Pharmacology
Mark Wilczynski
Many conditions affecting the hand and wrist are amendable to medical management. Medications may be dispensed for therapeutic and prophylactic reasons; to aid in diagnosis; or to provide analgesia and anesthesia. The most common methods of administering the medications include oral, intra-articular injection, extra-articular injection, intramuscular injection, and intravenous injection. Prior to administration of medication, a thorough health history (i.e., additional health problems, current medications, allergies, etc.) should be obtained to avoid potential adverse outcomes.
I. Local Anesthetics
Local anesthetics reversibly impede impulse conduction along axons and other excitable membranes that utilize voltage-gated sodium channels to generate action potentials. Cocaine was the first local anesthetic to be isolated. Many other agents have subsequently been developed. They may be grouped into esters or amides based upon their chemical structure (Tables 4.1 and 4.2). Esters are more prone to hydrolysis and therefore have a shorter duration of action; in addition, esters are more likely to cause allergic reactions in susceptible patients. In general, the duration of analgesia can be lengthened by the addition of a vasoconstrictive substance such as epinephrine. Classic teaching was that local anesthetics augmented with epinephrine should never be used in the hand or fingers, but recent reports indicate that this may be safely used and is being used with increasing frequency, initially in Canada and now throughout the United States. If there is a concern about the perfusion following the use of epinephrine in a digit, 0.5% Phentolamine Mesylate can be injected to reverse the effect of epinephrine, causing vasodilation and increased perfusion. It is administered by direct injection at the site of infiltration.
Local anesthetics are used to prevent pain in well-defined regions of the body. Desired duration of action should guide agent selection. In hand surgery, local anesthetics are generally infiltrated into the operative field or injected near major nerve trunks to provide anesthesia in their sensory distribution. Local anesthetics are neurotoxic at high concentrations, and injection either directly into nerves or into the peripheral circulation should be avoided. They may also be administered intravenously at a site
distal to an inflated tourniquet to provide regional anesthesia (Bier block). Techniques for peripheral nerve blockade can be found in Chapter 3.
distal to an inflated tourniquet to provide regional anesthesia (Bier block). Techniques for peripheral nerve blockade can be found in Chapter 3.
TABLE 4-1 Esters | ||||||||
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TABLE 4-2 Amides | ||||||||||||||
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II. Antibiotics
Antibiotics are substances that inhibit microbial growth. They are used to prevent infection in the perioperative period as well as to treat existing infection. Antibiotic therapy is most effective when it is directed against organisms likely to be encountered. In the hand, the most common pathogen is Staphylococcus aureus. It is found in 50% to 80% of hand infections. Other common organisms are Streptococcus and Gram-negative species. Broad spectrum therapy for long periods of time can be detrimental.
There are four general mechanisms through which antibiotics are effective against microbes.
Inhibition of cell wall synthesis
Increase in cell membrane permeability
Ribosomal inhibition
Interference with DNA metabolism
A. Inhibition of Cell Wall Synthesis
These antibiotics include the penicillins, cephalosporins, vancomycin, bacitracin, aztreonam, and imipenem. Penicillins and cephalosporins prevent polysaccharide cross-linking in the bacterial cell wall by inhibiting the transpeptidase enzyme activity. Cephalosporins have been divided into first, second, and third generations. First-generation cephalosporins are largely antistaphylococcal drugs. Second-generation** and third-generation cephalosporins have increasing Gram-negative coverage. Vancomycin is active against Gram-positive microbes. It is primarily used to treat methicillinresistant S. aureus (MRSA) and Staphylococcus epidermidis. It is also used in those with penicillin and/or cephalosporin hypersensitivity.
B. Increase in Cell Membrane Permeability
These agents bind to sterols in the cell membrane and disrupt its structural integrity. Migration of ions and macromolecules into the cell causes cell death. These agents include nystatin, amphotericin, and polymyxin. Nystatin and amphotericin are antifungal agents. Polymyxin is active against some Gram-negative bacteria.
C. Ribosomal Inhibition
These agents are bacteriostatic or bactericidal. Bacteriostatic drugs reversibly bind to bacterial ribosomes inhibiting protein synthesis. In hand surgery, the most relevant drugs in this category are the macrolides (clindamycin and erythromycin). Clindamycin is effective against all anaerobes and most Gram-positive cocci. It is particularly useful in the treatment of community-acquired MRSA. Erythromycin can be used to treat S. aureus in penicillin-sensitive patients. Other bacteristatic drugs in this category include chloramphenicol and tetracycline.
Bactericidal drugs bind to the 30s subunit causing mRNA to be misread. Agents in this category include the aminoglycosides (gentamicin**, streptomycin, tobramycin, amikacin, and neomycin). These drugs are particularly effective against Gram-negative bacilli.
D. Interference with DNA Metabolism
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