Species differences in pharmacodynamics: Some examples

Appreciation of species variation in response to drugs is essential for the most effective application of available drugs in each species. Such variation may be due to differences in responding systems in different species. These may be: anatomical or histological differences; differences in receptor type and distribution; or differences in the nature and distribution of intermediary substances. This paper discusses examples of species differences in response related to pharmacodynamics, concentrating on 4 groups of substances: namely substances (1) involved in anaphylactic reactions, (2) acting on the sympathetic nervous system, (3) affecting the central nervous system, and (4) with effects on the reproductive system.

1. In anaphylactic reactions the release, distribution and effects of mediators, including histamine, 5-hydroxytryptamine, dopamine, kinins, slow reacting substance of anaphylaxis (SRS-A), eosinophil chemotactic factor, neutrophil chemotactic factor, platelet activating factor and prostaglandins, vary. The distribution of H₁ and H₂-histamine receptors for example varies even between different species of ruminants. Successful inhibition of anaphylactic or allergic reactions necessitates the correct choice of antagonist for the affected species, e.g. antihistamines may be expected to be effective in guinea pigs and dogs but prostaglandin antagonists would be more useful in cattle.
2. Sympathomimetics and α and β adrenergic receptor blocking drugs have different metabolic effects and effects on sweating in different species, e.g. horses, ruminants and rats.
3. Substances, including analgesics and anaesthetics, which affect the central nervous system, may produce depression in some species but excitation in others (e.g. morphine, ketamine) due to differences in distribution of neurotransmitters. Some drug susceptibilities are genetically controlled.
4. The effects of substances on the reproductive systems of different species can be more readily predicted as differences in the regulation of oestrus are appreciated.

Species variation in responses to immunostimulants and antibiotics are also referred to. Theoretically the responses of different species to a given drug might be predicted from a full understanding of the pharmacology of the drug and of comparative physiology, biochemistry and anatomy. In practice this is frequently not possible.