PA2131 – PharmaNUS

Category: PA2131 (page 1 of 4)

From Sensitivity to Tolerance: Understanding Aspirin Desensitisation

I was confused when I met a patient with documented aspirin sensitivity who was still taking low-dose aspirin every day. If aspirin can trigger bronchospasm, why would they continue using it? And how does this desensitisation process actually work?

This question opens the door to a critical intersection of pharmacology, immunology, and respiratory medicine. Aspirin sensitivity is common enough to matter clinically, yet nuanced enough that its mechanisms can be confusing when first studying the pharmacology of non-steroidal anti-inflammatory drugs (NSAIDs). Here is a concise guide to help you understand what’s going on and why desensitisation can be a life-changing intervention for some patients. Continue reading

The Unexpected Link Between Sunscreens and Local Anaesthetics

November 27, 2025 / phcdgs / 0 Comments

An auntie told me she reacts to both some older PABA-containing sunscreen brands and to the benzocaine lozenges you can buy at pharmacies. Are PABA-containing sunscreens actually related to ester local anaesthetic allergies, and why do these reactions happen?

When you hear the acronym PABA, you might think vaguely of “old-fashioned sunscreens.” But PABA is also a structural motif in ester-type local anaesthetics: a fact that connects dermatology, pharmacology, and anaesthesia in surprisingly meaningful ways. Understanding this link not only sharpens pharmacology knowledge but also helps you anticipate adverse reactions and counsel patients more confidently. Continue reading

Uroselectivity of Tamsulosin vs Alfuzosin vs Prazosin for BPH?

October 3, 2025 / phcdgs / 0 Comments

We always hear that tamsulosin is the go-to for BPH, but I’m confused about where alfuzosin and especially prazosin fit in. If prazosin is also an alpha-1 blocker, why is it basically never used for BPH unless the patient also has hypertension? Aren’t they all doing the same thing? And honestly, is this whole idea of ‘prostate selectivity’ real, or is it just a marketing story?

Lower urinary tract symptoms (LUTS) caused by benign prostatic hyperplasia (BPH) are among the most common issues you will encounter in older men. Two of the most frequently prescribed drugs for BPH, alfuzosin and tamsulosin, belong to the same class of α₁ (alpha-1)-adrenergic blockers but differ in receptor selectivity, side-effect profile, and clinical nuances. Another α₁-blocker, prazosin, sometimes enters the discussion but is used far more often for refractory chronic hypertension and PTSD-related nightmares than for BPH.

Pasireotide: A Next-Generation Somatostatin Analogue

September 12, 2025 / phcdgs / 0 Comments

Pasireotide is a newer drug than octreotide? I don’t remember learning this drug in the GIT system block. Is pasireotide going to replace octreotide?

When students first learn about somatostatin analogues, the emphasis is usually on octreotide, a drug used in gastrointestinal (GIT) medicine for conditions such as secretory diarrhoea, carcinoid syndrome, variceal bleeding, and pancreatic fistulae. Octreotide’s role in suppressing endocrine and GI secretions makes it valuable in acute inpatient care.

Pasireotide, however, belongs to a newer generation of somatostatin analogues that were engineered with a very different purpose. Unlike octreotide, which is best at binding SSTR2 and controlling GIT hypersecretion, pasireotide targets multiple receptor subtypes, especially SSTR5, allowing it to treat endocrine disorders that octreotide often cannot. This makes pasireotide central to the modern management of Cushing’s disease and treatment-resistant acromegaly.

Racedotril vs Loperamide: A Smarter Choice for Paediatric Diarrhoea?

August 26, 2025 / phcdgs / 0 Comments

What is the difference between racedotril and loperamide? Why is racedotril called an antisecretory?

When faced with a case of acute diarrhoea, clinicians often reach for anti-diarrhoeal agents, but not all drugs are created equal. Two options are loperamide, an opioid receptor agonist, and racedotril, an enkephalinase inhibitor. Though both reduce stool output, they differ in their mechanism of action, safety profile, and clinical applications.

Which fruit to avoid with fexofenadine?

September 27, 2023 / phcdgs / 0 Comments

It is advised to avoid taking fexofenadine with fruit juices. But does this apply to all fruit juices or only grapefruit juice? And what about tomato juice – are tomatoes not also fruit? And why the warning only about the juice – what happens if you eat the fruit instead of drinking the juice?

Grapefruit and Drug Metabolism – A Closer Look at CYP Interactions: Many of us might have come across warnings about the potential interaction between grapefruit juice and certain medications. Let’s delve deeper into the science behind this. Grapefruits, along with other specific citrus fruits like pomelos and Seville oranges (often termed as bitter oranges or sour oranges), are rich in polyphenols, notably furanocoumarins. These compounds play a crucial role in inhibiting various cytochrome P450 enzymes, including CYP3A4, CYP1A2, CYP2C9, and CYP2D6.

Why does this matter? The inhibition of the CYP3A4 enzyme, in particular, impedes its ability to effectively metabolize certain drugs. As a result, there can be an unintended increase in the drug levels within the bloodstream, amplifying the risk of side effects or even toxicities. It’s noteworthy that CYP3A4 is pivotal for the metabolism of a wide range of medications. Consequently, grapefruit’s interaction can potentially affect the efficacy and safety of medications such as statins (targeting high cholesterol), calcium channel blockers (for managing hypertension), calcineurin inhibitors (used in immunosuppression), and benzodiazepines (prescribed for anxiety and insomnia).

Fruit and Fexofenadine – Reduced Absorption: Contrary to the increased plasma concentration of drugs seen following inhibition of CYP enzymes, fruit juices decrease intestinal absorption of the second-generation H1 antihistamine, fexofenadine. The mechanism behind this interaction involves intestinal transporters, specifically organic anion-transporting polypeptides (OATPs).

Why are peripheral effects of AChE inhibitors predominantly parasympathomimetic?

August 30, 2023 / phcdgs / 0 Comments

Acetylcholinesterase (AChE) inhibitors will prevent the breakdown of acetylcholine (ACh) and so increase ACh levels. Increased ACh levels at autonomic nervous system ganglia should activate both the sympathetic and parasympathetic nervous systems. However, the adverse effects of AChE inhibitors outside of the CNS are mostly parasympathomimetic. Why do AChE inhibitors not stimulate the sympathetic nervous system as well?

Acetylcholinesterase (AChE) inhibitors increase the concentration of acetylcholine (ACh) at synapses by blocking its breakdown. This will activate both the sympathetic and parasympathetic systems, as the preganglionic neurons in both systems release ACh.

However, the impact of AChE inhibitors is more prominent on the parasympathetic nervous system for several reasons:
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When sympathetic and parasympathetic systems collide: The dominance of excitatory effects

August 30, 2023 / phcdgs / 0 Comments

When the autonomic nervous system ganglia are activated (for example, by low-dose nicotine), both the sympathetic and parasympathetic nervous system innervations of target organs and tissues are simultaneously stimulated. However, the “fright, fight or flight” sympathetic and “rest and digest” parasympathetic nervous systems have opposing effects in most target organs and tissues. So why do the sympathetic and parasympathetic nervous systems not just cancel each other out when activated at the same time?

It is true that in the realm of autonomic nervous system functioning, the sympathetic and parasympathetic systems often represent two sides of the same coin. These systems largely produce opposing effects on the same target organs and tissues. However, what happens when both systems are simultaneously activated? Contrary to intuitive thinking, they don’t simply cancel each other out. Instead, the dominion of activation or excitatory effects takes centre stage.

The Principle of Dominant Excitation: When both the sympathetic and parasympathetic systems are co-activated, it isn’t a zero-sum game. Rather than neutralizing each other, the excitatory effects from each system generally prevail. This principle is observed in a variety of physiological contexts. Continue reading

Why do corticosteroids increase circulating neutrophils?

August 27, 2023 / phcdgs / 0 Comments

Corticosteroids are anti-inflammatory, reducing the number and activity of various inflammatory cell types, including lowering blood lymphocyte, monocyte, and basophil counts and preventing neutrophils from reaching sites of inflammation. So why do corticosteroids increase the number of neutrophils in circulation?

The effects of corticosteroids reducing the infiltration of neutrophils to sites of inflammation within tissues and increasing the number of neutrophils staying in circulation are two sides of the same mechanism.

Surface expression of proteins, such as L-selectin, is involved in the rolling capture and adherence of neutrophils to blood vessel walls, which is necessary to enable extravasation through blood vessel walls and migration into tissues. Corticosteroids acting via glucocorticoid receptors regulate the expression of many genes involved in inflammatory responses. Continue reading

Dose-dependence of COX-2 selectivity of coxibs

May 9, 2021 / phcdgs / 0 Comments

Coxibs are pro-thrombotic, but if given at a high dose, there would be COX-1 inhibition resulting in an antiplatelet effect and hence bleeding would occur. Therefore, would the two effects not cancel each other out, or would the prothrombic effect still be the predominant effect?

The pro-thrombotic effect still dominates since, for coxibs, the COX-2 inhibition is always more than the COX-1 inhibition.

Coxibs are selective inhibitors of COX-2. Selective inhibition of COX-2 results in shunting of the precursor arachidonic acid over to the COX-1 pathway. With COX-2 inhibited and COX-1 functional, there is a relative increase in the ratio of the thromboxane A2 (TXA2) produced via COX-1 to prostaglandin I2 (PGI2) or prostacyclin produced via COX-2, and also in some cell types via COX-1. As TXA2 promotes platelet aggregation, while PGI2 inhibits platelet aggregation, the increased ratio of TXA2 over PGI2 favours platelet aggregation, so there is an increased risk of thrombosis.

Although coxibs are selective for COX-2, the selectivity is dose-dependent. Therefore, at higher doses, there will be more inhibition of COX-1. However, in the case of the balance between the risk of thrombosis versus the risk of bleeding, there is little impact because, as the dose increases, there will still be more inhibition of COX-2 than COX-1. So the ratio of TXA2 to PGI2 remains in favour of thrombosis.

Importantly, the dose-dependence of the selectivity for COX-2 is significant with regards to the gastrointestinal adverse effects. A major advantage of the coxibs is that they have a lower risk of upper gastrointestinal tract (GIT) adverse effects as they do not inhibit COX-1 in the stomach. However, if the dose is increased, there is greater inhibition of COX-1 and, therefore, less sparing from upper GIT adverse effects.