New Antibiotic That is 1000 times more powerful against bacterial resistance

New Antibiotic That is 1000 times more powerful against bacterial resistance

Scientists re-engineered an old version of antibiotic into a life saving drug that is more effective against all those bacteria which were resistant to previous one.because resistance of certain bacteria against antibioics is the major problem to the world health these days.
The World Health Organisation warns antibiotic resistance is one in all the most important threats to international health, food security and development, with major diseases becoming harder to treat as a result of the medication used on them are getting less effective.

The antibiotic, vancomycin, has been prescribed by physcians for 60 years and bacterium are only currently becoming resistant to it.The New Antibiotic That is 1000 times more powerful against bacterial resistance is the newer version of vancomycin .
Researchers at The Scripps research Institute (TSRI) in America have made some changes in Vancomycin and build it 1000 time more powerful than the prevailing one .This antibiotic attack the microorganism from three different sites making it a lot of harder for them to develop resistance.
According to Researchers this version of antibiotic will be ready within the next 5 years.
The researchers said physcians could use the modified type of vancomycin without concern of resistance emerging.

According to some Reports approximately 50,000 people die per annum in USA and Europe because of the development of resistance against antibiotics.

Previous studies by the Researchers team showed it absolutely was possible to add two modifications to vancomycin, a drug they labeled “magical” as a result of its strength against infection, to make it even more potent and reduce the number of the drugs required to have a similar impact.This means that scientists will build a third modification which interferes with a bacterium’s cell wall in a very new way,with promising results. Combined with the previous modifications, this alteration offers vancomycin a 1000 fold increase in activity.

Quinolones and Fluoroquinolones

Quinolones & Fluoroquinolones

 

Introduction:

Quinolones and Fluoroquinolones are a group of synthetic broad spectrum antibiotics.These antibiotics were also isolated from natural resources. One of the most important member of quinolone group of antibiotic was Nalidix Acid.The Problem with this compound was that it was narrow spectrum and it has moderate gram negative activity but it has no gram positive activity.Apart from this issue the nalidix acid was poorly distributed in the body and that is why quinolones are not effective for systemic bacterial infections.so with the passage of time scientist added flourine with mother compound i.e Nalidix acid to improve their activity  so “a group of broad spectrum antibiotics which are flourinated analogues of nalidix acid are called fluoroquinolones ”
These antibiotics are the most famous drugs these days because of their good absorption and spectrum of activity against all type of bacteria and these agents can be effectively used in systemic infections.

Why they are so important ?

A)Very Good Oral Absorption.
B)Very good distribution means deep peneteration in the tissues very effiently.because of their deep penetretion they can kill intracellular organisms.e.g chlamydia,TB,Legionella,brucella.
C)Newer agents are very broad spectrum.
D)They have high potency.
E)They are very well tolerated (Very safe drugs compare to other antibiotic drugs)

What is the mechanism of action of quinolones on bacteria?
OR
How does quinolone work?
OR

Mechanism of action of Quinolones and Fluoroquinolones :

  • These drugs are bactericidal But the question is how they kill the bacteria ?
    Quinolones And Fluoroquinolones are acting on enzymes called topoisomerases or DNA Gyrase.They inhibit bacterial replication by interfering with their DNA replication pathway. DNA is the core genetic material of the cells, and is responsible for correct functioning of the cell. During protein synthesis and DNA replication, the double-stranded DNA must unwind into one stranded structure, that allows for complementary base pairing to occur and synthesis of messenger RNA to procede. Normally This moving of DNA within the bacterium is completed by enzymes called DNA topoisomerase type 2 or DNA gyrase There are two functional Domains Of Topoisomerase 2 enzyme i.e Nuclease domain And Ligase domain.Basically this DNA gyrase (Nuclease Domain) cut the one side of two stranded DNA  and then (Ligase domain ) reseal it after unwinding.This Process continue and the bacteria keep growing but quinolones and fluoroquinolones inhibit or didn’t allow the enzyme Ligase sub doamin to refix or reseal the broken or cut edge of DNA and that is why the bacteria is unable to replicate or even synthesize proteins.First & Second Generation fluoroquinolones Work On this Enzyme .
  • There is another enzyme which is called topoisomerase type 4 which is little different from the type 2 enzyme they also have two domains but the nulcease domain has two sub domain which is responsible for cutting of untangled DNA into fragments the mechanism of fluoroquinolones is same like Topoisomerase 2 they inhibit the function of Ligase and make it dysfunctional.Nuclease domain keep on cutting the DNA into fragments but the ligase is not able to reseal it and the DNA Convert into small fragments and bacteria die.Third and Fourth generation Work Best on both type 2 and type 4 Topoisomerases.And that is the reason Third and Fourth Generation drugs are more broad spectrum in activity .
  • Initially the quinolone and fluoroquinoles first and second generation drugs were best work on gram negative bacteria.but the newer group work on both gram negative and gram positive .

 

  • Mnemonics For Mechanism:
  • Quinolones & Fluoroquinolones: Topple the Queen“: Quinolone interferes withTopoisomerase II.

Classification of quinolones and fluoroquinolones

The first generation i.e Nalidix acid is only quinolone other 3 classes are flouroquinolones.All Other compounds are the derivaties of Nalidix acid.Following are some classes of quinolones and fluoroquinolones ;

  • A)First Generation:
  • Nalidix acid
    B)Second Generation :
  • Ciprofloxacin
  • Norfloxacin
  • Ofloxacin
  • Lomefloxacin
  • Enoxacin
    Norfloxacin don’t absorb very well and they are not used most commonly While ciprofloxacin is the most commonly used drug in this class.
    C)Third Generation :
  • Levofloxacin
  • Gatifloxacin
  • Sparfloxacin
    (D)Fourth Generation :
  • Moxifloxacin
  • Trovafloxacin

Spectrum of activity 

1)First Generation Nalidix acid is moderatly effective (Not very effective) against gram negative bacteria.This drug is not used these day because of poor distribution in the body so it is use in rare uncomplicated urinary tract infections.because this drug is eliminated from the body through renal system and it concentrate into urinary system.

2)Second Generation
They become more effient against gram negative as compare to Nalidix acid.And Also have some less gram positive coverage but keep in mind it doesn’t work on streptococcus pneumoniae .
Ciprofloxacin is also effective against atypical organism like chalymdia ,mycoplasma both of these organism cause respiratory tract infections.
Means second generation has expanded its spectrum from moderate to more effective against gram negative bacteria some added benefits to gram positive bacteria and to atypical organisms.

Ciprofloxacin show more activity against pseudomonas aeruginosa than other fluoroquinolones.

Ciprofloxacin and ofloxacin are also good against Mycobacterium tuberculosis,mycobacterium Fortuitum and Mycobacterium Kansasii.but if use alone these are effective against M.avium infection.So for M.avium treatment they have to be combined with other antituberculous drugs.

Norfloxacin shows least activity against both gram postive and gram negative organisms.

Uses / Indications Of Ciprofloxacin

Where not to use this antibiotic ?
Don’t use this antibiotic more often because of the development of resistant strain and due to over usage, ciprofloxacin is failing against bacteria because of development of resistance.
Every doctor know there is one resistance type of organism i.e MRSA (Methicillin resistance staphylococcus aureus )it is resitant to many other antibiotic and the latest news is even ciprofloxacin is failing on this .
Don’t use this antibiotic in Pneumococcus and Enterococcus infections .

Where to Use Ciprofloxacin ?
A)GIT :Its very effective in traveller diarhea caused by toxic ecoli.
B)Ciprofloxacin is more effective in cystic fibrosis due to infection by pseudomonas auregenosa.
Usually flouroquinolones is contraindicated in children under the age of 18 because in animal model it is approved that flouroqinolones can damage the cartilages and they can produce arthropathy so it should not be used in pregnant women.

C)Ciprofloxacin and Ofloxacin are effective in treatment of typhoid fever .

D)Ciprofloxacin can be used to eradicate the nasopharyngeal carrier -state with meningococci.

E)Ciprofloxacin is the drug of choice in the treatment and prevention of anthranx.

3)Third Generation: Levofloxacin
Good against gram negative but has more activity against gram positive including streptococcus pnemoniea means levofloxacin can be used in pnemonia and that is why this is also called respiratory quinolones .
Levofloxacin is also effective against chlamydia ,mycoplasma and atypical pnemonia.

Levofloxacin and sparfloxacin show improved activity against streptococci and also effective against penicillin resistant pneumococci.

Levofloxacin
DON’T Use this antibiotic
if you are allergic to this drug or other drugs of this class like ciprofloxacin,norfloxacin,moxifloxacin.

Avoid taking antacids, vitamin or mineral supplements, sucralfate  or didanosine powder or chewable tablets within 2 hours before or after you take levofloxacin.

Before taking levofloxacin, tell your doctor if you have muscle weakness ,kidney or liver disease,or trouble breathing,seizures,joint problems, diabetes, myasthenia gravis, a history of head injury of brain tumor, a condition called pseudotumor cerebri, a personal or family history of Long QT syndrome,low levels of potassium in your blood,or if you have ever had an allergic reaction to an antibiotic.

Levofloxacin may cause swelling or tearing of a tendon, especially in the Achilles’ tendon of the heel. These effects may be more likely to occur if you are over 60, or if you have had a kidney,heart, or lung transplant.
if you take steroid medication, Stop taking levofloxacin and call your doctor at once if you have sudden pain, swelling, tenderness, stiffness.

Uses of levofloxacin
Levofloxacin is used to treat bacterial infections that cause bronchitis or pneumonia,means that action of this drug is more extended against pneumococci and also used to treat people who have been exposed to anthrax or plague.
Levofloxacin is also used to treat bacterial infections of the sinuses,skin,kidneys, bladder, or prostate.

4)Fourth Generation.Moxifloxacin
Levofloxacin and moxifloxacin both are called respiratory quinolones .
Its spectrum of activity further broaden against gram positive cocci and gram positive bacilli .
Moxifloxacin can kill the anaerobic organisms and that is why this can be used in mixed infections .

Moxifloxacin ,Gatifloxacin,Sparfloxacin and Gemifloxacin are effective against gram positive organism especially against pneumococci and to some extent staphylococci.

Moxifloxacin Uses
Moxifloxacin is used to treat a variety of bacterial infections. It works by stopping the growth of bacteria.

Moxifloxacin is used to treat bacterial infections, including:
community acquired pneumonia,throat, sinus, and lung infections stomach infections skin infections

Don’t Touch It : Drug That Can Kill You If You Touch It

Drug That Can Kill You If You Touch It
Photo Credit: RT.com

Drug That Can Kill You If You Touch It :US police have issued an imperative public alert when a series of deaths from a Drug That Can Kill You If You Touch It .

The opioid referred to as furanyl fentanyl – a powerful version of the artificial painkiller analgesic 50 times more stronger than heroin– will cause a fatal overdose simply by being absorbed through the skin. It’s reportedly caused nineteen deaths within the state of Georgia over the last year.

The warning comes when 10kgs of pills and powder were taken over during a raid on a pill industrial plant in January, Georgia Bureau of Investigation (GBI) employees became alarmed once they discovered that a box containing pills marked ‘Oxycodone’, a non-hazardous opioid, was in fact furanyl fentanyl.

The (GBI) has reacted to the quantity of overdoses and incidents associated with the drug, as well as others, by provision a public safety alert Thursday.

The drug was placed on the Schedule I list of controlled substances last year after being related to 128 deaths across 5 states in 2015 and 2016. Schedule I is reserved for medication with the very best levels of addictiveness.
“U-47700 and furanyl fentanyl are each Schedule I medication and employed in a similar manner as heroin. Schedule I medication have a high potential for abuse and no presently accepted medical treatment use within the U.S. The medication are distributed in either powder or Tablet form,” GBI said in a very statement.

“Because furanyl Fentanyl and U-47700 are fatal at terribly low doses, law enforcement and therefore the public should use caution once handling these medication. they’ll be inhaled or absorbed through the skin and are very deadly within the smallest quantities.”

Gwinnett County Deputy Shannon Volkadov said: “When I acknowledged what I truly had, [I was] undoubtedly slightly frightened as a result of the quantity that was submitted. something could have happened, however fortunately with the protecting gear and therefore the staff that I had, every thing went Ok.”

According to a GBI Crime research lab chemist Dineen Kilcrease“Oxycodone to the touch it’s still going to be terribly safe. To the touch Furanyl analgesic might fully be fatal, simply through the skin.”

Fentanyl itself has been on the increase within the US in recent years, surpassing heroin because the most ordinarily detected drug in fatal opioid overdoses in Long Island and Connecticut. Last year, the drug was responsible for 188 fatal overdoses in Connecticut, according to figures from the state’s chief doctor.

50 Pharmacology Facts That Every Student Should Know

Pharmacology Facts

Pharmacology is a very vast Subject Thats why  Its very difficult to summarise every Pharmacology Facts in one article,this list goes some way toward that goal.We Have Made a list of Very important Pharmacology Facts These facts are listed on the basis of mechanisms of action,Drugs Interaction,Uses,Side Effects and Other clinical factors.Hope These Pharmacology Facts will Help Every Student In Medical exams.

Pharmacology Facts

(1)Aspirin Increase the risk of bleeding in olders,those who drink alcohol and those who take NSAIDs and other blood thinning agents.

(2)First Generation Antihistamine Such as chlorphenramine,Diphenhydramine,Dimenhydrinate-cause more sedation than their second generation equivalents such as acrivastine,cetrizine,loratidine and fexofenadine .These second generation has less penetration through the blood brain barrier.These medicine are used in the treatment of hay fever and Allergy.

(3)ACE Inhibitors are known to cause Continous Dry cough-Because of the accumulation of Kinins in the lungs.Patient are sometimes then switched to ARBs (Anhiotensin receptor blockers)-Though Cough May persist.

(4)Amoxicillin is typically the first choice drug in the treatment of otitis media (Inflammation of the middle ear).

(5)Clavulanic Acid Is A beta -Lactamse inhibitor,Meaning it inhibit the enzyme i.e Beta lactamases this enzyme is responsible for the breakdown of antibiotics that contain beta lactam ring.

(6)Paracetamol Overdose causes depletion of glutathione,the compound responsible for ejecting toxic NAPQI(N.acetyl-p-benzoquinone imine) .Acetylcysteine can be administered to fill/restore glutathione levels.

(7)Statins drugs are associated with an increased risk of muscle damage/pain (myopathies)and in some cases can lead to the potentially fatal rhabdomyolysis.

(8)Proton Pump inhibitors like esomeprazole,lansoprazole and pantoprazole inhibit the final step production of acid in the stomach by irreversibly blocking the H+/K+ Atipase of gastric parietal cells.

(9)H2 Receptor Blockers also inhibit or block the production of acid but not in the final phase.Ranitidine and Famotidine are longer acting than cimetidine,With fewer drug reactions and fewer adverse effects.

(10)Tetracycline causes tooth discolouration and phototoxicity.Tetracycline absorption is impaired by drugs or foods containing calcium,magnesium,iron or aluminium iron.

(11)Flouroquinolones like ciprofloxacin and moxifloxacin are associated with an increased risk of tendon damage.

(12)Beta Blockers should be avoided in asthamtic patients because of their potential to precipitate acute asthamtic attacks.

(13)Protamine sulfate is used as antidote to heparin toxicity.

(14)Methyldopa ,Labetalol and Nifedipine are the drugs of choice for hypertension in pregnant womens.

(15)Aminoglycosides like Gentamicin and tobramycin are associated with nephrotoxcity and ototoxicity.

(16)Salbutamol is a short acting beta 2 agonist and is a bronchodilator.its side effects include headache,tachycardia(fast heart rate) tremors,anxiety and dizziness.

(17)Opioids such as morphine,heroin,oxycodone,and fantanyl stimulate the parasympathetic nervous system,causing constricted pupil.This is a common identifier of opioid toxicity.

(18)Calcitonin is used to treat osteoporosis in womens who are atleast 5 years past menopause.

(19)Pramipexole is a dopamine agonist which is used to treat Parkinson disease and restless legs syndrome.

(20)Methotrexate is an antifolate,immunosuppressant drug used to treat various types of cancer and autoimmune diseases.side effects include fatigue,hair loss,nausea,ulcerative stomatitis,leukopenia and hepatoxicity and is teratogenic.This drug cause folate deficiency.

(21)Narrow therapeutic window drugs like Digoxin,lithium and warfarin need close monitoring because very small changes in dose can have very serious clinical consequences.

(22)There are two types of Insulin analogue i.e short and long acting analogues.Short acting analogues includes insulin glulisine,insulin aspart,and insulin lispro.
Long acting include insulin detemir and insulin glargine.insulin degludec is an ultra long acting insulin analogue.

(23)Naproxen is an NSAID Used to treat pain and inflammation and is associated with an intermediate risk of stomach ulceration,compared to low risk ibuprofen,and high risk indomethacin.

(24)isoniazid in combination with other drugs used for the treatment of TB (Tuberculosis).Side effect includes elevated liver enzymes ,reduced blood count,peripheral neuropathy and pyridoxine dificieny.

(25)Acetylsalicylic acid or ASA toxicity can cause ringing of the ear (Tinnitus)

(26)Don’t Use Narcotics in patient with head trauma.

(27)Don’t Give antacids with food because it delay gastric emptying.

(28)Avoid Warfarin with acetaminophen and acetylsalicylic acid because it increase bleeding and increased INR.

(29)Hydroxycholoroquine is an antimalarial drug also used to treat rheumatoid arthritis.its chronic use is associated with eye toxicity.That is why patient should be monitored for the presence of any ocular damage.

(30)Senna is used in the treatment of constipation.it is recommended to be taken at bedtime because it takes 6-12 hours to show effect.

(31)Furosemide is used to treat edema in CHF (Congestive cardiac failure),Kidney disease and liver diseases.Side effects includes ototoxicity ,increased urination,hyperglycemia,hyperuricemia,,hypokalemia and hypotension.

(32)Fusidic acid is used to treat skin infections of gram positive organism.

(33)Warfarin is an anticoagulant that works by inhibting the vitamin k dependent synthesis clotting factors 2,7,9 and 10.Risk increase in the first phase of therapy.

(34)Antitussive drugs like codeine,pholcodine,and dextromethorphan are used to suppress cough.

(35)Antifungal Drugs work by inhibiting the enzyme,lanosterol-14alpha-demethylase,this enzyme responsible for converting lanosterol into ergosterol.

(36)Domperidone is a Selective D2 receptor antagonist.its used as an antemetic and gastroprokinetic agent.

(37)Global Pharmaceutical Market is more than $300 Billion.

(38)Lipitor is the best selling drug of all time.

(39)Insulin is one of the most commonly used drugs that cause adverse effects.

(40)Antihypertensive drugs like ganglion blocker drugs are not used these days because of serious adverse effects.

(41)Atomoxetine is used to treat attention deficit hyperactivity disorder (ADHD)it inhibit norepinephrine and serotinine transporters.side effects include dry mouth,nausea,decreased appetite,trouble in sleep,drowsiness and dizziness.

(42)Ziprasidone should be taken with food to enhance bioavailibility.it is a typical antipsychotic drug.

(43)Metformin is the first line drugs in the treatment of type 2 diabetes and long term use and high doses could lead to vitamin B12 malabsorption and its subsequent dificiency.

(44)Antidote is a greek word used to “give against”are those agents used to oppose the effects of poison with out causing damage to the normal cells.

(45)Maximum dose of paracetamol is 4 grams per day other wise will cause hepatotixcity.

(46)MRSA(Methicillin resistant staphylococus aureus) Super bug is a bacterium responsible for various difficult to treat infection in humans .

(47)Benzodiazepine are classified in term of their elimination half life .short acting benzodiazepine includes trizolam,alprazolam,midazolam and oxazepam while intermediate acting drugs include lorazepam,clonazepam,temazepam, and long acting benzodiazepines include diazepam,flurazepam,cholrdiazepoxide.

(48)Drug of choice in hypertensive emergencies is sodium nitroprusside.

(49)5-HT3 antgonist drugs like,ondansetron,palonosetron and granisetron are used to treat nausea and vomiting,especially effective in treating nausea and vomiting caused by chemotherapy.

(50)Drugs of choice in Congestive cardiac failure are ACE inhibtors like enalapril,lisinopril .

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