What's the "FUZZ" about drug promotional literature. Are FDCs of Iron with multivitamins rational???

💦Iron is given for iron deficiency anaemia. 

💦In this condition, there is no role of other vitamins unless and untill there is a concurrent deficiency of the other vitamins. 

💦Addition of other vitamins is generally harmless, but adds up significantly to the cost. 

💦This does not ascribe to the principles of rational pharmacotherapy which is so vital for the rational  practice of Medicine. 

💦That's why essential drug and rational prescribing is repeatedly stressed in your syllabus.

💧 Commercial organizations often promote their products out of context to earn revenue. 

💧 As practitioners of modern medicine, it is imperative on our part to exercise our knowledge and judgment in every prescription and not get carried by commercial promotions and incentives. 

💧 If you go through the NATIONAL LIST OF ESSENTIAL MEDICINE , you will not find such irrational Fixed Dose Combination in the list. 

💧 Prescription should be based in safety, efficacy, affordability and availability. 

💧 Talking in the same line, critical analysis of Drug Promotional Literature has been included in undergraduate syllabus so that Indian Medical Graduates can understand and "filter" the "Right" from the "Wrong" in Drug Promotional Literature provided by the commercial pharmaceutical companies. 

💧 And prescribe on the principles of "Essential Medicine" that is in the best interests of self and society.

The magic of furosemide

In acute pulmonary oedema, there is collection of fluid in alveoli.

The sequence of events is as follows.

👉Left ventricle is unable to pump adequate blood either due to systolic or diastolic failure.

👉Increased filling pressure in the left ventricle.

👉Transmission of increased filling pressure to left atrium, and then to pulmonary veins and then to pulmonary capillaries.

👉Increased pressure in the pulmonary capillaries causes oozing of fluid from pulmonary capillaries to alveolar lumen. This is pulmonary oedema.

Action of furosemide

👉Furosemide causes increase in systemic venous capacitance.

👉Fluid shifts from pulmonary circulation to systemic circulation.

👉Decrease in pulmonary hydrostatic pressure.

👉Back flow of fluid from alveoli to pulmonary capillaries.

👉Reversal of pulmonary edema.

👉The change in systemic hemodynamics occurs even before the diuretic action and therefore furosemide provides prompt relief in acute pulmonary oedema.

Life is a cosmos, not a chaos! Unraveling the conundrum of the rhythmic processes of pharmaco-kinetics

 The maximum absorption of any orally administered drug occurs through the small intestine irrespective of the drug being acidic. 

The reasons for this phenomenon are-

1. Gastric Transit time is much less.

2. Acidic drugs are initially absorbed in the stomach, but because of "ion trapping" in the gastric cells, further absorption is hindered.

3. The surface area of the small intestine is manifold higher than the stomach, so the majority of the drug molecules are absorbed through the small intestine.

Absorbtion and distribution are not isolated process. They occur simultaneously. It means as soon as some molecules are absorbed in circulation, distribution starts instantly. As the unionic fraction is distributed to tissues, the equilibrium shifts from ionic to unionic in the blood. This goes on till the Cmax is reached. Remember, that elimination is also a process which is occuring simultaneously with absorption and distribution. So after Cmax is reached, the movement of drug molecules is reversed. In other words, after Cmax is reached, the rate of transport of drugs molecules from the tissues to the blood becomes greater than the rate of transport from the  blood to the tissues.

In a more holistic sense, absorption, distribution, metabolism and elimination occur simultaneously as soon as the first molecules of the drug reach the systemic circulation.

I hope you remember the plasma concentration time curve.

In the absorbtion phase, the rate of absorption is more than the rate of elimination. At Cmax, the rate of absorption is equal to the rate of elimination. In the post absorption phase, the rate of elimination is more than the rate of absorption. In the elimination phase, absorption is complete and only elimination occurs. 

All throughout the absorbtion, post-absorption and elimination phase, distribution keeps on "tickering" in it's "own capacity". Distribution is a two way transport process of drug molecules across the cell membrane of tissue cells. The rate of movement of drug molecules across the cell membrane depends upon the concentration of the drug in plasma, the rate of ionisation, lipid solubility of the drug, molecular weight of the molecule and presence of specific transporters for the drug molecules in the cell membrane.

Adverse effects of thiazide diuretics and their mechanism

😧😨 Hypokalemia

👉 Thiazides inhibit Na+/Cl- transporter at DCT

👉 Increased Na+ in distal nephron

👉 Increased exchange with K+. in distal nephron

👉 Increased excretion of K+ in urine

👉 Hypokalemia

 

😧😨 Metabolic Alkalosis

👉 Thiazides inhibit Na+/Cl- transporter at DCT

👉 Increased Na+ in distal nephron

👉 Increased exchange with H+. in distal nephron

👉 Increased excretion of H+ in urine

👉 Metabolic Alkalosis

 

😧😨 Hyperglycemia

👉 Thiazides exert a weak, dose-dependent stimulation of ATP sensitive K+ channel in beta cells of pancreas

👉Hyperpolarisation of cell membrane potential of beta cells

 

👉 Inhibition of insulin release from beta cells

 

👉 Hyperglycemia

 

😧😨 Hyperlipidemia

👉 May be due to impaired insulin secretion. Exact cause not known

😧😨 Hyponatremia

👉  Thiazides inhibit Na+/Cl- transporter at DCT

👉 Increased Na+ excretion in urine

👉 Increased water loss in urine

👉 Hypovolemia

👉Increased ADH secretion in response to hypovolemia

👉 Increased water re-absorption in collecting duct

👉 Dilutional hyponatremia

😧😨 Hyperuricemia

👉 Uric acid is secreted into proximal tubule by organic acid transporters from basal to luminal side.

👉 This increases uric acid excretion in urine

👉 Thiazides also use the same transporter for secretion into the nephron lumen to reach their site of action at the distal tubule.

👉 Competition between uric acid and thiazide diuretics decrease uric acid secretion into the tubular lumen

👉 This leads to hyperuricemia

😧😨 Weakness, fatigue, paresthesia, impotence and loss of libido

👉 Most likely due to hypokalemia and volume depletion

 

Evanescent action of acetylcholine on Dog BP

 The word evanescent means 'fast disappearing'.

Acetylcholine is an ubiquitous neurotransmitter acting in many neuronal pathways in both the central and peripheral nervous system.

The action of acetylcholine at the post-synaptic receptors is rapidly terminated  because of fast degradation of acetylcholine by acetylcholine-esterase in the synaptic cleft.

The human body also contains an enzyme in the plasma analogous to acetyl-choline esterase. The enzyme is known as butyrlcholineesterase or pseudocholineesterase which can degrade any exogenously administered cholineester including acetyl choline. 

The enzyme is also present in plasma of dogs. 

So, when acetycholine is administered by intravenous route in a dog, there is fall in mean blood pressure (due to peripheral vasodilatation, M3 receptors) and fall in heart rate ( M2 receptors) but the effect is rapidly terminated due to fast degradation of acetylcholine by pseudocholineesterase. Therefore, the effect of injected acetylcholine on dog BP is evanescent.  

Drug Synergism

 When two drugs are administered simultaneously, not necessarily by the same route,the drugs may act in the same or opposite directions. This phenomenon is known as drug  synergism.

 Literally, synergism means working together.

Synergism can be positive or negative.

 In positive synergism, the effect of two drugs combined together is greater than the sum of the effect of the two drugs used singly. 

Positive synergism is also known as supra-additive effect or potentiation. 

In negative synergism, the effect of the two drugs combined together is less than the sum of the effect of the drugs used singly. 

Negative synergism is better known as antagonism. 

In some synergistic combination, the effect of the two drugs combined together is simply the sum of the effect of the two drugs used singly. This is known as additive synergism.

 Additive synergism is useful in conditions where the dose of the two drugs in combination can be reduced to minimize the side effects associated with the individual drugs.

Thiazide diuretics in Diabetes Insipidus

  Anti-diuretic action of thiazides is secondary to increased renal sodium excretion.

 👉Thiazide diuretics inhibit the NaCl co-transporter in the renal distal convoluted tubule 

👉 Initially, this increases renal sodium loss in the urine

👉 The renal sodium loss causes extracellular volume contraction

👉 This leads to decrease in GFR.

 👉In response, there is increased proximal tubular sodium and water re-absorption.

 👉 Therefore, less water and solutes are delivered to the distal tubule and collecting duct

👉  So, finally, there is less loss of water and solutes in the urine