Pharmacotherapy of rheumatic diseases and systemic diseases of connective tissue. Pharmacotherapy of allergic conditions.

Pharmacotherapy of rheumatic Pharmacotherapy of rheumatic diseases and systemic diseases of diseases and systemic diseases of

connective tissue. Pharmacotherapy connective tissue. Pharmacotherapy of allergic conditionsof allergic conditions

RHEUMATIC DISEASESRHEUMATIC DISEASES

Rheumatic diseases (rheumatism) are Rheumatic diseases (rheumatism) are painful conditions that affect millions. painful conditions that affect millions. These diseases cause inflammation, These diseases cause inflammation, swelling, and swelling, and painpain in the joints or in the joints or muscles.muscles.

Some rheumatic diseases like Some rheumatic diseases like osteoarthritisosteoarthritis are the result of "wear and are the result of "wear and tear" to the joints. Other rheumatic tear" to the joints. Other rheumatic diseases, such as diseases, such as rheumatoidrheumatoid arthritisarthritis, , happen when the immune system goes happen when the immune system goes haywire; the immune system attacks the haywire; the immune system attacks the linings of joints, causing linings of joints, causing jointjoint painpain, , swelling, and destruction.swelling, and destruction.

Rheumatism is a medical term once frequently Rheumatism is a medical term once frequently used to describe disorders associated with many used to describe disorders associated with many different parts of the body. Most often, people different parts of the body. Most often, people associate rheumatism with associate rheumatism with arthritisarthritis, or with , or with rheumatic fever, a complication of rheumatic fever, a complication of strepstrep throatthroat that that can result in damage to the can result in damage to the heartheart. However, the . However, the term rheumatism might apply to the symptoms of term rheumatism might apply to the symptoms of numerous conditions that can cause pain and/or numerous conditions that can cause pain and/or weaknessweakness..

Some conditions that were once given the general Some conditions that were once given the general label of rheumatism or called label of rheumatism or called rheumatic diseases rheumatic diseases include, rheumatoid arthritis, osteoarthritis,include, rheumatoid arthritis, osteoarthritis, lupuslupus, , fibromyalgiafibromyalgia, and , and tendonitistendonitis. Frequently . Frequently autoimmune disorders, since they remained autoimmune disorders, since they remained unnamed but caused pain as well as affecting other unnamed but caused pain as well as affecting other organs, were classed as rheumatism. Illnesses like organs, were classed as rheumatism. Illnesses like lupus were particularly susceptible to being called lupus were particularly susceptible to being called rheumatism. Later understanding of the actions of rheumatism. Later understanding of the actions of these illnesses show that the problem is not these illnesses show that the problem is not dysfunction of the joints, but rather dysfunction of the joints, but rather immuneimmune systemssystems that can attack joints, muscles and organs. that can attack joints, muscles and organs.

Some forms of rheumatism are called Some forms of rheumatism are called non-non-articular rheumatism and may affect the articular rheumatism and may affect the soft tissues causing pain throughout the soft tissues causing pain throughout the body. Conditions like tendonitis and body. Conditions like tendonitis and fibromyalgia fall into this category. As fibromyalgia fall into this category. As well, non-articular rheumatism can be well, non-articular rheumatism can be localized to specific areas in the body. localized to specific areas in the body. BursitisBursitis is a non-articular form of is a non-articular form of rheumatism that affects and inflames the rheumatism that affects and inflames the bursabursa, which are special sacs that , which are special sacs that protect joints and overlapping muscles. protect joints and overlapping muscles. Bursitis most frequently occurs at the Bursitis most frequently occurs at the site of one joint that may have been site of one joint that may have been injured through overuse. injured through overuse.

FFibromyalgiaibromyalgia

OsteoarthritisOsteoarthritisOA is not a normal part of aging; it usually affects OA is not a normal part of aging; it usually affects

the knees, hips, lower back, neck, and fingers.the knees, hips, lower back, neck, and fingers. The signs and symptoms of OA include:The signs and symptoms of OA include: Pain in joint Pain in joint Joint swelling Joint swelling Joint may be warm to touch Joint may be warm to touch Joint stiffness Joint stiffness Muscle weakness and joint instability Muscle weakness and joint instability Pain when walking Pain when walking Difficulty gripping objects Difficulty gripping objects Difficulty dressing or combing hair Difficulty dressing or combing hair Difficulty sitting or bending overDifficulty sitting or bending over   To diagnose OA, doctor will ask To diagnose OA, doctor will ask the patientthe patient about about

medical history and symptoms and do a physical medical history and symptoms and do a physical exam. Blood tests may help rule out other exam. Blood tests may help rule out other typestypes ofof arthritisarthritis or medical problems. A joint fluid sample or medical problems. A joint fluid sample from an affected joint may also be examined to from an affected joint may also be examined to eliminate other medical problems.eliminate other medical problems.

OsteoarthritisOsteoarthritis

Rheumatoid ArthritisRheumatoid Arthritis

RA is sometimes called a crippling disease. That's RA is sometimes called a crippling disease. That's because it can result in permanent because it can result in permanent jointjoint damagedamage and and deformity.                                                                       deformity.                                                                                       

RA signs and symptoms include:RA signs and symptoms include: Joint pain, stiffness, and swelling Joint pain, stiffness, and swelling Involvement of multiple joints (symmetrical pattern) Involvement of multiple joints (symmetrical pattern) Other organ involvement Other organ involvement Joint stiffness, especially in the morning Joint stiffness, especially in the morning Fatigue Fatigue Fevers Fevers Lumps called rheumatoid Lumps called rheumatoid

nodules                                                                  nodules                                                                  To diagnose RA, doctor will ask about medical history To diagnose RA, doctor will ask about medical history

and do a physical examination. Also, X-rays and blood and do a physical examination. Also, X-rays and blood tests will likely be taken. One blood test may be for tests will likely be taken. One blood test may be for rheumatoidrheumatoid factorfactor; it is positive in 70% to 80% of ; it is positive in 70% to 80% of those with RA.those with RA.

Rheumatoid ArthritisRheumatoid Arthritis

LupusLupusSLE or systemic lupus erythematosus is another autoimmune SLE or systemic lupus erythematosus is another autoimmune

disease; the cause of SLE is unknown. disease; the cause of SLE is unknown. Lupus signs and symptoms include:Lupus signs and symptoms include: Joint pain Joint pain Fatigue Fatigue Joint stiffness Joint stiffness Rashes, including theRashes, including the""butterfly rashbutterfly rash"" across the cheeks   across the cheeks   Sun sensitivity Sun sensitivity Hair loss Hair loss Discoloration of the fingers or toes when exposed to cold Discoloration of the fingers or toes when exposed to cold

(called Raynaud's phenomenon) (called Raynaud's phenomenon) Internal organ involvement, such as the kidneys Internal organ involvement, such as the kidneys Blood disorders, such as anemia and blood clots Blood disorders, such as anemia and blood clots Chest pain from inflammation of the lining of the heart or Chest pain from inflammation of the lining of the heart or

lungs lungs Seizures or Seizures or

strokes                                                                              strokes                                                                              To diagnose lupus, doctor will ask about medical history, do a To diagnose lupus, doctor will ask about medical history, do a

physical exam, and order lab tests of blood and urine physical exam, and order lab tests of blood and urine samples. One blood test is the antinuclear antibody test samples. One blood test is the antinuclear antibody test (ANA).  Most people with lupus have a positive ANA blood (ANA).  Most people with lupus have a positive ANA blood test.test.

SSystemic lupus erythematosusystemic lupus erythematosus

Ankylosing SpondylitisAnkylosing SpondylitisAnkylosing Spondylitis (AS) usually starts gradually as lower Ankylosing Spondylitis (AS) usually starts gradually as lower

back pain. The hallmark feature of AS is the involvement of back pain. The hallmark feature of AS is the involvement of the joints at the base of the spine. This is where the spine the joints at the base of the spine. This is where the spine attaches to the pelvis, also known as the sacroiliac joints.attaches to the pelvis, also known as the sacroiliac joints.

Ankylosing spondylitis is more common in young men, Ankylosing spondylitis is more common in young men, especially from the teenage years to age 30.especially from the teenage years to age 30.

AS symptoms include:AS symptoms include: Gradual pain in the lower back and buttocks Gradual pain in the lower back and buttocks Lower back pain that worsens and works its way up the Lower back pain that worsens and works its way up the

spine spine Pain felt between the shoulder blades and in the neck Pain felt between the shoulder blades and in the neck Pain and stiffness in the back, especially at rest and on Pain and stiffness in the back, especially at rest and on

arising arising Pain and stiffness get better after activity Pain and stiffness get better after activity Pain in the middle back and then upper back and neck Pain in the middle back and then upper back and neck

(after 5-10 (after 5-10 years)                                                                              years)                                                                             

With progression of AS, the spine may become stiffer. It may With progression of AS, the spine may become stiffer. It may become difficult to bend for common everyday activities.become difficult to bend for common everyday activities.

To diagnose AS, doctor will ask about medical history and To diagnose AS, doctor will ask about medical history and perform a physical exam. X-rays of the back looking at the perform a physical exam. X-rays of the back looking at the sacroiliac joints may help in making an AS diagnosis. A sacroiliac joints may help in making an AS diagnosis. A positive blood test for HLA-B27 protein may help confirm a positive blood test for HLA-B27 protein may help confirm a diagnosis.diagnosis.

Ankylosing SpondylitisAnkylosing Spondylitis

Sjogren's SyndromeSjogren's SyndromeSjogren's syndrome is an inflammatory, autoimmune Sjogren's syndrome is an inflammatory, autoimmune

disease. It can occur with other autoimmune diseases disease. It can occur with other autoimmune diseases such as RA and lupus, but also on its own. Although the such as RA and lupus, but also on its own. Although the cause of Sjogren's is unknown, it is more common in cause of Sjogren's is unknown, it is more common in women.                                                                             women.                                                                             

Sjogren's signs and symptoms include:Sjogren's signs and symptoms include: Dry eyes (the glands in eyes do not give adequate tears) Dry eyes (the glands in eyes do not give adequate tears) Eye irritation and burning Eye irritation and burning Dry mouth (the glands in mouth do not give adequate Dry mouth (the glands in mouth do not give adequate

saliva) saliva) Dental decay, gum disease, thrush Dental decay, gum disease, thrush Swelling of the parotid glands on the sides of the face Swelling of the parotid glands on the sides of the face Joint pain and stiffness (rarely) Joint pain and stiffness (rarely) Internal organ diseases (rarely) Internal organ diseases (rarely) To diagnose Sjogren's syndrome, doctor will do a physical To diagnose Sjogren's syndrome, doctor will do a physical

exam and ask about medical history. Blood tests and exam and ask about medical history. Blood tests and other tests may also be performed. A simple biopsy of other tests may also be performed. A simple biopsy of the inner lip or other area may help confirm the the inner lip or other area may help confirm the diagnosis.diagnosis.

Sjogren's SyndromeSjogren's SyndromeVenus Williams Diagnosed With Sjogren’s Syndrome

DDrugs used to treat rugs used to treat arthritis:arthritis:

Painkillers (analgesics) - These reduce pain. They Painkillers (analgesics) - These reduce pain. They are used for many different types of arthritis and are used for many different types of arthritis and are often used together with other drugs. are often used together with other drugs.

Non-Non-steroidalsteroidal anti- anti-inflammatoryinflammatory drugsdrugs ( (NSAIDsNSAIDs)) - These reduce inflammation of the joint as well - These reduce inflammation of the joint as well as pain. They are used for many different types as pain. They are used for many different types of arthritis, often along with other drugs. of arthritis, often along with other drugs.

Disease-modifying anti-Disease-modifying anti-rheumaticrheumatic drugsdrugs ( (DMARDsDMARDs)) - This group of drugs is used mainly in - This group of drugs is used mainly in the treatment of rheumatoid arthritis but also in the treatment of rheumatoid arthritis but also in some other rheumatic diseases. They reduce some other rheumatic diseases. They reduce pain, swelling and stiffness. pain, swelling and stiffness.

CorticosteroidsCorticosteroids ( (steroidssteroids)) - These drugs are very - These drugs are very effective in controlling inflammation. effective in controlling inflammation.

NSAIDs can be very effective against inflammation, but they do NSAIDs can be very effective against inflammation, but they do not prevent tissue damage. Even when NSAIDs are controlling not prevent tissue damage. Even when NSAIDs are controlling

the inflammation, the joint or organ damage of arthritis can the inflammation, the joint or organ damage of arthritis can continue to get worse. NSAIDs only lessen pain and discomfort. continue to get worse. NSAIDs only lessen pain and discomfort.

They do not affect underlying disease.They do not affect underlying disease.

Non steroidal anti-inflammatory drugs (NSAIDs) are examples of drugs Non steroidal anti-inflammatory drugs (NSAIDs) are examples of drugs that act on enzymes. NSAIDs inhibits the enzyme cyclo-oxygenase (COX) that act on enzymes. NSAIDs inhibits the enzyme cyclo-oxygenase (COX) which catalyses a reaction in the biochemical pathway that results in the which catalyses a reaction in the biochemical pathway that results in the production of prostaglandins, important mediators in the inflammatory production of prostaglandins, important mediators in the inflammatory

response.response.

NSAIDsNSAIDs.. Mechanism(s) of Mechanism(s) of Action Action

The more an NSAID blocks COX-1, the greater is its The more an NSAID blocks COX-1, the greater is its tendency to cause ulcers and promote bleeding. One tendency to cause ulcers and promote bleeding. One NSAID, NSAID, celecoxibcelecoxib (Celebrex), blocks COX-2 but has (Celebrex), blocks COX-2 but has

little effect on COX-1, and is therefore further little effect on COX-1, and is therefore further classified as a selective COX-2 inhibitor. Selective classified as a selective COX-2 inhibitor. Selective

COX-2 COX-2 inhibitorsinhibitors cause less bleeding and fewer cause less bleeding and fewer ulcers than other NSAIDs.ulcers than other NSAIDs.

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

were known long before their mechanism of action were known long before their mechanism of action was elucidated and were for this reason classified by was elucidated and were for this reason classified by chemical structure or origin. Newer substances are chemical structure or origin. Newer substances are

more often classified by mechanism of action. more often classified by mechanism of action.

SalicylatesSalicylates AspirinAspirin ( (acetylsalicylicacetylsalicylic acidacid) ) DiflunisalDiflunisal SalsalateSalsalate

NSAIDsNSAIDs

Propionic acid derivativesPropionic acid derivatives IbuprofenIbuprofen NaproxenNaproxen FenoprofenFenoprofen KetoprofenKetoprofen FlurbiprofenFlurbiprofen OxaprozinOxaprozin Acetic acid derivativesAcetic acid derivatives IndomethacinIndomethacin SulindacSulindac EtodolacEtodolac KetorolacKetorolac DiclofenacDiclofenac (Safety alert by FDA) (Safety alert by FDA) NabumetoneNabumetone

NSAIDsNSAIDs

Enolic acid (Oxicam) derivativesEnolic acid (Oxicam) derivatives PiroxicamPiroxicam MeloxicamMeloxicam TenoxicamTenoxicam DroxicamDroxicam LornoxicamLornoxicam IsoxicamIsoxicam Fenamic acid derivatives( Fenamates )Fenamic acid derivatives( Fenamates ) MefenamicMefenamic acidacid MeclofenamicMeclofenamic acidacid FlufenamicFlufenamic acidacid TolfenamicTolfenamic acidacid

NSAIDsNSAIDs

Selective COX-2 inhibitors (Coxibs)Selective COX-2 inhibitors (Coxibs) CelecoxibCelecoxib (FDA alert) (FDA alert) RofecoxibRofecoxib (withdrawn from market) (withdrawn from market) ValdecoxibValdecoxib (withdrawn from market) (withdrawn from market) ParecoxibParecoxib FDA withdrawn FDA withdrawn LumiracoxibLumiracoxib TGA cancelled registration TGA cancelled registration EtoricoxibEtoricoxib FDA withdrawn FDA withdrawn FirocoxibFirocoxib used in dogs and horses used in dogs and horses SulphonanilidesSulphonanilides NimesulideNimesulide (systemic preparations are banned by (systemic preparations are banned by

several countries for the potential risk of several countries for the potential risk of hepatotoxicity) hepatotoxicity)

OthersOthers Licofelone acts by inhibiting LOX (lipooxygenase) & Licofelone acts by inhibiting LOX (lipooxygenase) &

COX and hence known as 5-LOX/COX inhibitor COX and hence known as 5-LOX/COX inhibitor

NSAIDs are generally indicated for the NSAIDs are generally indicated for the symptomatic relief of the following symptomatic relief of the following

conditions: conditions: Rheumatoid arthritis Rheumatoid arthritis Osteoarthritis Osteoarthritis Inflammatory arthropathies (e.g. ankylosing spondylitis, Inflammatory arthropathies (e.g. ankylosing spondylitis,

psoriatic arthritis, Reiter's syndrome) psoriatic arthritis, Reiter's syndrome) Acute gout Acute gout Dysmenorrhoea (menstrual pain) Dysmenorrhoea (menstrual pain) Metastatic bone pain Metastatic bone pain Headache and migraine Headache and migraine Postoperative pain Postoperative pain Mild-to-moderate pain due to inflammation and tissue Mild-to-moderate pain due to inflammation and tissue

injury injury Pyrexia (fever) Pyrexia (fever) Ileus Ileus Renal colic Renal colic They are also given to neonate infants whose ductus They are also given to neonate infants whose ductus

arteriosus is not closed within 24 hours of birth arteriosus is not closed within 24 hours of birth Aspirin, the only NSAID able to irreversibly inhibit COX-Aspirin, the only NSAID able to irreversibly inhibit COX-

1, is also indicated for inhibition of platelet aggregation.1, is also indicated for inhibition of platelet aggregation.

Complications of NSAIDsComplications of NSAIDsNSAIDs are safe drugs. However, they have many side NSAIDs are safe drugs. However, they have many side effects. The side effects happen more often when they effects. The side effects happen more often when they are used over long periods of time, which is common are used over long periods of time, which is common

in arthritis patients. Some of the side effects can in arthritis patients. Some of the side effects can become very serious. become very serious.

GI EffectsGI EffectsNSAIDs irritate the NSAIDs irritate the gastrointestinalgastrointestinal (GI) tract (the digestive (GI) tract (the digestive

system--your esophagus, stomach, and intestines). They system--your esophagus, stomach, and intestines). They increase the production of gastric acid, and they harm the increase the production of gastric acid, and they harm the gastric lining. NSAIDs aggravate ulcers and GI bleeding. Up gastric lining. NSAIDs aggravate ulcers and GI bleeding. Up to 5 percent of people who use NSAIDs for a year develop to 5 percent of people who use NSAIDs for a year develop ulcers, bleeding, or tears in the GI tract. The risks are higher ulcers, bleeding, or tears in the GI tract. The risks are higher for older patients, patients with a history of GI problems, and for older patients, patients with a history of GI problems, and patients with heart disease.patients with heart disease.

Blood Effects Blood Effects NSAIDs make it harder for the platelets in your blood to clump NSAIDs make it harder for the platelets in your blood to clump

together at the site of an injury. This can cause bleeding together at the site of an injury. This can cause bleeding problems. Aspirin especially has this effect. Before you have problems. Aspirin especially has this effect. Before you have surgery, you should stop taking aspirin for two weeks to surgery, you should stop taking aspirin for two weeks to prevent bleeding problems.prevent bleeding problems.

Liver EffectsLiver EffectsNSAIDs can be toxic to your liver. You will not feel this, but NSAIDs can be toxic to your liver. You will not feel this, but

elevated levels of certain liver enzymes can easily be seen in elevated levels of certain liver enzymes can easily be seen in blood tests. Liver function almost always returns to normal blood tests. Liver function almost always returns to normal when you stop taking NSAIDs. when you stop taking NSAIDs.

Kidney EffectsKidney EffectsNSAIDs can make it hard for your kidneys to get rid of NSAIDs can make it hard for your kidneys to get rid of

some kinds of wastes. If you have a history of kidney some kinds of wastes. If you have a history of kidney problems, or if your disease may affect your problems, or if your disease may affect your kidneys, your doctor will use NSAIDs with caution.kidneys, your doctor will use NSAIDs with caution.

Other EffectsOther EffectsSome people get skin reactions and rashes from Some people get skin reactions and rashes from

NSAIDs. Some get a combination of runny nose, NSAIDs. Some get a combination of runny nose, polyps in the nose, and asthma. Different kinds of polyps in the nose, and asthma. Different kinds of NSAIDs can have different side effects. NSAIDs can have different side effects. SalicylatesSalicylates can cause problems with hearing. Other kinds of can cause problems with hearing. Other kinds of NSAIDs can cause headaches and confusion, NSAIDs can cause headaches and confusion, especially in elderly patients. Many of the possible especially in elderly patients. Many of the possible side effects depend on your health and the disease side effects depend on your health and the disease for which you are being treated.for which you are being treated.

Individuals can react very differently to the same Individuals can react very differently to the same NSAIDs. You and your doctor must work together to NSAIDs. You and your doctor must work together to find the type and dose of NSAID that controls your find the type and dose of NSAID that controls your symptoms without causing unwanted side effects.symptoms without causing unwanted side effects.