Table 1: Mechanism of action and side effects of some synthetic regimens used in the treatment of CVD, DM, and RA.

(brand names)
MechanismSide effectsStructure

Cardiovascular diseases

(i) Inhibiting the production of TXA2 by inactivation of COX-1 and COX-2 enzymes(i) Stomach bleeding
(ii) Risk of hemorrhagic stroke ↑
(iii) Gastric ulcers
(iv) Stomach upset
(v) Heartburn
(vi) Nausea
(vii) Epigastric distress
(viii) Dyspepsia
(ix) Thrombocytopenia
(x) Fibrinolytic activity ↑

(i) Inhibiting ACE which catalyzes the formation of angiotensin II (a strong vasoconstrictor)(i) Dizziness
(ii) Lightheadedness
(iii) Tiredness
(iv) Dry cough
(v) Nausea
(vi) Vomiting
(vii) Blurred vision
(viii) Chest pain
(ix) Confusion
(x) Sweating

(i) Inhibiting the Na-K-ATPase membrane pump resulting in an increase in intracellular sodium(i) Dizziness
(ii) Fainting
(iii) Fast pounding or irregular heartbeat or pulse
(iv) Slow heartbeat
(v) Nausea
(vi) Vomiting
(vii) Headache
(viii) Loss of appetite
(ix) Diarrhea

(i) Decreasing arterial smooth muscle contractility and vasoconstriction by inhibiting the influx of calcium ions through calcium channels(i) Dizziness
(ii) Lightheadedness
(iii) Swelling ankles/feet
(iv) Flushing
(v) Fatigue
(vi) Palpitations
(vii) Edema
(viii) Tightness in the chest
(ix) Wheezing

5Isosorbide dinitrate
(i) It is converted into NO which activates the enzyme guanylate cyclase that stimulates the synthesis of cGMP which then activates a series of protein kinase-dependent phosphorylations in the smooth muscle cells eventually resulting in vasodilation(i) Headache
(ii) Dizziness
(iii) Lightheadedness
(iv) Nausea
(v) Flushing
(vi) Unusual bleeding
(vii) Bruising
(viii) Rapid heart rate
(ix) Difficulty with breathing

Diabetes mellitus

1Metformin (Glucophage®)(i) Activating AMPK to inhibit hepatic glucose production
(ii) Increasing AMPK activity in skeletal muscle for glucose uptake by GLUT4 deployment to the plasma membrane
(i) Lactic acidosis
(ii) Dyspepsia
(iii) Nausea
(iv) Diarrhea
(v) Vomiting
(vi) Weakness

(i) Activating PPARγ receptors to modulate the insulin-sensitive genes transcription for the reduction of insulin resistance(i) Weight gain
(ii) Risk of bladder cancer
(iii) Sore throat
(iv) Muscle pain
(v) Tooth problems
(vi) May cause heart failure
(vii) Fluid retention
(viii) Peripheral edema

(i) Binding and inhibiting the ATP-sensitive potassium channels SUR1 receptor on the pancreatic cell surface, which causes membrane depolarization and opens the calcium channels for insulin exocytosis(i) Nausea
(ii) Vomiting
(iii) Diarrhea
(iv) Increased appetite
(v) Heartburn
(vi) Stomach fullness
(vii) Weight gain
(viii) Hypoglycemia

(i) Reversibly binding to pancreatic α-amylase and intestinal α-glucoside hydrolases to inhibit the hydrolysis of complex carbohydrates to glucose (i) Diarrhea
(ii) Gas
(iii) Upset stomach
(iv) Constipation
(v) Stomach pain
(vi) Nausea
(vii) Loss of appetite
(viii) Jaundice

5Human insulin
(Humulin R®)
(i) Binding to the IR and stimulating the downstream signaling molecules which regulates the GLU4 and PKC activity(i) Pain
(ii) Mild itching
(iii) Redness
(iv) Swelling at the injection site
(v) Mild weight gain
(vi) Hypoglycemia

Rheumatoid arthritis

(i) Inhibiting dihydrofolate reductase which is involved in purine metabolism
(ii) Inhibiting T-cell activation
(iii) Selectively downregulating B cells
(iv) Inhibiting methyltransferase activity, which leads to deactivation of immune system enzyme activities
(i) Nausea
(ii) Bloody vomiting
(iii) Stomach pain
(iv) Drowsiness
(v) Dizziness
(vi) Black, tarry stools
(vii) Sores in the mouth or lips
(viii) Blurred vision
(ix) Confusion
(x) Convulsions

(i) Inhibiting stimulation of the TLR-9
(ii) Inhibiting the production of rheumatoid factor
(i) Nausea
(ii) Stomach cramps
(iii) Loss of appetite
(iv) Diarrhea
(v) Dizziness
(vi) Headache
(vii) Convulsions
(viii) Weakness
(ix) Sore throat
(x) Fever
(xi) Unusual bleeding
(xii) Bruising

3Sulfasalazine (Azulfidine®)(i) Inhibiting NF-κB and exerting anti-inflammatory and/or immunomodulatory activities(i) Stomach upset
(ii) Nausea
(iii) Vomiting
(iv) Loss of appetite
(v) Headache
(vi) Dizziness
(vii) Unusual tiredness
(viii) Fever
(ix) Sore throat
(x) Skin rash or itching
(xi) Bleeding gums
(xii) Dark urine

(i) Inhibiting mitochondrial enzyme dihydroorotate dehydrogenase and thus inhibiting the reproduction of rapidly dividing cells, especially autoimmune lymphocytes(i) Diarrhea
(ii) Nausea
(iii) Dizziness
(iv) Skin rash
(v) Alopecia
(vi) AST ↑
(vii) ALT ↑
(viii) Bloody or cloudy urine
(ix) Cough
(x) Headache
(xi) Vomiting
(xii) Sore throat

(i) Binding and neutralizing the activity of TNFα
(ii) Inhibiting the release of IL-1β from monocytes
(i) Fever
(ii) Cough
(iii) Sore throat
(iv) Runny nose
(v) Frequent urination with burning sensation
(vi) Joint pain
(vii) Body aches
(viii) Headache
(ix) Loss of voice
(x) Ear congestion

AMPK: AMP-activated protein kinase; GLUT4: glucose transporter 4; SUR1: sulfonylurea receptor 1; IR: insulin receptor, PKC: protein kinase C; PPARγ: peroxisome proliferator-activated receptor gamma; ATP: adenosine triphosphate; TXA2: thromboxane A2; COX: cyclooxygenase: AST: aspartate aminotransferase; ALT: alanine aminotransferase; ACE: angiotensin converting enzyme; NO: nitric oxide; cGMP: cyclic guanosine 3′,5′-monophosphate.