STRATEGIES OF RESOLVING CONFLICTS AT THE WORKPLACE

CONFLICT RESOLUTION

REPLICATION AND MULTIPLICATION OF HIV IN THE HUMAN BODY AND IT'S PREVENTIVE MEASURES

 

OBJECTIVES OF THE DISCUSSION:  By the end of this presentation, the medical student/reader will be able to;

1.  Describe a brief history in relation to the emerging of HIV

2.  Outline the way through which HIV virus is contacted

3.  Distinguish between the people at high risk of developing HIV compared to the rest of the community.

4.  Describe the infectious cycle of HIV

5.  Outline the goals of antiretroviral drugs and finally

6.  Outline the preventive measures that can be employed to combat HIV

REPLICATION AND MULTIPLICATION OF HIV IN THE HUMAN BODY:  The human immune virus and it's associated illness HIV/AIDS has been one of the most troublesome medical conditions since the early 70s and 80s to date.  In Uganda, this disease is said to have started from South Western part of the country in The district of Rakai, and spread across the country and abroad.  Although this illness initially was regarded as a curse and the community perceived it as a cultural and supernatural phenomenon, and lots of myths and misconceptions were developed for the condition, scientific investigations proved that the disease was, and is actually viral by origin and several drugs have been developed against it and they have proved to be effective in reducing the burden of the disease.  Currently 1000s of individuals are taking Antiretroviral drugs to cub the spread of HIV and it's related complications and generally there is an improvement in the quality of life for those living with HIV/AIDS.  However, the disease still posses a great burden and in recent epidemiological studies, it is indicated to have reversed the predicted trends towards it's prevention to spread especially true, in the previous Millennium Development goals (MDG 2015) were it did the reversal.  We are currently watching the next move with Sustainable development goals 2030. 

The brief microbiology shows that, the virus occurs in two strains namely; HIV 1 which is the commonest in the tropical areas of Eastern Africa, and HIV 2 which is more common in parts of West Africa.  Several sources state it that this disease has more prevalence in African countries however evidence shows that the disease is affecting all the continents at varying percentages.  In this article we are going to look at the way, this deadly predator enters the human body and and be able to multiply.  If you have not been following us, you can also read the discussion below about it's progression to AIDS;  HIV progression to AIDS

WAYS THROUGH WHICH THE VIRUS IS ACQUIRED:  First, let us look at the most common ways of exposure to HIV infection.  Although many people thing the direct way we can get HIV is via copulation, this is actually a minor route for many because the transmission via that route can be prevented and or modulated.  Ok let's take it as number one for that matter because it is the most commonly known and visible to everyone on the go;

1.  Unprotected sex intercourse: Having sex without use of a condom is one way and this is especially true due to possibilities of sores in the genitals of any or all the partners.  HIV is not confined to male-female copulation alone but can also result from oral sex and homosexual practices as well.  Our greatest fear with unprotected sexual intercourse, lies behind the fact that many couples are negligent in testing themselves before any issues happen and for those that endeavor to test themselves, the idea of sexual network is still a major concern.

2.  Mother to child transmission:  There are many ways a pregnant mother can transmit HIV to hear newly born baby if the delivery process is not conducted well.  During delivery of a baby, there are chances that if the process is not handled with care, an HIV positive mother can pass on the virus to her newborn baby.  This is because, the blood spilling is much during the delivery procedures and therefore require attention from a trained medical personnel.

Delivery is not the only way HIV can be transmitted to a newborn, there are many other ways that we shall be seeing in our next discussions concerning the Mother-to-child-transmission of HIV.

3.  Sharing of equipment such as blade, injection needles and other medical equipment:  This can happen both between person to person in the community settings, and between a patient, and a careless medical workers.  As the the sharing of equipment in fact may be intended especially in the case of a resource limited setting, there is a need to ensure the HIV status between the sharing partners.  We are lucky nowadays the coming of technology and industrialization is putting us in plenty of almost everything we may need but I witnessed in the early 90s, an injection needle being boiled before being used to administer drugs to another patient.

4.  Via blood transfusions:  The other possibility of acquiring HIV is via being transfused with blood from an HIV positive blood donor.  This in fact does not only transmit HIV alone but also, other blood borne diseases including but not limited to Tuberculosis and hepatitis.  I talked more about this in my article about; Blood transfusion and the human body.

5.  Inappropriate medical practices:  Inappropriate medical/clinical practices are some of the leading transmission ways of exposing health workers to HIV infection.  These include but not limited to; handling patients and hospital waste without donning gloves, frequent accidental needle pricks, injuries from used medical equipment and accidental exposure to infectious fluids such as amniotic fluids during labor assistance.  It happened to once during my clinical years way back in 2012 while attending and assisting a mother to deliver in labor suit, when I did not have a face mask and as I was doing the procedures, I oriented myself poorly that when the membranes raptured, the amniotic fluids splashed into my eyes.  It was more frustrating to know that we had already tested the mother and she was HIV positive and actively on ART.  Likely enough, it was such a time that Post-exposure prophylaxis (PEP) was already implemented and I was one person to benefit from it after the scenario.

THE FOLLOWING INDIVIDUAL ARE AT RISK OF CONTACTING HIV:  When we talk of a risk we mean; these are individuals with increased chances of contacting HIV virus compared to the rest of the population.

1.  Homosexuals

2.  Intravenous drug abusers

3.  Couples having unprotected sexual intercourse before screening.

4.  Individuals with multiple sexual partners

5.  Commercial sexual workers

THIS IS WHAT HAPPENS WHEN HIV ENTERS YOUR BODY:  Now that we have seen the ways we can contact the HIV, let us see what actually happens after the virus has entered the body.  There is one thing that is special with this virus, it only has receptors on the type of immune cell known as T-cell or in simple terms, the CD4 cell.  The surface of the CD4 cell, lies surface types of glycoproteins that facilitate it's entry inside the cell where it will be able to replicate and multiply.

The other important aspect of the HIV virus is that it does not curry out it's own activities but instead, uses cellular metabolic pathways to carry out it's activities.  In fact the HIV virus is special in it's own ways that; it reverses the normal genetic pathways where the DNA molecule multiplies into two in a process known as replication, and produce RNA in a process known as transcription, which produces proteins in a process we call translation.  This is known as the "Central dogma of microbiology".

To have a brief look at the individual virus, we call it a viral particle and with it, comes a pack of 2 viral RNA strands, the enzymes integrase, reverse transcriptase, and protease all enveloped in a capsule. Now, as the viral particle enters the human CD4 cell, the capsule is opened and the viral components mentioned above are poured into the cytoplasm of the human CD4 cell.  The viral components now starts to give the CD4 cell orders, to synthesize, a viral DNA portion from the available viral RNA strands using cellular nucleotides.  This is the process known as, reverse transcription.  If you are not familiar with some of the terms we are using here, never mind the microbiological and biochemistry feel free to skip to the next part of the discussion.  This is especially true for non medical personnel reading this blog.  Also, in my previous discussions I looked at some of the molecules I am mentioning here and you can use the links below to read about them; Deoxyribonucleic acid (DNA), Ribonucleic acid (RNA), Nucleotides.

We stopped at the production of a viral DNA portion from viral RNA stands and now at this stage, the enzyme viral integrase incorporates this viral genome into the CD4 or human DNA stand or genome.  The result of this, is a lengthy DNA molecule of the CD4 cell, containing portions of the viral genetic information.  Remember all this is happening on the expense of the cellular energy and now when the process of DNA replication starts, viral portions will as well be replicated, yielding more viral RNA strands and subsequent viral proteins for the maturation and assembly of new viral particles.  Once this is done, the newly formed viral particles will go out of this CD4 cell by the process of exocytosis, and infest more and more CD4 cells and cycle continues.  I already discussed the process through which HIV infest and destruct the CD4 cells in a separate discussion you can find it in the link below;  Invasion of Human CD4 cell by the human immune virus.

THESE ARE THE TARGETS OF ANTIRETROVIRAL DRUGS ON THE HIVVIRUS:  Now that we have seen the way the virus enter and disrupt the cellular functioning, the drugs that are used to reduce on this burden also known as Antiretroviral drugs (ARVs) target special processes of the viral replication cycle as follows;

1.  Some will be able to inhibit the virus from entering the CD4 cell at the plasma membrane level and this class of drugs is known as Fusion inhibitors.

2.  The other class will inhibit the production of viral DNA from viral RNA strands usung cellular nucleotides and we shall call those, Nucleoside Reverse Transcriptase inhibitors (NRTIs).

3.  The third class will be able to inhibit the actual enzyme involved in production of the viral DNA from the viral RNA strands, and remember from the beginning the viral particle comes equipped with this enzyme; Reverse transcriptase.  Then we shall call the group of drugs falling here, Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).

4.  The fourth class will be effective by inhibiting the incorporation of the formed viral DNA portion into the human or CD4 DNA strand, by affecting the action of the enzyme integrase, responsible for that process.  We shall therefore call these class of drugs, Integrase Inhibitors.

5.  The final or one of the last class, will be able to inhibit the maturation of the formed viral particles and therefore they will not be able to go out of the CD4 cell to affect other CD4s or if they go out, they will be be immature and therefore with no virulence.  These drugs will be interfering with the enzyme Protease and we shall call the class, Protease inhibitors.

In a separate discussion, we shall be able to look at some of specific drug names as they appear in all the 5 sub classes mentioned above, and the possible combinations that causes synergism in order for the therapeutic regimen prescribed to be effective but before we leave this section of the discussion, don't forget to read about general classification of drugs from the link below; Classification of pharmaceutical products and drugs.

THIS IS THE WAY HIV CAN BE PREVENTED:  Now let us come up with the preventive measures of HIV.  First, and foremost, for mature adults the most trusted and reliable means focuses on regular testing and diagnosis for those looking for sexual partners.  The most outstanding goal here, is to have safe sexual practices as long as the couple tests HIV negative, and prevent the consequences that may result from discordancy.  The next strategy to that will be avoiding multiple sexual partner or as the campaign says; get off the sexual network and increase trustworthiness among the couples.  If all these may not be possible all the time then at least maximize the proper use of condoms.  The preventive measure on the same issue is ensuring safe sexual practices like we saw at the beginning that or sex and homosexuality can as well predispose you to contact HIV.

The other preventive measure will be looking as good and safe clinical practices including proper use of medical gears, emphasis on Standard Operating Procedures and proper disposal of medical wastes.  For the health workers, the Prevention of Mother to Child Transmission (PMTCT) is already on the go and documentations from researchers indicate a reduced number of newborns to HIV positive mothers however, we will have a need to address more and more the practice of pregnant mothers especially from rural setting, to deliver from health facilities and get assisted by trained medical personnel.  In some of our next discussions, we shall be talking about what has been put forward to reduce the incidence of HIV in newborns and those affected with HIV during and following birth.

CONCLUSION:  HIV is one of the current global burdens with no radical cure established yet.  It's prevalence is higher in developing countries especially sub Saharan Africa and it continues to spread, reversing the expected trends from many Governments.  It was very much deadly in the 80s and 90s but the coming of antiretroviral drugs, there is some relief for the last two decades.  Many families now are living with HIV and on drugs, but they are living happy life following counseling and compliance to the medications.  The documented mortality rates that happened in the 80s before the drugs were available, is now far reduced and there is hope that with increasing discovery of more and more therapeutic regimens for HIV will finally eliminate the disease and we live an HIV free ecosystem.

RELATED;

1.  HIV PROGRESSION TO AIDS

2.  BLOOD DONATION, TRANSFUSION AND THE HUMAN BODY

3.  TUBERCULOSIS

4.  HEPATITIS

5.  DNA, THE GENETIC MATERIAL

6.  RIBONUCLEIC ACID, RNA, THE GENETIC MATERIAL

7.  NUCLEOTIDE, THE BUILDING BLOCKS OF RNA AND DNA

8.  INVASION OF THE HUMAN CD4 CELLS BY THE HUMAN IMMUNE VIRUS

9.  CLASSIFICATION OF DRUGS

REFERENCES

THERAPEUTIC INDEX AND THERAPEUTIC WINDOW

 

INTRODUCTION:  Administering a dose of the drug that produces an optimum therapeutic response for each individual patient is only one component of effective pharmacotherapy. Medical practitioners must also be able to predict whether the dose is safe for the patient and this is one other thing that is fully tested during clinical trials.  Frequency distribution curves can also be used to represent the safety of a drug. For example, the median lethal dose (LD₅₀) is often determined in preclinical trials, as part of the drug development process. The LD₅₀ is the dose of drug that will be lethal in 50% of the investigation group of animals. As with ED₅₀, a group of animals will exhibit considerable variability in lethal dose; what may be a nontoxic dose for one animal may be lethal for another.

DETERMINATION OF THERAPEUTIC INDEX:  To examine the safety of a particular drug, the LD₅₀ can be compared with the ED_50. For example, 10 mg of drug X is the average effective dose, and 40 mg is the average lethal dose. The ED₅₀ and LD₅₀ can then be used to calculate an important value in pharmacology, a drug’s therapeutic index, which is the ratio of a drug’s LD₅₀ to its ED₅₀.  

THERAPEUTIC WINDOWS:  Now that we have looked at therapeutic index as a ration, therapeutic window on the other side, is a range between the drug that can cause a desired effect in 50% also known as Effective dose 50 (ED50) of the investigational animals to the drug dose that can cause toxicity in 50% of the investigational animals also known as Toxic dose 50 (TD50).

INTERPRETATION OF THERAPEUTIC INDEX:  The larger the difference between the two doses, the greater the therapeutic index. In the example above, the therapeutic index is 4 (40 mg ÷ 10 mg). Essentially, this means that it would take an error in magnitude of approximately 4 times the average dose to be lethal to a patient. Thus, the therapeutic index is a measure of a drug’s safety margin.  The higher the value, the safer the medication.

MEDICAL IMPLICATIONS OF THERAPEUTIC INDEX:  The therapeutic index offers the medical personnel practical information on the safety of a drug and a means to compare one drug with another. Because the LD₅₀ cannot be experimentally determined in humans, the median toxicity dose (TD₅₀) is a more practical value in a clinical setting. The TD₅₀ is the dose that will produce a given toxicity in 50% of a group of patients. The TD50 value may be extrapolated from animal data or based on adverse effects recorded in patient clinical trials.

 

RELATED;

1. PHASES OF CLINICAL TRIALS

2. DRUG DISCOVERY AND DEVELOPMENT

3. RANDOMISATION

4.  PHARMACOLOGY AND THERAPEUTICS

REFERENCES

DYNAMICS OF DRUGS AND THE HUMAN BODY

 

DYNAMICS OF DRUGS IN THE HUMA BODY:  Today we are living in a drug World where in more than 99% of medical interventions, there will be introduction of a given drug with an intention to cure the underlying disease.  Day to day, drugs are increasingly becoming available to us in big numbers and we keep taking in drugs in our bodies either traditional or conventional pharmaceutical products as they are being discovered, developed and distributed.  But for a non medical personnel or for someone with little or no knowledge about such substances, less is known about the possible interaction of such drugs with our bodies not even the possible adverse effects or drug-drug interactions that we may encounter.  It will actually Suprise you to know the for every substance we meet, there is a an increasing potential to get toxicity from it.  

There is also constant fear that our incredibly increasing self administration of medical compounds will once cause a bigger burden of disease exaggeration like it has never been before.  This being via introduction of antimicrobial drug resistance and this is a great topic of concern these days.  If you have not been following my articles, you can click on the link below to read more about drug resistance.  Antimicrobial drug resistance, a topic of concern.  In this article we are going to look at the brief goings of some of the most common medications that we encounter on a daily basis, the reason we take them and the possible predictable outcomes of such substances and if possible, the possible toxicities from them.

FORMULATION OF DRUGS:  Drugs are formulated in different ways basing on the systems they are intended to act upon.  Some are formulated as capsules for swallowing, some as tablets, others like suspensions and for topical agents as ointments.  For each drug formulation, there are intentions as to why it was did that way and not in any way should a patient manipulate a drug without prior advice from a trained medical personnel.  Let's say you are give capsules to swallow, it is not advisable at all to open such capsules.  The reason drugs are formulated differently is something to do with their pharmacokinetics and pharmacodynamics which we discussed earlier and if you would like to read more about them, click on the links below.  Any attempt to modulate the drug from it's original formulation will change either it's absorption, distribution of metabolism by the body.  Pharmacokinetics of drugs  Pharmacodynamics of drugs

It should be noted however that, as long as many drugs may be tablets, there maybe their equivalents in syrups, suspensions and or ointments and it turns out that, you only have to use any drug formulation prior to consultation from a trained medical personnel.

ROUTES OF DRUG ADMINISTRATION:  First, before any drug is taken, there must be a specific route it should undertake.  Some drugs are taken via the mouth and we shall later be relating to that as the oral route, other are taken via the nose and we shall be taking that as inhalational route, while for others the drug is injected into the vein and muscle tissue and we shall be addressing those and intravenous and intramuscular route of drug administration respectively. If you have not been following us, click here to read more about routes of drug administration.

Each of the drug routes used during drug administration has a purpose and not at any point a drug should be administered via a non intended route.

MECHANISM OF ACTION:  For any drug, there must be a way it interacts with the human body and or microbes and cause a desire effect, which we sometimes we refer to as the drug's pharmacodynamics.  It is pharmacodynamics actually that gives a clinician the order of writing a prescription.  The mechanism action also helps in understanding the possible side effects, adverse effects and if any the toxic effects of that particular drug and to get details, let us look at a few examples.

1.  An infection by Salmonella bacteria will require a drug that can kill the bacteria and in that case, and antibiotic will be indicated, with it's mechanism of action being bacteriacidal.

2.  An asthmatic attack will mean we are having impared gaseous exchange and in that case one of the drugs to be indicated, will have a potential to widen the brochi, being a brochodilator by mechanism of action.

EXCRETION OF DRUGS FROM THE BODY:  Once taken in and they have finished exerting their effects or reached peak desire concentrations, drugs must be eliminated from the body.  This happens to either the unchanged drug or metabolites and end products of such drugs.  The chief organs and systems that play this role include the kidney that eliminates most of the drugs via the urine, the gastrointestinal tract that eliminates components through faeces, and for some via the skin and respiratory system.

RELATED;

1.  DYNAMICS OD THE HUMAN BODY-SYSTEM MAKEUP

2.  THE INTRAMASCULAR ROUTE OF DRUG ADMINISTRATION

3.  DYNAMICS OF INFECTIOUS DISEASES

4.  THE HUMAN KIDNEYS

5.  ANTIMICROBIAL DRUG RESISTANCE

CELLULAR CHANGES IN THE HUMAN BODY

CELLULAR CHANGES IN THE HUMAN BODY