Chemistry Made Simple : Catenation

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Catenation is the bonding of atoms of the same element into a series, called a chain.

A chain or a ring shape may be open if its ends are not bonded to each other (an open-chain compound), or closed if they are bonded in a ring (a cyclic compound).

Catenation occurs most readily with carbon, which forms covalent bonds with other carbon atoms to form longer chains and structures

Carbon is most well known for its properties of catenation, with organic chemistry essentially being the study of catenated carbon structures (and known as catenae).

However, carbon is by no means the only element capable of forming such catenae, and several other main-group elements are capable of forming an expansive range of catenae, including silicon, sulphur  boron and phosphorus

Pharmacology Made Simple : Antibiotics : Tetracyclines

Pharmacology Made Simple : Antibiotics : Tetracyclines

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Tertracycline:

Tetracycline is in the tetracyclines family of medications. 

It works by blocking the ability of bacteria to make proteins.

Tetracycline was originally made from bacteria of the Streptomyces type.

Mechanism of action:

Tetracycline inhibits protein synthesis by blocking the attachment of charged aminoacyl-tRNA to the A site on the ribosome. Tetracycline binds to the 30S subunit of microbial ribosomes. 

Thus, it prevents introduction of new amino acids to the nascent peptide chain.

The action is usually inhibitory and reversible upon withdrawal of the drug. Mammalian cells are less vulnerable to the effect of tetracyclines, despite the fact that tetracycline binds to the small ribosomal subunit of both prokaryotes and eukaryotes (30S and 40S, respectively). 

This is because bacteria actively pump tetracycline into their cytoplasm, even against a concentration gradient, whereas mammalian cells do not. This accounts for the relatively small off-site effect of tetracycline on human cells.

Clinical Uses :

Tetracycline is an antibiotic used to treat a number of infections.

This includes acne, cholera, brucellosis, plague, malaria, and syphilis.

It is taken by mouth.

Side Effects :

Common side effects include vomiting, diarrhea, rash, and loss of appetite.

Other side effects include poor tooth development if used by children less than eight years of age,

kidney problems, and sunburning easily.

Use during pregnancy may harm the baby.

Medical uses:

It is first-line therapy for Rocky Mountain spotted fever (Rickettsia),

Lyme disease (B. burgdorferi),

Q fever (Coxiella), psittacosis, and

Mycoplasma pneumoniae and to eradicate nasal carriage of meningococci.

Tetracycline tablets were used in the plague outbreak in India in 1994.

Spectrum of bacterial susceptibility

Tetracyclines have a broad spectrum of antibiotic action.

Originally, they possessed some level of bacteriostatic activity against almost all medically relevant aerobic and anaerobic bacterial genera, both Gram-positive and Gram-negative, with a few exceptions, such as Pseudomonas aeruginosa and Proteus spp., which display intrinsic resistance.

However, acquired (as opposed to inherent) resistance has proliferated in many pathogenic organisms and greatly eroded the formerly vast versatility of this group of antibiotics.

Resistance amongst Staphylococcus spp., Streptococcus spp., Neisseria gonorrhoeae, anaerobes, members of the Enterobacteriaceae, and several other previously sensitive organisms is now quite common.

Tetracyclines remain especially useful in the management of infections by certain obligately intracellular bacterial pathogens such as Chlamydia, Mycoplasma, and Rickettsia.

They are also of value in spirochaetal infections, such as syphilis, leptospirosis, and Lyme disease. Certain rare or exotic infections, including anthrax, plague and brucellosis, are also susceptible to tetracyclines. These agents also have activity against certain eukaryotic parasites, including those responsible for diseases such as malaria and balantidiasis.

Precautions:

Discolor permanent teeth (yellow-gray-brown), from prenatal period through childhood and adulthood.

Be inactivated by Ca2+ ions, so are not to be taken with milk, yogurt, and other dairy products.

Be inactivated by aluminium, iron, and zinc, not to be taken at the same time as indigestion remedies (common antacids and over-the-counter heartburn medicines).

Cause skin photosensitivity, so exposure to the sun or intense light is not recommended.

Cause drug-induced lupus, and hepatitis.

Cause microvesicular fatty liver.

Cause tinnitus.

Interfere with methotrexate by displacing it from the various protein-binding sites.

Cause breathing complications, as well as anaphylactic shock, in some individuals.

Affect bone growth of the fetus, so should be avoided during pregnancy.

Fanconi syndrome may result from ingesting expired tetracyclines.

Caution should be exercised in long-term use when breastfeeding. Short-term use is safe.

Pharmacology Made Simple : Antihypertensives : Enalapril

Enalapril

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Enalapril,is a medication that belongs to the angiotensin-converting-enzyme inhibitor (ACEi) family of medications. used to treat high blood pressure, diabetic kidney disease, and heart failure.

For heart failure it is generally used with a diuretic such as furosemide.



Mechanism of action


Normally, angiotensin I is converted to angiotensin II by an angiotensin-converting enzyme (ACE). Angiotensin II constricts blood vessels, increasing blood pressure.

Enalaprilat, the active metabolite of enalapril, inhibits ACE. Inhibition of ACE decreases levels of angiotensin II leading to less vasoconstriction and decreased blood pressure.



Pharmacokinetics

Pharmacokinetic data of enalapril:

Onset of action: about 1 hour
Peak effect: 4–6 hours
Duration: 12–24 hours
Absorption: ~60%
Metabolism: prodrug, undergoes biotransformation to enalaprilat.



Route of administration :

It is given by mouth or injection into a vein.

Onset of effects are typically within an hour when taken by mouth and last for up to day.

Medical uses

Enalapril is used to treat hypertension, symptomatic heart failure, and asymptomatic left ventricular dysfunction.

It has been proven to protect the function of the kidneys in hypertension, heart failure, and diabetes, and may be used in the absence of hypertension for its kidney protective effects.

It is widely used in chronic kidney failure.

Furthermore, enalapril is an emerging treatment for psychogenic polydipsia.

A double-blind, placebo-controlled trial showed that when used for this purpose, enalapril led to decreased water consumption (determined by urine output and osmality) in 60% of patients.



.
Side effects

Common side effects include headache, tiredness, lightheadedness with standing, and cough.

Serious side effects include angioedema and low blood pressure.

Use during pregnancy is believed to result in harm to the baby.

The most common side effects of enalapril include increased serum creatinine (20%), dizziness (2–8%), low blood pressure (1–7%), syncope (2%), and dry cough (1–2%).

The most serious common adverse event is angioedema (swelling) (0.68%) which often affects the face and lips, endangering the patient’s airway.

Angioedema can occur at any point during treatment with enalapril, but is most common after the first few doses.

.





Enalaprilat was developed partly to overcome these limitations of captopril. The sulfhydryl moiety was replaced by a carboxylate moiety, but additional modifications were required in its structure-based design to achieve a potency similar to captopril. Enalaprilat, however, had a problem of its own in that it had poor oral availability. This was overcome by the researchers at Merck by the esterification of enalaprilat with ethanol to produce enalapril.

Pharmacology Made Simple : Medications used in treatment of Heart Failure : Nebivolol

Nebivolol:

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Nebivolol is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and also for left ventricular failure.

It is highly cardioselective under certain circumstances.




β1-selectivity

Beta blockers help patients with cardiovascular disease by blocking β receptors, while many of the side-effects of these medications are caused by their blockade of β2 receptors.

For this reason, beta blockers that selectively block β1 adrenergic receptors (termed cardioselective or β1-selective beta blockers) produce fewer adverse effects (for instance, bronchoconstriction) than those drugs that non-selectively block both β1 and β2 receptors.



In a laboratory experiment conducted on biopsied heart tissue, nebivolol proved to be the most β1-selective of the β-blockers tested, being approximately 3.5 times more β1-selective than bisoprolol.

However, the drug's receptor selectivity in humans is more complex and depends on the drug dose and the genetic profile of the patient taking the medication.



The drug is highly cardioselective at 5 mg.In addition, at doses above 10 mg, nebivolol loses its cardioselectivity and blocks both β1 and β2 receptors.

While the recommended starting dose of nebivolol is 5 mg, sufficient control of blood pressure may require doses up to 40 mg).

Furthermore, nebivolol is also not cardioselective when taken by patients with a genetic makeup that makes them "poor metabolizers" of nebivolol (and other drugs) or with CYP2D6 inhibitors.

As many as 1 in 10 whites and even more blacks are poor CYP2D6 metabolizers and therefore might benefit less from nebivolol's cardioselectivity although currently there are no directly comparable studies.

Vasodilator action :

Nebivolol is unique as a beta-blocker.Unlike carvedilol, it has a nitric oxide (NO)-potentiating, vasodilatory effect via stimulation of β3 receptors.Along with labetalol, celiprolol and carvedilol, it is one of four beta blockers to cause dilation of blood vessels in addition to effects on the heart.

Antihypertensive effect :

Nebivolol lowers blood pressure (BP) by reducing peripheral vascular resistance, and significantly increases stroke volume with preservation of cardiac output.

The net hemodynamic effect of nebivolol is the result of a balance between the depressant effects of beta-blockade and an action that maintains cardiac output.


Pharmacology of side-effects :

Several studies have suggested that nebivolol has reduced typical beta-blocker-related side effects, such as fatigue, clinical depression, bradycardia, or impotence.However, according to the FDA.



Contraindications:

Nebivolol is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), severe hepatic impairment (Child-Pugh > B) and in patients who are hypersensitive to any component of the product.

Nebivolol is also associated with warnings regarding abrupt cessation of therapy, cardiac failure, angina and acute myocardial infarction, bronchospastic diseases, anesthesia and major surgery, diabetes and hypoglycemia, thyrotoxicosis, peripheral vascular disease, non-dihydropyridine calcium channel blockers use, as well as precautions regarding use with CYP2D6 inhibitors, impaired renal and hepatic function, and anaphylactic reactions.


Contraindications Summay :

Severe bradycardia
Heart block greater than first degree
Patients with cardiogenic shock
Decompensated cardiac failure
Sick sinus syndrome (unless a permanent pacemaker is in place)
Patients with severe hepatic impairment (Child-Pugh class B)
Patients who are hypersensitive to any component of this product.


Adverse drug reactions


Headache
Paresthesia
Dizziness
History

Pharmacology Made Simle : Antihypertensives : Amlodipine

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Amlodipine

Mechanism of action :

Amlodipine is an angioselective calcium channel blocker and inhibits the movement of calcium ions into vascular smooth muscle cells and cardiac muscle cells which inhibits the contraction of cardiac muscle and vascular smooth muscle cells.




Amlodipine inhibits calcium ion influx across cell membranes, with a greater effect on vascular smooth muscle cells. This causes vasodilation and a reduction in peripheral vascular resistance, thus lowering blood pressure. Its effects on cardiac muscle also prevent excessive constriction in the coronary arteries



The mechanisms by which amlodipine relieves angina are:

Stable angina:

Amlodipine reduces the total peripheral resistance (afterload) against which the heart works and reduces the rate pressure product, thereby lowering myocardial oxygen demand, at any given level of exercise.

Variant Angina: 

Amlodipine blocks spasm of the coronary arteries and restores blood flow in coronary arteries and arterioles in response to calcium, potassium, epinephrine, serotonin, and thromboxane A2 analog in experimental animal models and in human coronary vessels in vitro.



Pharmacokinetics

The nitrogen-containing ring is oxidized, and two of the side chains are hydrolyzed.

Amlodipine is well absorbed by the oral route with a mean oral bioavailability around 60%; the half-life of amlodipine is about 30 h to 50 h, and steady-state plasma concentrations are achieved after 7 to 8 days of daily dosing.
Its long half-life and high bioavailability are largely in part of its high pKa (8.6); it is ionized at physiological pH, and thus can strongly attract proteins.




Side effects :

Some common dose-dependent side effects of amolodipine include vasodilatory effects, peripheral edema, dizziness, palpitations, and flushing.

Peripheral edema (fluid accumulation in the tissues) occurs at rate of 10.8% at a 10-mg dose (versus 0.6% for placebos), and is three times more likely in women than in men.

It causes more dilation in the arterioles and precapillary vessels than the postcapillary vessels and venules.

The increased dilation allows for more blood, which is unable to push through to the relatively constricted postcapillary venules and vessels; the pressure causes much of the plasma to move into the interstitial space.

Amlodipine-association edema can be avoided by adding ACE inhibitors or angiontensin II receptor antagonist.

Common but not dose-related side effects are fatigue , nausea , abdominal pain , and somnolence.

Side effects occurring less than 1% of the time include: blood disorders, impotence, depression, peripheral neuropathy, insomnia, tachycardia, gingival enlargement, hepatitis, and jaundice.



Overdose

Amlodipine overdose toxicity can result in widening of blood vessels, severe low blood pressure, and fast heart rate.

Toxicity is generally managed with fluid replacement, monitoring ECG results, vital signs, respiratory system function, glucose levels, kidney function, electrolyte levels, and urine output.Vasopressors are also administered when low blood pressure is not alleviated by fluid resuscitation.



Combination therapy

Amlodipine can be given as a combination therapy with a variety of medications:

Amlodipine/atorvastatin, where amlodipine is given for hypertension or CAD and atorvastatin prevents cardiovascular events, or if the person also has high cholesterol.

Amlodipine/aliskiren or amlodipine/aliskiren/hydrochlorothiazide if amlodipine alone cannot reduce blood pressure. Aliskiren is a renin inhibitor, which works to reduce primary hypertension (that with no known cause) by binding to renin and preventing it from initiating the renin–angiotensin system (RAAS) pathway to increase blood pressure.

Hydrochlorothiazide is a diuretic and decreases overall blood volume.

Amlodipine/benazepril if either drug has failed individually, or amlodipine alone caused edema. Benazepril is an ACE inhibitor and blocks the conversion of angiotensin I to angiotensin II in the RAAS pathway.

Amlodipine/olmesartan or amlodipine/olmesartan/hydrochlorothiazide if amlodipine is insufficient in reducing blood pressure. Olmesartan is an angiotensin II receptor antagonist and blocks part of the RAAS pathway.

Amlodipine/perindopril if using amlodipine alone caused edema. Perindopril is a long-lasting ACE inhibitor.
Amlodipine/telmisartan, where telmisartan is an angiotensin II receptor antagonist.
Amlodipine/valsartan or amlodipine/valsartan/hydrochlorothiazide, where valsartan is an angiotensin II receptor antagonist.

Contraindications

The only absolute contraindication to amlodipine is an allergy to amlodipine or any other dihydropyridines.

Other situations occur, however, where amlodipine generally should not be used.

In patients with cardiogenic shock, where the heart's ventricles are not able to pump enough blood, calcium channel blockers exacerbate the situation by preventing the flow of calcium ions into cardiac cells, which is required for the heart to pump.

While use in patients with aortic stenosis (narrowing of the aorta where it meets the left ventricle) since it does not inhibit the ventricle's function is generally safe, it can still cause collapse in cases of severe stenosis.

In unstable angina (excluding variant angina), amlodipine can cause a reflex increase in cardiac contractility (how hard the ventricles squeeze) and heart rate, which together increase the demand for oxygen by the heart itself.

Patients with severe hypotension can have their low blood pressure exacerbated, and patients in heart failure can get pulmonary edema. Those with impaired liver function are unable to metabolize amlodipine to its full extent, giving it a longer half-life.

Amlodipine's safety in pregnancy has not been established, although reproductive toxicity at high doses is known. Whether amlodipine enters the milk of breastfeeding mothers is also unknown.

Pharmacology Made Simple : Combination of Antihypertensives : Zestoretic

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Zestoretic

This medication is used to treat high blood pressure.

Lowering high blood pressure helps prevent strokes, heart attacks, and kidney problems.

This product contains two medications: lisinopril and hydrochlorothiazide.

Lisinopril is an ACE inhibitor and works by relaxing blood vessels so that blood can flow more easily.

Hydrochlorothiazide is a "water pill" (diuretic) that causes one to make more urine, which helps body get rid of extra salt and water.

This product is used when one drug is not controlling blood pressure.



Lisinopril

Lisinopril is a drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of high blood pressure, heart failure, and after heart attacks and diabetic nerve pain.

It is also used for preventing kidney and eye complications in people with diabetes. Its indications, contraindications, and side effects are as those for all ACE inhibitors.


Caution should be used in the following populations, as dose adjustments may be required.

Kidney problems

The dose must be adjusted in those with poor kidney function. Dose adjustments may be required when creatinine clearance is less than or equal to 30mL/min.

Pregnancy and breastfeeding

Lisinopril has been assigned to pregnancy category D by the FDA. Animal and human data have revealed evidence of lethal harm to the embryo and teratogenicity associated with ACE inhibitors.

Birth defects have been associated with use of lisinopril in any trimester. However, there have been reports of death and increased toxicities to the fetus and newly born child with the use of lisinopril in the second and third trimesters.

The label states, "When pregnancy is detected, discontinue Zestril as soon as possible.Mothers should not breastfeed while taking this medication because of the lack of safety data that currently exists.


Contraindications

Treatment with lisinopril should be avoided for people who have a history of angioedema (hereditary or idiopathic) or who have diabetes and are taking aliskiren.

Adverse effects

People taking lisinopril for the treatment of hypertension may experience the following side effects:

Headache
Dizziness
Cough (
Difficulty swallowing or breathing (signs of angioedema), allergic reaction (anaphylaxis)
Hyperkalemia
Fatigue
Diarrhea
Some severe skin reactions have been reported rarely, including toxic epidermal necrolysis and Stevens-Johnson syndrome.

Thiazide

Thiazide  is a type of molecule and a class of diuretics often used to treat hypertension (high blood pressure) and edema (such as that caused by heart failure, liver failure, or kidney failure).

When administered acutely thiazides lower blood pressure by causing diuresis, a fall in plasma volume and a reduction in cardiac output. However, after chronic use thiazides cause a reduction in blood pressure by lowering peripheral resistance (i.e. vasodilation).

The mechanism of this effect is uncertain but it may involve effects on 'whole body' or renal autoregulation, or direct vasodilator actions either through inhibition of carbonic anhydrase or by desensitizing the vascular smooth muscle cells to the rise in intracellular calcium induced by norepinephrine.

Other Uses :

Thiazides also lower urinary calcium excretion, making them useful in preventing calcium-containing kidney stones. This effect is associated with positive calcium balance and is associated with an increase in bone mineral density and reductions in fracture rates attributable to osteoporosis.

By a lesser understood mechanism, thiazides directly stimulate osteoblast differentiation and bone mineral formation, further slowing the course of osteoporosis.

Because of their promotion of calcium retention, thiazides are used in the treatment of

Dent's disease
Hypocalcemia
Nephrolithiasis (idiopathic hypercalciuria)
Bromide intoxication
Nephrogenic diabetes insipidus


Contraindications

Hypotension
Allergy to sulphur-containing medications
Gout
Renal failure
Lithium therapy
Hypokalemia
May worsen diabetes

Thiazides reduce the clearance of uric acid since they compete for the same transporter, and therefore raise the levels of uric acid in the blood. Hence they are prescribed with caution in patients with gout or hyperuricemia

Chronic administration is associated with hyperglycemia.

Thiazides cause loss of blood potassium, while conserving blood calcium.

Thiazides can decrease placental perfusion and adversely affect the fetus so should be avoided in pregnancy.

Side Effects

Hypokalemia

Thiazide diuretics reduces potassium concentration in blood through two indirect mechanisms: inhibition of sodium-chloride symporter at distal convoluted tubule of a nephron and stimulation of aldosterone that activates Na+/K+-ATPase at collecting duct.

Inhibition of sodium-chloride symporter increases availability of sodium and chloride in urine. When the urine reaches the collecting duct, the increase in sodium and chloride availability activates Na+/K+-ATPase, which increases the absorption of sodium and excretion of potassium into the urine.

Reduction of Total Body Volume

Long term administration of thiazide diuretics reduces total body blood volume. This activates the renin–angiotensin system, stimulates the secretion of aldosterone, thus activating Na+/K+-ATPase, increasing excretion of potassium in urine. Therefore, ACE inhibitor and thiazide combination is used to prevent hypokalemia.

Other Side Effects : 

Hyperglycemia
Hyperlipidemia
Hyperuricemia
Hypercalcemia
Hyponatremia
Hypomagnesemia
Hypocalciuria

Pharmacology Made Simple : Typhoid Vaccine

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Typhoid Vaccine

Also known as Vi Capsular Polysaccharide Typhoid Vaccine is a colourless and transparent injection in liquid form containing Vi capsular polysaccharide .

Composition is 0.5 ml that contains purified Vi capsular polysaccharide of Salmonella Typhu 25 mcg.

Indications:
Prevention of Typhoid fever in adults and children over 2 years of age.

Dosage :
 A single intramuscular injection of  Typbar 0.5 ml for adults and children over 2 years of age.

The protection lasts for upto  3 years.


Revaccination is needed once every 3 years to maintain protection.

Precautions:
Immunisation should be postponed in febrile subjects or in persons with acute infection.


Contraindications:

1. Hypersensitivity to any constituent of vaccine.


2. Pregnancy and lactation:
The risk during pregnancy is currently not exactly known.

Adverse Effects:

Mild pain at injection site.

Erythema /. Induration at injection site.

Mild fever in 1 - 5 %  of cases.

Pharmacology Made Simple : Ivabradine

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Ivabradine

Ivabradine is a medication which is used to reduce heart rate while fully preserving myocardial contra ction and relaxation,AV conduction and ventricular depolarisation as well as blood pressure.

It is a specific and selective inhibitor of if ion channel.After binding to this receptor,it reduces the slope for  diastolic depolarisation and prolongs diastolic duration and thus decreasing the heat rate.

It is available in 5 mg and 7.5 mg tablets.

In Shift Trial : Systolic Heart Failure Treatment with the if Inhibitor Ivabradine Trial ,it was found that :

Ivabradine significantly reduced the relative risk of hospitalisation for worsening HF or CV death by 18%.

Ivabradine reduced the relative risk of hospitalisation for worsening Heart Failure by 26%.

Ivabradine reduces myocardial infarction in patients with Angina by 73%.

Other uses:
Ivabradine canbe successfully used in patients who are unable to tolerate maximum doses of beta blockers.

In Summary, Ivabradine can be used for:

Exclusive Heart Rate reductions
Reducing admission to hospital for MI and coronary revascularization.
Has no negative inotropic effect.
Is safe in patients with LVSD already on Beta Blocker

Pharmacology Made Simple : Polysaccharide Iron Complex

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Pharmacology Made Simple : Polysaccharide Iron Complex

Polysaccharide Iron Complex (PIC) is available in capsules of 150 mg.

They are excellent choice for treatment of iron deficiency anemia in pregnancy.

After treatment with PIC , clinical parameters such as red blood cell count,hemoglobin and haematocit improved significantly.

After 8 weeks of treatment with PIC 300 mg ,in a patient with Anemia ,the net increase in Hb of 9.5 mg/dl was by 2.6 mg / dl and haematocrit of 30.3 % was by 6.3 %.

Usual adult dose of Polysaccharide Iron complex is 150 mg capsule 1 to 2 daily and can be taken regardless of meal.

For patients having difficulty in swallowing of capsules,the PIC capsule can be opened and the powder can be diluted in liquid or sprinkled on food.

This medication is an iron supplement used to treat or prevent low blood levels of iron (e.g., for anemia or during pregnancy). Iron is an important mineral that the body needs to produce red blood cells and keep you in good health.

How to use Polysaccharide Iron 150

Iron is best absorbed on an empty stomach (usually if taken 1 hour before or 2 hours after meals). If stomach upset occurs, you may take this medication with food. Avoid taking antacids, dairy products, tea.

Side Effects

Constipation, diarrhea, stomach cramps, or upset stomach may occur. These effects are usually temporary and may disappear as your body adjusts to this medication.
Iron may cause your stools to turn black, an effect that is not harmful.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

Precautions

This medication should not be used if you have certain medical conditions. Before taking this medication, consult your doctor or pharmacist if you have: iron overload disorder (e.g., hemochromatosis, hemosiderosis).

Before taking this medication, tell your doctor or pharmacist your medical history, especially of: use/abuse of alcohol, liver problems, stomach/intestinal problems (e.g., ulcer, colitis).

If your brand of iron supplement also contains folic acid, be sure to tell your doctor or pharmacist if you have vitamin B12 deficiency (pernicious anemia) before taking it.
Folic acid may falsely improve certain laboratory tests for vitamin B12 deficiency without actually treating this anemia. Untreated vitamin B12 deficiency may result in serious nerve problems (e.g., peripheral neuropathy symptoms such as numbness/pain/tingling sensations).

Chewable tablets of this medicine may contain aspartame. If you have phenylketonuria (PKU) or any other condition that requires you to restrict your intake of aspartame (or phenylalanine), consult your doctor or pharmacist about using this drug safely.

Liquid preparations of this product may contain sugar and/or alcohol. Caution is advised if you have diabetes, alcohol dependence, or liver disease.
During pregnancy, this medication should be used only when clearly needed.
This medication passes into breast milk. Consult your doctor before breast-feeding.

Interactions

Before taking this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially: certain antibiotics (e.g., penicillamine, chloramphenicol, quinolones such as ciprofloxacin/norfloxacin), bisphosphonates (e.g., alendronate), levodopa, methyldopa, thyroid replacement drugs (e.g., levothyroxine).

Avoid taking this medication at the same time as antacids or tetracycline antibiotics. Wait at least 2 hours between taking this medication and an antacid or tetracycline.

If your brand of iron also contains folic acid, be sure to tell your doctor or pharmacist if you take certain anti-seizure drugs (e.g., hydantoins such as phenytoin).

This medication may interfere with certain laboratory tests (e.g., fecal occult blood tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

Pharmacology Made Simple : Erythromycin

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Pharmacology Made Simple : Erythromycin

Erythromycin is an antibiotic useful for the treatment of a number of bacterial infections.

This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. 

It may also be used during pregnancy to prevent Group B streptococcal infection in the newborn.

Erythromycin may be used to improve delayed stomach emptying. It can be given intravenously and by mouth.

An eye ointment is routinely recommended after delivery to prevent eye infections in the newborn.

Mechanism of Action :

Erythromycin displays bacteriostatic activity or inhibits growth of bacteria, especially at higher concentrations .It binds to the 50s subunit of the bacterial rRNA complex, protein synthesis and subsequent structure and function processes critical for life or replication are inhibited.

Erythromycin interferes with aminoacyl translocation, preventing the transfer of the tRNA bound at the A site of the rRNA complex to the P site of the rRNA complex. Without this translocation, the A site remains occupied, thus the addition of an incoming tRNA and its attached amino acid to the nascent polypeptide chain is inhibited. 

This interferes with the production of functionally useful proteins, which is the basis of this antimicrobial action.

Side Effects:

It is generally safe in those who are allergic to penicillin.

Erythromycin also appears to be safe to use during pregnancy.While generally regarded as safe during breastfeeding its use by the mother during the first two weeks of life may increase the risk of pyloric stenosis in the baby.

Common side effects include abdominal cramps, vomiting, and diarrhea. More serious side effects may include Clostridium difficilecolitis, liver problems, prolonged QT, and allergic reactions.

This risk also applies if taken directly by the baby during this age.

It is in the macrolide family and works by decreasing bacterial protein production.

Interactions:

Erythromycin is metabolized by enzymes of the cytochrome P450 system, in particular, by isozymes of the CYP3A superfamily, CYP3A.

The activity of the CYP3A enzymes can be induced or inhibited by certain drugs (e.g. dexamethasone) which can cause it to affect the metabolism of many different drugs, e.g. erythromycin. If other CYP3A substrates — drugs that are broken down by CYP3A  such as simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin (Lipitor)—are taken concomitantly with erythromycin, levels of the substrates increase, often causing adverse effects.

A noted drug interaction involves erythromycin and simvastatin, resulting in increased simvastatin levels and the potential for rhabdomyolysis. Another group of CYP3A4 substrates are drugs used for migraine such as ergotamine and dihydroergotamine; their adverse effects may be more pronounced if erythromycin is associated.

Earlier case reports on sudden death prompted a study on a large cohort that confirmed a link 

between erythromycin, ventricular tachycardia, and sudden cardiac death in patients also taking drugs that prolong the metabolism of erythromycin (like verapamil or diltiazem) by interfering with CYP3A4.

Hence, erythromycin should not be administered to people using these drugs, or drugs that also prolong the QT interval. Other examples include terfenadine (Seldane, Seldane-D), astemizole (Hismanal), cisapride (Propulsid, withdrawn in many countries for prolonging the QT time) and pimozide (Orap). Theophylline, which is used mostly in asthma, is also contraindicated.

Erythromycin and doxycycline can have a synergistic effect when combined and kill bacteria (E. coli) with a higher potency than the sum of the two drugs together.

This synergistic relationship is only temporary. After approximately 72 hours, the relationship shifts to become antagonistic, whereby a 50/50 combination of the two drugs kills less bacteria than if the two drugs were administered separately.

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.

Pharmacology Made Simple : Antimicrobials : Cefexime

Salmonella and Shigella case significant mobidity and motality among children woldwide

Increased microbial resistance reslts in greater burden of disease.

Cefexime and Typhoid Fever:

Typhoid continues to pose a challenge even 100 years after its discovery.

Typhoid is a common cause of morbidity among young children worldwide including children below 2 years of age.

Cefexime exhibits low MIC 90 and high concentration against Typhoid fever.

MIC 90 against Salmonella typhi : 0.25 micrograms/ml2

Mean concentration in bile : 199.3 micrograms/ml3

Cefexime effectively treats MDR and NMDR Typhoid Fever with High Cure Rates.

Cefexime shows significant clinical efficacy of around 100 % with low rates of relapse.

Cefexime in Shigellosis Management :

Shigellosis is primarily a childhood disease in both developed and developing countries.

Over 163.2 million cases are reported in developing countries.

Cefexime exhibits low MIC 90 against Shigella species.

Cefexime is effective in treatmemt of suspected shigellosis in areas of high resistance to co-trimoxazole.

Pharmacology Made Simple : Oral Hypoglycemics : Combination of Sitagliptin and Metformin

Combination of Sitagliptin and Metformin 50 mg / 500 mg :


A combination of Sitagliptin and Metformin 50 mg / 500 mg produces a greater reduction in HbA1c compared to Metformin alone.

A substantial number of patients : 49.2 % in the Sitagliptin =+ Metformin FDC group had an HbA1c < 7.0 % at week 18 as compared with 34.2% in Metformin monotherapy group.

31.8 % of patients with Sitagliptin - Metformin FDC Group achieved an HbA1c of < 6.5 % compared with 16.0 % in Metformin monotherapy group.

Treatment with Sitagliptin - Metformin FDC results in lower incidence of abdominal pain and diarrhea compared with Metformin monotherapy.

This combination improves glycemic control as well as beta cell function.

Sitagliptin - Metformin combination compared with Glipizide- Metformin combination led to better maintenance of Beta cell function after 2 years of treatment.

Disposition Index : an assessment of Beta cell responsiveness in relation to insulin sensitivity remained stable over 2 years with Sitagliptin - Metformin but declined from baseline with Glipizide - Metformin.

Pharmacology Made Simple : Antihypertensives : Valsartan

Valsartan

This is an ARB : Angiotensin Receptor Blocker.

It is available in 40 mg , 80 mg and 160 mg tablets.

It provides round the clock effective and reliable Blood Pressure Control.

In Diabetic hypertensive patients,it doesnot adversely affect glucose and lipid metabolism and even improves it.

It is also safe and well tolerated in patients with nephropathy.

In post MI  patients,the incidence of side effects lik hypotension,cough and increased serum creatinine is lower with ARBs than ACE Inhibitors.

When added with a hydrochlorothiazide diuretic ,it can be used effectively to lower Mean Systemic Diastolic Blood Pressure / MSDBP and Mean Systemic Systolic Blood Pressure / MSSBP in patients with Essential Hypertension.