Penicillins

Mechanism of action and classification

Penicillins represent a crucial class of antimicrobial agents belonging to the broad group of $\beta$-lactam antibiotics. The fundamental mechanism of their action lies in the specific disruption of bacterial wall formation. In pharmacology, they are classified as cell wall synthesis inhibitors.

It is important to understand that penicillins are not the only drugs with a similar mechanism. The same classification group, whose action is aimed at destroying the cell wall, includes:

• All other $\beta$-lactam antibiotics (including cephalosporins);
• Glycopeptides;
• Cycloserine;
• Bacitracin;
• Phosphonic acid derivatives.

Immediate-type allergic reactions (Type I)

The main clinical problem a physician faces when prescribing penicillins is their high allergenicity. They act as typical triggers for anaphylactic-type reactions (Type I, or immediate-type reactions).

Pathogenesis: This type of allergy is strictly mediated by immunoglobulin E (IgE) classes. Specific antibodies bind tightly to antigens located on the surface of mast cells. This interaction triggers rapid mast cell degranulation, leading to a massive release of histamine into the systemic bloodstream.

Clinical presentation depends on the severity of the process:

• Mild to moderate course: the patient develops an itchy rash in the form of urticaria, local edema, allergic rhinitis, and profuse lacrimation.
• Severe course: life-threatening bronchospasm occurs, laryngeal edema rapidly increases, which can culminate in anaphylactic shock.

Immune complex reactions (Type III)

In addition to immediate anaphylaxis, penicillins (along with sulfonamides) are typical triggers for immune complex-type allergic reactions (Type III).

Development mechanism: Unlike the first type, several classes of immunoglobulins are involved in the pathological process simultaneously: IgG, IgM, and IgE. Large circulating complexes consisting of three components—"antigen + antibody + complement"—are formed in the bloodstream. These macromolecular structures circulate in the blood, settle on the vascular endothelium, and cause severe damage to it.

Clinical manifestations: Vascular damage by immune complexes leads to the development of serum sickness. Its classic symptoms include:

• Pronounced fever;
• Systemic lymph node enlargement (lymphadenopathy);
• Joint pain (arthralgia) or inflammation (arthritis);
• Appearance of urticaria and intense pruritus.

Cross-allergy and contraindications

An extremely important safety aspect when working with $\beta$-lactam antibiotics is the presence of cross-allergy. Since penicillins and cephalosporins share a similar chemical structure, the immune system of a sensitized patient may attack both classes of drugs.

For patients with a documented history of allergy to penicillin-class drugs, the prescription of cephalosporins is strictly contraindicated.

The physician must not use cephalosporins (such as cephalexin, cefazolin, or ceftriaxone) if the patient has previously experienced the following after taking penicillins:

• Anaphylaxis;
• Angioedema;
• Urticaria.

Ignoring this rule carries a direct risk of developing severe cross-allergic reactions.

Class and exam questions

What else to study on this topic

• Cytolytic type of allergic reactions (Type II) and drugs that cause it (methyldopa, quinidine, metamizole sodium).
• Cell-mediated delayed-type allergic reactions (Type IV) and the mechanisms of contact dermatitis development.
• Pharmacokinetics, classification, and spectrum of action of cephalosporins.
• Features of $\beta$-lactam antibiotic use in severe renal and hepatic impairment.
• Use of cephalosporins in pregnancy and lactation (FDA Category B).

Other topics in the "Additional Topics" section

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.