ANTIMICROBIAL PHARMACODYNAMICS

Antimicrobial

Antimicrobial is a general term given to substances including medicines that kill or slow the
growth of microbes.

Microbe is a collective name given to bacteria (Staphylococcus aureus), viruses (influenza,

which causes the "flu"), fungi (e.g., Candida albicans, which causes some yeast infections), and
parasites (e.g., Plasmodium falciparum, which causes malaria).

Examples of antimicrobial agents:

• Tetracycline (one antibiotic used to treat urinary tract infections)

• Oseltamivir or Tamiflu (antiviral that treats the flu)
• Terbinafine or Lamisil (antifungal that treats athlete’s foot)

Pharmacodynamics

Pharmacodynamic interactions include the concurrent administration of drugs having the same
(or opposing) pharmacologic actions and alteration of the sensitivity or the responsiveness of the
tissues to one drug by another.

Pharmacodynamics, sometimes described as what a drug does to the body, involves receptor
binding (including receptor sensitivity), postreceptor effects, and chemical interactions.
Pharmacodynamics, with pharmacokinetics (what the body does to a drug) helps explain the
relationship between the dose and response, example, the drug effects. The pharmacologic
response depends on the drug binding to its target. The concentration of the drug at the receptor
site influences the drug's effect.

A drug's pharmacodynamics can be affected by physiologic changes due to disorders, aging, or

other drugs. Disorders that affect pharmacodynamic responses include genetic mutations,
thyrotoxicosis, malnutrition, myasthenia gravis, Parkinson's disease, and some forms of insulin-
resistant diabetes mellitus. These disorders can change receptor binding, alter the level of
binding proteins, or decrease receptor sensitivity. Aging tends to affect pharmacodynamic
responses through alterations in receptor binding or in postreceptor response. Pharmacodynamic
drug—drug interactions result in competition for receptor binding sites or alter postreceptor
response.
Pharmacodynamic Drug Interactions

Additive Pharmacodynamic Effects. When two or more drugs with similar pharmacodynamic
effects are given, the additive effects may result in excessive response and toxicity. Examples
include combinations of drugs that prolong the QTc interval resulting in ventricular arrhythmias,
and combining drugs with hyperkalemic effects resulting in hyperkalemia.

Antagonistic Pharmacodynamic Effects. Drugs with opposing pharmacodynamic effects may

reduce the response to one or both drugs. For example, drugs that tend to increase blood pressure
(such as nonsteroidal anti-inflammatory drugs) may inhibit the antihypertensive effect of drugs
such as ACE inhibitors. Another example would be inhibition of the response to benzodiazepines
by the concurrent use of theophylline.

Although dramatic advances have been made in the study of drug interaction mechanisms over
the past few decades, there is still much to learn. Thus, many of the mechanism concepts useful
today will be refined in the future, yielding a picture closer to the truth. It also should be kept in
mind that for some drug-drug interactions more than one mechanism may be occurring
simultaneously.

Antimicrobial (Drug) Resistance

Antimicrobial resistance is the ability of microbes, such as bacteria, viruses, parasites, or fungi,
to grow in the presence of a chemical (drug) that would normally kill it or limit its growth.

Diagram showing the difference between non-resistant bacteria and drug resistant bacteria. Non-
resistant bacteria multiply, and upon drug treatment, the bacteria die. Drug resistant bacteria
multiply as well, but upon drug treatment, the bacteria continue to spread.
Antimicrobial Agents in the Treatment of Infectious Disease

Microorganisms that Produce Antibiotics

1. Penicillium and Cephalosporium molds produce beta-lactam antibiotics such as

penicillin and cephalosporin and their relatives. They also produce the base molecule for
development of semisynthetic beta-lactam antibiotics, such as amoxacillin and ampicillin.
Beta-lactams are used to treat about one-third of outpatients with bacterial infections.

2. Actinomycetes, mainly Streptomyces species, produce tetracyclines, aminoglycosides

(streptomycin and its relatives), macrolides (erythromycin and its relatives),
chloramphenicol, ivermectin, rifamycins, and most other clinically-useful antibiotics that
are not beta-lactams. Actinomycetes are the mainstay of the antibiotics industry.

3. Bacillus species, such as B. polymyxa and B. subtilis, produce polypeptide antibiotics

(e.g. polymyxin and bacitracin), and B. cereus produces zwittermicin. Bacillus species
have the relatively rare ability to form a type of resting cell called an endospore. Bacilli
are Gram-positive, rod-shaped, aerobic bacteria that live in the soil. They play an
important ecological role in aerobic decomposition, biodegradation and mineral
recycling.