Antimicrobial drugs and drug resistance

Antimicrobial drugs and drug resistance

Antimicrobial drug: It is a drug which can used to treat a microbial infection.

Antimicrobial- It is general a group of drugs they are antifungals, antivirals , antibiotics , and antiprotozoal.

Antimicrobial

Antimicrobial is a general term given to substances including medicines that slow the growth of microbes or kill it.

Microbe is a collective name given to viruses (e.g., influenza virus, which causes the flu), bacteria (e.g. Some staph infections which causes by Staphylococcus aureus), parasites (e.g., Plasmodium falciparum, Plasmodium sp, which make malaria), and fungi (e.g., Candida albicans, which make some yeast infections)

Examples of antimicrobial agents:

Terbinafine or Lamisil - antifungal that treats athlete's foot

Oseltamivir or Tamiflu- antiviral that treats the flu

Tetracycline - one antibiotic used to treat urinary tract infections 

Antibiotic

Antibiotic is a medicine designed to kill or slow the growth of fungi and some bacteria. Antibiotics are commonly used to fight against bacterial infections but cannot fight against the infections caused by viruses or bacteria

Example of an antibiotic:

Zithromax (Z-Pak) or Azithromycin 

Vancomycin is the last line of defense for certain methicillin-resistant Staphylococcus aureus infections.

Antibacterial

Antibacterial is the term given to substances that kill or slow the growth of bacteria when treating human and environmental surfaces. These include substances that aid in proper hygiene.

Examples of antibacterial-containing commercial products are:

Hand soaps, foams, gels etc.

VRE and MRSA

Examples of antimicrobial (drug) resistance:

Vancomycin-Resistant Enterococci (VRE)

Methicillin-Resistant Staphylococcus aureus (MRSA)

Drug resistance

Antimicrobial and antibacterial drug resistance is the spatial quality of microbes, such as viruses, bacteria, fungi, or parasites, to grow in the presence of a drug or chemical that would normally limit its growth or kill it. It reduction in effectiveness of a drug activity such as an antibacterial  or an antimicrobial in curing a disease.

Diagram- It is showing the difference main between drug resistant bacteria and drug non-resistant bacteria.

Anticancer drugs and their side effects

Anticancer drugs are defined as the medications which helps in the effective treatment of malignant, or cancerous, disease. They are also known as chemotherapeutic drugs or antineoplastic drugs. They can be used in single-drug therapy or in combination therapy. Alkylating agents, natural products, antimetabolites and hormones are the several classification of anti-cancer drugs.

Classification of Anticancer drugs

Cytotoxic drugs: These are the medicines which helps in preventing the growth and replication of the cancers cells using chemicals that are toxic to the cells. They can also be used to treat several other disorders are multiple sclerosis and rheumatoid arthritis. As their action is not targeted tightly they can produce side effects both to the patients and others who become exposed.

Targeted drugs: It is one of the major modalities of medical treatment. Rather than by simply interfering with all rapidly dividing cells, it blocks the growth of cancer cells by interfering with specific targeted molecules needed for tumor growth and carcinogenesis. Combine biologic, cytotoxic mechanisms and antibody-drug conjugates are the modalities of targeted therapy.

Hormonal Drugs: Hormone replacement therapy works by replacing estrogen hormone that is no longer being made by the body. Combinations of progestin and estrogen are used to treat certain symptoms of menopause. Hormonal pills contain the hormones progestin and estrogen, which are like the hormones that are normally made by the ovaries.

Chemotherapy:

Along with the anticancer drugs the treatment called Chemotherapy is also used. It is one of the cancer treatment which uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. It may aim to prolong life, given with a curative intent or to reduce symptoms called palliative chemotherapy. It is one of  the medical discipline which specifically devotes to pharmacotherapy for cancer, called medical oncology. It can cure cancer by killing the cancer cells. It can also kill normal cells causing following side effects.

• anemia
• Tiredness
• Mouth soreness
• Nausea, vomiting
• Loss of appetite
• Constipation or diarrhea
• Hair loss
• Skin changes or reactions
• Pain or nerve changes
• Changes in fertility and sexuality

Pharmacokinetics and Drug Metabolism

Pharmacokinetics is a branch of pharmacology which explains the fate of substances administered to a living organism. Pharmaceutical drugs, food additives, cosmetics pesticides are the chemical xenobiotics. It aims in discovering the fate of a chemical from the moment that it is administered up to the point at which it is eliminated from the body and helps in analyzing the chemical metabolism. Pharmacokinetics is the study of how an organism affects a drug.

Route of administration and the dose of administered drug affects the properties of chemicals. Metabolic changes of the substance in the body, routes of excretion of the metabolites of the drug after administration through the mechanisms of absorption and distribution are described by the pharmacokinetics. These may affect the absorption rate.

Following are the five-process involved in Pharmacokinetic process:

·         Liberation –It is the process of release of drug from the formulation.

·         Absorption – which includes the process of a substance entering the blood circulation.

·    Distribution – which includes the dispersion or dissemination of substances throughout the fluids and tissues of the body.

·       Metabolism – which includes the recognition of the foreign substance by the organism and the process of irreversible conversion of parent compounds into daughter metabolites

·     Excretion – which includes the removal of the substances from the body. In rare cases, some drugs irreversibly accumulate in body tissue.

The role of the liver in drug distribution:

Hepatic portal system takes the part of the blood stream after the drug is absorbed by the GI tract. Lipids are absorbed by the lymphatic system whereas most of the drugs are absorbed into hepatic portal system and then delivered into the blood by the thoracic duct into the superior vena cava.

Digested food is taken to the liver by hepatic portal system. Where it is stored in the liver, processed and distributed. In the same way this may happen to the drug and the drug would be metabolized before reaching the rest of the body. Drugs metabolized by the liver will have high hepatic first pass. Drugs with a very high hepatic first pass are metabolized by the liver which are not given orally.

Neuropharmacology

Neuropharmacology is the scientific study of the effects of drugs on the nervous system. Its primary focus is the actions of medications for psychiatric and neurologic disorders as well as those of drugs of abuse. Neuropharmacology also uses drugs as tools to form a better understanding of normal nervous system functioning.

There are two main branches of neuropharmacology:

Behavioral neuropharmacology: Which focuses on the study of how drugs affect human behavior (neuropsychopharmacology), including the study of how drug dependence and addiction affect the human brain.

Molecular neuropharmacology: Which helps in developing drugs that have beneficial effects on neurological function by studying the of neurons and neurochemical interactions.

These filed are closely connected, since both are concerned with the interactions of neuropeptides, enzymes, neurohormones, second messengers, neuromodulators, neurotransmitters, co-transporters, ion-channels and receptor proteins in the central and peripheral nervous systems.

The history of neuropharmacology is started with just four drugs and now innumerable drugs are approved being available in clinical practices for neurologist. Drugs are the chemical

substances that are characterized in four groups. The first group in which drugs acts as pharmacodynamic agent i.e., sedatives, analgesics etc. The second involves the drugs that act on central nervous system i.e., antidepressant, hypnotic drugs etc. The third category includes the drugs that have chemotherapeutic action i.e., sulfonamides, antimicrobial etc. The last groups involved the supplementary agents like vitamins.

Brain imaging, both PET and fMRI, are now being used for study of drug action on the brain in vivo. To guide a maintenance of proper doses and blood levels of some CNS drugs, therapeutic drug monitoring is important.

The goal of neuropharmacology is to apply information about drugs and their mechanisms of action to develop safer, more effective treatments and eventually curative and preventive measures for a host of nervous system abnormalities. Drugs that act on the nervous system, including antidepressant, antianxiety, anticonvulsant, and antipsychotic agents, are among the most widely prescribed medications. These medications help in treating many different neurological disorders, including pain, neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, psychological disorders, addiction, and many others.

A Powerhouse approach to Cancer treatment: Targeting Mitochondria

Drug targeting is defined as the ability of a drug molecule to accumulate in the target organ or tissue selectively such that the concentration of the drug at the disease site is high, while its concentration in nontarget organs and tissues is low, preferably, below certain minimal level to prevent any toxic effect.

Role of the Mitochondria that plays in human health and disease has rendered many contributions to the field of "Mitochondrial Medicine". Their main function is to supply the adenosine triphosphate (ATP). Their main job is to oxidizing glucose to provide energy for the cell. The process makes ATP and is called cellular respiration. Therefore, mitochondria are known as "the powerhouse of the cell.

Molecules located on or inside mitochondria are considered prime pharmacological targets and a wide range of efforts are underway to exploit these targets to develop targeted therapies for various diseases including cancer. Mitochondria are known to play a key role in the complex apoptotic mechanism and trigger cell death via several mechanisms that include disrupting electron transport and energy metabolism, releasing or activating proteins that mediate apoptosis and altering cellular redox potential.

The selective accumulation approach to targeting mitochondria of cancer cells

This approach requires two levels of specific accumulation; drug accumulation in the tumor and then drug accumulation in the mitochondria of cancer cells.

·         Molecular modification approaches for selective accumulation in mitochondria

·         Nanocarrier based approaches for selective accumulation in mitochondria

There are numerous molecules currently in use or being tested in clinical trials that act on mitochondria. Several clinically approved anticancer drugs such as paclitaxel, VP-16 and vinorelbine as well as an increasing number of experimental anticancer drugs such as, ceramide, MKT077 and CD437 acid have been found to act directly on mitochondria to trigger apoptosis.

As discussed so far, targeting mitochondrial molecules in the development of cancer therapy relies on the two basic interpretations of targeting via selective action on the target and selective accumulation at the target site where the term target must represent a molecule and not a tissue or cell location. 

Contribution of Biopharmaceuticals

A Biopharmaceutical are the therapeutic products synthesized by the biotechnological processes. They are derived from biological sources such as organs and tissues, microorganisms, animal fluids, or genetically modified cells and organisms. Different from totally synthesized pharmaceuticals, they include vaccines, blood, blood components, allergenics, somatic cells, gene therapies, tissues, recombinant therapeutic protein, and living cells used in cell therapy. The use of proteins as drugs has been highlighted mainly by the high versatility of these biomolecules, which have different physiological roles in the human body including as catalysts, receptors, membrane channels, macromolecule carriers, and cellular defense agents.

They are produced by:

·         Recombinant DNA Technology

·         Gene therapy

·         Tissue culture

·         Transgenics

Humulin: In olden days insulin was synthesized using pancreas of slaughtered cattle, pigs or salmon. The process led in low yield of insulin which was quite difficult and tedious. Due to the presence of foreign proteins some patients developed allergy and other side effects. Due to disadvantages of animal insulin Humulin was produced. It is also sometimes referred to as rHI, under the trade name Humulin, was developed by Genentech. It is the first such substance approved for therapeutic use. Production of Humulin was done by recombinant DNA technology where E. coli bacteria used for synthesizing two DNA sequences for A and B chains of human insulin and then introduced them in plasmid of E. coli. Insulin is a proteinaceous hormone secreted by beta-cells of islets of Langerhans of pancreas which helps to decrease the blood glucose level.

Advantages of Humulin

·         It has high absorption rate and show its effectiveness in short duration.

·         It causes fewer autoimmune and allergic reactions as compared to animal insulin.

·         It is less expensive compared to animal insulin

Side effects of Humulin: Many medications can cause side effects: Side effects can be mild or severe, temporary or permanent. headache, hunger, nausea, nervousness, numbness or tingling of the lips, fingers, or tongue, sweating, tiredness, Anxiety, blurred vision, confusion, difficulty concentrating, difficulty speaking, dizziness, drowsiness, fast heartbeat, trembling, weakness are the side effects caused by consuming Humulin.

ACE Inhibitors and Beta Blockers in treating Cardiotoxicity caused by Trastuzumab

Recent advancements in cancer therapies have helped many patients with breast cancer to achieve better outcomes and longer survival. However, this progress causes the Cardiotoxicity, associated with anticancer therapies, which ranges from subclinical abnormalities to irreversible life-threatening complications, such as cardiomyopathy or congestive heart failure.

Chemotherapeutics drugs or other medications you may be taking to control your disease may cause the cardiotoxicity where heart may not be able to pump blood throughout body by the damaged heart muscles.

One such treatment is by using the Trastuzumab which is a monoclonal antibody used in the treatment of HER2-receptor positive metastatic breast cancer. Which can be used alone or in combination with other chemotherapeutic agents. In addition, it has been indicated that Herceptin can impair the regenerative capacities of human resident cardiac stem cells. Statistical study has been proved that One in four women treated with trastuzumab develops potentially dangerous cardiac problems.

It has been recommended that patients receiving adjuvant treatment with trastuzumab should have adequate cardiac monitoring, using transthoracic ECHO or radionuclide ventriculography multiple-gated acquisition (MUGA) scans at baseline, and then at 3, 6, and 9 months after starting this treatment.

Dr. Maya Guglin and his colleagues conducted multicenter clinical trial and showed that ACE inhibitor or a beta-blocker would prevent decreased LVEF that is Cardiotoxicity.

ACE Inhibitors such as Lisinopril helps the blood vessels to enlarge or dilate, and as a result blood pressure is reduced. This lower blood pressure makes it easier for the heart to pump blood and can improve the function of a failing heart by inhibiting the activity of the Angiotensin converting enzyme (ACE) which leads to the production of Angiotensin II which is potent chemical produced by the body that primarily circulates in the blood. It causes the muscles surrounding blood vessels to contract, thereby narrowing the blood vessels which finally leads to the cause of Cardiotoxicity.

Beta blockers such as Carvedilol serves by blocking the effect of hormone adrenaline also known as Epinephrine. Medications that reduces the blood pressure by helping to open the blood vessels. Which helps in reducing the blood pressure.