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Strategies in the design of new drugs

With the advent of the Covid-19 pandemic, coronavirus disease discovered in 2019, caused by the Sars-Cov-2virus, public attention has largely focused on how globalwork is being done to discover a vaccine that is effective against this coronavirus as well as new drugs. This article will talk about drugs, not vaccines, which I will leave for another article.

Basics

There is first place to define some basic concepts:
Drug. It is the active substance in a medicine. A chemical compound of defined structure that has a terapentic or diagnostic application.
Medication. It is the association of an active substance or drug with everything necessary for it to be dosed and reach the patient.
Pharmaceutical/Medical/Terapetic Chemistry. It seeks to elucidate the relationship between its structure, its chemical properties and its biological response, in order to provide the necessary knowledge for the creation of new drugs.

Classification of drugs according to their terapeutic action

Drugs can be classified according to their terapeutic action in:

  • Terapeutic action on specific organs, such as the central nervous system, thyroid gland, etc..
  • Action on pathological syndromes, such as anticonvulsants, antilipidemia, etc..
  • Action on a specific target or receiver, such as local anesthetics, antihypertensors, etc.

It can also be classified according to its terapentic action and structure in: antibiotics β-lactam and tetracycline antibiotics.

Non-commercial/commercial nomenclature

Several forms can be used for the naming of drugs:
IUPAC and IUB rules. It starts by putting a name according to IUPAC (International Union of Pure and Applied Chemistry) and the IUB. The problem with this name is that the names are extremely long.
International common name or generic name. An attempt is made to have a unique, non-ancient name for each drug, simpler than the chemical and regardless of the manufacturer. Indicates kinship between substances belonging to the same pharmacological group. Applicable to classes of compounds that have a similar terapeutic action such as penicillins.
• CommercialNomenclature .

Particles indicative of the pharmacological group

Most drugs have a name that has a particle that has a meaning. They can also have trade names.
Particle Pharmacological group
-acted Synthetic polypeptides with lacorticotrophin-like action
-acetaminophen Acetaminophen-related pain relievers
Andr Androgen steroids
-arol Anticoagulants of the dicumarol group
-azepam Diazepam group drugs
Barb Derivatives of barbiturate acid, with hypnotic activity
Bowl Anabolic steroids
-buzona Anti-inflammatory painkillers from the lafenilbutazone group
-cocaine Local anesthetics
cef- Antibiotics derived from cephalosporic acid
-cilina Antibiotics derived from penicilonic acid
-dipine Calcium channel blockers derived from lanifedipine
Estr Estrogenic drugs
-fiber Drugs from the cl fib t ofibrato group
-formina Hypoglycemic agents of the phenformin group
Gest Progesthenic steroids
gli- Hypoglycaemic sulfonamides
-io Quaternary ammonium compounds
-metacin Anti-inflammatory drugs of the indomethacin group
-mycine Antibiotics produced by Streptomyces
myth- Nucletoxic neoplastics
-nidazol Antiprotozoaries of the metronidazole group
-olol Beta adrenergic blockers, propranolol
-ionid Esteroires for topical use with aceton group
-orex Anorexics derived from phenylethylamine
-oxacino Antibacterials of the nalidexic acid group
-pramina Drugs in the imipramine group
-pril( ato) Angiotensin-converting enzyme inhibitors
-profene Anti-inflammatory drugs in the ibuprofen group
Prost Prostaglandins
-relina Hormoneshipofisary release stimulating peptides
Salt Salicylic acid derivatives
sulfa- Antibacterial sulfonamides
-terol Phenylethylamine-derived bronchodilators
-tiazida Diuretics of the chlorothiazide group
-tidine H2 antihistamines of the cimetidine group
-trexate Folic acid antagonists
-verina Papaverin-related spasmolytics
Vir Antiviral substances
For example, IUPAC calls a 2-acetoxybenzoic acid drug. The common name is aspirin and the trade name is Aspirin (R)..

fármacos drugs
Figure 1. Aspirin. Source: https://pubchem.ncbi.nlm.nih.gov/compound/Aspirin#section=2D-Structure

Mechanism of action of drugs

After prescribing a medicine, a number of phases occur that would be:

  • Pharmaceutical phase, consisting of administration and release into the bloodstream.
  • Pharmacokinetic phase. This phase answers the question of what does the body do with the phase it? In this case Absorption, Distribution, Metabolism and Elimination, ADMEisdistinguished.
  • Pharmacodynamic phase. Answer the question of what does the drug do in the body?

Pharmacodynamics

It consists of the interaction between drugs and their biological targets. The drug interacts with lipids, carbohydrates, proteins (whether enzymes or membrane receptors) and nucleic acids.

  1. Lipids. The number of drugs is relatively small. They alter the lipid squeal by varying the physicochiic properties of the cell membrane.
  2. Carbohydrates. The function is molecular recognition (bacteria and viruses recognize cells that infect through polysaccharides chains) and regulation and growth at the cellular level. The mechanism of action of the drug is to bind to the carbohydrate so that it is not recognized by the bacteria or the virus.
  3. Proteins. They are the biological targets of the vast majority of drugs. Drugs interact with enzymes and membrane receptors.
  4. Nucleic acids. They act directly on nucleic acids by altering replication, transcription or translation processes, leading in many cases to cell death. They are, for example, anticancer drugs.

Pharmacokinetics

These are ADME processes. The optimal therapeutic efficacy of a drug will depend on:

  • Their interaction with the biological target and its pharmacological response.
  • From the intra-organic cycle of the drug.

What the body does to the drug is what we call pharmacokinetics and we need to talk about ADME processes:

  • Absorption, systemic availability.
  • Distribution, fat-solubleity and plasma protein binding.
  • Metabolism, biotransformations are performed.
  • Excretion, is eliminated by urine, sweat, breathing, etc.

Stages in the discovery and development of new drugs

Two stages can be distinguished:

  • Previous stages. Where a disease is chosen. The biological target is chosen and a bioassay is performed.
  • Key stages. They would be the discovery stage, optimization stage and development stage.
    • Discovery stage. Identification of new active substances, usually called the seed.
    • Optimization stage. Chemical modification of the head-as-you-go compound in order to increase its potency or selectivity, or to decrease its toxicity.
    • Development stage. Clinical trials, manufacture and marketing of the drug.

Drug approval process

The development of a drug is a slow process that can reach 11 years from the identification of an eligible obstetric drug to its introduction into the medina.

These are clinical phases:

  1. Preclinical trials: in vitro and in vivo studies (animals).
  2. Phase I: trials in healthy volunteers to study tolerance and safety range. ADME Studies.
  3. Phase II: trials in volunteer patients to determine efficacy in healing, side effects and dosage.
  4. Phase III: trials in a large number of patients for more information on efficacy in healing, side effects and dosage.
  5. Phase IV: comparison with other drugs marketed.

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