt balance in the kidney.

 COX-2 inhibitors are thought to act only at

sites of trauma and injury to more specifically
block the inflammatory reaction.
 New NSAIDs blocks only COX-2 but not
COX-1; leaves protection for the
stomach lining intact (no gastric
bleeding and ulcers) but still delivers
relief for pain and inflammation.
 COX -2 inhibitor approved by US-FDA is:
 celecoxib (Celebrex)

 Drugs similar to COX -2 inhibitor which allow

some stomach protection are:
 meloxicam (Mobic)
 nabumetone ( Relafen)
 NSAIDs are indicated for relief of
the signs and symptoms of
rheumatoid arthritis and
osteoarthritis, for relief of mild to
moderate pain, for treatment of
primary dysmenorrhea, and for
fever reduction.
 Side effects:
 Anorexia, nausea and vomiting (n/v),
diarrhea, edema, rash, purpura,
tinnitus, fatigue (related to prostaglandin
activity in the CNS), dizziness,
lightheadedness, anxiety, confusion,
fluid retention with edema.
 Adverse effects:
 GI bleeding
 often cause for discontinuance of the drug
 Life threatening:
 Blood dyscrasias, cardiac
dysrhythmias, nephrotoxicity,
anaphylaxis
Indication:
Treatment of mild to moderate pain,
fever, or signs and symptoms of the
common cold or flu; musculoskeletal
pain associated with arthritis and
rheumatic disorders
 Actions:
 Acts directly on the hypothalamus
to cause vasodilation and sweating,
which will reduce fever; mechanism
of action as an analgesic is not
understood.
 Adverse effects: Rash, fever, chest pain, liver
toxicity and failure, bone marrow
suppression.

 NSAIDs block prostaglandin synthesis at

COX-1 and COX-2 sites. This blocks
inflammation but also blocks protection of
the stomach lining, as well as the kidneys’
regulation of water.
 Salicylates
 Para-chlorobenzoic acid derivatives or
indoles
 Phenylacetic acids
 Propionic acid derivatives
 Fenamates
 Oxicams
 Selective COX-2 inhibitors
 acetylsalicylic acid –(ASA)
 Oldest anti-inflammatory agent
 Should not be taken with other
NSAIDs – it decreases the blood
level and effectiveness of
NSAIDs
 Aspirin is well absorbed in the GI tract
 Should be taken with water, milk, or
food.
 EC or buffered form can decrease
gastric distress – should not be crushed
or broken.
 Should not be taken during the last trimester
of pregnancy – it may cause premature
closure of ductus arteriosus in the fetus.

 Should not be taken by children with flu

symptom because it may cause the
potentially fatal Reye syndrome.
 Onset of action – within 30 minutes

 Peaks in 1 to 2 hours
 Duration of action average 4-6 hours

 It may take a week or longer for therapeutic

anti-inflammatory effect.
 Should not take diflunisal if they are
hypersensitive to aspirin.
 indomethacin (Indocin) –potent prostaglandin
inhibitor;
 used for: rheumatoid arthritis, gouty arthritis,
and osteoarthritis
 Highly protein bound
 (90%) high potential for toxicity)
 Very irritating to the stomach-should be taken with
food
 sulindac (clinoril)
 tolmetin- ( Tolectin)- not highly protein bound
 1. Diclofenac sodium (Voltaren XR-analgesic
and anti-inflammatory effect s are similar to
that of aspirin but it has minimal to no
antipyretic effect
 Indicated for rheumatoid arthritis,
osteoarthritis and ankylosing spondylitis
 Available in PO, extended release, and topical
1% gel preparation
 Adverse Reaction similar to NSAIDs
 2. Ketorolac (Toradol) – is the first injectable
NSAIDs.
 It inhibits prostaglandin synthesis but it has
greater analgesic properties than other anti-
inflammatory agents.
 Recommended for short – term management
of pain
 For post surgical pain – with analgesic
efficacy superior to those of opioid analgesic.
Ketorolac (Toradol) – is the first injectable
NSAIDs.
 It is administered intramuscularly in
doses of 30 to 60 mg every 6 hours for
adults.
 Also available in PO,IV, and intranasal
preparations
 Relatively new group of NSAIDs
 -are aspirin like but have stronger effects and
create less GI irritation

 Drugs in this group are highly protein

 Better tolerated than other NSAIDs
 Ibuprofen (Motrin) most widely used
 Fenoprofen calcium (Nalfon)
 Naproxyn-(Naprosyn)
 Ketoprofen (Orudis)
 Flurbiprofen (Ansaid)
 Oxaprozin (Daypro)
 NSAIDs used for acute and chronic arthritic
conditions
 Should not be taken by those who have
history of peptic ulcer

 Two fenamates are:

 Meclofenamate sodium monohydrate
(Meclomen)
 Mefenamic acid (Ponstel)
 Piroxicam (Feldene)
 Indicated for long term arthritic conditions such
as rheumatoid arthritis and osteoarthritis
 Well tolerated and has long half life which allows
it to be taken once daily.
 Should not be taken with aspirin / other NSAIDs
 Is highly protein bound and may interact with
another highly protein - bound drug if taken
together
 Gastric irritation when taken
without food
 Sodium and water retention
 Alcoholic beverages may increase
gastric irritation when taken with
NSAIDs- should be avoided
 Not to take aspirin and acetaminophen with
NSAIDs- possible GI bleeding
 Many herbal products may interact with
NSAIDs (dong quai, feverfew, garlic,ginger,and
gingko)
 Inform dentist before a procedure
 Warn female patients not to take NSAIDs 1-2
days before menstruation to avoid heavy
menstrual flow if discomfort occurs –
acetaminophen may be prescribed
 Pregnant women to avoid NSAIDs
 Desired effects of NSAIDs/ DMARDs may
take several weeks to
 Report occurrence of the following :
 n/v (nausea ,vomiting), peripheral
edema, GI upset, purpura or
petechiae, or dizziness

 Diet: take NSAIDs with food

 - decrease inflammation and pain

 Drug of choice for patients with severe

arthritic conditions who need high doses of
an anti-inflammatory drug, because large
doses of NSAIDs may cause peptic ulcer and
gastric bleeding.
 celecoxib (Celebrex)- is classified as
COX-2 inhibitor
 Nabumetone (Relafen)is a similar
drug – however it is not a “true”
COX-2 inhibitor.
 It inhibits COX-2 more than COX-1
 Celebrex – COX-2 inhibitor
 Celexa – selective serotonin
reuptake inhibitor
 Cerebyx- (hydantoin
anticonvulsant)
 Such as Prednisone, Prednisolone and
dexamethasone frequently used anti-
inflammatory agents –

 Controls inflammation by suppressing or

preventing many components of the
inflammatory process at the injured site
 - include immunosuppressive agents
, immunomodulators, and
antimalarials.

 DMARDs help alleviate the

symptoms of rheumatoid arthritis –
p 346
 Treat refractory rheumatoid arthritis (does
not respond to anti-inflammatory drugs

 azathioprine ( Imuran)
 cyclophosphamide (Cytoxan)
 methotrexate (Mexate)

 Primarily used to suppress cancer growth and

proliferation , might be used to suppress
inflammatory process of RA
 Treat moderate to severe rheumatoid
arthritis by disrupting the inflammatory
process and delaying disease progression.

 Interleukin (IL-I) receptor antagonists and

tumor necrosis factor (TNF) blockers are two
groups of immunomodulators
 Anakinra (Kineret) an IL-I receptor antagonist
blocks the activity of IL-I by inhibiting it from
binding to interleukin receptors located in
cartilage and bone.

 IL-I is a proinflammatory cytokine that

contributes to synovial inflammation and
joint destruction
 TNF blockers bind to TNF and block it from
attaching to TNF receptors on synovial cell
surfaces - -thus delay inflammatory process

 Etanercept(Enbrel)-first TNF blocker-sc

 infliximab (Remicade)-iv
 adalimumab (Humira)-sc
 leflunomide (ARAVA)-orally
 Both IL-I receptor antagonists and TFN
blockers predispose the patient to severe
infection and should be discontinued when an
infection occurs.

 Immunomodulators are usually very

expensive
 May de used to treat RD(rheumatoid
arthritis) when other methods of treatment
fail- though the mechanism of action is
unclear.

 Maybe used in combination with NSAIDs –may

take 4-12 weeks to take effect.
 Gout- inflammatory condition that attack
joints, tendons,and other tissues.(joint of the
big toe)

 Maybe called gouty arthritis

 Characterized by a uric acid metabolism
disorder and a defect in purine (protein)
metabolism
 Antiinflammatory Gout Drug
 Inhibits migration of leukocytes to the
inflames site.

 Effective in alleviating acute symptoms of

gout but is not effective in decreasing
inflammation occurring in other
inflammatory disorders.
 It does not inhibit uric acid synthesis and does
not promote uric acid excretion.

 Should not be used if patient has severe renal ,

cardiac, or GI problem.

 Gastric irritation is common problem so it

should be taken with food.
 Allopurinol (Zyloprim)
 Not an anti-inflammatory instead it inhibits
the final steps of uric acid biosynthesis thus
lowers serum uric acid levels, preventing the
precipitation of the attack.

 Used as a prophylactic to prevent gout.

 Drug of choice for chronic tophaceous gout
also for patients with renal impairment
 Allopurinol (Zyloprim)
 Used as a prophylactic to prevent
gout.
 Drug of choice for chronic
tophaceous gout also for patients
with renal impairment
 Allopurinol (Zyloprim)

 Useful for patient with renal obstruction

caused by uric acid stones and for patients
with leukemia and polycythemia vera.

 Given to patient who do not respond to

uricosuric drugs such as probenicid
 Uricosurics:
 probenecid (Benemid)
 Increase the rate of uric acid excretion by
inhibiting its reabsorption.

 Effective in alleviating chronic gout but not

used during acute attacks.
 Can be taken with colchicine-by giving small
doses before starting probenicid.
 Uricosurics:
 Sulfinpyrazone (Anturane)
 more potent than probenicid

 Severe blood dyscrasia might occur

 P 348
 chrysotherapy
gold is taken up by macrophages, which
then inhibit phagocytosis; it is reserved
for use in patients who are unresponsive
to conventional therapy and can be very
toxic.
 Drug in focus:
 Aurothioglucose (Solganal),
 Treatment of selected cases of adult and juvenile
rheumatoid arthritis, most effective early in
disease.
 Actions: Taken up by macrophages, which
inhibits phagocytosis and release of lysosomal
enzymes that cause damage associated with
inflammation.
 Adverse effects: Dermatitis, nausea, vomiting,
stomatitis, anemia,interstitial pneumonitis,
acute tubular necrosis.
 ➧ Immune stimulants assist the immune
system to fights specific pathogens or cancer
cells; in doing so they cause flu-like
symptoms (lethargy, muscle and joint aches
and pains, anorexia, nausea).
 ➧ Interferons are used to treat various
cancers and warts.
 ➧ Interleukins stimulate cellular immunity
and inhibit tumor growth.
 Indications: Hairy cell leukemia, malignant
melanoma, AIDS related Kaposi sarcoma,
chronic hepatitis B and C, intralesional
treatment of condylomata acuminata in patients
18 years of age or older.
 Actions: Inhibits the growth of tumor cells and
enhances the immune response
 Adverse effects: Dizziness, confusion, rash, dry
skin, anorexia, nausea, bone marrow
suppression, flu-like syndrome.
 Indications: Metastatic renal cell carcinoma in adults;
treatment of metastatic melanomas (orphan drug
use).
 Actions: Activates human cellular immunity and
inhibits tumor growth through increases in
lymphocytes, platelets, and cytokines.
 Adverse effects: Mental status changes, dizziness,
hypotension,
 sinus tachycardia, arrhythmias, pruritus, nausea,
vomiting,
 diarrhea, anorexia, gastrointestinal (GI) bleed, bone
marrow
 suppression, respiratory difficulties, fever, chills, pain.
 Immune suppressants are used to depress the
immune system when needed to prevent
transplant rejection or severe tissue damage
associated with autoimmune disease.
 Research is ongoing to extend the use of
various immune suppressants to other
situations, including various autoimmune
disorders.
 Increased susceptibility to infection and
increased risk of neoplasm are potentially
dangerous effects associated with the use of
immune suppressants. Patients need to be
protected from infection, injury, and invasive
procedures.
 Indications: Prophylaxis for organ rejection in
kidney, liver, and heart transplants (used with
corticosteroids); treatment of chronic
rejection in patients previously treated with
other immuno-suppressants; treatment of
rheumatoid arthritis and recalcitrant
psoriasis.
 Actions: Reversibly inhibits
immunocompetent lymphocytes; inhibits T
helper cells and T suppressor cells,
lymphokine production, and release of
interleukin-2 and T-cell growth factor.
 Adverse effects:
 Tremor, hypertension, gum
hyperplasia, renal dysfunction,
diarrhea, hirsutism, acne, bone
marrow suppression.
 Immunity - relative resistance to a disease
 May be active or passive
 Active immunity results from the body
making antibodies against specific proteins
for immediate release if that protein re-
enters the body.
 Passive immunity results from
preformed antibodies to a specific
protein, which offers protection
against the protein only for the life
of the circulating antibodies
 Immunizations are given to
stimulate active immunity in a
person who is at high risk for
exposure to specific diseases
 Are a standard part of preventive
medicine
 Diphtheria , Pertussis, tetanus, Haemophilus
influenzae B, hepatitis B, hepatitis A,
chickenpox, poliovirus, meningitis, measles,
mumps, rotavirus, and rubella,

 The bacille-Calmette Guerin (BCG) vaccine

for tuberculosis =widely used worldwide but
in USA
 human papillomavirus (HPV) vaccine is now
recommended for cervical cancer protection
 Vaccines can be made from
chemically inactivated
microorganisms, or from live,
weakened viruses or bacteria.
 Toxoids are vaccines that are made
from the toxins produced by the
microorganism that are altered so
that they are no longer poisonous
but still have the recognizable
protein antigen that will stimulate
antibody production.
 Immune sera provide preformed
antibodies to specific proteins for
people who have been exposed to
them or are at high risk for
exposure.
 The term immune sera typically
refers to sera that contains
antibodies to specific bacteria or
viruses.
 Anti toxins are immune sera that have
antibodies to very specific toxins that might
be released by invading pathogens.
 Antivenins are immune sera that
have antibodies to venom that
might be injected through spider or
snake bites
 Serum sickness- a massive immune reaction –
occurs more frequently with immune sera
than with vaccines.

 Patients need to be monitored for any history

of hypersensitivity reaction, and emergency
equipment should be available.
 Patients should be advised to keep a written
record of all immunizations or immune sera
used.

 Booster doses for various vaccines may be

needed to further stimulate antibody
production.
The End

Thank you
 Research about the latest trends in vaccines.
Try to divulge to good and the bad side of
vaccines.
 Photocopy the actual article.
 Write your summary (15 pts.) and reaction (10
pts.) to a ½ crosswise yellow paper.
 To be submitted Wednesday next week up to
5 pm only.