The growth of this industry is directly linked to technological advancements which know no halts. Can you just imagine the rate at which the digital world improves?

The old black and white TV sets in the seating room changed to flat screen LCD monitors, the big walkman with a single cassette and radio is now a 64 Gb tiny iPod with thousands of videos, the very heavy radio phones are now small touch screen phones with wireless internet and TV options,    The very bulky computers are now palmtops in your pocket, the boring brick game you carried to school is now a fully multimedia psp, wii or Nintendo.

Shopping can easily be done today using the internet or mobile phone with instant home delivery.

While surfing, I came across a unique auction site. The stock is impeccable and the prices down to earth, beside you can chat online in case help is needed.    It is a very impressive way to get items by bidding, just like playing a game with others for some seconds and stand a chance of winning hundreds or thousands of dollars. It’s so easy to use that you get the latest gadgets at cents, with anything to lose.

For the game fans this is an opportunity you cannot afford to miss. Check these beautiful surprises I found on this auction site, ps3 at little or nothing cost.  The new Nintendo is even more attractive

Even those who never played games before will bid for the wii after all you can get it for almost nothing.

Wait a minute, do you think that is all, there is more in store that what I saw because i see new stuff on every log in; iPods, laptops, digital cameras, Flat screen monitors and more.

Hurry up, 5 free bids when you register. This is one thing too good to be true but very true.
Elvizy

The first and most common method of transmission of the virus is unprotected sexual intercourse with an infected person. The virus is easily passed across because of its extremely high survivability in body fluids. Dr William O’connor stated that nearly every fluid in the body can transmit the virus, including saliva, blood, sweat and tears

Recent findings about the HIV virus are even more frightful and present slim chances for an AIDS free tomorrow.

A recent study showed that the HIV virus can survive for up to seven days on dry surfaces out of the body and fourteen days on wet surfaces. This was confirmed by the Pasteur Institute though the media talks less of this.

Micro lesions are normally found in the mouth, and if blood in those tiny pores is infected then we can contract HIV virus through passionate kissing. It was observed on a survey that fifty percent of test group had blood in their saliva and the figure was even greater after brushing.

Blood transfusion presents a very high risk of contracting the virus. At least 10000 Americans have been infected as a result of blood transfusion though blood banks carry out their best, chances of AIDS free blood is never 100 percent

The risk of contracting the virus is so great and medical personnel are at the frontline.  The Medical world news mentioned more than 5000 doctors, dentists and health personnel infected with the virus. This is because medical equipments are no longer as safe as those who sterilize them emphasize. Studies by Dr Lewis and his team reveals that the HIV virus has some chases of escaping from the chemical disinfectant used to sterilize the dentists tools and so poses a risk almost similar to handling of an infected syringe.

Read the post title,  If the blood of one partner contains  HIV on web-articles.info

Che Elvis

Presented by Che elvis

BACKGROUND

There has been a general and rising interest among nation states on environmental issues, most especially environmental protection of water sources since after the United Nation’s Conference on Environment and Development (UNCED), which is also called the ‘Earth Summit”, held in Rio de Janeiro, Brazil in June 1992. It was the summit that sensitized most national governments, Municipal councils and city or towns worldwide to re-examine issues of the environment in general and water sources in particular along side with those of development. Theoretically this conference expected Nations and their citizens to recognize the rather complimentary relationship which exist between development and the environment. Practically, most nations even began to redefine national security to include the protection of water sources from both internal and external aggression (Chiras, 1994).

INTRODUCTION

River Ndongo as it is called locally is a stream that passes through Molyko in Buea down towards Mile 14. It joins others streams at Mutengene and probably heads towards the sea in Limbe. The water is used for vary purposes along its path; drinkable at its source, agriculture particularly tomatoes at UB gate, general cleaning and laundry water around the Dirty south parts of Molyko, car wash at Mile 14 and Mutengene

The River originates at Ndongo quarters(which is named after the river) as a clean underground spring which is “pure” and drinkable. The BOD at the source is less than 3mg per Litre and it is classified as class 1A, but the purity decreases significantly downstream. Ndongo quarter is around Boston, between Molyko and Bunduma, Buea.

The people there have no alternate source of water such as pipe borne water and have to use their underground spring despite some of the problems that occur.

WATER PROBLEMS FACED

Firstly the inhabitants of this locality have serious water problems as seasons change. During the dry season, strong winds carry a lot of dust that settles on the water even at the source and since the inhabitants are stereotyped on the fact that their parents drank it for generations, they do not filter before drinking. Where as in the heart of the rainy season on the other hand, dissolved greenhouse gases go into the stream as well as dirty water from runoff, giving the water a brown coluor and making it undrinkable.

The inhabitants themselves, especially children are the main sources of major problems faced. If some one defecates around the source for instance, the smell scares off those who come to fetch water giving the impression that the water is dirty.

Also inhabitants swim when they return from their farms just at the point where drinking water is carried, making the water contaminated at that point.

Apart from swimming, some inhabitants go as much as dumping refuge too close to the source which increases the concentration of microorganism close to the source that can lead to serious infection problems.

Being in a volcanic region, the purity of the underground spring can be accounted for by the heavy filtration processes taking place underneath facilitated by volcanic rocks, but during earth tremors like in Mt Fako eruptions, the water becomes very unsafe for drinking.

Very little scientific work is carried out in the river despite the close to 400 persons who depend on it for drinking. Previous work shows that the source has almost negligible traces of heavy metals which could be related to volcanic activity.

Another problem is risk of pandemics such as cholera due to pollution from various sources, both defined and undefined.

WHO IS RESPONSIBLE?

The first people to blame for the water problems are the inhabitants who do very little to maintain hygiene at the source. The inhabitants swim, do laundry and deposit refuge quite close to the source that can easily result in pollution problems.

Also, nature is responsible for the water problems faced at Ndongo quarter. The inhabitants only depend on the underground spring supplied by the aquifers which are water buried strata beneath the ground and cannot explain the purity of the aquifer at any specific point in time. Heavy leaching for instance can pollute and aquifer and hence springs.

Also nature causes changes in climate that go a long way in dirtying the water. Rain brings dissolved greenhouse gases as well as runoffs while winds carry dust that settles on the stream.

Another party to take responsibility for the water problems faced is the Government.

The locality is inhabited mainly by farmers and unfortunately is not supplied by pipe borne water probably because the inhabitants find it needless to complain to the Government, says an inhabitant. Inhabitants are therefore forced to rely uniquely on the underground spring even after the rains when the water appears slightly brown.

Also the Government has failed to do much research on the spring so as to publicly declare its purity or impurity in specific seasons. Inhabitants therefore survive on the hope of its purity.

SOLUTIONS PROPOSED

1 Sensitization

The inhabitants should be sensitized on how to keep their water source clean. Clean up campaigns should be organized on daily or weekly basis to cut grass around the source and remove all dirt dumped even several meters from the source. Individuals dumping refuge should be sanctioned by the quarter head and it should be a pleasant responsibility to maintain purity of the stream.

2 Filtration and purification

Inhabitants should be thought to use simple purification techniques such as sand and cotton in bottles such that pollution should be minimized despite the problems encountered as seasons change. Filtration and purification such as the use of Chlorine can greatly reduce or even avoid completely the chance of outbreak of a pandemic. Click here to learn a  simple filtering experiment

3 Introduction of pipe borne water

If pipe borne water is brought to this locality by the government a great deal of problems will be solved especially those that cannot be avoided at the local level as seasons change. In this way, at such periods inhabitants will simply run to their taps as the water has gone through several steps of filtration and purification.

Already, however, the local community has introduced community water at some points which is free for every one.

4 Scientific research

Research should be carried out such that purity of the water source should be documented. Research can also predict contamination right before time such as mountain tremors that release heavy metals to aquifers and consequently to springs.

CONCLUSION

The government of Cameroon was part of the ‘Earth Summit’ in 1992 and is taking great measures in environmental protection particularly water sources.

Ndongo is one of the neighbourhoods that benefit from underground water as unique source of consumable water and therefore deserves some protection as stipulated in the summit.

Ndongo river serves several purposes beyond drinking, ranging from agriculture to carwash.

Inhabitants face many problems including pollution due to seasonal changes, poor waste disposal near the stream and risk of possible outbreak of pandemics

Both nature, the inhabitants themselves and the government is responsible for the problems faced by the inhabitants drinking from the stream.

Some of the solutions proposed to counter the problems encountered include; sensitization of the general public on hygienic practices, filtration and purification before consumption, introduction of pipe borne water to supplement natural supply and improvement on research work to predict purity or possibility of pandem

REFERENCES

Inhabitants of Ndongo quarters

CHM 402 notes by Dr Lydia Lifongo and Dr Tening

Cornelius M, Lambi  2001,  Environmental issues: Problems and Prospects,  page 23

David Waugh, An Integrated Approach to Geography

LIST  OF  INHABITANTS INTERVIEWED

1. YONI NJIE
2. PETER AGBOR
3. MBAKO FRANCIS
4. EYAMBI PRISCILIQ
5. EPOSI  ANABEL
6. NDIFOR FRANK
7. ISAIAH CHE
8. FONJONG
9. ENGEMA

10. BAH DAMIEN

11. GWENDOLIE

12. MUH NOBERT ADAMU

13. EYONG SHU

UB  STUDENTS  DRINKING  FROM THE SOURCE

14. NELSON EYONG ARREY

15. TAKAN CHUNG HARRISON

16. ETAH TIKU

17. ZACH CHIDI

18. VICTOR ANJONEK

19. NEH MIRABEL

Abstract
The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g.-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to _1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug’s target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with
transposons often facilitating the incorporation of the multiple resistance genes into the host’s genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Here in case histories one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa—are reviewed to illustrate the varied ways in which resistant bacteria develop.

INTRODUCTION

Resistance to antimicrobial agent is a recognized health problem for past years. Bacterial where known to pose a lot of problems to antibiotics due to their resistance to the drugs. Resistance to drugs by bacterial is a means developed by bacterial to survive in the milieu within which there are found. Drugs are substance that modifies the response of a tissue to it environment. They bind to receptors to elicit a biological response. Antibiotic resistant bacterial has increased as many organisms (example; Staphylococcus aureus) have developed resistance to several antibiotics; hence the search of new antibiotics is mainly due to the worrying ability of bacterial to acquire resistance to modern drugs. According to the World Head Organisation (WHO), Staphylococcus aureus is responsible for many serious community and nosocomially acquired infections, being the most frequently isolated bacterial pathogen from patients with hospital-acquired infections, especially immunocompromised patients with implants or prostheses. Asymptomatic S. aureus colonization occurs intermittently in children and adults, most commonly in the anterior nasal vestibule, but occasionally on the skin, hair, nails, axillae, perineum, and vagina. Before the introduction of antimicrobials in the 1940s, the mortality rate of S. aureus invasive infection was about 90%. The initial success of antibiotherapy was rapidly countered by the successive emergence of penicillin-resistant, then methicillin-resistant S. aureus (MRSA) strains and, since 2002, by that of vancomycin-resistant strains. The development of antibiotic resistance in S. aureus is a strong incentive that spurs vaccine development.
Antibiotics have different site of action on the bacterial cell; this implies that, bacterial develop resistance depending on the site of action of the antibiotics. Nevertheless, some bacterial are resistant to many antibiotics by different mechanism of action, and it has become very difficult to fight such bacterial.
Bacterial have developed resistance to drug by many mechanism among which is drug resistance by mutation, drug resistance by genetic transfer, drug resistance by decrease permeability ability of the drug to the membrane of the bacterial, modification of the active site of the enzyme attack by the antibiotics and finally, the over production of enzyme that inactivate the antibiotics.
The enzymes that are involved in drug resistance include; penicillinases for the penicillin antibiotics, cephalosporinase for the cephalosporin antibiotics, the beta lactamases for the beta lactam antibiotics and many others.
The fight against bacterial resistance has brought many scientists together to develop strategies to combat the situation among which is the search for new antibiotics from natural product chemistry or other means but most important is the aspect of combination therapy which has brought more light to the fight against bacterial drug resistance.

Antibiotic resistance
Antibiotic resistance is the ability of a microorganism to withstand the effects of antibiotics. It is a specific type of drug resistance. Antibiotic resistance evolves via natural selection acting upon random mutation, but it can also be engineered by applying an evolutionary stress on a population. Once such a gene is generated, bacteria can then transfer the genetic information in a horizontal fashion (between individuals) by plasmid exchange. If a bacterium carries several resistance genes, it is called multiresistant or, informally, a superbug. The term antimicrobial resistance is sometimes used to explicitly encompass organisms other than bacteria.

Figure G: Effects of different antibiotics on growth of a Bacillus strain. The right-hand image shows a close-up of the novobiocin disk (marked by an arrow on the whole plate). In this case some individual mutant cells in the bacterial population were resistant to the antibiotic and have given rise to small colonies in the zone of inhibition.
Antibiotic resistance is not a recent phenomenon. On the contrary, this problem was recognized soon after the natural penicillin was introduced for disease control, and bacterial strains held in culture collections from before “the antibiotic era” has also been found to harbor antibiotic-resistance genes. However, in some cases the situation has now become alarming, with the emergence of pathogenic strains that show multiple resistance to a broad range of antibiotics. One of the most important examples concerns multiple-resistant strains of Staphylococcus aureus in hospitals. Some of these strains cause serious nosocomial (hospital-acquired) infections and are resistant to virtually all the useful antibiotics, including methicillin, cephalosporins and other beta-lactams that target peptidoglycan synthesis, the macrolide antibiotics such as erythromycin and the aminoglycoside antibiotics such as streptomycin and neomycin, all of which target the bacterial ribosome
Antibiotic resistance can also be introduced artificially into a microorganism through transformation protocols. This can aid in implanting artificial genes into the microorganism. If the resistance gene is linked with the gene to be implanted, the antibiotic can be used to kill off organisms that lack the new gene.
Why is resistance a concern?
There are a number of reasons why bacterial resistance should be a concern for physicians. First, resistant bacteria, particularly staphylococci, enterococci, Klebsiella pneumoniae, and Pseudomonas spp, are becoming common placein healthcare institutions. Bacterial resistance often results in treatment failure, which can have serious consequences, especially in critically ill patients. Inadequate empiric antibacterial therapy, defined as the initial use of an antibacterial agent to which the causative pathogen was not susceptible, has been associated with increased mortality rates in patients with bloodstream infections due to resistant Pseudomonas aeruginosa, Staphylococcus aureus, K pneumoniae, Escherichia coli, Enterobacter spp, coagulase-negative staphylococci, and enterococci. Prolonged therapy with antimicrobial agents, such as vancomycin or linezolid, may also lead to the development of low-level resistance that compromises therapy, but that may not be detected by routine susceptibility testing methods used in hospital laboratories.
Resistant bacteria may also spread and become broader infection-control problems, not only within healthcare institutions, but in communities as well. Clinically important bacteria, such as methicillin-resistant S aureus (MRSA) and extended-spectrum lactamase (ESBL) producing E coli, are increasingly observed in the community. Infected individuals, including children, often lack identifiable risk factors for MRSA, and appear to have acquired their infections in a variety of community settings. Community- associated MRSA strains are typically less resistant to antimicrobial agents than healthcare-associated MRSA, but are more likely to produce toxins, such as Panton–Valentine leukocidin. The spread of resistant bacteria within the community poses obvious additional problems for infection control, not just in long-term care facilities but also among sport teams, military recruits, and even children attending day care centers a task that is complicated by the increased mobility of our population. Finally, with respect to the cost-containment pressures of today’s healthcare environment, antibacterial drug resistance places an added burden on healthcare costs, although its full economic impact remains to be determined.
Causes and risk factors
Antibiotic resistance can be a result of horizontal gene transfer and also of unlinked point mutations in the pathogen genome and a rate of about 1 in 108 per chromosomal replication. The antibiotic action against the pathogen can be seen as an environmental pressure; those bacteria which have a mutation allowing them to survive will live on to reproduce. They will then pass this trait to their offspring, which will result in a fully resistant colony.
Several studies have demonstrated that patterns of antibiotic usage greatly affect the number of resistant organisms which develop. Overuse of broad-spectrum antibiotics, such as second- and third-generation cephalosporin, greatly hastens the development of methicillin resistance. Other factors contributing towards resistance include incorrect diagnosis, unnecessary prescriptions, improper use of antibiotics by patients, the impregnation of household items and children’s toys with low levels of antibiotics, and the administration of antibiotics by mouth in livestock for growth promotion.
Researchers have recently demonstrated the bacterial protein LexA may play a key role in the acquisition of bacterial mutations.

ORIGIN OF DRUG RESISTANCE
Human inability to respect the complete medication period given to them has mark a rapid increase in drug resistance by bacterial. When incomplete medication is carried out by a patient, it makes the bacterial to develop resistance against that drug, because the bacterial will develop new ways (factors) to prevent the conditions it is exposed to. By doing so, the bacterial cell wall may become impermeable to the drug, or produce enzymes that deactivate the drug and many others. So it is convenient to always take the complete medication given. Bacterial have become resistant to many drugs by developing certain factors which are explicitly given as follows;
Drug resistance by mutation:
Bacterial have the ability to multiply very rapidly, such rapid multiplication also pose a chance to the bacterial to undergo mutation which will render the bacterial cell resistance to a particular drug. The mutation can be the change in the bacterial structure, or the enzymes attacked by the drug changes it’s structure or composition. This works in line with the fact that patients do not always complete the course of their antibiotic treatment given that the symptoms of their illness have disappeared. To elaborate, the drug becomes foreign to its target due to mutation at the drug target.
Drug resistance by genetic transfer:
Genetic materials can be transferred from one bacterial cell to another by transduction or by conjugation. This therefore means that bacterial are capable of exchanging genetic materials and hence, a resistant bacterial cell can transfer the gene responsible for its resistance to a drug to a non resistant bacterial cell and this therefore cause the latter to be resistant to the same antibiotics.
In transduction, plasmids which are small segment of genetic information of a bacterial are transferred by means of bacterial viruses or bacteriophage. If the plasmid which contains the gene for resistance to a particular antibiotic agent leaves a resistant bacterial cell to a non resistant bacterial cell, then it will cause the latter to acquire resistance to that antibiotic. For example, the genetic information required to synthesize beta- lactamase can be pass on in this way and hence rendering bacterial resistance to beta- lactam antibiotic agent.
Conjugation is a method used mainly by Gram negative rod-shaped bacterial; it involves two bacterial cells building a sex bridge through which genetic information can pass. Hence, the bacterial cell passes genetic information directly to each other.
Change in permeability to bacterial cell:
Bacterial can undergo mutation which causes a decrease in permeability of the drug to the bacterial cell. Hence, causing the bacterial to be non susceptible to the attack of the drug. The mutation can be due to the change in polarity of the cell wall or cell membrane of the bacterial which repels the drug. The bacterial might develop a new protective coat which is impermeable to the drug. Many bacterial have developed resistance through this means.

Drug resistance by the production of drug deactivating enzymes:
Bacterial can produce enzymes that deactivate the antibiotics. These enzymes deactivate antibiotics by modifying them to inactive compounds.
Some of the enzymes produced by the bacterial include; penicillinase, cephalosporinase, beta- lactamase and much more. As an example, the beta- lactamases deactivates beta- lactam antibiotics by breaking the beta- lactam ring essential for activity.
Antibiotic usage in agriculture: creates a reservoir of resistance genes
One of the fiercest public debates at present concerns the use of antibiotics in agriculture and veterinary practice. The reason for concern is that the same antibiotics (or, at least, antibiotics with the same mode of action on bacteria) are also used for human therapy. Thus, it is possible that the irresponsible use of antibiotics for non-human use can lead to the development of resistance, which could then be passed onto human pathogens by transfer of plasmids. The greatest concern of all centres on the routine use of antibiotics as feed additives for farm animals – to promote animal growth and to prevent infections rather than to cure infections. It has been difficult to obtain precise figures for the amounts of antibiotics used in this way. But the scale of the potential problem was highlighted in a recent report by the Soil Association, which collated figures on the total usage of different types of antibiotic for humans and for animals:

Antibiotic resistance in genetically modified crops
A further source of concern is the widespread use of antibiotic-resistance genes as “markers” in genetically modified crops. Most of the companies insert antibiotic-resistance genes as “markers” during the early stages of developing their Genetically Modified( GM corps). This enables the scientists to detect when the genes that they are most interested in (herbicide-resistant genes or insecticidal toxin genes) have been inserted into the crop. The antibiotic-resistance genes then have no further role to play, but they are not removed from the final product. This practice has met with criticism because of the potential that the antibiotic-resistance genes could be acquired by microorganisms. In some cases these marker genes confer resistance to “front line” antibiotics such as the beta-lactams
Looking at penicillin, some bacterial develop resistance by producing enzymes called; amidases which slits off the R-side chain from the amino group of the 6-aminopenicilanic acid (6-APA). Also, metabolically inactive organisms are phenotypically resistant to penicillin but genotypically fully susceptible to penicillin. Such organism can act as “persisters” both in vitro and in vivo.
CASE STUDIES

E coli: Development of Resistance to Third-
Generation to penicillin

E coli is a common cause of urinary tract infections and bacteremia in humans, and is frequently resistant to aminopenicillin, such as amoxicillin or ampicillin, and narrow spectrum cephalosporins. Resistance is typically mediated by the acquisition of plasmid beta- lactamases which hydrolyze and inactivate these drugs. Some E coli strains develop resistance to third-generation cephalosporins and monobactams (aztreonam) commonly arising through mutation of the enzymes. Resistance to cephamycins and other lactams such as amoxicillin may arise as a result of changes in the porins in the outer membrane (proteins that form the water-filled channels through which drugs and other molecules enter the bacterial cell). Such changes decrease or eliminate the flow of small hydrophilic molecules like lactam drugs across the membrane. The following case illustrates the interaction of these mechanisms of resistance. A 4-year-old girl was admitted to an
Urban hospital in Atlanta with a plastic anemia and bacteremia. Blood cultures collected during her first week in the hospital were positive with E coli isolates that were resistant to ampicillin and narrow-spectrum cephalosporins but remained susceptible to third-generation cephalosporins. Over the next 3 weeks, the child received a variety of antimicrobial agents directed against E coli and other suspected bacterial pathogens in an attempt to treat her persistent fevers and bacteremia. The antibacterial agents included penicillins (ticarcillin, oxacillin, and mezlocillin), aminoglycosides (gentamicin), and third-generation cephalosporins.

ACTION OF PENICILLIN
The antibacterial effect of penicillin was discovered by Alexander Fleming in 1929. He noted that a fungal colony had grown as a contaminant on an agar plate streaked with the bacterium Staphylococcus aureus, and that the bacterial colonies around the fungus were transparent, because their cells were lysing. Fleming had devoted much of his career to finding methods for treating wound infections, and immediately recognized the importance of a fungal metabolite that might be used to control bacteria. The substance was named penicillin, because the fungal contaminant was identified as Penicillium notatum. Fleming found that it was effective against many Gram positive bacteria in laboratory conditions, and he even used locally applied, crude preparations of this substance, from culture filtrates, to control eye infections. However, he could not purify this compound because of its instability, and it was not until the period of the Second World War (1939-1945) that two other British scientists, Florey and Chain, working in the USA, managed to produce the antibiotic on an industrial scale for widespread use.

Structure A showing Fleming’s slide

Structure of penicillin
Penicillin is a bicyclic compound consisting of a four membered beta- lactam ring fused to a five membered thiazoridine ring. The skeleton of the molecule reveal that it is derived from the amino acid valine and cysteine. The acyl side chain “R” varies depending on the make up of the fermentation as shown below;

Structure Activity Relationship

From the synthesis of great analogs of penicillin studies, reveals the following conclusion about the activity of the structure of penicillin;
• The strain beta lactam ring most be present
• The free carboxylic acid at position three is essential
• The bicyclic system is important because it confers strain of the beta lactam ring, the greater the strain the greater the activity and also the greater the instability of the molecule to other factors.
• The stereochemistry of the bicyclic ring
With respect to the acyl amino side chain is essential for activity.
From all the above observations, it is clear that very little variations can be done on the structure of the penicillin molecule. One of the penicillin analogs is penicillin G for which “R” is a benzyl group, as it is shown below;

Penicillin G

Why are there so few clinically useful antibiotics?
Several hundreds of compounds with antibiotic activity have been isolated from microorganisms over the years, but only a few of them are clinically useful. The reason for this is that only compounds with selective toxicity can be used clinically – they must be highly effective against a microorganism but have minimal toxicity to humans. In practice, this is expressed in terms of the therapeutic index – the ratio of the toxic dose to the therapeutic dose. The larger the index, the better is its therapeutic value.

It will be seen from the table above, that most of the antibacterial agents act on bacterial wall synthesis or protein synthesis. Peptidoglycan is one of the major wall targets because it is found only in bacteria. Some of the other compounds target bacterial protein synthesis, because bacterial ribosomes (termed 70S ribosomes) are different from the ribosomes (80S) of humans and other eukaryotic organisms. Similarly, the one antifungal agent shown in the table (griseofulvin) binds specifically to the tubulin proteins that make up the microtubules of fungal cells; these tubulins are somewhat different from the tubulins of humans
BRIEF PROPERTIES OF PENICILLIN G
The two natural penicillins obtained from culture filtrates of Penicillium notatum or the closely related species P. chrysogenum are penicillin G and the more acid-resistant penicillin V. They are active only against Gram-positive bacteria (which have a thick layer of peptidoglycan in the wall) and not against Gram-negative species, including many serious pathogens like Mycobacterium tuberculosis (the cause of tuberculosis). Nevertheless, the natural penicillins were extremely valuable for treating wound pathogens such as Staphylococcus in wartime Europe.
An expanded role for the penicillin came from the discovery that natural penicillin can be modified chemically by removing the acyl group to leave 6-aminopenicillanic acid and then adding acyl groups that confer new properties. This modern semi-synthetic penicillin such as Ampicillin, Carbenicillin and Oxacillin has various specific properties such as:
• Resistance to stomach acids so that they can be taken orally,
• a degree of resistance to penicillinase (a penicillin-destroying enzyme produced by some bacteria)
• extended range of activity against some Gram-negative bacterial.
Although the penicillin are still used clinically, their value has been diminished by the widespread development of resistance among target microorganisms and also by some people’s allergic reaction to penicillin.

ACID SENSITIVITY OF PENICILLIN
Penicillin is recognized to be acid sensitive in the stomach and this has made them to be inactive orally. There are three reasons which account for the acid sensitivity of penicillin.
Ring strain:
The bicyclic system of the penicillin molecule consists of a four membered ring and a five membered ring. As a result, penicillin suffers large angle torsional strain. Acid catalyzed ring opening relieved this strain by breaking open the high strain four membered ring.
A highly reactive beta- lactam carbonyl group:
The carbonyl group in the beta- lactam ring is highly susceptible to nucleophiles and as such does not behave as a normal tertiary amide which is usually quite resistant to nucleophlic attacks. This difference in reactivity is due to the fact that stabilization of the carbonyl is possible in the tertiary amide but impossible in the beta- lactam ring. The beta- lactam nitrogen is unable to feed its lone pair of electron into the carbonyl group since this would require the bicyclic ring to adopt an impossible strain plat system. As a result, the lone pair of electron is delocalized on the nitrogen atom and the carbonyl group is far more electrophilic than expected for a normal tertiary amine. A normal tertiary amine is far less susceptible to nucleophiles since resonance structure reduces the electrophilic character of the carbonyl group.
Influence of the acyl side chain:
The neighboring acyl group can actively participate in the mechanism of the beta- lactam ring opening by attacking the carbonyl group of the beta- lactam ring, hence it is self destructive.
Tackling the problem of acid sensitivity
It is then very necessary to solve the problem of acid sensitivity of penicillin. From the above factors, nothing can be done about the problem of ring strain and the problem of the highly reactive beta- lactam carbonyl. In this view, only the third factor can be solved by reducing the neighboring participation of the acyl amino side chain, which is to make it difficult if not impossible for the acyl amino side chain carbonyl group to attack the beta- lactam carbonyl which will lead to the breaking of the beta- lactam ring. This point is solved by introducing an electron withdrawing group to the carbonyl carbon of the acyl amino side chain. By inductive pulling effect, the electron withdrawing group pulls electrons from the carbonyl oxygen and reduces its tendency to act as a nucleophile. An example is penicillin V (pen V).
How penicillin is destroyed by beta- lactamase
Bacterial develop resistance to penicillin by secreting an enzyme (beta- lactamase) that hydrolysis penicillin before it can interfere with bacterial cell wall synthesis. Beta- lactamase destroy penicillin by breaking the beta- lactam ring which is necessary for the activity of penicillin.
Mechanism of action of penicillin.
Penicillin is a beta lactam anti biotic was inhibits bacterial cell wall synthesis.
In contrast to animal cells, bacterial posses a rigid outer layer, the cell wall which “corsets” the bacterial cell, which posses an unusually high internal osmotic pressure. Injury in the cell wall or inhibition of it formation can lead to lyses of the cell. In hypertonic environment, damaged cell wall, leads to formation of spherical bacterial “protoplast” limited by the fragile cytoplasmic membrane. In the environment of ordinary tonicity, the protoplast explodes, and the cell dies, meaning penicillin is bactericidal.
Beta-lactam antibiotics work by inhibiting the formation of peptidoglycan cross-links in the bacterial cell wall. The β-lactam moiety (functional group) of penicillin binds to the enzyme (DD-transpeptidase) that links the peptidoglycan molecules in bacteria, which weakens the cell wall of the bacterium (in other words, the antibiotic causes cytolysis or death due to osmotic pressure). In addition, the build-up of peptidoglycan precursors triggers the activation of bacterial cell wall hydrolysis and autolysins, which further digest the bacteria’s existing peptidoglycan.
Gram-positive bacteria are called protoplasts when they lose their cell wall. Gram-negative bacteria do not lose their cell wall completely and are called spheroplasts after treatment with penicillin.
Penicillin shows a synergistic effect with aminoglycosides, since the inhibition of peptidoglycan synthesis allows aminoglycosides to penetrate the bacterial cell wall more easily, allowing its disruption of bacterial protein synthesis within the cell. This results in a lowered Minimum Bactericidal Concentration (MBC ) for susceptible organisms.
SIDE EFFECTS
Common adverse drug reactions (≥1% of patients) associated with use of the penicillins include diarrhea, hypersensitivity, nausea, rash, neurotoxicity urticaria, and/or super infection (including candidiasis). Infrequent adverse effects (0.1–1% of patients) include fever, vomiting, erythema, dermatitis, angioedema, seizures (especially in epileptics), and/or pseudo membranous colitis.
Pain and inflammation at the injection site is also common for parenterally administered benzathine benzylpenicillin, benzylpenicillin, and, to a lesser extent, procaine benzylpenicillin.
Although penicillin is still the most commonly reported allergy, less than 20% of all patients who believe that they have a penicillin allergy are truly allergic to penicillin; nevertheless, penicillin is still the most common cause of severe allergic drug reactions.
Allergic reactions to any β-lactam antibiotic may occur in up to 10% of patients receiving that agent. Anaphylaxis will occur in approximately 0.01% of patients. It has previously been accepted that there was up to a 10% cross-sensitivity between penicillin-derivatives, cephalosporins, and carbapenems, due to the sharing of the β-lactam ring. However recent assessments have shown no increased risk for cross-allergy for 2nd generation or later cephalosporins. Recent papers have shown that a major feature in determining immunological reactions is the similarity of the side chain of first generation cephalosporins to penicillins, rather than the β-lactam structure that they share.
Fighting penicillin drug resistance
Chemist have developed new methods of fighting penicillin drug resistance, among this methods is;
• The development of drugs that inhibit beta-lactamases, an example is clavolanic acid, if such a drug is given alon side with penicillin, the antibiotics is not destroyed. This is an example of a prodrug that has no therapeutic effect but acts by protecting a therapeutic drug. A sulfone is also a beta-lactamase inhibitor which is obtained by oxidizing the penicillin sulfur atom with a peroxyacid.
• Another means of fighting resistance is by developing new targets.

CONCLUSION

References
: http://www.pharminfo.com/
PCH 362 therapeutic agents Dr. Akam 2007/2008.
McManus MC. Mechanisms of bacterial resistance to antimicrobial
agents. Am J Health Syst Pharm. 1997;54:1420 –1433.
Drlica K, Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones.
Microbiol Mol Biol Rev. 1997;61:377–392.
Yao J, Moellering RJ. Antibacterial agents. In: Murray PR, Baron EJ,
Jorgensen JH, Pfaller MA, Yolken RH, eds. Manual of Clinical Microbiology,
8th ed. Washington, DC: ASM Press; 2003:1039 –1073.
Petri WAJ. Antimicrobial agents: sulfonamides, trimethoprim-sulfamethoxazole,
quinolones, and agents for urinary tract infections. In:
Brunton LL, Lazo JS, Parker KL, eds. Goodman & Gilman’s The
Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-
Hill, 2006;1111–1126.
Storm DR, Rosenthal KS, Swanson PE. Polymyxin and related peptide
antibiotics. Annu Rev Biochem. 1977;46:723–763.
Carpenter CF, Chambers HF. Daptomycin: another novel agent for
treating infections due to drug-resistant gram-positive pathogens. Clin
Infect Dis. 2004;38:994 –1000.

Hallowed be thy compounds,

thy mixtures come

Thy electrons be associated with protons

as it is a mystery

Give us good reactions in our daily experiments

And forgive us, our unbalanced equations

As we forgive all electrons that trespass the continuum

And lead us not into explosions

But deliver us from killing

For thine is the power, in reactants and reagents

For ever and ever, Chemistry without end

Amen

http://elvizy.com

By Che Elvis

DAY ONE:

Tole neighborhood

We started a little late than expected but much of what we set for was achieved. The village setting was used for the Grass field medley and the tea background was well exploited.

The south African songs were done last and just before sunset, a thousand birds were directly over head in the sky while the tapes were turning, also a cock crew just as a chorister was tuning the Grass field medley Ikafaweh. I just know its God’s way of saying “Am with you guys”

DAY TWO:

The Mayor’s Residence

This was supposed to be the most active day but unfortunately it rained very heavily in the morning. We were almost frustrated at UB Junction and we kept singing.

This however turned into a blessing as the rains made the backgrounds even brighter and colorful. Just take a look

DAY 3:

Molyko

Shooting on the 3^rd day was done in two phases; during the day on campus and at night in UB Junction. It was certainly the most tiring day and lucky enough the work was complete. The last shot was taken at 1: AM

It started with a slight rain “God’s blessing”, for about 15minutes. This rain touched all choristers since we were a little off shade and just like magic we became more motivated.

The first shot featured Mofa and  Ms Justin “Ma Jus”. How nice! Take a look

There were so many people behind the scene, both in the field and in the studio. You can see the extensive list in the DVD or VCD’s which are already scrambled for in CD shops.

Main Cameraman

ALL PICTURES TAKEN BY

Che Elvis	Pamela	O. Marinus	Leonard

To get CDs, contact the following persons:

• President     +237-7595-9009
• A. Justine    +237-7737-1914
• O. Marinus    +237-9932-7243
• Romeo    +237-7777-4195

Written by: Che Elvis N. “Elvizy”

For: www.elvizy.com

info@elvizy.com

Tel: +237-7493-2363

Step 1. Start easy

No need to start off rhyming “the toasty cow’s utter” with “most o’ my flow’s butter”. No need to even rhyme. Just forget everything else and flow. The rhythm can be simple, the words might be second-grade level, but you’re still freestyling as long as you make it up. This was my first freestyle rap, which I spit when I was 11 months old:

I am funny,
I like bunnies,
Touch my tummy,
Mummy

Step 2. Keep flowing

You’re going to make mistakes. You’re going to sound stupid. Make your first freestyle rap verses your stupidest verses just to get them out of the way. Keep flowing. Can’t think of a rhyme? Keep flowing! Stutter over words? Keep flowing. It’s inevitable that at some point some of your lines won’t rhyme, won’t make sense, or that you will inadvertently diss yourself. (I knew one guy who accidentally dissed himself all the time when we were freestyling.) Just keep flowing. If you make a mistake, do your best to incorporate your mistake into your next lines like Eminem did on this freestyle:

I take a beat and loop it,
I take a beat and choop it,
Choop it? What does that mean?
I don’t know but I got fat jeans on,
And I already said that,
I don’t know where my head’s at,

Another technique to use when you find yourself in a bind is to whip out a quick filler. Fillers are just little phrases that you can insert occasionally to give you more time to think of a dope line. Every emcee has his own fillers. For example, Eyedea says “I grab the microphone.” Jin often says, “I’m (nasty) when I’m freeing.” I usually say, “You know what I’m sayin’?”

Try to come up with a few fillers that you feel comfortable using. They’ll bail you out of some awkward pauses. As you get better, you can rely less heavily on your fillers.

Step 3. Rhyme in your mind ahead of time

Here’s the biggest trick to freestyle rapping: as soon as you know what word you’re going to end line 1 with, your mind should start racing to find out a word you can use at the end of line 2. Let’s say your first line is, “I’m colder than a Dairy Queen Blizzard.” As soon as you realize that you’re going to end the line with “Blizzard,” you should immediately think of something that rhymes with that word and might possibly be related:

wizard
lizard
scissor
miss her
pins hurt

Pick one and then try to carve the second line to lead toward that word. Let’s say you pick “wizard,” your next line might be:

I’m colder than a Dairy Queen Blizzard,
This is Lord of the Rings, you’re the hobbit, I’m the wizard,

If you pick “scissor,” you might say:

I’m colder than a Dairy Queen Blizzard,
A rebel since I was five, went running with scissors,

The real trick of freestyling is to have your mind constantly racing ahead of what you’re saying. This isn’t easy, but you’ll get quicker with practice.

Step 4. Write

Writing raps will help you freestyle. When you write, rhymes become embedded in your head, and you’re more likely to be able to pull these rhymes off the top of your head in a freestyle.

For the most part, you should never spit a long pre-written verse at a cipher, but you can certainly use rhyming words and shorter phrases that you’ve worked out beforehand. When Proof rhymes “Ewoks, treetops, and Reeboks” in a freestyle, you better believe he’s thought of those rhymes ahead of time. He’s still freeing, but he’s using rhyme words he’d already worked out.

Sitting down and writing every day will improve your freestyles. It will expand your memory of rhyming words, and it will give you experience working these words into clever lines. It’s also a good idea to write a few multi-purpose bars that you can spit at a freestyle in case you get really stuck. Put those lines in a “Break Out Rhymes In Case of Emergency” box, and smash the glass when you need help. This isn’t cheating; it’s shrewd.

When you’re writing these “in case of emergency” lines, make them strong and interesting, but not too ridiculously amazing. In other words, don’t do this:

Turn the beat up, it’s all that I need, (free)
Rocking my pumas … and my white tee, (free)
Hit or miss, this penetrates the uranium nucleus, (written)
Smoke crews like a hookah plus I’m nuking your crib, (written)

You don’t want your “emergency” rhymes to be that obvious. Try to write rhymes that generally match your level of freestyle but are clever and smart.

Step 5. Rap about things around you

This is definitely the best way to prove to the crowd that you’re really freestyling and not just spitting something you wrote in your room the night before. It’s also a huge crowd-pleaser, ‘cause it’s impressive and it makes everyone real glad that they’re hanging out with you. Rap about things you see. Incorporate objects, actions, people, clothing, situations, and sounds into your rap. When I’m in the shower, I’ll rap about what kind of soap I’m using:

Trying hard to get clean, maybe just a smidgen,
Make my Dove dirty, oh, now I call it pigeon

At a battle competition, this is crucial. You’ve got to spit things specific about your opponent. These are the hardest-hitting punches. Take Iron Solomon’s opening lines against The Saurus in a battle on the streets of New York. He looks his opponent up and down, sees that he’s wearing shorts, and then spits:

Maybe you should have come here rocking a better flannel,
Or at least some long pants,
You should have checked the weather channel.

One of the freestyle kings is a rapper from North Carolina named Spectac, who can spit a rhyme off the top of his head that sounds like it was pre-written. I’ve heard Spectac freestyle for 40 minutes straight over various beats, and I’ve seen him in action at a show, getting some kid to walk around the audience pointing at things and Spec rhymes about it. I asked Spectac what it takes to freestyle. Here’s what he told me:

“Honestly, first of all, you have to have a love for the music and not just the hip-hop genre. You have to love the instrumental. Once you have the passion for it, anybody can develop the ability to freestyle. It comes down to how much time you’re willing to invest in practicing that part of the art. When I’m freestyling, I’m thinking ahead. I’m definitely thinking ahead. At the same time, I don’t get too far ahead of myself. You try to enjoy it with the crowd. Enjoy the punch lines, but keep yourself focused on the fact that the party isn’t over.”

Step 6. Include metaphors

Metaphors and similes are an advanced but important part of freestyle rapping. They are often found in a rapper’s funniest and cleverest lines, and they really differentiate beginners from skilled emcees. A rapper like Lil Wayne lays down verses that straight-up drip with similes and metaphors. He’s the one who is balling like “Rawlings and Spalding,” who is a giant like “fee fi fo fum,” who is counting (money) all day “like a clock on the wall.” Not only does he drop lots of similes, he drops clever, original similes. So do like he does. Don’t just say “sharp as a knife.” Say:

I’m sharp as Samurai swords…
I’m extra sharp like cheddar…
I’m sharp as a Schick Quattro…

Metaphors and similes are really the backbone of an advanced rapper. Learn how to use metaphors correctly. Your rhymes will not only be funnier and smarter, they’ll sound better too. Take these lines from rapper Chingo Bling: “I’m fly like Big Pun on prom night with a cummerbund.” You know that is fly!

Step 7. Reference current events

Just as good as referencing something nearby is referencing something timely. Let’s say, for example, that you are at a cipher, rapping with some of your friends (dissin’ each other, just goofin’ around), and the day before you remember reading that Star Jones recently lost 200 pounds. How dope is it if you throw that in your rhymes:

You big now, but you ‘bout to get cut down,
Faster than Star Jones dropping 200 pounds

I recently heard an emcee reference soaring gas prices:

Fast? Son, that ain’t fast—
I’m rising faster than the price of gas

Whether it’s related to sports, politics, music or celebrities, if it’s in the news, reference it. As Wordsworth says, “I just try to think of what’s important to the people in my surroundings and try to speak on it.”

Step 8. Pass the mic like it’s contagious

Rap in ciphers—groups of two or more rappers playing off each other, trading verses. This is a great way to improve, and it’s definitely fun. One of your friends can beat box, you can throw a beat on the stereo, or just freestyle over nothing. Take turns, cutting in whenever you want or when someone “passes you the mic.” (You probably won’t have an actual mic). Never drop the invisible mic! Pick it up and pass it!

Work off other people’s rhymes. If they throw in something about the Bible, pick up that theme and run with it. Try to stick to similar topics, or riff off topics in creative ways. Expand on or reference their lines. When my friends and I cipher, we like to kick about random stuff that we all know about, like our personal lives.

Me:
Got no girlfriend, and girls are good for your health,
Know what I mean? Uh, at least I work for myself,
You see me here, kid, and I rhyme crazy,
Used to have a job reading to a rich blind lady,

Zach:
You rhyme crazy, and sometimes you rhyme lazy,
But I love this rap game, ‘cause rhyming is my baby,
Visually, lyrically I’m known as a mystery,
Y’all couldn’t even see me on HDTV,

It’s always good to pick up the rhyme scheme of the person right before you. In a great freestyle between Brooklyn rappers Mos Def and Talib Kweli (back when they were together as Blackstar), Mos Def ends his first verse asking Kweli if he’s with it. Kweli responds, “I’m always with it…” Later Kweli spits rhymes about some emcees looking wack, then he passes the mic to Mos who continues the rhyme, saying that they always look wack “cause look at the way they dress.” These are the best freestyles: raps that connect with the rhyme sounds and topic of the rappers around you. In the best-case scenario, the rhymes intertwine like the fibers in a Shredded Wheat biscuit.

Step 9. When you’re in a cipher, think ahead

One of the great things about rapping in ciphers is that after you spit one verse you get a break before you spit again. This break is your best friend. It’s during this break that you’ll be listening and responding to your friends’ verses. But you’ll also be planning out your next verse.

Whenever I’m in a cipher, I never like to get back on the mic until I’ve composed four to six quality lines in my head. To be most impressive, these lines will be about things around you, or they’ll be about something your friend said in his verse. Let’s say your friend is wearing a shirt that has Daffy Duck on it. While he’s spitting, you can write a line like this:

I know you’ve had a tough year and had some crappy luck,
But why you gotta wear a shirt with Daffy Duck?

That’s not an amazing line, but I guarantee you that in a cipher people will go nuts over that. (Make sure to point at his shirt as you say it). I always try to think of two or three of those rhyming couplets before I spit again. Usually I’ll drop one right away and then use the other two later in the verse.

Step 10. Listen and practice

Freestyling, like sculpting or shooting three-pointers, takes an insane amount of practice. Practice as much as you can. Freestyle with homeless people, with your friends, and with your family. Listen to pro rappers who freestyle and try to analyze their styles. Rap all the time; practice all night and day. Practice might not make perfect, but it makes real good!

Keep me posted about your progress and the challenges you phase.

Che Elvis “Elvizy”

www.elvizy.com

info@elvizy.com

Copied from www.flocabulary.com

University of Buea

Abstract

Herbal medicine, sometimes referred to as herbalism or Botanical Medicine is the use of herbs for their therapeutic or medicinal value .A herb is a plant or plant part valued for its medicinal, aromatic or savory qualities. Herbs produce and contain a variety of chemical substances that act upon the body and treat many diseases.

The use of plants in the treatment of diseases is more commonly used because medicinal plants are more efficient and less toxic. Plants also are of a natural source, hence are less costly when prepared. Medicinal plants also have an advantage over drugs because they can be consumed in their natural form, whereas drugs must first of all be prepared before consumption. Major pharmaceutical companies are presently conducting research on plant materials due to their potential medicinal value.

Introduction

The brain is made up of interrelated neural systems that regulate their own and each others activity. These divisions make it easier for the brain to function efficiently since it is responsible for carrying out many other activities. The sympathetic nervous system is vitally involved in the homeostatic regulation of a wide variety of functions such as heart rate, force of cardiac contraction, blood pressure and fatty acid metabolism. Stimulation of the sympathetic nervous system normally occurs in response to physical activity, physiological stress and other situations in which the organ is provoked. Because the functions that are mediated by the sympathetic nervous system are diverse, agents that mimic or alter its activity are useful in the treatment of several clinical disorders like shock, cardiac failure, hypertension and many others.

Drugs that affect the Central Nervous System may selectively relieve pain or fever, suppress disorder or movements or prevent seizures. They may as well induce sleep or arousal, reduce the desire to eat or reduce the tendency of vomiting and hence may be used to treat anxiety, mania, depression or schizophrenia without altering consciousness.

The major scientific challenge is an attempt to understand the way the brain functions and the major goals include:

1) To use drugs to dissect the mechanisms that operate in the normal Central Nervous System

2) To develop appropriate drugs to correct events in the abnormal Central Nervous System.

CHAPTER ONE

LITERATURE SURVEY

History of medicinal plants

Herbal medicine has a long and respected history. Many familiar medications of the twentieth century were developed from ancient healing traditions that treated health problems with specific plants. Today, science has isolated the medicinal properties of a large number of plants, and their healing components have been extracted and analyzed. Many plant components are now synthesized in large laboratories for use in pharmaceutical preparations. For example , vincristine (an antitumor drug), digitalis (a heart regulator) and ephedrine (a bronchodilator used to decrease respiratory congestion) were all originally discovered through research on plants.

Chemistry of medicinal plants

The use of plants in the treatment of diseases is attributed to their secondary compounds. They are called “secondary” compounds because they have no known functions in primary physiological processes like photosynthesis and respiration. Many classes of secondary compounds such as alkaloids and steroidal glycosides are found in medicinal plants.

i) Alkaloids are a chemically diverse group. They contain nitrogen which is usually found in rings although there are exceptions where the nitrogen atoms are not included in the rings e.g. epinephrine and ephedrine.

ii) Steroidal glycosides contain sugar molecules. The steroidal molecules are the same as those found in animal hormones produced by the pituitary glands and sex organs.

Advantages of medicinal plants over synthesized drugs

Herbs are medicinal plants (also called phytomedicals) that can be administered either as a whole plant or plant part while synthetic drugs are synthesized chemically in the laboratory to produce drugs not found in nature. Most of these drugs are derived from plants by extracting the active ingredients from the plant, replicating its structure in the lab and mass producing it.

Herbal medicines have three main advantages over synthetic drugs.

1) Their long term use already indicates that they provide a high degree of safety and efficacy for human consumption.

2) Plant materials are less costly to prepare.

3) With medicinal plants, there is a reduced incidence of adverse drug interaction which is common to most therapies using synthetic drugs.

Herbal drugs are considered less potent than prescribed medicines. Drugs contain one highly active ingredient while herbs may have several active ingredients that are chemically similar. Herbal ingredients work synergistically to contribute to the therapeutic effect of each individual ingredient.

Herbalism

Herbalism which is healing with plants is sometimes considered as a collection of home-made remedies to be applied to one symptom or another provided the ailment is not too serious. However, we often forget that herbal medicine provides a good system of healing and prevention of disease. It is the oldest and most natural form of medicine. When skillfully applied, herbal medicine offers very real and permanent solutions to very real problems. Herbalism should not be confused with Traditional medicine. Nowhere is the efficacy of herbalism more evident than in problems related to the nervous system. Stress, anxiety, tension, and depression are intimately connected with most illnesses. Because they are organic substances and not man-made synthetic molecules, they possess a natural affinity for the human organism. They are extremely efficient in balancing the nervous system, restoring a sense of well-being and relaxation is necessary for optimum health and for the process of self-healing.

Rather than using a whole plant, pharmacologists identify, isolate, extract and synthesize individual components, thus capturing the active properties. However, in addition to active ingredients, plants contain minerals, vitamins, volatile oils, glycosides, alkaloids, bioflavonoids and other substances that are important in supporting a particular herbs’ medicinal properties. These elements also provide an important natural safeguard. Isolated or synthesized active compounds can become toxic in relatively small doses; it usually takes a much greater amount of a whole herb, with all of its components to reach a toxic level.

What is a mental disorder?

According to the diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, a mental disorder is any clinically significant behavioural or psychological syndrome characterised by the presence of distressing symptoms, impairments of functioning, a significantly increased risk of suffering death, pain, disability or loss of freedom.

Mental disorders are assumed to be the manifestation of behavioural or psychological dysfunction in the individual.

Types of mental disorders.

There are many different conditions that are recognized as mental illnesses. The more common types include;

Anxiety disorders: Responding to certain objects or situations with fear and dread, as well as with physical signs of anxiety and nervousness. They include panic disorder, social anxiety disorder and specific phobias

Mood disorders: Involve persistent feelings of sadness or periods of feeling too happy or fluctuation from extreme happiness to extreme sadness. Examples are mania and bipolar disorder.

Psychotic disorders: Involve distorted awareness and thinking. Symptoms include hallucinations and delusions e.g. schizophrenia.

Eating disorders: Involve extreme emotions, attitudes and behaviours involving weight and food e.g. anorexia nervosa, bulimia nervosa.

Impulse control and addiction disorders: Involve the inability to resist urges or impulses to perform acts that could be harmful to themselves and others e.g. pyromania (starting fires), kleptomania (stealing).

Personality disorders: Involve extreme and inflexible personality traits that are distressing to the person and/or problems in work, school or social relationships.

Some other very common illnesses include epilepsy , coma, dizziness, migraines, neurosis, amnesia, neuralgia.

Causes of mental illness

Although the exact cause of most mental illnesses is not known, it is becoming clear through research that many of these conditions are caused by a combination of biological, psychological and environmental factors;

i) Biological factors: Some mental illnesses have been linked to an abnormal balance of special chemicals in the brain called neurotransmitters. Neurotransmitters help nerve cells in the brain communicate with each other. If these chemicals are out of balance or are not working properly, messages may not make it through the brain correctly, leading to symptoms of mental illness. In addition, defects in or injury to certain areas of the brain have also been linked to some mental conditions. Other biological factors that may be involved in the development of mental illness include;

• Genetics: Susceptibility can be passed on in families through genes.
• Infections: Certain infections have been linked to brain damage
• Brain defects or injury: Defects in or injury to certain areas of the brain have been linked to some mental illness.
• Prenatal damage: Disruption of early fetal brain development or trauma that occurs at time of birth.
• Poor nutrition and exposure to toxins such as lead.

ii) Psychological factors:

• Severe psychological trauma suffered as a child, such as emotional, physical or sexual abuse.
• An important early loss, such as the loss of a parent
• Neglect
• Poor ability to relate to others.

iii) Environmental factors

• Death or divorce
• Living in poverty
• Feelings of inadequacy, low self-esteem, anxiety, anger or loneliness
• Changing jobs or schools
• Social or cultural expectations

Sometimes, mental problems may come as a result of excessive smoking of things like marijuana, tobacco, Indian hemp and many others.

Symptoms of mental disorders

Symptoms vary depending on the type and severity of the condition. They may also vary depending on the age group. Some general symptoms include:

In adults:

• Confused thinking
• Long-lasting sadness or irritability
• Excessive fear, worry or anxiety.
• Dramatic changes in eating or sleeping habits.
• Strong feelings of anger
• Delusions and hallucinations (seeing or hearing things that are not really there)
• Increase inability to cope with daily problems and activities
• Many unexplained physical problems
• Thoughts of suicide
• Denial of obvious problems

In older children and pre-teens

• Changes in sleeping and eating disorders
• Excessive complaints of physical problems.
• Intense fear of gaining weight
• Drug abuse and/or alcohol
• Frequent outbursts of anger
• Defying authority, skipping school, stealing or damaging property.

In younger children

• Changes in school performance
• Excessive worry or anxiety
• Persistent nightmares
• Persistent disobedience
• Hyperactivity

Classification of some medicinal plants used to treat mental disorders

Other herbs used in treatment of mental disorders include;

Platago asiatica, Scruphularia ningpoensis, Ilex pubescens which are traditional Chinese medicines prescribed for treating depression like ailments

Passiflora incarnata, Evolvulus alsinide, Scutellaria lateriflora are studied for their activity against irritation of the brain, nervousness, restlessness, sleeplessness.

Humulus lupulus, Convolvulus pluricaulis are considered for their activity against mild to moderate anxiety.

Celastrusa paniculatus, Acorus calamus, Piper longum are claimed as brain tonics.

Essential oils can be used in aromatherapy room diffuser to reduce depression and anxiety. The oils like that of Citrus bergamia (Bergamot), Juniperus virginiana (cedar wood), Anthemis nobilis (chamomile), Lavendula officinalis (lavender), Citrus lemon (lemon), Rosa centifolia (Rose), Santalum album (sandal wood) are mainly used in treatment of mild to severe depression, anxiety and stress. These oils are mainly used in the form of inhalation, bath, massage or steam treatments. However, their use is limited to external application. Some of them like Bergamot oil may cause phototoxicity, while others like lavender oil may result in skin irritation and rashes. Some like cedar wood oil and chamomile oil are restricted during pregnancy.

Even the layman can do much to reduce stress and sooth frayed nerves. Drinking chamomile , lemon balm or linden tea is preferable to coffee for anyone having sleeping difficulties or anyone who wishes to have a greater sense of inner calmness. Twenty minutes out-of-breath exercise (walking, swimming or cycling) will go a long way as a natural antidote to the tension that results from a stressful day at the office, and it will have the unexpected bonus of improving circulation, increasing metabolic rate and enhancing heart and liver function which are all associated with the nervous system.

The B-vitamins as found in whole-wheat bread, wheat germ, brewer’s yeast and liver (organically produced) provide ideal nourishment for the nervous system and can be wisely substituted for the stimulant foods such as white flour, sugar, junk foods and their harmful chemical additives.

Methods of preparation of medicinal plant extracts

Medicinal plants can be prepared in many different ways depending on the part of the plant being used, the illness being treated and the major constituents of the plant. Some methods used in preparing medicinal plants for use include;

1) Tinctures: They contain alcohol. In a tincture, alcohol is employed to extract and concentrate the active properties of the herb. Alcohol is also a very effective natural preservative. Because a tincture is easily assimilated in the body, it is a very effective way to administer herbal compounds. The full taste of the herb comes through very strongly in a tincture. Children and adults too may find the taste of some herbs unpleasant. Goldenseal for example is bitter-tasting

In order lesson, the amount of alcohol in a tincture, mix the appropriate dose with one -quarter cup of very hot water. After about five minutes, most of the taste of the alcohol will have evaporated.

2) Extracts: Extracts can be made with alcohol, like tinctures, or the essence of the herb can be leached out with water. Extracts offer essentially the same advantages and disadvantages that tinctures do. They are the most concentrated form of herbal treatment and therefore the most cost-effective. They are easy to administer, but have a strong herbal taste.

3) Capsules and tablets: They contain a ground or powdered form of raw herbs. In general, there are little differences between the two in terms of clinical results. Because finely milled herbs degrade quickly, it is important that herbs be freshly ground and then promptly encapsulated or tableted, within twenty four hours of being powdered. With the exception of certain herbal concentrates in capsule from, both capsules and tablets tend to be much less strong and potent than tinctures and extracts.

4) Decoctions: This involves boiling the plant parts in water for about 15-20 minutes

5) Infusions: Infusions make use of dried or fresh herbs in boiled water.

6) Pills: The dried and powdered drug is mixed thoroughly with honey and cooked.

7) Syrups: Cane sugar is dissolved in boiling water and the decoction fluid is added .

Poultice or paste: The plant material is ground with little oil, water and honey.

9) Juices: The fresh plant material is pounded, filtered and then squeezed to extract the juice.

Toxic effects of medicinal plants

Over the past decade, there have been certain cases of adverse effects produced by these plants which are sometimes life threatening. These toxic effects may come as a result of contamination with excessive use of banned pesticides during treatment and collection of plant materials, microbial contamination, heavy metals, chemical toxins. Chemical toxins may come from unfavourable or wrong storage conditions or chemical treatment due to storage.

Toxic effects may also come as a result of unprofessional practice of the manufacturer. Since plants contain many active ingredients, if not used properly, they can provoke adverse reactions.

CHAPTER TWO

EXPERIMENTAL

CASE STUDY: Bombe Health Centre for Mental Problems and other Chronic

Illnesses.

This is a centre run by Dr. Zack Maghang who is responsible for the treatment of people suffering from mental problems and other chronic diseases. He keeps his mental patients in a house which is divided into different sections depending on the intensity of the problem. Those whose cases are chronic are usually chained since they are very aggressive and dangerous while those with milder cases are kept in different rooms.

Treatment

Generally, treatment here is the same for all the patients irrespective of the cause of the illness and the intensity. The only thing that varies is the duration of treatment. If a patient is brought to the centre as soon as the problem starts, he can be treated within a week.

When a patient is first brought to the centre, he is given some snuff-like medicine to inhale. The purpose of this is to clear the patients brain. After a period of about 2 hours, the patient is administered some droplets through the nose in order that all the liquid in the patients head goes out. This liquid leaves through both the mouth and the nostrils. This calms down the patient and he is then allowed to sleep. The following morning , as soon as the patient wakes up, his hair is shaved to let it cool. Some leaves are boiled in water and then used to bath the patient. The patient is rubbed with some medicinal oil which is made up of a mixture of palm oil and some medicinal plant. This process is carried out every morning. The essence of this is just to let the patient to be conscious of the fact that he must take a bath every morning.

The patient is then given malaria and typhoid drugs alongside the other drugs that are being administered. The malaria medicine is prepared using tree bark and it is boiled with some other leaves. The patient receives this medicine in the morning while he is given a valium-like medication in the evening to allow the patient to sleep. This treatment goes on daily till the patient recovers.

Sometimes, these patients have nightmares and are unable to sleep. In this case, some dried leaves are burnt to produce incense. This causes them to sleep very well. The medications given to the patients are usually given through the ears, the eyes, the nose or the mouth. This is the ensure that when the patient recovers, he regains all his senses. This is because when the brain is affected, the various senses could also be affected. When a patient starts complaining of body pains and aches it implies that the patient is recovering. While the patients are receiving treatment, they are being taken care of by their relatives who provide food and clothing . sometimes, those who have recovered and are able to reason help in taking care of the others. When not treated at the early stage, like any other illness, it becomes chronic and more difficult to treat.

CHAPTER THREE

RESULTS

Analysis show that the majority of mad people are women. Women are the weaker sex and are generally less resistant to pain than men. When a woman undergoes a lot of stress or pain, the probability of having mental problems is greater than in men who are more resistant. An example is during child birth.

Results have shown that these medicinal plants are very effective in the treatment of mental problems because they are less toxic and have not produced any cases of death so far. All the patients receiving this treatment have been able to regain consciousness. Also, it is worth mentioning that when the patients are recovering, they are able to tell what led to the madness and sometimes they are able to tell at what time and place, though most of them feel very ashamed after recovery.

In cases where the problem was as a result of excessive smoking, most of the patients after recovery still desire going back to continue with the smoking.

Conclusion

Some of the most common causes of mental disorders are excessive smoking and drug abuse and the teenage age group are more exposed to these problems since most of these activities are carried out by teenagers.

As soon as it is discovered that an individual is showing any of the symptoms mentioned, he should immediately be taken for check up. This reduces the risk of the person’s situation becoming chronic and more difficult to treat.

Recommendations

There is need for a rigorous study of various traditionally but not scientifically proven herbs at the pre-clinical and clinical levels.

The environmental related factors can be controlled by implementing standard operating procedures which will lead to good agricultural practice, good laboratory practice, good supply practice and good manufacturing practice for producing these medicinal products from their natural sources.

Since mental illnesses are diverse and individual patients are biochemically unique, a larger number of drugs will increase the probability of finding a beneficial medication

References

http://www.skepticsfiles.org/weird/nerveshr.htm

http://www.webmd.com/anxiety-panic/mental -health-causes-mental-illness

The illustrated Encyclopedia of Natural Remedies, Norman Shealey

A consumer’s guide to avoiding Drug Induced Death or Illness, Sidney M. Wolfe

Presented by Mbakwa Terence,

University of Buea

INTRODUCTION

1.1 Origin of Hypertension

The vascular system in animals ends up in arterioles and veins which supply and take blood to and from the individual tissues respectively. The normal flow of blood (pressure) in these vessels might be altered, being reduced (hypotension) or increased (to cause hypertension). Thus, hypertension is a disease of the vascular-system, particularly of the arterioles and veins. Hypertension could result from an increase in blood volume or an increase in cardiac output, and also from the resistance to blood flow caused by vaso constriction of veins and arterioles.

Hypertension or elevated blood pressure can result from a number of variable causes, which could be known or unknown. Depending on whether causes are known or unknown, hypertension can be divided into two:

1. Essential or primary hypertension which is hypertension originating from unknown causes, and accounts for 90 – 95% of all hypertensive cases. It occurs mostly in adults, at age of above 40 years.
2. Secondary hypertension which accounts for 5 – 10% of all hypertensive cases. By definition, it is hypertension that can be attributed to an identifiable cause; for example, renovascular disease which elevates blood pressure by activating the rennin-angiotensin – aldosterone system. It can also be caused by a variety of endocrine diseases (e.g. pheochromocytoma) and excessive secretion of adrenaline.

In essential hypertension, it does not follow that the lowering of blood pressure with drugs is thus accomplished by reversing the disease process that caused it. But, if blood pressure is lowered by any mechanism, great benefit result.

1.2 Problem Set

Hypertension in patients is of different varying degrees. By this, both primary and secondary hypertension can be classified by the degree of increased cardiovascular risk and the extent to which blood pressure is elevated.

In most patients, treatment of hypertension is a lifetime project to reduce cardiovascular risk. In some patients with marked elevated blood pressure, it is necessary to decrease blood pressure in hours or days. These uncommon situations are referred to as hypertensive emergencies or urgencies respectively. Blood pressure normally increases progressively over months or years. As such, an increase risk of cardiovascular disease develops gradually over the said period. Chronic hypertension then results from the resultant loss of vascular elasticity and compliance. Therapy in this condition requires a longer term control of blood pressure.

Hypertensive emergencies with larger increase in blood pressure pose an immediate life-threat on target organs such as the heart, aorta, brain, kidney etc. The pharmacotherapeutic objective here is to control blood pressure within minutes or hours. This can be achieved by quick intravenous drug administration, but carefully end in stages.

The degree of hypertension is based on the level of blood pressure.

Table as presented by the Joint National Committee 1993.

OBJECTIVE

The aim for the treatment of hypertension is to reduce the cardiac output and blood volume, and also to reduce the peripheral and/or vascular resistance.

The primary sign of hypertension is high-blood pressure. Thus, the treatment of this sign itself, (by reducing it) is a primary objective in the treatment. This can be achieved by drugs whose mechanism of action is to alter;

v blood volume,

v cardiac output,

v peripheral resistance as well as vascular resistance

There is an expectation that a reduction of blood pressure will limit the development of subsequent organ pathology.

The tissue targets for antihypertensive drugs are:

v The sympathetic nerves, which release the vasoconstrictor, norepinephrine.

v The kidney, which regulates blood volume.

v The heart, which generate cardiac output

v The arterioles, which determine peripheral vascular resistance.

v The endothelial cells, which regulate circulating levels of the endogenous hypertensive and hypotensive agents, such as angiotensive II and nitric oxide, respectively.

v The central nervous system, (CNS) which senses the blood pressure and controls its set point by regulating some systems involved in blood pressure control.

2.0 CLASSES OF DRUGS FOR TREAMENT

2.1 Non – Drug Treatment

Though not dependent on drugs, non drug treatment is the first-choice therapy. Patients are advised to avoid activities that predispose to cardiovascular diseases and to do the following recommendations:

v To exercise,

v To reduce body weight, in case of overweight

v In some cases, to restrict dietary salt in take

v Stop smoking

v Restrict ethanol intake

v Treat lipoprotein disorders carefully

2.2 Drug Treatment Classes

Hypertension is a disease affecting targets that are controlled by the nervous system. As such, drugs that can act on the nervous system, whether sympathetic or parasympathetic are useful, in addition to others which may not affect the nervous system. Thus, the available classes of drug treatment include:

v Diuretic/Thiazides

v Sympatholytics

v Direct – acting vasodilators

v Calcium antagonists

v Renin-angiotensin cascade inhibitors (also with the angiotensin II receptor antagonists, losartan).

Essential hypertension is a process of variable causes, course and severity, with the treatment intensity being correspondingly variable. In contrast with the treatment of other diseases, the variation in the intensity of treatment is not achieved by simply increasing the dose of the drug(s) used. Rather, it can be achieved by stepwise addition of drugs as required to return blood pressure to normal. Different patients have specific needs, thus the drug addition will depend on the patient.

2.3 DIURETICS.

Diuretics are useful antihypertensive but their benefits may not be related to diuresis. Diuretic (and/or thiazides) are often used to initiate treatment invariably. Three types of diuretics are used in treating hypertension:

v Thiazides

v Loop diuretics

v Potassium – sparing agents

Though are all diuretics, their effects vary, since their hypotensive effects are not due to diuresis.

2.3.1 Thiazides/Thiazide Diuretics

Thiazides are relatively effective antihypertensives but are only moderately effective diuretics. The thiazides do not lower blood pressure in normotensive humans (humans with normal blood pressure) but will reduce blood pressure in patients with essential hypertension, to about 10% or even more. It has been suggested recently that diuretics (especially thiazides) may produce their effects in hypertension by modulating the activity of potassium ion (K⁺) channels.

The ATP – regulated K⁺ channels in resistance – arterioles may be activated by thiazides. This molecular action leads to membrane hyperpolarization, which opposes smooth muscle Ca²⁺-entry and contraction and, at the system level, reduces peripheral vascular resistance.

Thiazide diuretics (e.g bendrofluazide and hydrochlorothiazide (HCT)), and thiazide – like drugs which are sulfonamide derivative such as chlorthalidone are actively transported by a probenecid – sensitive secretary mechanism into the proximal renal tubule. As diuretic, this group of agents acts on the luminal membrane of the cortical dilating segment of the distal convuluted tubule, to bring about a reduction in blood pressure. Thiazides may cause male sexual dysfunction and an increase in sodium ion (Na⁺) concentration in the distal convuluted tubule which impairs K⁺ absorption, (leading to an increase in K⁺ excretion), called kaliuresis and possibly hyperkalemia.

The potassium – sparing diuretics may be used to avoid hyperkalemia. This group of drugs act at the cortical collecting duct, to alter the exchange of Na⁺/K⁺ and H⁺ as controlled by endogenous aldosterone.

chlorothiazide

2.3.2 Thiazide diuretics in combination with other drugs

The administration of a thiazide on its own causes only a slight decrease (about 10%) in blood pressure. Their effect is boosted when they are administered with another hypertensive drug, possibly from amongst drugs discussed here below. With this combination, the thiazide acts to reduce the amount of the potent drug necessary.

3 SYMPATHOLYTICS

These are a heterogeneous group of antihypertensive drugs that have a variety of actions in the cardiovascular system. The activity of the sympathetic nervous system plays a pivotal rule in acute regulation of blood pressure. The sympatholytic drugs act by inhibiting one or more component of this activity. This system mechanism can be achieved in a variety of different ways:

v Action on the vasomotor center in the brain to reduce the sympathetic system tone, centrally.

v Peripheral action on adrenergic neurotransmission at pre- or postsynaptic sites or on receptors activated by circulating epinephrine and neurally released norepinephrine.

Most sympatholytic agents posses both direct and indirect tissue mechanism of action, since they may directly affect nervous tissue function. Other drugs such as β adrenoceptor antagonists act directly on norepinephrine and epinephrine receptors in the cardiovascular system.

v The selective sympatholytics are used recently. The noneselective are rarely used because of their adverse effects.

3.1 Beta (β) Adrenoceptor Antagonists

These are the second most widely used antihypertensives; The mechanism of action of these drugs as a class, in the treatment of essential hypertension is not known, for certainty. But with each, the molecular and tissue effects and benefits will depend upon specific properties of the drug.

v The molecular mechanism of action is generally regarded to be competitive antagonism of adrenoceptors, although β adrenoceptor antagonism may also contribute to the benefit achieved with some drugs.

v The cellular mechanism is not known in general but known for β₁ and β₂ antagonists.

v The tissue mechanism is likewise unclear. β adrenoceptor antagonists may act in the central nervous system (CNS) to reduce sympatholytic tone, in the heart to reduce heart rate and cardiac output and in the kidney to reduce rennin production. They commonly reduce peripheral resistance, but it is not clear how the effect occurs.

3.1.1 β₁ Adrenoceptor Antagonists e.g Atenolol and metoprolol

metoprolol

Historically, the β₁ adroneceptor antagonists have been described as ‘cardioselectives, although these agents will affect any tissue that expresses β₁ adrenoceptors. The β₁ adrenoceptor antagonists antagonize the effects of norepinephrine and ephinephrine on heart rate. They have a less effect on the airway which also posses or express β₁ adrenoceptors. Nonetheless, β₁ and β₂ selectivity is only relative. Thus, these drugs are not safe enough for patients with asthma, except under special circumstances (when no other antihypertensive is tolerated but some form of drug therapy is essential).

3.1.2 β₁ Adrenoceptor partial agonist: e.g. pindolol

Some partial agonists of β₁ adrenoceptors are used in the treatment of hypertension (e.g. pindolol). These drugs inhibit excess β₁ adrenoceptor activity during sympathetic hyperactivity, but achieve an overall β₁ agonist effect when sympathetic tone is low. Historically, these drugs have been described as β₁ blockers with intrinsic sympathomimetic activity. However, this description is not precise as the agents are quite specifically partial agonists. They reduce blood pressure to a similar degree as β₁ adrenoceptor antagonists, but evoke less reduction in resting heart rate.

3.2 ₁ Adrenoceptor antagonists

Prazosin was the first selective agent with the molecular mechanism of postsynaptic ₁ adrenoceptor antagonism. Prazosin and newer drug analogues such as terazosin and doxazosin act directly on the effector component of the sympathetic neuroeffector junction, namely ₁ adrenoceptors. They are expressed in abundance in arteriole resistance – vessels where they mediate a vasoconstrictor tone. The tissue mechanism of ₁ adrenoceptor antagonists is therefore the inhibition of this tone. Norepinephrine normally limits its own neural release by acting on presynaptic ₂ receptors (negative feedback).

prazosine

Drugs that block ₂ receptors therefore tend to increase norepinephrine release from the sympathetic nerve terminals. Unrestricted norepinephrine release in the heart causes excess stimulation of postsynaptic β₁ adrenoceptors and tarchyardia. Consequently, nonselective  (₁ and ₂) antagonists are not useful antihypertensives. Because prazosin has selectivity for ₁ receptors, the negative feedback mechanism remains in tact. This means that the drug’s therapeutic effectiveness is not compromised by tarchycardia.

3.3 ₂ Adrenoceptor agonists: E.g Clonidine;

Centrally acting ₂ adrenoceptor agonists such as clonidine and  – methyldopa mimic the autoinhibitory effects of norepinephrine on sympathetic activity without producing sympathomimetic effects. This is due to their relative selectivity for ₂-receptors. The mechanisms of action are as follows:

v The molecular mechanism of action is ₂ adrenoceptor agonism.

v The direct tissue mechanism of action is reduction in the activity of the vasomotor center in the brain, leading to a fall in sympathetic nervous activity. This leads to a secondary tissue mechanism of action; a reduction in peripheral resistance as a result of arteriolar relaxation.

Clonidine is a widely used ₂ agonist whereas -methyldopa is a pro-drug which is metabolized via a two-step enzymatic process in the CNS to -methylnorepinephrine which is an ₂ agonist. In the CNS, -methylnorepinephrine stimulates the vasopressor centers in the brainstem, which results in a reduction of sympathetic outflow. Renal blood flow is well maintained with -methyldopa. As such, it has been widely used in hypertensive patients with renal insufficiency or, cerebrovascular disease. -methyldopa is also recommended in hypertensive pregnant women because it has no adverse effect on fetus, despite crossing the blood-placenta barrier.

It should be noted that this class of drug is generally not preferred for the treatment of hypertension.

clonidine

3.4 Reserpine

Reserpine has adrenergic neuron blocking actions resulting in arteriolar vasodilation and a reduced cardiac output. Though being a reduced-hypotensive drug on its own, reserpine is extremely useful in combination with a thiazide diuretic or a postural hypotensive agent.

Reserpine is an alkaloid of the genus Rauwolfia and is usually purified from snakeroot, most often, from Rauwolfia (Serpentine rauwolfia).

reserpine

reserpine

3.4.1: Mechanism of action

Reserpine is transported into peripheral sympathetic nerve terminals by uptake (which is the same mechanism of norepinephrine reuptake into nerves) and its mechanism of action are as follows:

v Its molecular mechanism of action is inhibition of the norepinephrine pump (an-ATP- and Mg²⁺- dependent uptake molecule) located on the storage vesicles for norepinephrine in the neural cytoplasm

v Its cellular mechanism of action is a reduction of the norepinephrine (and other amines) content of neuronal storage vesicles, which can also be regarded as amine depletion from storage vesicles. These storage vesicles are often within sympathetic nerves, blood vessels and the hypothalamus in the brain. The depletion of the amines from the storage sites implies an initial rise in the circulation of these amines.

v Its direct tissue mechanism of action is a reduction of the nerve action potential – mediated release of norepinephrine from sympathetic nerve terminals.

v Its indirect tissue mechanism of action is arteriolar vasodilation and reduced cardiac output.

3.6 Guanethidine:

Guanethidine and related guanethidine compounds including guanadrel, bethanidine, and dibrasoquin are, like reserpine, transported into peripheral sympathetic nerve terminals by uptake. However, their molecular and cellular mechanisms of action differ from those of reserpine. Two molecular and cellular mechanisms act in parallel to reduce the activity of the sympathetic nervous system.

guanethidine

3.6.1 Mechanism of action

v One molecular mechanism is competition with norepinephrine for the intracellular norepinephrine pump. The drugs are actually taken up and stored in the adrenergic vesicles in preference to norepinephrine. They are said to act like false – transmitters since a stimulation of these nerves will result to their release, instead of norepinephrine. This is the associated molecular mechanism and the direct tissue mechanism of action is a reduction of nerve action potential – mediated release of norepinephrine from the sympathetic nerve terminals.

v The second molecular mechanism is binding to the inner surface of the neurolemma. The associated cellular mechanism is the reduction of fusion between storage vesicles and the neurolemma, known as the true “adrenergic neuron blocking” action. The associated tissue mechanism of action is a reduction of nerve action potential – mediated release of norepinephrine from sympathetic nerve terminals. The tissue mechanism is a reduction in cardiac output as a result of a reduction in heart rate.

There are two consequences that result from the common path way used by the uptake of Guanethidine as well as reserpine and the reentry of norepinephrine.

1. Sympathomimetics agent such as ephedrine, phenoxybenzamine, cocain, and antipsychotics that block the reentry of norepinephrine can prevent or reserve the action of Guanethidine and reserpine.
2. A transient initial sympathometic effect arises following the blockage of norepinephine by guanethidine. This effect is often apparent in humans after intravenous administration.

Both Guanethidine and reserpine analogs share two common adverse effects:

v Postural hypotension which is a sudden fall in blood pressure on suddenly standing up. It results from a loss of sympathetic mediated reflex. There is also venous pooling of blood in the lower limb, and a fall in cardiac output which may cause fainting.

v A generalized block of sympathetic neurotransmission. The existence of these adverse effects and newer safer drugs has led to the use of Guanethidine only in patients with severe hypertension, who are unresponsive to other drugs.

3.7 Calcium channel blockers (CCB).

The ca²⁺ antagonists are increasingly being used in the treatment of hypertension. These drugs fall into three main groups, based on their chemical structure, with two mentioned here.

3.7.1: The 1, 4 – dihydropyridines, nifedipine, nicardipine and amlodipine are the most vascular – selective group and most effective antihypertensive ca²⁺ channel blockers (or antagonists). Nifedipine however is a slow CCB that also inhibits and binds to intracellular calcium binding proteins.

3.7.2: The phenethylakylamine, verapamil, and the benzothiazepine, are less vascular selective and may also affect the arteroventricular (AV) node, causing AV block. They are therefore associated with cardiac conduction problems especially when given with B₁ adrenoceptor antagonists.

Elderly hypertensive patients respond well to CCB. However, people of African origin are less responsive. The CCB have a rapid onset of action and reduce blood pressure within half an hour after administration. They reduce muscle tension in arteries, expanding them and creating more room for flow. They also relax the heart muscles.

It should be noted that, despite their ability to control hypertension, there is growing awareness that ca²⁺ antagonists may actually increase mortality in patients with hypertension. The mechanism by which this occurs is not known.

4 DIRECT – ACTING VASODILATORS

Agents that dilate arterioles by a molecular mechanism that is not ₁ adrenoceptor antagonism or L-type ca²⁺ channel blockage are called direct acting vasodilators. These agents are increasingly being used in the treatment of hypertension. An example is Hydralazine.

4.1 Hydralazine

Hydralazine is the only direct-acting vasodilator in treating mild to moderate hypertension, usually as a second – or third – line drug. It is also still used as a parenteral treatment in hypertensive emergencies and in hypertensive pregnant women, because of a long safety record in this setting.

Mechanism of action

The molecular and cellular mechanisms of action are to increase cyclic Guanine monophosphate (cGMP) following activation of guanylyl cyclase, resulting in relaxation of smooth muscle in precapillary resistance-vessels. This thus leads to a reduction in blood pressure due to a reduction in peripheral resistance.

4.2 Minoxidil

Minoxidil is highly effective in reducing blood pressure, especially in severe hypertension and also when there is renal failure. This drug is more effective than hydralazine and produces dilation of resistance – vessels. It works at the molecular level by activating ATP- sensitive potassium (K⁺) channels leading to the hyperpolarisation of smooth muscle sarcolemma. The ca^{2+ _} influx via the L-type ca²⁺ channels is subsequently reduced. Like hydralazine, it should be given in combination with diuretics and adrenoceptor antagonists, to prevent reflex increase in cardiac output and fluid retention which may be profound in some patients. A common adverse effect of minodixil is facial hair growth, which limits the use of this drug in women but has resulted in its use to treat male pattern baldness.

5 The Angiotention converting Enzyme (ACE) Inhibitors / Antagonists.

The Angiotensins are peptides found in humans, with angiotensin I being an inactive decapeptide which is converted into the active octapeptide, Angiotensin II. This conversion is done by the Angiotensin converting enzyme (ACE).The effects of Angiotensin II are numerous, all of which contribute to elevating blood pressure. It constricts arterioles and stimulates aldosterone release from the adrenal cortex; in turn, aldosterone stimulates Na⁺ re-absorption in the kidney.

Thus, the use of ACE inhibitors to block the ACE activities will lead to a reduction in blood pressure. The use of Angiotensin II receptor antagonists will also result to a reduction in blood pressure.

5.1 Mechanism of action

The ACE inhibitors have the following mechanisms of action:

v The molecular mechanism of action is the inhibition of the ACE activity, by direct blockade.

v The resultant cellular Mechanism of action is a reduced Angiotensin II synthesis and reduced metabolism of some vasodilating kinins e.g Braddykinin.

ACE inhibitors are useful for all types and severity of hypertension, and are widely used. They reduce mortality and are classified into chemical classes depending on whether they contain phosphinyl, carboxyl or sulfhydryl moieties. An example of an ACE inhibitor that contains the sulfhydryl moity is captopril. It causes vasodilation and reduces Na⁺ retention.

Other ACE inhibitors which are commonly used include; lisinoprie which is the most commonly used ACE inhibitor in the USA, enalapril and benazepril. These drugs contain the carboxyl moiety. These have slower onset and longer duration of action compared to captopril. The inhibitor fosinopril has the phosphinyl moiety.

The tissue respond to ACE inhibitors include:

v A reduction in peripheral resistance with little change in heart rate or cardiac output.

v A reduction in Na⁺ retention, secondary to altered aldosterone levels.

6.0 OTHER ASPECTS

6.1 COMBINATION TREATMENT

Useful in the pharmacotherapy approach of controlling elevated blood pressure is the combination of two or more drugs.

It should be noted that the diuretics are often used invariably to treat or initiate treatment of hypertension. As such, they are suitable for combination with most drugs to enhance control/treatment. The adrenoceptor antagonists/-diuretic combination is the most common.

With the diuretics aside, other combinations can still hold; the β adrenoceptor antagonists and the Ca²⁺ antagonists (dihydropyridine Ca²⁺ antagonists only) are usually well tolerated, provided they are combined in right dosage.

Note should be taken in that the β₁ antagonists in combination with nondihydropyridine Ca²⁺ antagonists is dangerous. An example of such drug is verapamil. It has been noticed that this combination causes asystole, severe bradycardia and hypotension.

6.2 Drugs in Progress

Renin inhibitors are a new class of drugs that reduce angiotensin II levels. Several rennin inhibitors have been developed with high potency and long duration of action. However, the oral bioavailability of currently available agents is too slow to achieve effective plasma concentrations in humans.

6.3 Treatment for hypertensive emergencies

Hypertensive emergencies are the results of extensive and acute damage of hypertension on some target organs. This condition puts the patient’s life in great danger, and no particular level of blood pressure provides the diagnosis, but only dependent on the clinical presentation. An example of hypertensive emergency is pulmonary edema.

An example of a drug that can be used in the treatment of hypertensive emergencies is sodium nitroprusside which is a directly acting vasodilator, and is administered intravenously. It has a rapid onset of action and efficiency. This drug can cause an abrupt fall in blood pressure. Thus, it is important to monitor the blood pressure constantly.

7. CONCLUSION

Drug treatment of essential hypertension has gone a long way in relieving pain in patients with this illness. The level of relief will vary between individuals and with the class of drug used. If a class of a drug does not act well in a patient, then, the drug has to be switched to another drug. Care and precaution should be taken in switching as individual drugs have certain steps to follow before switching is done. The degree of hypertension varies from mild through moderate to hypertensive emergencies. There are classes of drugs that best fit with each condition. In cases where it might be necessary, combination treatment is recommended in order to achieve a greater effect of the drugs.

Reference

Curtis sutter, Walter, Hoffmann: Integrated pharmacology, 2^nd edition, 2004.

F.H meyers, Jawltz, Goldfien: Review of medical pharmacology, 6^th edition, 1978.

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