Principles of drug action

Topical routes of drug administration are where the drug is applied directly to the site of action. Many medicines are applied directly for example, hydrocortisone can be rubbed into the skin to relieve a local area of inflammation. The anticholinesterase neostigmine is dropped directly onto the eye surface to relieve glaucoma, a condition characterised by raised intra-ocular pressure which if untreated can lead to blindness. 

Intravenous (IV) Into a vein. Because the drug enters directly into the circulation, there is no absorption phase this means that the peak plasma concentration is reached almost immediately. This route is used when a rapid onset of action is required. 

Intramuscular (IM) Into skeletal muscle. This route is used to deliver depot antipsychotic drugs like fluphenazine and haloperidol decanoate, which are used in the treatment of schizophrenia. 

Subcutaneous (SC) Into the layer just under the skin this is most commonly associated with insulin in diabetes mellitus. 

Intrathecal (IT) Into the subarachnoid space between two of the membranes (meninges) separating the spinal cord from the vertebral column. This route is used for drugs that do not penetrate the blood-brain barrier, but which are required for their central action (e.g., antibiotics). Drugs can also be injected spinally (into the epidural space) for local anaesthesia or analgesia. 

Second messengers are specific intracellular components that are indirectly stimulated by the first messengers to activate intracellular components such as certain enzymes termed protein kinases (PKs). The most studied second messengers are calcium ion, inositol trisphosphate (IP3), diacylglycerol (DAG), cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP). 

Synaptic responses mediated by receptorgated ion channels and G-protein-linked receptors have considerably different time courses. The direct effects of ligand-gated channels are rapid and transitory, usually ending in less than 1 ms, whereas those mediated by G-protein-linked receptors are slower in onset (requiring at least 100 ms to develop) and can be very long in duration (minutes). 

Usually, PKs are activated by second messengers and they are often named after these second messengers (cAMP-dependent PK for example). However, there are also other types of PKs that are not second-messenger-dependent. Among these are protein tyrosine kinases (which phosphorylate substrate proteins specifically on tyrosine residues), casein kinases, and numerous others. -  

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Limbird, L. E., Cell Surface Receptors A Short Course on Theory and Methods, 2nd ed., Nijhoff, Boston, 1996. Pratt, W. B. and Taylor, P., Principles of Drug Action, Churchill Livingstone, New York, 1990 (see, in particular, Chapters 1 and 2). 

Nebert DW, Weber WW. Pharmacogenetics. In Pratt WB, Taylor P eds. Principles of Drug Action The Basis of Pharmacology. New York Churchill Livingston, 1990. 

Gll. Goldstein, A., Aronow, L., and Kalman, S. M. Principles of Drug Action. The Basis of Pharmacology. Harper (Hoeber), New York, 1968. 

Goldstein A, Aronow L, Kalman SM (1968) The absorption, distribution and elimination of drugs — passage of drugs across the placenta. In Goldstein A, Aronow L, Kalman SM ed. Principles of drug action the basis of pharmacology. New York, Harper and Row, p 179. 

Although the specific pragmatic guidelines for use of these various therapeutic modalities for depression have not been emphasized, the reader should now have a basis for the rational use of antidepressant and mood-stabilizing drugs founded on application of principles of drug action on neurotransmission via actions at key receptors and enzymes. 

Gotte M. Inhibition of HIV-1 reverse transcription basic principles of drug action and resistance. Expert Rev Anti Infect Ther. 2004 2 707-716. 

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