Type 2 diabetes the most common type of DM affecting 90% of the people in which either the beta cells of the pancreas are unable to produce insulin or the body cannot utilize or respond to the insulin.
Now a research team from the UK has discovered a gene that causes the destruction of the beta islets of Langerhans that produces insulin that contributes to producing type-2 DM.
By blocking the gene TNFR5 halted the destruction process, a discovery that leads to new hope in the treatments of Type-2 DM.
The research team was lead by Dr.Mark Tuner of the School of Science and Technology, at Nottingham University in the UK.
They say that it is certain that a long time use high fat and high sugar diet can worsen the destruction of beta islet cells in Type-2 DM people with uncleared reasons.
But, now they cleared it after research with a number of genes they found that the gene TNFR-5 had the highest sensitivity to glucose and fatty acids and overexpression of this gene in response to the high fat and sugar diet leads to the development of type 2 DM.
Hence they said blocking this gene halted he destruction according to their Laboratory tests.
It has been found out that occasional coffee drinking is riskier than regular coffee drinking. A research was carried out with a group of occasional coffee drinkers and another group of regular coffee drinkers.
The result has shown those occasional coffee drinkers because of the deep fluctuation of the concentration of caffeine in their blood are prone to have higher risks of blood pressure and other cardiovascular complications.300 ml of black coffee consumption can elevate blood pressure within two hours and last for several hours. Hence a drink of coffee may affect the blood pressure measurement results if it was consumed just before the B.P. measurements by the occasional drinkers.
Also coffee drinking by occasional drinkers may interfere with their B.P.medications, such as calcium channel blockers.
Research has shown that Felodipine a calcium channel blocker used to reduce the B.P when used along with a cup of coffee has elevated the B.P. instead of reducing it.
These are because in occasional coffee drinkers the concentration of caffeine deeply fluctuates even if they drink the coffee with a two days gap.
After a cup of coffee the caffeine concentration remains in the blood for two days only. Within two days the blood is almost cleaned off most of the caffeine content. Then by another drink of coffee at the end of the second-day caffeine reenter into the blood as a fresh candidate and may have all its effects freshly. Hence a drink of coffee on every alternate day too are considered as occasional drinks and the body cannot tolerate caffeine as with the regular drinkers.
Regular daily drinking of coffee will be tolerated by the body and the maintenance of a fixed concentration of caffeine in the blood may not complicate blood pressure and other cardiovascular irregularities.
These products are not endogenous substances and hence they are not true autocoids. They are alkaloids of ergot fungi. Yet they are discussed here because of their important actions on smooth muscles as similar to autocoids.
Ergot alkaloids are a group of compounds produced by the fungus Claviceps purpurea.
Ergot alkaloids are mainly acting on adrenergic, serotonergic, and dopamine receptors.
Physiology:-
1.Hallucinations and delusions on overdoses
2.Psychoses and neuro problems on higher doses
3.Vasoconstrictions
4.Uterine stimulation
Therapeutical Use
1. Ergotamine is used to treat migraine by reducing cerebrovascular pulsations
2. Bromocriptine is used to treat hyperprolactinemia
3. Ergotamine and Ergonovine is used to control postpartum hemorrhage
Side Effects
1.Gangrene due to prolonged vasoconstriction which can be reversed by sodium nitroprusside.
Serotonin a central nervous system stimulating hormone found in the CNS neurons was already discussed in this blog as CNS stimulants. But in addition, to being as a neuronal biochemical this hormone is present in each and every cell of our body tissue as an autocoid without being secreted into the blood system directly.
Chemically it is a derivative of tryptamine with a hydroxyl ion at the 5th position.
Of course tissue serotonin is not secreted into the blood but blood platelets are containing serotonin.90% of the body's serotonin are present in blood platelets and the enterochromaffin cells of the digestive systems.
Pharmacologically serotonin is known as a hormone of ecstasy and pleasure, and a low level of it produces sadness. The body synthesizes serotonin from the aminoacid L-tryptophane and a good supply of food enriched with L-tryptophane serves as
antidepressants.
Sesame seeds are rich in L-Tryptophane.
Serotonin is acting through its seven major types of 5-HT receptors subtypes.
Serotonin is mostly metabolized by mitochondrial monoamine oxidase enzymes.
Physiology
1.Neurotransmission
2.Regulation of pituitary functions(as an autocoid)
3.General vasoconstriction except for skeletal muscle and heart where it causes vasodilation(as an autocoid)
4.Contraction of GI smooth muscle(as an autocoid)
5.Stimulation of pain receptors(as an autocoid)
6.Precursor to melatonin
Sumatriptan an antimigraine drug is the serotonin agonist
Sumatriptan has side effects of dizziness, muscle weakness, and neck pain.
Antagonists
1.Ketanserin that lowers blood pressure
2.Ondansetron is used to relieve nausea and vomiting in post-surgical procedures and chemotherapy.
3. Cyproheptadine is used to treat smooth muscle contractions.
The above antagonists also block H-1 and alpha receptors.
Chemically prostaglandins are derivatives of prostanoic acid a 20 carbon fatty acids contain a pentagonal carbon ring.
In general prostaglandins are synthesized by our body from fatty acid eicosatetraenoic acid or arachidonic acid. As being these are all eicosanoids they are considered as true hormones.
Prostaglandins are very important biologically active substances in our bodies identical to hormones. In the beginning they were extracted from the seminal secretions of prostate glands. But nowadays they are found to be present in almost all tissues of our body. Even a nanogram of the chemicals is biologically very active.
Classifications
Prostaglandins are classified as A, B, and E.
They are classically abbreviated as PGA, PGB, and PGE. These classifications are further differentiated and related to the presence or absence of keto or hydroxyl groups at positions 9 and 11.
Subscripts relate to the number and position of double bonds in the aliphatic chain.
Pharmacology
Endogenous prostaglandins are biological substances that affect many body functions.
Many external stimuli which may be chemical, mechanical insults are causing the release of prostaglandins which contributes to the signs and symptoms of the inflammatory processes such as reddening, edema, pain, and itching.
Prostaglandin releases are responded by our body physiologically with vasodilation, in many vascular beds and vasoconstrictions in isolated areas.
Prostaglandin-Es inhibit platelet aggregation, relax bronchial and GI smooth muscle, contract uterine smooth muscle, and inhibit gastric acid secretion. The gastric acid secretion block is done along with Prostaglandin-I.
Alternatively the Prostaglandin-Ds and Fs are causing contractions of bronchial and gastric smooth muscle.
In general all prostaglandins are increasing renal blood flow, increase diuresis with loss of sodium, and potassium in urine but paradoxically increases renin secretion.
They also cause diverse endocrine and metabolic effects.
Clinical Indications
PG-E Analogues
Alprostadil (Prostin VR Pediatric):-It is used for temporary maintenance of a patent ductus arteriosus, in awaiting corrective surgery for congenital heart defects.
Alprostadil(Caverject) To treat impotence due to erectile dysfunction.
Misoprostol:-To prevent and treat NSAIDs induced gastric ulcers. To induce abortion.
Also the other PGE analogs such as Dinoprostone(Prostin-E2, Prepidil, Cervidil)and Carboprost(Hemabate) are used to induce safe abortion. Also they are used to ease the labor during pregnancy by inducing cervical ripening.
Autocoids are endogenous chemicals by which the body heals and correct itself during some stressful and painful situations.
Auto means in Greek 'self' and Akos means 'medicine or remedy' and hence by the name they are body's 'self medicines'.
Autocoids are considered as true hormones that are secreted locally and are not secreted into the blood. But they involve a variety of pharmacological actions. Hence they are also considered as local hormones.
There are many prototype autocoids are secreted in our body. They are,
1.Histamine
2.Serotonin
3.Prostaglandins
4.Kinins
and others like leukotrienes, and interleukins etc.etc.But here we will deal with the first three autocoids as they are the prototypes and not secreted into the blood.
1.Histamine and Antihistamines
Chemistry
Histamine is a bio-amine derived from the amino acid Histidine present in the protein-rich foods. Histidine an amino acid is decarboxylated by the enzyme L-histidine decarboxylase into histamine.
Histamine is widely present in the body in the granules of mast cells and basophils.
Mechanism and Effects
Histamine when released from the mast cells by external or internal allergen stimulants acts on its own receptors such as H-1 and H-2.
These receptors are located on our body cell surfaces and mediate numerous varieties of pharmacological responses.
Physiological Effects
1.Constriction of bronchioles(H1)
2. Constriction of intestinal smooth muscle(H1)
3.Stimulates sensory nerves mediating pain and itching(H1)
4.Lower Blood Pressure (H2)
5.Stimulates gastric acid secretions(H2)
6.Increases permeability of skin capillaries(H2)
Clinically histamine has no medical use. But medicinally antihistamines have a variety of use.
Classifications
A.H-1 Antagonists
1.Ethylenediamine:-Tripelennamine
2.Alkylamines:-Chlorpheniramine maleate
3.Azines:-Promethazine
4.Piperidines:-Cyproheptadines
B.H-2 Antagonists
These are heterogenous congeners of histamine
1.Cimetidine
2.Ranitidine
3.Famotidine
4.Nizatidine
In general action of histamine on
1.H-1 Receptors
1.Allergy
2.Anaphylactic reactions such as bronchoconstriction, vasodilation, increased capillary permeability, and spasmodic contractions of Gastrointestinal smooth muscles.
Competitively the inhibit the action of histamine on these receptors by their similarity of structures. Thus they limit the histamine effect on bronchial smooth muscle, capillaries, and GI smooth muscle.
These drugs also prevent the allergy-induced itching and pain of the skin and mucous membranes.
H-2 Antagonists
They limit the histamine effect of gastric acid secretions.
Therapy
Histamine has no medicinal and clinical value, yet it can be used as a diagnostic agent to test gastric function. However other gastric stimulants safer as diagnostic agents.
H-1 antagonists are mostly used as anti-allergic agents to reduce itching, urticaria, seasonal cold, and conjunctivitis.
H-2 antagonists are used to relieving from hyper acid secretions.
Toxicity
H-1 Antagonists:-
1.CNS depression
2.Sedation
3.Tiredness
4.Nausea and Vomiting
5.Anticholinergic effects such as dry mouth, urinary retention, and constipation.
Teratogenic effects(not suitable in pregnancy and lactation)
Peripheral H-1 antagonists such as terfenadine and astemizole are devoid of sedation fatigue and anticholinergic side effects.
But these drugs on elevation in plasma have serious cardiovascular effects such as QT prolongation in ECG, cardiac arrest, torsades de points, and ventricular arrhythmias.
Terfenadine is contraindicated with ketoconazole, macrolides as these compounds will reduce its liver metabolism and elevate plasma levels of terfenadine.
H-2 Antagonists:-
1.CNS effects like confusion and dizziness
2.Hepatic failure
3.Kidney failure
4. High doses of cimetidine cause androgenic effects like impotence and gynecomastia in men and galactorrhea in women
