Drugs That Cause Porphyria Attacks | Mnemonic BIG SOCCER PLAYER

By -VHTC

16 July

What Is Porphyria?

Porphyria is a group of rare metabolic disorders caused by defects in heme biosynthesis. Heme is an essential component of hemoglobin, and its synthesis involves a multi-step enzymatic pathway. Disruption at any point can lead to the accumulation of porphyrin precursors, resulting in neurological and/or cutaneous symptoms.

Types of Porphyria

Porphyria is broadly categorized into:

Type	Subtypes	Key Features
Acute	Acute intermittent porphyria (AIP), Hereditary coproporphyria (HCP), Variegate porphyria (VP)	Abdominal pain, neurological symptoms
Cutaneous	Porphyria cutanea tarda (PCT), Erythropoietic protoporphyria (EPP)	Skin blistering, photosensitivity
Mixed	VP and HCP can show both acute and skin symptoms	Combination of above

Acute Intermittent Porphyria (AIP) is the most common acute porphyria and is highly sensitive to medications that induce porphyrin production.

Why Some Drugs Trigger Porphyria

Certain drugs induce enzymes in the cytochrome P450 system, particularly ALA synthase, the first enzyme in heme synthesis. This increases the production of porphyrin precursors, which then accumulate due to enzyme blockages, triggering acute attacks.

Mnemonic: BIG SOCCER PLAYER

To remember the list of porphyrogenic drugs, use the mnemonic:

BIG SOCCER PLAYER

B – Barbiturates
G – Griseofulvin
S – Sulfonamides
O – Oral Contraceptive Pills (OC Pills)
C – Chlordiazepoxide
C – Chlorpropamide
E – Estrogens
R – Rifampicin
P – Phenytoin

This mnemonic links a popular sport (soccer) with a vivid memory to help students and clinicians remember key porphyrogenic drugs.

Detailed List of Drugs That Cause Porphyria

1. Barbiturates

Used as sedatives or anticonvulsants (e.g., phenobarbital). Strong enzyme inducers and common porphyria triggers.

2. Griseofulvin

Antifungal agent used for dermatophytosis. Induces cytochrome P450 enzymes.

3. Sulfonamides

Antibiotics (e.g., sulfamethoxazole-trimethoprim) known to precipitate acute attacks.

4. Oral Contraceptive Pills (OCPs)

Estrogen-containing contraceptives worsen porphyria due to hepatic enzyme induction.

5. Chlordiazepoxide

A benzodiazepine used for anxiety and alcohol withdrawal. Some benzos are porphyrogenic.

6. Chlorpropamide

A sulfonylurea used for diabetes mellitus. Replaced by newer agents due to risk of hypoglycemia and porphyria.

7. Estrogen

Hormonal therapy (for HRT or PCOS) can induce porphyria symptoms.

8. Rifampicin

Anti-TB drug that induces liver enzymes and exacerbates porphyric crises.

9. Phenytoin

A hydantoin anticonvulsant. Strong P450 inducer and commonly triggers attacks.

Pathophysiology: How Drugs Worsen Porphyria

Many drugs upregulate ALA synthase, increasing production of aminolevulinic acid (ALA) and porphobilinogen (PBG). Due to enzyme deficiency downstream (e.g., PBG deaminase in AIP), these precursors accumulate, leading to:

Neurotoxicity
Autonomic dysfunction
Gastrointestinal symptoms
Mental status changes

Clinical Features of Drug-Induced Porphyria

Acute Attack Symptoms

Severe abdominal pain (not explained by exam or imaging)
Nausea and vomiting
Hypertension and tachycardia
Neuropathy (weakness, paresthesia)
Seizures
Mental confusion or psychosis
Dark-colored urine (port wine appearance)

Cutaneous Symptoms (in mixed porphyrias)

Blisters on sun-exposed areas
Hyperpigmentation
Increased skin fragility

Diagnosis of Acute Porphyria

Key Diagnostic Tests:

Urinary PBG: Elevated during acute attacks
Urinary ALA
Plasma porphyrins
Genetic testing: Confirms type of porphyria
Liver function tests: Often deranged

Note: Avoid delay in diagnosis; symptoms are often misattributed to surgical or psychiatric causes.

Management and Emergency Treatment

Immediate Management

Stop the offending drug immediately
Hospitalization for monitoring
High carbohydrate diet or IV glucose (downregulates ALA synthase)
Hemin therapy (IV heme arginate): Gold-standard treatment

Supportive Care

Pain relief (avoid opioids like barbiturates)
Antiemetics (choose non-porphyrogenic options)
IV fluids and electrolyte correction

Safe Drugs in Porphyria

Here are some medications considered safe in porphyria patients:

Drug Class	Safe Options
Analgesics	Paracetamol, NSAIDs
Antibiotics	Penicillin, Cephalosporins
Antihypertensives	Beta-blockers, ACE inhibitors
Antiemetics	Ondansetron
Anxiolytics	Lorazepam
Antiepileptics	Levetiracetam, Gabapentin

Always verify with up-to-date drug safety databases (e.g., NAPOS).

Patient Education and Prevention

Wear a medical alert bracelet.
Keep a drug safety card listing unsafe medications.
Inform all healthcare providers about porphyria status.
Avoid fasting, stress, and alcohol.
Maintain a balanced, carbohydrate-rich diet.
Schedule regular monitoring for liver function and porphyrin levels.

FAQs on Drugs Causing Porphyria

Q1: Can I take antibiotics if I have porphyria?

Yes, but avoid sulfonamides. Safer options include penicillin and cephalosporins.

Q2: Are all anticonvulsants dangerous in porphyria?

No. While phenytoin is unsafe, levetiracetam and gabapentin are safe alternatives.

Q3: How soon do symptoms appear after drug exposure?

Symptoms can begin within hours to days after exposure, depending on the drug and individual susceptibility.

Q4: Are over-the-counter medications safe?

Not all. Avoid herbal remedies and NSAIDs unless verified safe. Always consult your doctor.

Q5: Is porphyria curable?

No, but with careful management and avoidance of triggers, most patients lead a normal, active life.

Conclusion

Porphyria is a rare but serious metabolic disorder that can be life-threatening if triggered by certain medications. With the help of the BIG SOCCER PLAYER mnemonic, you can remember the major drug culprits and avoid them in clinical practice.

Key Takeaways:

Always review drug safety before prescribing.
Use hemin and high-carb therapy during acute attacks.
Educate patients for long-term prevention.