Then it happened. A driver behind him surged forward, flashing headlights and shouting from a rolled down window. Something inside John, something he didn’t recognize as fully himself, rose like a flash-flood. He stepped out of the car. Words flew, harsh and hot. A minor shove. A misstep. A fall.

And suddenly someone was hurt. The police came. The reports were written. And John, sitting alone in a small, echoing cell, realized that sometimes a life doesn’t crumble in a long, slow descent—it collapses in thirty seconds of unguarded anger.

It wasn’t planned. It wasn’t wanted. It simply…happened. Like an anaphylactic reaction, sudden, overwhelming, and profoundly destructive.

Medicine offers a remarkable parallel. Some of the body’s most violent reactions appear to erupt without warning, yet they are often the culmination of processes that have been unfolding quietly for years.

Johanna had no reason to fear a peaceful Sunday picnic, until a single bite of a cookie made with a trace of hazelnut awakened an old immune memory buried deep within her body. Within minutes her lips tingled, her skin flushed, and her throat tightened as her immune system, mistaking the harmless nut for a mortal enemy, unleashed a tidal wave of histamine that constricted her airway and dropped her blood pressure. Panic blurred the moment, but a friend quickly injected epinephrine, the medicine racing through her bloodstream like a calming command that opened her airways and steadied her pulse. The episode seemed instantaneous, but in truth the reaction was years in the making. Before that picnic, Johanna’s immune system had already encountered the allergen, misidentified it as dangerous, and stored that mistake in its memory. The cookie did not cause the reaction out of nowhere. It merely awakened a response that had been waiting silently beneath the surface.

In medicine, anaphylaxis is the body’s form of a lightning strike; a rapid, life-threatening allergic reaction. It is a serious, potentially fatal medical emergency that is rapid in onset and requires immediate medical attention regardless of the availability of on-site treatments while not under medical care.

Within minutes, a simple trigger like a peanut, a bee sting, or even a medication can send the immune system into chaos. The body panics. The airways narrow. Blood pressure collapses. The entire system reacts disproportionately to a threat that, under normal circumstances, would be harmless, like Johanna above gasping for breath after eating a cookie, or a hiker stung by a bee feeling her throat close, or a patient given an antibiotic erupting in hives, dizzy, and pale.

When a severe allergic reaction occurs, every second matters. The first and most important treatment is epinephrine, a medication usually injected into the thigh. It acts quickly, interrupting the body’s dangerous overreaction before it becomes fatal. The airways relax, blood pressure rises, and circulation begins to stabilize. Additional doses or intravenous fluids may sometimes be required, but the principle remains the same: the faster the reaction is interrupted, the greater the chance of recovery. Doctors may also administer intravenous fluids to support blood flow, while the patient is laid flat with the legs slightly elevated to help restore circulation to the heart and brain.  

Other medications, such as antihistamines and steroids, may help relieve symptoms, but they are not substitutes for epinephrine. Individuals who have previously experienced anaphylaxis are strongly advised to carry an epinephrine auto-injector (commonly known as an EpiPen) and wear medical identification. Even when symptoms improve after treatment, emergency medical evaluation remains essential, as the reaction can recur unexpectedly.  

Fortunately, anaphylaxis is relatively rare. Although estimates vary, it affects only a small percentage of the population, and with prompt recognition and treatment, survival rates are exceptionally high. It tends to occur more in young people and in women. Nearly everyone who receives timely hospital care recovers.  

What actually causes anaphylaxis?

Before someone ever has an anaphylactic reaction, their immune system must first “learn” to recognize an allergen (such as peanuts, bee venom, or certain medications). During this first exposure, sensitization (immune memory formation) takes place, and the immune system mistakenly identifies the allergen as a threat. Then, it produces IgE antibodies that attach to mast cells and basophils. These IgE-coated cells “wait” for the next exposure.

Anaphylaxis happens during the next exposure (which might be years later). When exposed, the allergen binds to the IgE antibodies and mast cells release massive amounts of histamine and other mediators. This causes anaphylaxis in the form of hives, swelling, low blood pressure, airway tightening, etc.

Anaphylaxis symptoms usually occur within minutes of exposure to an allergen. Sometimes, however, anaphylaxis can occur a half-hour or longer after exposure. In rare cases, anaphylaxis may be delayed for hours. Signs and symptoms include:

• Skin reactions, including hives and itching and flushed or pale skin

• Low blood pressure (hypotension)

• Constriction of the airways and a swollen tongue or throat, which can cause wheezing and trouble breathing

• A weak and rapid pulse

• Nausea, vomiting or diarrhea

• Dizziness or fainting

Genetics can predispose someone to allergies (e.g., family history of atopy), but anaphylaxis itself is not genetically predetermined. It still requires exposure, sensitization and IgE antibody production.

Lessons from anaphylaxis

Just as the immune system can overreact to a small trigger, the heart can overreact to a small frustration. Anger can arrive suddenly without invitation, without calculation. A word misunderstood, a gesture interpreted as disrespect or a horn honked impatiently.

And instantly, the soul releases its own internal “mediators” such as adrenaline, cortisol, and tunnel vision. Then, judgment collapses, empathy becomes constricted, and perspective disappears.

What anaphylaxis is to the body, anger is to the spirit. Both are reactions far greater than the triggers that provoke them. Anger may appear to erupt in an instant, but like anaphylaxis, it is built slowly. Years of unprocessed stress, patterns of reaction learned in childhood, ego sensitivities left unexamined, and emotional habits repeated until they become automatic all lie beneath the surface. A single insult may ignite the explosion, but the invisible fuel has been accumulating quietly for years. Just as immune memory primes the body for anaphylaxis, emotional memory primes the mind for anger.

Even prophets teach us that anger is human, but mastery of anger is divine guidance.

Prophet Muhammad (peace be upon him) understood the physiology of emotion long before modern neuroscience. He taught: “When one of you becomes angry while standing, let him sit. If the anger does not leave him, let him lie down” (Sunan Abu Dawud 4782). And in another teaching, he advised ablution (wudu), saying anger is “from fire” and water extinguishes it. These are not merely symbolic instructions—they are antidotes. Sitting eases the body’s tension, lying down disarms the fight-or-flight response, and washing with water cools the face, slows the heartbeat, and interrupts the physiological surge of anger before it gains control.   

These are emotional epinephrine, quick, simple, and deeply effective. They not only calm the immediate reaction, but they also slowly re-educate the emotional-memory system, changing the default response. Prophet Muhammad (peace be upon him) was teaching the spiritual equivalent of resetting immune memory, reducing oversensitivity and interrupting automatic reactions.

In the Battle of Uhud, when the archers disobeyed the Prophet’s explicit command and abandoned their posts, the consequences were severe. The Muslim army suffered painful losses. Yet the Prophet (peace be upon him) did not publicly shame those responsible, did not single them out by name, and did not allow anger to fracture the unity of the community. Even his Companions refrained from identifying them.

His calmness repaired what disobedience had damaged. His mercy became more memorable than the mistake itself. His positive approach was confirmed in the Qur’an: “So by mercy from God, [O Muhammad], you were lenient with them. And if you had been rude [in speech] and harsh in heart, they would have disbanded from about you. So, pardon them and ask forgiveness for them and consult them in the matter. And when you have decided, then rely upon God. Indeed, God loves those who rely [upon Him]” (Al Imran 3:159).

Jesus (peace be upon him) reminds us that spiritual maturity is not the absence of passion but the discipline of response: “Blessed are the peacemakers, for they shall be called children of God.”—Matthew 5:9.

James is quoted in the New Testament as follows: “Be slow to anger, for human anger does not produce the righteousness of God.”—James 1:19–20.

Moses (peace be upon him) struggled with a fiery temperament. When he struck the Egyptian man, he regretted it deeply (Qur’an 28:15–16). When he saw his people worshipping the calf, he reacted strongly—but afterward prayed for them (Qur’an 7:150).

Fethullah Gülen reminds us to shape our hearts into sanctuaries, each with a humble chair reserved for every soul God sends our way. He uses the metaphor of the heart as a sanctuary to call for emotional restraint and moral readiness in the face of others. By reserving a “humble chair” for every person we encounter, Gülen emphasizes unconditional hospitality rather than judgment or dominance. This image challenges the reflexive nature of anger, encouraging a pause between stimulus and response. In this way, it suggests that compassion can regulate emotional reactions much like balance in the immune system prevents anaphylactic overreaction.

Just as the immune system can be trained away from overreaction, the soul can be trained away from explosive anger. Both require memory to be re-written, habits to be relearned, and the inner terrain to be cultivated patiently.

To prevent anaphylaxis, we avoid triggers, strengthen resilience, and carry epinephrine. Similarly, we can prevent destructive anger, if we can cultivate the following in our spiritual journey:

With mindfulness, we can notice irritation before it grows. With self-awareness, we can know the history behind reactions. Practicing patience through remembrance (dhikr), meditation, and stillness can strengthen our resilience. Reducing chronic stressors can help us build healthy boundaries. Having generous, merciful assumptions about others reduces anger.

There is a Turkish proverb that “Sharp vinegar harms its own container.” Anger is vinegar. Before it burns others, it corrodes the heart that holds it.

Anaphylaxis teaches us how the body collapses when overwhelmed. Anger teaches us how relationships, reputations, and inner peace can collapse in a fleeting moment of emotional shock.

Let us learn to love people, to be gentle with their faults, and to show mercy, not because they are perfect, but because mercy is the epinephrine of the soul.

References

1. https://www.mayoclinic.org/diseases-conditions/anaphylaxis/symptoms-causes/syc-20351468.

2. Shaker MC, et al. Anaphylaxis — A 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. Journal of Allergy and Clinical Immunology. 2020; doi:10.1016/j.jaci.2020.01.017.

3. Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, Geller M, Gonzalez-Estrada A, Greenberger PA, Sanchez Borges M, Senna G, Sheikh A, Tanno LK, Thong BY, Turner PJ, Worm M. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020 Oct 30;13(10):100472. doi: 10.1016/j.waojou.2020.100472. PMID: 33204386; PMCID: PMC7607509.

4. https://en.wikipedia.org/wiki/Anaphylaxis

Medicines and vaccines have transformed the prevention and treatment of diseases. In addition to their benefits, medicinal products may also have side effects, some of which may be undesirable and/or unexpected.

For example, thalidomide was introduced in the late 1950s as a sedative and a treatment for morning sickness in pregnant women. By the early 1960s, reports began to emerge of severe birth defects associated with its use, including phocomelia, a condition characterized by the malformation of limbs. The thalidomide crisis resulted in significant human suffering and marked a turning point in drug regulation. Thalidomide was sold in over 46 countries, with the highest number of cases reported in Germany, the UK, Canada, and Australia. It’s estimated that around 10,000 babies were born with thalidomide-related birth defects worldwide. These numbers underscore the profound impact of the thalidomide crisis on public health and drug regulation. The crisis prompted significant changes in drug regulation, leading to the enactment of stricter testing and approval processes, such as the 1962 Kefauver-Harris Amendment in the U.S.

All medicines and vaccines undergo rigorous testing for safety and efficacy through clinical trials before they are authorized for use. However, the clinical trial process involves studying these products in a relatively small number of selected individuals for a short period of time. Certain side effects may only emerge once these products have been used by a heterogenous population, including people with other concurrent diseases, and over a long period of time (Figure).

Figure. Overview of investigation into drug safety in the United States.

· Medicines may affect the body in unintended, harmful ways. These effects, called side effects, adverse events or adverse reactions, represent the risks of taking medication. An adverse drug reaction (ADR) can be defined as ‘an appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product; adverse effects usually predict hazard from future administration and warrant prevention, or specific treatment, or alteration of the dosage regimen, or withdrawal of the product.’ Since 2012, the definition has expanded to include reactions resulting from errors, misuse, or abuse, as well as suspected reactions to unlicensed or off-label uses of medicines, in addition to those occurring with authorized use at normal doses. Adverse drug reactions have been observed and monitored for many years: In 1937, 107 deaths, many in children, occurred in the United States from the use of a cough syrup that used diethylene glycol as a solvent. This event led to the 1938 Food, Drug, and Cosmetic Act, which for the first time required proof of safety prior to marketing.

· In 1955, over 40,000 children developed abortive polio (51 of whom were permanently paralyzed) and five died from a polio vaccine made by Cutter Laboratories that was not effectively inactivated during manufacturing. The incident also sparked a polio epidemic in the families and communities of those immunized with the defective vaccine, leading to an additional 113 people who were paralyzed and five more deaths. In ensuing law suits, it was determined that pharmaceutical companies could be held liable for harm from their products even if there was no negligence.

· In 1961, more than 10,000 children worldwide were born with severe birth defects (phocomelia) due to in utero exposure to thalidomide, a drug that had been used to treat pregnancy-related nausea. Even though thalidomide had not been released in the United States, this event led to the Kefauver–Harris Amendment, which strengthened the requirements for safety testing and for the first-time required proof of efficacy prior to a drug being marketed. This public health disaster also spurred the development of formal spontaneous reporting systems for pharmacovigilance, which are still the primary method of identifying safety issues in approved medications.

· In the 1970s, it was discovered that diethylstilbestrol caused clear cell adenocarcinoma of the cervix and vagina in women exposed in utero decades earlier.

· In 1984, psoralen and ultraviolet A (PUVA) was definitively linked to an increased risk of squamous cell carcinoma, approximately 10 years after the first description of PUVA therapy for psoriasis. It took over 20 years to establish a link between PUVA and melanoma, which remains controversial.

· Of drugs approved by the US Food and Drug Administration (FDA) between 1996 and 2012, one-third received boxed warnings and more than 40% of these drugs acquired the warning a median time of 4 years after approval.

· Since 2000, many of the prescription drugs removed from the market include classes of medications that are commonly prescribed, such as antihistamines (e.g., terfenadine), nonsteroidal anti-inflammatory agents (rofecoxib, valdecoxib), antibiotics (trovafloxacin), lipid-lowering medications (cerivastatin), and an immunosuppressant for the treatment of psoriasis (efalizumab).

· Between 2008 and 2015, 29% of boxed warnings issued to drugs on the US market were new and 32% were major updates to previous warnings.

· The incidence of adverse drug reactions has remained relatively unchanged over time, with research suggesting that between 5% and 10% of patients may suffer from an ADR at admission, during admission or at discharge, despite various preventative efforts.

· In 2012, McKinsey & Company estimated that the cost of 50 to 100 million preventable, error-related adverse drug events ranged from $18 billion to $115 billion.

It is important to quickly identify new risks or changes to known risks associated with the use of medicines. Timely actions must be taken to minimize these risks, maximize the benefits, and promote the safe and effective use of medicines by patients. These activities are collectively known as pharmacovigilance.

Pharmacovigilance, also known as drug safety, is the pharmaceutical science concerned with the “collection, detection, assessment, monitoring, and prevention” of adverse effects associated with pharmaceutical products. The term “pharmacovigilance” is derived from the Greek wordpharmakon(meaning drug) and the Latin wordvigilare(to keep watch). As such, pharmacovigilance focuses primarily on adverse drug reactions, defined as any noxious and unintended response to a drug, including lack of efficacy. Medication errors—such as overdose, misuse, abuse, and drug exposure during pregnancy or breastfeeding—are also of interest, even when no adverse event has occurred, due to their potential to result in harm.

In recent years, the scope of pharmacovigilance has expanded to include:

· Herbals

· Traditional and complementary medicines

· Blood products

· Biologicals

· Medical devices

· Vaccines

Many other issues are also relevant to the science of pharmacovigilance, including:

· Substandard medicines

· Medication errors

· Reports of lack of efficacy

· Use of medicines for unapproved indications with insufficient scientific support

· Case reports of acute and chronic poisoning

· Assessment of drug-related mortality

· Abuse and misuse of medicines

· Adverse interactions between medicines and chemicals, other drugs, or food

Pharmacovigilance activities include:

• Collecting and managing data on the safety of medicines
• Looking at the data to detect “signals” (any new or changing safety issue)
• Evaluating the data and making decisions with regard to safety issues
• Pro-active risk management to minimize any potential associated risks
• Acting to protect public health (including regulatory action)
• Communicating with and informing stakeholders and the public
• Audit of the outcomes and key processes involved.

The specific aims of pharmacovigilance are to:

· Improve patient care and safety in relation to the use of medicines and all medical and paramedical interventions

· Enhance public health and safety concerning the use of medicines

· Contribute to the assessment of the benefits, harms, effectiveness, and risks of medicines, thereby encouraging their safe, rational, and more effective—including cost-effective—use

· Promote understanding, education, and clinical training in pharmacovigilance, along with effective communication to the public

Information received from patients and healthcare providers via pharmacovigilance agreements, as well as other sources such as the medical literature, plays a critical role in providing the data necessary for pharmacovigilance to take place. In order to market or to test a pharmaceutical product in most countries, adverse event data received by the license holder (usually a pharmaceutical company) must be submitted to the local drug regulatory authority.

Ultimately, pharmacovigilance is concerned with identifying the hazards associated with pharmaceutical products and with minimizing the risk of any harm that may come to patients. Companies must conduct a comprehensive drug safety and pharmacovigilance audit to assess their compliance with worldwide laws, regulations, and guidance.

The activity that is most commonly associated with pharmacovigilance and which consumes a significant number of resources for drug regulatory authorities (or similar government agencies) and drug safety departments in pharmaceutical companies, is that of adverse event reporting. Adverse event reporting involves the receipt, triage, data entry, assessment, distribution, reporting (if appropriate), and archiving of adverse event data and documentation. The source of adverse event reports may include spontaneous reports from healthcare professionals or patients, solicited reports from patient support programs, reports from clinical or post-marketing studies, reports from literature sources, reports from the media (including social media and websites), and reports reported to drug regulatory authorities themselves. For pharmaceutical companies, adverse event reporting is a regulatory requirement in most countries. This reporting also provides data to these companies and drug regulatory authorities that play a key role in assessing the risk-benefit profile of a given drug.

Organizations such as World Health Organization (WHO), International Council for Harmonization (ICH), The Council for International Organizations of Medical Science (CIOMS), and International Society of Pharmacovigilance play a key collaborative role in the global oversight of pharmacovigilance.

The number of National Centers participating in the WHO International Drug Monitoring Program has grown from 10 in 1968, when the program began, to 67 in 2002, and continues to increase. The centers vary considerably in size, resources, support structure, and scope of activities. Collecting spontaneous reports of suspected adverse drug reactions remains their core activity.

In conclusion, maintaining balance in life is essential in all aspects. The usefulness of almost anything can diminish and even become harmful when used excessively. Although medicines play a vital role in healthcare, their effects must be closely monitored to prevent potential adverse events. In addition, with the rapid spread of drug information worldwide—especially highlighted during the COVID-19 pandemic—there is a growing need for routine and timely communication between National Centers and national regulatory authorities. Many regulatory bodies across different regions have established strong collaborations to share safety data, discuss regulatory decisions, and align on policies. Regular dialogue and coordination among National Centers are crucial to ensuring the safe and effective use of medicines.

References

1. https://www.who.int/teams/regulation-prequalification/regulation-and-safety/pharmacovigilance

2. Offit P. The Cutter incident, 50 years later. N Engl J Med. 2005;352(14):1411–1412.

3. Talbot JC, Nilsson BS. Pharmacovigilance in the pharmaceutical industry. Br J Clin Pharmacol. 1998 May;45(5):427-31. doi: 10.1046/j.1365-2125.1998.00713.x. PMID: 9643613; PMCID: PMC1873545.

4. Solotke MT, Dhruva SS, Downing NS, Shah ND, Ross JS. New and incremental FDA black box warnings from 2008 to 2015. Expert Opin Drug Saf. 2018;17:117–123.

5. Coleman JJ, Pontefract SK. Adverse drug reactions. Clin Med (Lond). 2016 Oct;16(5):481-485. doi: 10.7861/clinmedicine.16-5-481. PMID: 27697815; PMCID: PMC6297296.

6. Ebel T, George K, Larsen E, Neal E, Shah K, Shi D (October 2012). “Strength in unity:The promise of global standards in healthcare” (PDF). gs1.org. McKinsey & Company.