Biomedical Engineering Reference
In-Depth Information
production of strongly oxidizing gold(III) metabolites and a better understanding of the mechanism
of gold preparations is indeed needed in order to produce more effective and less toxic gold-based
drugs.
10.6.6 Z
INC
Zinc is involved in a large number of biological processes and today more than 200 proteins
containing Zn
2+
are known. Among these, many essential enzymes are found that catalyze the
transformation or degradation of proteins, nucleic acids, lipids, and the like. Besides, the zinc ion
stabilizes many different proteins like insulin. Obviously, zinc dei ciency will lead to severe
pathological effects.
Carbonic anhydrase is a zinc containing enzyme that catalyzes the hydrolysis of CO
2
:
CO
2
+ H
2
O « H
+
+ HCO
_
and is of fundamental signii cance in respiration. The catalytic process occurs 10
7
times faster in
the presence of the zinc enzyme compared with the uncatalyzed reaction. Certain antiepileptic
pharmaceuticals like acetazil amide coordinate directly to zinc(II) in the active center of the carbonic
anhydrase enzyme and thus obstructs the catalytic transformation of carbon dioxide. With accumu-
lation of CO
2
in the blood stream pH drops, and it has been suggested that this perturbs the gamma-
aminobutyric acid (GABA, an inhibitory neurotransmitter) concentration in brain cells, either by
increasing the GABA synthesis or by blocking the process of degradation (see Chapter 15).
10.6.7 A
NTIMONY
AND
B
ISMUTH
Antimony and bismuth have been applied in medicine for centuries due to their antiparasitic and
antibacterial properties. Sb(III) and Bi(III) are borderline metal ions and exhibit a high afi nity for
oxygen, nitrogen, and sulfur. Unlike Sb, where the +5 oxidation state is favored, the +3 oxidation
state is the most common and stable form of Bi.
Millions of people suffering from “leishmaniasis” worldwide, particularly in the developing
countries, are subject to intravenous treatment with drug formulations of pentavalent antimony,
Sb(V) complexes with polyhydroxy carbohydrate ligands. Very limited resources have been invested
by the developed world in optimizing these drugs. Thus, at the moment, patients infected with the
parasites
Leishmania
spp. undergo long treatments with extremely high “nontarget” doses of Sb,
which often result in severe side effects. Although, alternative antileishmania drugs are available in
the market, or are in the development phase, antimony-based drugs have remained the main treatment
worldwide since the 1930s (except for certain domains where resistance has curbed their use).
Sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime) are the two drugs
in current use and typically administered intravenously. The carbohydrate ligands in Pentostam
and Glucantime, gluconic acid, and
N
-methyl-d-glucamine, respectively, increase the general solubility
of antimony and may serve to deliver Sb to the macrophages, where the protozoa that cause
“leishmaniasis” undergo division.
Pentostam and Glucantime [both based on Sb(V)] are believed to be only prodrugs and
Sb(III) accounts for the active form of antimony at the target site. Antimony(III) possesses
higher antileishmania activity than Sb(V), but due to its higher toxicity it has no direct therapeutic
use. Trypanothione, the most abundant low molecular weight thiol-containing ligand in the
parasites (while nonexisting in human) may act as the reductant in the parasites. Once Sb(III)
is present in the parasite it can interfere with several enzymes and proteins, which eventually
destroys the parasite.
Although bismuth preparations have historically been applied in the treatment of a number of
diseases, including syphilis and hypertension, their application during the last decades has been
