PART-2-RHEUMATOID ARTHRITIS

RHEUMATOID-DIAGNOSIS AND THERAPY

 RA

Generally it is very difficult to diagnose RA at the early stages as it is mostly asymptomatic in the beginning.

RA diagnoses are based on their symptoms and laboratory findings as follows.

Diagnoses

 

1. Joint symptoms such as swelling, abnormal fluid collections in articular cavities, synovial thickening, and edema with pain on motion, indicates the presence of RA.

2. Subcutaneous nodules mostly occur in the sites exposed to external pressure such as elbow, shoulder, and wrist but also in other organs indicates the presence of RA. These nodules are rubbery, round, and firm masses can be identified with fingers.

3. A deeper diagnosis by X-radiation can indicate the presence of asymptomatic early RA by the presence of mild painless soft tissue swellings.

4. A blood test can show the presence of RA factors, heterogeneous antibodies present in most RA patients. 

5.ESR test may be high which indicates the presence of early RA.

6. The presence of normochromic, normocytic anemia may indicate the presence of RA.

Treatments

 

The treatments involve two methodological approaches such as Mechanical and Pharmacological.

Mechanical Methods

The patient should be trained with proper balanced daily exercises and rests as follows:-

1. In the beginning start with how to keep the joints in rest.

2. Start the exercise by step by step movements of the joints without straining them to strengthen the muscles.

3.when return to sleep train how to keep the joints by aligning them by the use of specially designed lightweight splints.

4. Complete immobilization should be avoided.

5. When the above methods fail a mild surgery to improve the functions and movements of hands and knees are advised.

Pharmacological Methods 

Analgesics and anti-inflammatory drugs such as aspirin and NSAIDs are beneficial. Paracetamol has not been used as it is not having any anti-inflammatory effects.

Anti-inflammatory drugs at their therapeutic dosage are riskier and the risk factors override the required therapeutic response.

Aspirin

We have already dealt with this drug in detail in another post (9-12-2015) in the same blog under the heading "Paracetamol, Aspirin and other NSAIDs".Please download it.

A piece of additional information is aspirin is the first-line drug to treat rheumatism. Aspirin is used in higher dosage to treat inflammation and it is more economical. But its risk factor overrides its benefits.

Mechanism

Aspirin is acting similar to other NSAIDs but to a lesser extent it is preventing the synthesis and release of prostaglandin.

Dose

4 to 6 gms daily

For side effects please refer to the post "Paracetamol, Aspirin, and Other NSAIDs" in this blog.

Other NSAIDs:-

They are ibuprofen, naproxen, sulindac, and piroxicam. Please refer to the following table.

Actions are similar to aspirin by inhibiting cyclooxygenase 1 and 2 and thereby inhibiting the synthesis and release of prostaglandin.

NSAIDs have the advantage over aspirin by producing the required effects in a much lower dosage than aspirin but are more expensive.

Special Precautions

1. They should be avoided in asthmatic patients as they can elevate bronchospasm. Aspirin is suitable for them.

2. Unlike aspirin NSAIDs reversibly affect the platelet function, hence safer than aspirin but still should be cautious in using them to those who have gastric bleeding.

Misoprostol is used to treat gastric hemorrhages caused by NSAIDs.(Misoprostol dosage:100 to 200 mcg four times daily along with NSAIDs treatment)

3.NSAIDs decrease the renal blood flow and renal failure may ensue in patients who already suffer from less renal flow due to CHF and Diuretic therapy. Sulindac is safer.

4.Liver failure

5.CNS effects such as drowsiness, dizziness, anxiety, tinnitus, and confusion, that disappear on continuous use. Headache is more common with indomethacin

6.Blood dyscrasias(Rare)

7. Naproxen and ibuprofen are safer than other NSAIDs in producing GI effects

Nabumetone causes lesser gastric irritation

Meclofenamate and Mefenamic acid may cause severe diarrhea

Piroxicam which has a longer duration of action may cause higher gastric bleeding. It should be avoided in elderly patients.

Indomethacin can cause more serious CNS effects than other NSAIDs.

Nonacetylated salicylates such as salsalate, choline salicylate are safer than aspirin in aspirin-sensitive patients as they do not have respiratory effects similar to aspirin.

RHEMATOID ARTHRITIS-PART-1

RHEUMATOID ARTHRITIS

Rheumatoid arthritis is an inflammatory chronic and systemic disease most apparently involved in the synovial joints. The inflammation can spread over extra-articular tendons and organ structures.

Criteria 

There are many criteria as follows:-

1.Morning Stiffness

Morning stiffness in any part of our body might have been experienced by somebody else especially at the knees or the feet. This may last for at least one hour.

2.Joints Swelling

At least three joints must have been experiencing swelling with fluid. The possible areas are the wrist, elbow, knee, ankle, and phalangeal (Hand and Feet Fingers) joints.

3.At least One Joint Area

At least one joint area in the hand such as the wrist, metacarpophalangeal(MCP), or proximal interphalangeal(PIP)

4.Symmetric

Simultaneous experience of arthritis in the bone joints at both sides of the body.

5.Subcutaneous Nodules(Rheumatoid nodules)

These nodules must be observed over bony prominences, extensor surfaces, or in juxta-articular regions by a physician.

6.Abnormal Presence Of Serum Rheumatoid Factor

It should be observed by a physician by any methodology

7.Radiological Changes

Bony erosions or decalcifications must be present in the hand or wrist x-ray.

Rheumatoid Arthritis (RA) is more common in women than men with a ratio of 3:1 respectively.

Occurrence

In general, the occurrence is rare (1 to 3%) in early ages, and medial at 30 to 40 years and more common at above 40 years. 

Etiological Factors

Although it is still not knowing the exact reasons yet the following might have been observed as the etiological factors.

1. A specific leukocyte antigen is often involving some inflammatory reaction if the individual is exposed to certain environment.75% whites have this antigen while 30% from the rest of the population is suffering from RA.

2. Some infectious diseases may also be as factors to precipitate RA.

Symptoms

1.Synovial swellings with inflammation, with fluid collection and edema. If left untreated the RA becomes chronic and the synovium becomes thick and boggy.

2. The thickened synovium grow inward across the cartilage results in cartilage degradation, loss of adjacent bone, and erosions.

3. The pain will produce by rub and press.

 

 

NEWS UPDATE-AGE NO BAR TO HIP SURGERY

AGE NO BAR FOR BONE SURGERIES

The news is very pleasant and induces hopes to the life expectancy of old aged people.

As the age increase the bones get weakened and more brittle.

Osteoporosis is more common in old aged people and is a hurdle to make a surgery to repair a broken hip in that age.

But now the news said regional anesthesia, better pain management, and implanting uncemented surgical parts make the procedure less risky.

There are two methods of hip repairs.1. Total hip replacement in which the whole hip bones and the ball are replaced.2.Hemiarthroplasty in which only the ball is replaced.

The first one is more complicated than the second one and holds more life expectancy.

Both can be possible at an old age but the most preferable one is hemiarthroplasty.

PART-IV-ECZEMA AND ITS CURE

ECZEMA-TREATMENTS

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 ECZEMA

PART-IX-CNS-STIMULANTS-Contd..-AMPHETAMINES

AMPHETAMINES

Amphetamines are central stimulants but they are frequently used as drugs of abuse. This we will see in a separate article in the other blog 'MAS PHARMACY AND HEALTH REVIEW'

Amphetamine is generally an equal mixture of the two enantiomers the Levo and dextro amphetamines

Further amphetamines are available in the market as follows:-

1.Methylamphetamine (Ritalin)

2.Methamphetamine (Methedrine or 'speed')

3.Dextroamphetamine (Dexedrine)

4.MDMA ('ecstasy')-Methylene Dioxy Meth Amphetamine

5.Bupropion

Amphetamines are chemically a derivative of the endogenous phenylethylamine.

Mechanism

Amphetamines are powerful central stimulants work by releasing norepinephrine and dopamine from their storage.

Physiology

Amphetamines by stimulating CNS through the release of catecholamines they mainly affect sleep centers of the hypothalamus which regulates the sleep cycles.

1. Amphetamine causes euphoria to the individuals who are addict to it. Euphoria is a kind of daydream or imagination of impossible thoughts associated with belief and confidence.

2. CNS stimulation reduces tiredness and fatigue, improves alertness, and cognitive ability.

3. Elevate B.P-Hypertension.

4.Elevate breathing

5. Blunts hungry.

6. Amphetamine is an aphrodisiac, a drug that stimulates sexual desire.

Clinical Use

1.To improve sleep disorders(Anti-Narcoleptic)

2.Attention Deficit Hyperactivity Disorders(ADHD) 

3.Appetite Control.

Route Of Administration

Oral

Metabolism and Kinetics

Amphetamine is well absorbed orally and 75 % is bioavailable in case of dextroamphetamine.

Amphetamine is a weak base with a pH of 9.9 and in the alkaline gut, it easily gets dissociated into the highly lipid-soluble free base and easily absorbed by the fatty gut villus.

15 to 40% are absorbed by the plasma proteins

Amphetamine is metabolized in the liver and excreted in the urine.

Amphetamine is eliminated by the body within two days of the last dosage taken.

Elimination is increased and the half-life is decreased by acid diets and vice versa.

Contraindication

Amphetamine should not be taken by those who are using MAOIs for their mobility disorders. Because MAO should not be inhibited any way if amphetamine is in usage as amphetamine is acting by releasing catecholamines from their stores which are metabolized by MAO. Inhibiting MAO will result in an excessive adrenergic crisis.

Adrenergic Crisis Treatments

Chlorpromazine a neuroleptic is the drug of choice to neutralize amphetamine poisoning as it effectively blocks the alpha-adrenergic receptors which are responsible for CNS disturbances and hypertension. 

PART-IX-CNS STIMULANTS-COFFEE AND SMOKING

CENTRAL STIMULANTS-COFFEE &SMOKING

CNS stimulants are drugs inducing increased motor activities, excitement, and decrease the feelings of tiredness.

1.METHYLXANTHINES

1.Caffeine

2.Theophylline

3.Theobromine

Theobromine is of little interest and it is mostly found in cocoa butter.

These drugs stimulate the CNS by a series of chemical and biological pathways involving an increase in cyclic guanosine monophosphate and cyclic adenosine monophosphate the two nucleotides which are increasing intracellular signaling to exhibit an increased motor activity and thereby stimulating the CNS.

Caffeine:-

 

The pharmacodynamical effects of caffeine are as follows:-

1. Centrally caffeine increases motor activity and alertness.

2.Heart and Bloodvessels-Caffeine increases heart rate (+chronotrophic) and contractility (+inotrophic)

3. Caffeine and its derivatives relax the smooth muscles of the bronchioles and dilate them to facilitate good ventilation. Hence drinking a cup of coffee would be beneficial during an attack of cold and asthma.

4. Caffeine is a weak diuretic and increases the excretion of sodium+,potassium+, and chloride-ions in the urine. Hence over a drink of coffee may lead to heavy loss of these ions.

5. Caffeine stimulates gastric secretions and thereby enhance acidity in the stomach. Hence care should be taken by those who suffer from peptic ulcers to avoid coffee drinks.

Side Effects

1.Insomnia

2.Agitation

3.Nausea and Vomiting

4.Convulsions

5.Cardiac Arrhythmias

Theophylline

 

Theophylline is already dealt with in detail in the post describes Asthma in this blog. Please refer to it.

2.NICOTINE

 

Physiology

Nicotine is having double action on the preganglionic receptors. Because of its specific actions at the preganglionic receptors the receptors are known as nicotinic receptors.

At low dosage it causes ganglionic stimulation by depolarization through acetylcholine. At high doses it causes ganglionic blockade.

At low dosage it causes arousal, relaxation, and improved attention through ganglionic stimulation.

At high doses it causes respiratory depression through medullary suppression through the ganglionic blockade.

Pharmacology

At Low Dose

Nicotine at a low dosage increases heart rate. constricting the blood vessels and thereby elevate B.P.

At High Dose:-

1. At a high dose, it slows the heart rate, dilates the blood vessels and thereby lower the B.P.

2. It causes many dysfunctions in our digestive system.

Nicotine increases acid secretions in the stomach and causes peptic and duodenum ulcers by impairing the secretions of sodium bicarbonate from the pancreas. 

Nicotine increases the stomach's susceptibility to H.pylori.

Nicotine weakens L.E.S.and thereby causes heartburn and G.E.R.D.

Nicotine causes the liver's ability to metabolize various toxic wastes and drugs ingested.

Nicotine causes Crohn's disease.

3. Nicotine causes severe urinary incontinence.

All the above effects are due to the ganglionic blockade of nicotine at high doses.

Clinical Uses

Fortunately nicotine has no therapeutic uses.

Kinetics

Nicotine is rapidly absorbed through the buccal mucosa, by inhalation, and by the skin.

Side Effects

1.Irritability

2.Tremors

3.Intestinal cramps

3.Diarrhea

4.Increased heart rate and B.P.

Withdrawal Symptoms For Addicts

1.Craving

2.Irritability

3.Restlessness

4.Anxiety

5.Stomach pain.

 

CNS DEPRESSANTS-PART-VIII-LOCAL ANESTHETICS

LOCAL ANESTHETICS

Local anesthetics are partial anesthetics that do not anesthetize the entire body. This is particularly useful for carrying out a surgical operation at a particular area of the body which can easily be desensitized without affecting the rest of the body. Also they are useful to reduce the pain impulses at an injured part of the body such as tooth pain.

TYPES OF LOCAL ANESTHETICS

In general there are two types of local anesthetics divided by their chemical structure. Structurally there are two portions in their molecule such as lipophilic (Affinity for fat) and hydrophilic (Affinity for water). There are two types of local anesthetics available determined by the bond linking the hydrophilic part to the lipophilic part.

They are either esters or amides

Esters

1.Cocaine

2.Benzocaine

3.Procaine

4.Tetracaine

Amides

1.Lidocaine (Xylocaine,or Lignocaine)

2.Mepivacaine

3.Bupivacaine

4.Prilocaine

Mechanism

Local anesthetics block the nerve conduction of pain impulses by inhibiting the voltage-gated sodium channels of the nerve cell membrane.

Small unmyelinated nerves that conduct pain,  heat, and autonomic activity are affected first.

With increasing concentration Pain fibers(A and C fibers) sensory(A-fibers) fibers followed by motor fibers(A-fibers) which are myelinated get affected.

Metabolism

Esters are more electrophilic and more rapidly metabolized by blood and tissue esterases and hence they have a shorter half-life and less toxic.

Amides are less electrophilic and slowly metabolized in the liver and hence they have a longer half-life and more toxic.

Clinical Indications

1.For surface anesthesia

2.Nerve blocks

3.Spinal and Epidural anesthesia

4. Lidocaine is also used as an antiarrhythmic systemically

With Epinephrine

To increase the duration of action of local anesthetics epinephrine is added which blocks the area to be anesthetized by vasoconstriction effects and thereby reduces the systemic absorption and enhances the local anesthetic actions.

Side Effects

1. Systemic effects will result in high doses and long time continuous use.

Cardiovascular effects like Depression of myocardial contraction(negative inotropic)

and hypotension.

But on the contrary cocaine causes systemic vasoconstriction and hypertension.

2.Lightheadedness(Headache)

3.Sensory disturbances

4.Convulsions

5. At high dose coma and death can occur.