Pharmacology Made Simple : Telmisartan

Telmisartan
Telmisartan is an angiotensin II receptor antagonist (angiotensin receptor blocker, ARB) used in the management of hypertension. It was discovered by Boehringer Ingelheim.

Telmisartan is indicated in the treatment of essential hypertension.

Mechanism of Action :

Telmisartan is an angiotensin II receptor blocker that shows high affinity for the angiotensin II receptor type 1 (AT1), with a binding affinity 3000 times greater for AT1 than AT2.

In addition to blocking the RAS, telmisartan acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism. It is believed that telmisartan's dual mode of action may provide protective benefits against the vascular and renal damage caused by diabetes and cardiovascular disease (CVD)

24 hour blood pressure correlates most closely with Target Organ Damage.

Highest incidence of cardiovascular events occurs in early morning hours when blood pressure remains elevated at night.

Blood pressure variability is an independent determinant of Target Organ Damage.

Temisartan contains longest half life among available Angiotensin receptor blockers.

Its half life is 24 hour plasma half life.

The long plasma half life ensures that the anti-hypertensive efficacy is maintained for the full 24 hour dosing interval including the early morning hours.

Telmisartan + Hydrochlorothiazide has powerful 24 hour systolic blood pressure reduction compared with Amlodipine and hydrochlorothiazide.

Telmisartan + Hhydrochlorothiazide provides 24 hour consistent BP control in obese hypertensive patients with type 2 diabetes.

Telmisartan provides better control even in risky early mornings.

Beyond BP reduction, telmisartan also secures from target organ damage.

It also displays cardio protective benefits including LVH and improving cardiac function following cardiac ischemia.

It also provides cerebroprotection as it can penetrate blood brain barrier

Renoprotection by promoting water and sodium excretion without affecting potassium or creatinine excretion in hypertensives.

Telmisartan provides 24 hours consistent BP control in obese hypertensive patients with type 2 diabetes.

Contraindications

Telmisartan is contraindicated during pregnancy. Like other drugs affecting the renin–angiotensin system (RAS), telmisartan can cause birth defects, stillbirths, and neonatal deaths. It is not known whether the drug passes into the breast milk. Also it is contraindicated in bilateral renal artery stenosis in which it can cause renal failure.

Side effects

Side effects are similar to other angiotensin II receptor antagonists and include tachycardia and bradycardia (fast or slow heartbeat), hypotension (low blood pressure), edema (swelling of arms, legs, lips, tongue, or throat, the latter leading to breathing problems), and allergic reactions.

Interactions

Due to its mechanism of action, telmisartan increases blood potassium levels. Combination with potassium preparations or potassium-sparing diuretics could cause hyperkalaemia (excessive potassium levels). Combination with NSAIDs, especially in patients with impaired kidney function, has a risk of causing (usually reversible) kidney failure.

Pharmacology Made Simple : Bosentan Monohydrate

Bosentan

Introduction:

Bosentan is a dual endothelin receptor antagonist used in the treatment of pulmonary artery hypertension (PAH).

Mechanism of Action :

Bosentan is a competitive antagonist of endothelin-1 at the endothelin-A (ET-A) and endothelin-B (ET-B) receptors. Under normal conditions, endothelin-1 binding of ET-A or ET-B receptors causes constriction of the pulmonary blood vessels. By blocking this interaction, bosentan decreases pulmonary vascular resistance

Uses :

Bosentan is used to treat people with moderate pulmonary arterial hypertension and to reduce the number of digital ulcers — open wounds on especially on fingertips and less commonly the knuckles in people with systemic scleroderma.

Bosentan is recommended as fist line therapy for PAH : Pulmonary Arterial Hypertension.

It efficiently improves exercise tolerance and patients quality of life.

There is improved survival rate in PAH patients on long term treatment.

Also,progression of PAH is stopped effectively by use of Bosentan.

It improves functional class (QoL) on long term use.

It is available as 62.5 and 125 mg tablets.

Side Effects:

In addition to the risk of causing birth defects and of causing liver damage, bosentan has a high risk of causing edema, pulmonary veno-occlusive disease, decreasing sperm counts, and decreases in hemoglobin and hematocrit.

Very common adverse effects (occurring in more than 10% of people) include headache, elevated transaminases, and edema.

Common adverse effects (between 1% and 10% of people) include anemia, reduced hemoglobin, hypersensitivity reactions, skin inflammation, itchiness, rashes, red skin, flushing, fainting, heart palpitations, low blood pressure, nasal congestion, gastro-esophageal reflux disease, and diarrhea.

Haematology Made Simple : Hereditary Spherocytosis

Hereditary Spherocytosis is an autosomal dominant disorder.

It is characterized by lack of spectrin in the red cell membrane which cases the cells to become spheres instead of being normal,flexible and durable biconcave discs.

The poorly flexible spherical cells are thus unable to pass through small fenestrations in the splenic red pulp and hemolysis takes place when the red cells are trapped within the spleen.

The treatment for most patients include : supportive care with oral folic acid and blood transfusions during periods of severe anemia.

Splenectomy is considered if patients have modrate to severe spherocytosis or are refractory to medical treatment.

However splenectomy is associated with severe sepsis risk upto 30 years after the procedure with encapsulated bacteria,most common being Streptococcus pneumoniae although it will abolish the risk of life threatening anemia and  regular blood transfusons.

To avoid this risk of sepsis, anti pneumococcal,Haemophilus and meningococcal vaccines should be given several weeks before the procedure.