The history of use of hormone replacement therapy in post menopausal women

 Estrogens are cardio protective. The cardiovascular health of women is seen to be better than their male counterparts till the date when menopause sets in and the level of the sex hormones declines in women. The development of pharmaceutical expertise to separate and purify the female sex hormones in the early part of the twentieth century opened vistas for their use in post-menopausal women. Very soon, hormone replacement therapy become widely popular for improving the physical, psychological and cardiovascular health of post-menopausal women. It was known long before that unimpeded estrogenic action results in endometrial proliferation and increases the risk of endometrial carcinoma. Therefore, from the very beginning, hormone replacement therapy involves the use of progesterone in a cycle manner along with oestrogen. Numerous observational studies showed the benefits of HRT on the cardiovascular health of women.The use of hormone replacement therapy for presumed cardiovascular benefit continued for many years. For the first time, a study sponsored by the National Institute of Health, the Women’s Health Initiative showed that Hormone replacement therapy is associated with increased cardiovascular morbidity. The landmark study resulted in the drastic decline of hormone replacement therapy in post-menopausal women. The present recommendation of HRT in post-menopausal women is restricted to control of vasomotor symptoms and atrophic vaginitis in early menopause and should be withdrawn as early as possible. HRT has also been found to increase breast cancer, gallstones and migraine.

 

To continue...

Mechanism of anti-hypertensive action of beta blockers

In current medical practice, beta blockers are classified into three classes

👄 Non-selective beta blockers (blocks both beta 1 and beta 2 receptors): 

            ACUTE EFFECT

                    Beta 1 blockade: 

                            👉 Decreased heart rate and decreased cardiac contractility

                            👉 Decreased cardiac output

                            👉 Systolic BP tends to decrease

                    Beta 2 blockade:

                            👉 Increased peripheral vascular resistance

                            👉 Diastolic BP tends to increase

               NET ACUTE EFFECT: No change in BP

                

               PROLONGED USE EFFECT:

                            👉 Decreased cardiac output

                            👉 Adaptation of resistance vessels to persistently reduced cardiac output

                            👉 Decrease in peripheral resistance

                            👉 Systolic BP decreases due to decreased cardiac contractility

                            👉 Diastolic BP decreases due to decreased peripheral resistance

                            

👄 Selective beta blockers (blocks only beta 1 receptor)

            

        ACUTE EFFECT

                    Beta 1 blockade: 

                            👉 Decreased heart rate and decreased cardiac contractility

                            👉 Decreased cardiac output

                            👉 Systolic BP tends to decrease

        

        PROLONGED USE EFFECT:

                            👉 Decreased cardiac output

                            👉 Adaptation of resistance vessels to persistently reduced cardiac output

                            👉 Decrease in peripheral resistance

                            👉 Systolic BP decreases due to decreased cardiac contractility

                            👉 Diastolic BP decreases due to decreased peripheral resistance

                            

👄 Beta blockers with additional alpha blocking property

 

    ACUTE EFFECT

                    Beta 1 blockade: 

                            👉 Decreased heart rate and decreased cardiac contractility

                            👉 Decreased cardiac output

                            👉 Systolic BP tends to decrease

                   Alpha blockade:

                             👉Decrease in total peripheral resistance

                             👉 Decrease in diastolic BP

                             👉 Compensatory increase in heart rate blockade by beta 1 receptor blockade

ORS tips for travel

 Practical off-label tip 😎

A one litre container may not be always handy.💭💭

Instead, a one litre bottle of packaged drinking water is easily available.💭💭💭

The ORS powder can be carefully emptied into the bottle of water.💭💭💭💭

The lid is capped and the bottle is shaken to dissolve the contents.💭💭💭💭💭

And the ORS is ready for consumption.💭💭💭💭💭

Two more important advice 

🎯 The prepared ORS should be used within 24 hours. If it remains after the period, it should be discarded and fresh ORS should be prepared.

🎯 The expiry date written on the sachet of the ORS powder should be checked before preparation. And not after consumption 😱😱

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