Medical Pharmacology Chapter 35  Antibacterial Drugs

Tetanus

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Introduction

  • Tetanus is manifest as increased muscle tone and spasms and is caused by a protein toxin released by Clostridium tetani.

    • Toxin enters axons and is transported to brainstem and spinal cord nerve cell bodies.

    • The toxin then moves transynaptically from post- to presynaptic terminals where release of inhibitory aminoacids GABA and glycine is blocked.

    • As a result of decreased inhibitory input, alpha-motoneuron activity is increased and rigidity results.

      • Disinhibition, in general, results in spasms and sympathetic hyperactivity.

    • Tetanospasmin and botulinum toxin may blocker acetylcholine release at neuromuscular junctions.

      • This blockade results in weakness or paralysis and recovery requires de novo sprouting of nerve terminals.

    • C. tetani is a ubiquitous, anaerobic, gram-positive rod found in soil and feces.

  • In spore form, C. tetani is resistant to many disinfectants and boiling (20 min)

  • In vegetative form, C. tetani is susceptible to antibiotic.

Clinical presentations

  • Sequence of muscle effects

    1.  Increased muscle tone of the masseter (lockjaw)

    2.  Dysphagia, neck, shoulder, back pain.

    3.  Abdominal and proximal limb stiffness

    4.  Facial muscle contraction (risus sardonicus)

    5.  Spasms of the back--arched back (opistotonus)

    6.  Generalized spasms

  • Autonomic dysfunction (severe cases):

    •  Hypertension

    •  Hyperpyrexia

    •  Tachycardia/arrhythmias

    •  Peripheral vasoconstriction (high circulating catecholamine levels)

Treatment

  • Remove source of toxin

  • Inactivate unbound toxin

  • Prevent muscle spasms

  • Respiratory and general patient support

  • Clean and debride the wound

  • Antibiotic treatment is of unproven value, but is used to eliminate vegetative cells that are producing toxin. Metronidazole (Flagyl) (preferred) and penicillin may be administered.

  • Antitoxin: neutralizes circulating toxin: Antitoxin reduces mortality. Human tetanus immune globulin (TIG) is preferred; alternatives: Equine tetanus antitoxin (TAT,shorter half-life ) may be used, although serum sickness and hypersensitivity reactions are common.

  • Control of muscle spasm:

    • Diazepam (Valium)--widely used;

    • Other options: lorazepam (Ativan), midazolam (Versed)(both by i.v. infusion such to short half-lives;

    • Barbiturates/chlorpromazine (Thorazine): second-line agents.

  •  Autonomic dysfunction:

    • Hypertension : Labetalol (Trandate, Normodyne) (alpha + beta receptor blockade);esmolol (Brevibloc); clonidine (Catapres);

    • Hypotension: volume expansion, vasopressors, chronotropic drugs, pacemaker

  • Prevention: Active Immunization;

  • Prognosis: With respiratory support, mortality rates as low as 10% have been reported; Poorer outcome is associated with neonates, the elderly, and in patients with a short incubation period. Recovery is often complete, but may taken months.

Abrutyn, E. Tetanus. In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, p. 901-904.

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