barbiturates, carbamazepine, chloramphenicol, diazepam, diclofenac, diphenhydramine,
enalapril, erythromycin, flucloxacillin, furosemide, imipramine, nifedipine, phenytoin,
and sulfonamides.
Porphyria is not the only disorder that may be inadvertently precipitated by the
administration of a drug. Malignant hyperthermia is a serious, life-threatening compli-
cation of general anesthesia with halothane, methoxyflurane, and succinylcholine. It
occurs in 1 in 20,000 people. Clinically, it is characterized by high body temperature
(41°C), muscle rigidity, and cardiovascular collapse.
8.8 Inorganic Substances as Drugs and Drug Design Targets
Traditionally, drug design has been practiced predominantly by organic chemists; hence,
most drug molecules are created primarily from four elements—carbon, oxygen, hydrogen,
and nitrogen—with the occasional use of sulphur. Regrettably, inorganic substances
(as either inorganic salts or organo-metallic complexes) have been largely ignored as either
drug targets or drugs themselves. The neglect of inorganic substances as therapeutics
arises in part from concerns regarding toxicity and in part from the fact that most medi-
cinal chemists are organic chemists rather than inorganic chemists. Arguably, this neglect
of inorganic substances is regrettable since inorganics may offer novel avenues to new
therapeutics, especially for indications in which the drug is administered for a short acute
period (e.g., antibiotics) rather than for prolonged chronic use.
When they are used medically, inorganic substances are given more commonly as
salts and only rarely, if ever, as the elemental metal. An inorganic salt consists of the
metallic cation and the counter anion. Within the human organism, inorganic salts play
a variety of normal roles, both functional and structural. As discussed in section 8.1.7,
from a functional perspective the metallic cations Na+,K+, and Ca2+are essential to the
transmembrane transmission of information via voltage-gated ion channels. Metallic
ions (e.g., Zn^2 +,Cu^2 +) are also found in some enzymes, termed metallo-enzymes; such
enzymes employ trace amounts of metal ion to aid their catalytic function. The impor-
tant role of these trace metallic ions was appreciated in the early days of TPN (total
parenteral nutrition) when individuals received complete nutritional support via intra-
venous solutions; the essential role of metallic ions was demonstrated when they were
eventually included in the TPN solutions. Metallic ions also play crucial structural
roles. This is most evident in the role of Ca^2 +salts in the structure of bone. Clearly, there
are many opportunities to exploit inorganic substances as either drugs or drug receptors.
8.8.1 Inorganic Substances as DrugsInorganic salts of metals such as gold, lithium, and bismuth have demonstrated utility
as therapeutics for a variety of disorders.
8.8.1.1 Antimony
Trivalent antimonials (8.93) and pentavalent antimonials (8.94) are sometimes used as
antiparasitic agents against leishmaniasis and schistosomiasis. Although the mechanism
532 MEDICINAL CHEMISTRY