Potential Targets of Drug Action

Drugs are designed to exert a selectiveinfluence on vital processes in order toalleviate or eliminate symptoms of dis-ease. The smallest basic unit of an or-ganism is the cell. The outer cell mem-brane, or plasmalemma, effectively de-marcates the cell from its surroundings,thus permitting a large degree of inter-nal autonomy. Embedded in the plas-malemma are transport proteins thatserve to mediate controlled metabolicexchange with the cellular environment.
Theseincludeenergy-consumingpumps (e.g., Na, K-ATPase, p. 130), car-riers (e.g., for Na/glucose-cotransport, p.178), and ion channels e.g., for sodium(p. 136) or calcium (p. 122)
(1).Functional coordination betweensingle cells is a prerequisite for viabilityof the organism, hence also for the sur-vival of individual cells. Cell functionsare regulated by means of messengersubstances for the transfer of informa-tion. Included among these are “trans-mitters” released from nerves, whichthe cell is able to recognize with thehelp of specialized membrane bindingsites or receptors. Hormones secretedby endocrine glands into the blood, theninto the extracellular fluid, representanother class of chemical signals. Final-ly, signalling substances can originatefrom neighboring cells, e.g., prostaglan-dins (p. 196) and cytokines.The effect of a drug frequently re-sults from interference with cellularfunction. Receptors for the recognitionof endogenous transmitters are obvioussites of drug action (receptor agonistsand antagonists, p. 60). Altered activityof transport systems affects cell func-tion (e.g., cardiac glycosides, p. 130;loop diuretics, p. 162; calcium-antago-nists, p. 122). Drugs may also directlyinterfere with intracellular metabolicprocesses, for instance by inhibiting(phosphodiesterase inhibitors, p. 132)or activating (organic nitrates, p. 120)an enzyme.
(2).In contrast to drugs acting from theoutside on cell membrane constituents, agents acting in the cell’s interior needto penetrate the cell membrane.The cell membrane basically con-sists of a phospholipid bilayer (80Å =8 nm in thickness) in which are embed-ded proteins (integral membrane pro-teins, such as receptors and transportmolecules). Phospholipid moleculescontain two long-chain fatty acids in es-ter linkage with two of the three hy-droxyl groups of glycerol. Bound to thethird hydroxyl group is phosphoric acid,which, in turn, carries a further residue,e.g., choline, (phosphatidylcholine = lec-ithin), the amino acid serine (phosphat-idylserine) or the cyclic polyhydric alco-hol inositol (phosphatidylinositol). Interms of solubility, phospholipids areamphiphilic: the tail region containingthe apolar fatty acid chains is lipophilic,the remainder – the polar head – is hy-drophilic. By virtue of these properties,phospholipids aggregate spontaneouslyinto a bilayer in an aqueous medium,their polar heads directed outwards intothe aqueous medium, the fatty acidchains facing each other and projectinginto the inside of the membrane.
(3).The hydrophobic interior of thephospholipid membrane constitutes adiffusion barrier virtually imperme-able for charged particles. Apolar parti-cles, however, penetrate the membraneeasily. This is of major importance withrespect to the absorption, distribution,and elimination of drugs.