Penicillin vs Amoxicillin

What is the difference between penicillin and amoxicillin? Well, both of them are antibiotics but do they work the same? Which one is better for strep throat, tooth abscess, tonsillitis and other conditions? Read on to find out.

What would your doctor do if you got a throat infection? Obviously, he would prescribe you an antibiotic for a week or so. Antibiotics are the mainstay of treatment for treating all sort of bacterial infections. The purpose of antibiotics is to either kill bacterial cells or halt their growth.  Antibiotics are divided into number of groups that differ from each other on the basis of their specificity, mechanism of action and efficacy. Among all groups of antibiotics, penicillins are the oldest ones. Penicillin was first derived in 19th century by Alexander Fleming from a fungus named Penicillium. Since its discovery, penicillin has been used for treating the wide variety of infections. As the medical science revolutionized over the years, the derivatives of penicillum were modified and the newer forms of penicillin came into being that have broader antibiotic spectrum as compared to the natural penicillin.

The purpose of this article is to compare the natural penicillin (penicillin G and V) with wide spectrum penicillin (amoxicillin) in terms of their mechanism of action, medical uses, antibiotic coverage, efficacy, pharmacokinetics and adverse reactions.

Penicillin

Being the oldest one, penicillin is the most widely used drug for treating infections. Other name used for penicillin is beta lactam drugs because they contain a beta lactam ring in their structure that is responsible for the antimicrobial activity of penicillin. Penicillin is of two type; one is benzylpenicillin or penicillin G that is given through intravenous route and the other one is phenoxymethypenicillin or penicillin V that can give through oral route. Other modified forms of penicillin are procaine penicillin and benzathine penicillin (intramuscular injection) that have a longer duration of action as compared to penicillin G and V.   The IUPAC name for penicillin G is (2S,5R,6R)-3,3-dimethyl-7-oxo-6-(2-phenylacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid and the IUPAC name for penicillin V is 3,3-Dimethyl-7-oxo-6-(2-phenoxyacetamido)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid (1). Penicillin is effective against the following bacteria:

• Gram positive cocci including streptococcus pyogenes, streptococcus pneumoniae, streptococcus viridians group and non beta lactamase producing staphylococci.
• Gram negative cocci including meningococci and neisseria gonorrhoeae
• Gram positive rods including bacillus anthracis, corynebacterium diphtheriae and listeria monocytogenes
• Spirochetes including treponema pallidum
• Non beta lactamase producing anaerobes like clostridium perfringens.

Penicillin G and penicillin V are quite similar to each other but penicillin V is less effective against gram negative bacteria as compared to penicillin G. However, penicillin V is more effective when given orally in comparison to penicillin G which is effective only when given intravenously. The brand names for penicillin are:

• Bacillin
• Pencillin-VK
• V-cillin-K
• Beepen VK
• Abocillin-V

Medical applications

Penicillin is not only used for curing the infection but it has also been proved to be effective in prophylaxis and prevention of various infections. Here are some infections that can be treated with penicillin:

• Tonsillitis
• Pharyngitis
• Skin infections
• Cellulitis
• Acute otitis media
• Sinusitis
• Bronchitis
• Pneumonia
• Diphtheria
• Lung abscesses
• Infective endocarditis
• Rheumatic heart disease
• Meningitis
• Septicemia
• Syphilis
• Anthrax
• Bone and joint infections
• Lyme disease
• Soft tissue infections
• Gas gangrene
• Leptospirosis

Dosage and intake methods

The only way to avail the benefit from penicillin is to take it in recommended dosage. The recommended dosage is different for penicillin G and V and varies with respect to age of the patient. Therefore, the recommended dose of penicillin is different for adults, children and neonates.  One needs to be very cautious before taking penicillin as the over dosage of penicillin can put you in a serious trouble. The recommended dosage of penicillin is given below (2):

Recommended dosage for penicillin G:

• For adults, the recommended dosage of penicillin G is 1 to 20 million units daily, divided into 4-6 doses. For serious infections, higher dose can b given by making adjustment in the recommended dosage.
• For children of 1month to 12 years of age, the amount of penicillin that should be given is 25,000 to 400,000 units/kg/day, in 4-6 divided doses.
• For neonates (1 week to 1 month of age), the recommended dosage of penicillin G is 75,000 to 150,000 units/kg/day, divided into 2-3 doses.
• For neonates of age less than 1 week, the recommended dose is 50,000 to 100,000 units/kg/day, in divided doses.

Recommended dosage for penicillin V:

Penicillin V is given orally and its dosage is different from penicillin V. The recommended dosage of penicillin V is as follows:

• For adults, the recommended dose of penicillin V is 0.25g to 0.5g every 6-8 hours.
• For children under the age of 12 years, the recommended dosage is 25-50mg/kg/d, divided in 4 doses.

Above mentioned recommended dosage should be kept in mind before taking penicillin. However, the slight variations can be made in the recommended dosage depending upon the type and severity of infection.

Precautions

Following precautions need to be considered while taking using penicillin:

• The first and foremost precaution is to use penicillin always in a recommended amount.
• Never take penicillin own your own for treating infections without consulting the doctor first.
• Tell your doctor first if you have any history of allergy to penicillin so he can prescribe you some other antibiotic in place of penicillin.
• You may feel symptomatic relief from infection within 2-3 days of penicillin intake but never try to discontinue the use of antibiotic before the recommended duration as it can increase the chances of recurrence of infection.
• Don’t forget to take the dose of penicillin daily. Skipping the dose may reduce the effectiveness of drug and make the infection worse.
• Penicillin should be given cautiously in patients with renal disorders, bleeding disorders, asthma and antibiotic related diarrhea.
• Careful monitoring of children and neonates should be done who are given antibiotics.
• In patient with renal impairment and reduced creatinine clearance, dose adjustment needs to be done before giving the drug because chances of side effects are quite high in such patients. Therefore, in patients of renal impairment, 20-50 percent of the recommended dosage is given depending upon the creatinine clearance of the patient.
• Penicillin can be given to pregnant ladies but they should be observed carefully for any side effects. However, in lactating mother, penicillin should be given with caution because it is secreted in breast milk, so the over dosage in mother can indirectly affect the baby too.

Mechanism of penicillin

Penicillin falls among those antibiotic that tend to inhibit the synthesis of bacterial cell wall (3). Before understanding the mechanism of action of penicillin, let’s have a review of structure of bacterial cell wall. Bacterial cell wall is composed of peptidoglycans and polysaccharides that are connected to each other in complex manner, responsible for maintaining the integrity of bacterial cell. Attached to these peptidoglycans are the proteins called penicillin binding proteins that are considered to be the target side of penicillin.

Penicillin binds to these penicillin binding proteins which in turn cause the deactivation of enzyme involved in the transpeptidation reaction or cross linking of peptidoglycans, a process considered to be of extreme importance in cell wall synthesis. Inhibition of this cross linking reaction leads to loss of cell wall integrity, making the cell wall weak. When cell wall gets weak, the water enters the cell through the outside environment and causes the lysis of cell. That was just one mechanism of penicillin action. Second mechanism through which the penicillin acts is the activation of those bacterial enzymes that tend to cause the autolysis of cells.

However, over the past few years those strains of bacteria have been emerging that show resistance to penicillin. The major mechanism through which bacteria show resistance to penicillin is the secretion of beta lactamase enzymes. Beta lactamase enzymes destroy the main beta lactam ring of penicillin that is crucial for its antimicrobial activity.  Due the production of beta lactamase, most of the staphylococci and almost all the gram negative rods are becoming resistant to penicillin. Besides the secretion of beta lactamase enzymes, a number of bacterial strains have modified their structure of penicillin binding proteins and have developed the efflux mechanisms that are thought to be responsible for providing resistance to bacteria.

Actions after intake; pharmacokinetics

When a drug enters the body, it undergoes through various changes that are known as pharmacokinetics. The four phases in the pharmacokinetics of penicillin are given below:

Absorption

Oral penicillin is absorbed mainly through the small intestine. However, the oral penicillin is highly labile to stomach acid. Stomach acid destroys the drug before it reaches its absorption site, thus reducing its effectiveness. Absorption of penicillin is also affected by food intake. When taken along with food, the effectiveness is reduced because the gastric emptying is delayed and the drug remains for longer time in the stomach which makes it vulnerable to stomach acid. Therefore, penicillin should be taken empty stomach or at least 30-60 minutes before taking meal or 2-3 hours after taking meal. Peak plasma concentration of penicillin V reaches within 30-60 minutes.

Penicillin G, in contrast to penicillin V, is poorly absorbed through intestine. Therefore it must be given intravenously or intramuscularly. When given intravenously or intramuscularly, the peak plasma concentration is obtained within 15-30 minutes.

Distribution

After absorption, penicillin is distributed throughout the body tissue. For this purpose it binds to plasma proteins. Plasma protein binding percentage of penicillin is 75-90 percent. Penicillin can cross placental barrier in pregnant females but it does not cause any harm to fetus. Penicillin does not penetrate brain or central nervous system until or unless the meninges are inflamed. Penicillin can also be secreted in breast milk of lactating mothers.

Metabolism

Penicillin does not undergo significant metabolism in the body. Most of the penicillin remains in unchanged form and is excreted as such.

Elimination

The main route of excretion of penicillin is through glomerular filtration and tubular system of kidneys. The plasma life of penicillin is about hour an hour to one hour. However, the procaine and benzathine form of penicillin are the slow release formulas with a slightly longer half life. Since penicillin is primarily excreted through kidneys, dose adjustment must be done in patients with renal impairment.

Overdosage

Over dosage or toxicity of penicillin occurs when it is taken in more than recommended amount. Over dosage of penicillin can lead to serious and life threatening complications. If you feel any of the symptoms of penicillin over dosage given below, immediately contact the nearby poison centre or hospital.

• Nausea
• Vomiting
• Diarrhea
• Skin rashes, itching and anaphylactic reactions
• Skin bruising or bleeding
• Seizures and fits
• Decreased urine output
• Fever, chill and body aches
• Blackouts and convulsions

Side effects

Side effects of penicillin are grouped into following categories:

Common or less serious side effects

Here are some common side effects of penicillin:

• Nausea
• Stomach pain or discomfort
• Feeling of being sick
• Skin rashes
• Headache
• Hairy tongue or thrush

Serious (and rare) side effects

Some serious side effects are:

• Skin hives or peeling
• Easy bruising and bleeding
• Decrease in urination
• Dermatitis
• Fever and chills
• Seizure, fits and convulsions
• Agitation and anxiety
• Anaphylactic shock

Drug interactions

• Probenecid and methotrexate are the drugs that decrease the tubular excretion of penicillin, leading to the higher concentration in the body and the increased chances of toxicity.
• Penicillin tends to reduce the effectiveness of oral contraceptives. Therefore another method of contraception should be opted while using penicillin.
• Herbal supplements should be avoided while using penicillin as they can affect its efficacy.

Amoxicillin

Amoxicillin is a semi synthetic drug that belongs to the aminopenicillin group of penicillin. In contrast to narrow spectrum penicillin G and V, amoxicillin has got a wide antibiotic spectrum and is effective against some gram negative rods too but, it is still susceptible to beta lactamase enzymes. However, its antibiotic activity is enhanced when taken along with beta lactamase inhibitor called clavulanic acid. The IUPAC name of amoxicillin is 2S,5R,6R)-6-{[(2R)-2-amino-2-(4-hydroxyphenyl)-acetyl]amino}-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-24-carboxylic acid (4).  The antibiotic coverage of amoxicillin is quite similar to penicillin but it is effective against some other bacteria as well including enterococcus bacterial species, Listeria monocytogenes, Escherichia coli, Haemophilus influenza, Salmonella, Shigella, Proteus mirabilis and Moraxella catarrhalis.

The brand names of amoxicillin are as follows:

• Amoxil
• Trimox
• Moxatag
• Moxilin

Medical applications

Amoxicillin is used for treating following infections:

• Sinusitis
• Acute otitis media
• Tonsillitis
• Bronchitis
• Pharyngitis
• Skin infections
• Urinary tract infections
• Gonorrhea
• Pneumonia
• Anthrax
• Bacterial endocarditis
• Salmonella infections
• Dental infections
• Amoxicillin is used along with clarithromycin for treating stomach ulcers (5).

Dosage and intake methods

Amoxicillin must be taken within recommended dosage limit to ensure drug safety. Any effort to take amoxicillin own your own, without knowing the recommended dose can bring you more harm than good. Amoxicillin when taken in excess can lead to various side effects.  Here is given the recommended dosage of amoxicillin:

• For adults (above the age of 12 years), the recommended dosage of amoxicillin is 250 mg to 500mg, three times a day.
• For children (under the age of 12 years), the recommended dosage of amoxicillin is 20-40mg/kg/day, divided in 4-6 doses.

Amoxicillin comes in the market in different formulations. Always measure the correct dose before using any formulation of amoxicillin. Here are some commonly used formulations of amoxicillin:

Amoxicillin tablets

Amoxicillin comes in the form of dry tablets, capsules and chewable tablets with varying strength of 250 mg or 500mg. Make sure to measure the correct dose before using this medicine and do consult the doctor once. Amoxicillin tablets should be taken with a large glass of water, twice or thrice a day. Amoxicillin tablets can be taken with food as well because food does not affect its absorption.

Amoxicillin liquid form

Amoxicillin is also available in liquid forms such as syrup and drop. Dosage of liquid medicine should be measured using the spoon provided with medicine. Do shake the liquid medicine thoroughly before using it.

Precautions

You need to keep in mind the following precautions while using amoxicillin:

• Don’t forget to read the label of medicine before using it.
• Make sure that the amount of amoxicillin you are using must not exceed the recommended dosage.
• Do not abrupt the use of amoxicillin suddenly. Complete the antibiotic course as recommended by doctor because abruption of the medication can make your symptoms worse.
• Amoxicillin is an anti bacterial drug. It should not be used for treating viral infections like common cold and flu.
• Do tell the doctor if you have a history of allergy to amoxicillin.
• Amoxicillin should be avoided in case of asthma, kidney diseases, mononucleosis and antibiotic related diarrhea.
• In patients with renal impairment, dose adjustment needs to be done to reduce the chance of drug toxicity.
• If given to pregnant and lactating women, careful observation should be done to lessen the risk of side effects.

Mechanism of amoxicillin

All bacteria need cell wall in order to survive the unfavorable environment of the body. Cell wall of bacteria stops the water from entering the cell and causing its lysis. Amoxicillin tends to halt the active multiplication of bacterial cells by inhibiting the protective cell wall synthesis. Like penicillin, amoxicillin inhibits the tranpeptidation  or cross linking reaction of peptidoglycans in the cell wall. However, in contrast to penicillin, the structural configuration of amoxicillin provides it with much more stability that tends to improve its antibiotic coverage. However, some bacteria like shigella and salmonella are becoming resistant to amoxicillin through the production of beta lactamase enzymes and alterations in penicillin binding proteins.

Actions after intake; pharmacokinetics

Here are given the four phases of pharmacokinetics of amoxicillin (6):

Absorption

Unlike penicillin, amoxicillin is stable to the action of stomach acid and is readily absorbed through the small intestine. Absorption of amoxicillin has nothing to do with food intake. That is why amoxicillin can be taken along with food as well. Once the dug is absorbed through intestine, the peak plasma concentration reaches within 1-2 hours.

Distribution

Amoxicillin is readily distributed throughout the body tissues and body fluids, except the CSF. It gains entry into CSF only when the meninges are inflamed. As compared to penicillin, the protein binding percentage of amoxicillin is just 20 percent.

Metabolism

The plasma half life of amoxicillin is approximately 60 minutes. Amoxicillin does not undergo extensive metabolism and the large amount of drug is excreted in urine in unchanged form.

Elimination

The main route of excretion of amoxicillin is through urine. Small amount of drug is also excreted in bile and feces. In patients with renal impairment there is delayed excretion of amoxicillin, so the chances of side effects are higher in these patients. Therefore, is such patients  the amount of drug to be given must be reduced to prevent the risk of drug toxicity.

Overdosage

Chances of toxicity get high when you take the drug without consulting the doctor or knowing the proper dosage. Immediately contact you health provider if you get any of the following symptoms of drug toxicity:

• Vomiting
• Chest tightness and difficult breathing
• Face swelling
• Skin hives and peeling
• Dark colored urine
• Reduced urine output
• Fatigue
• Pale skin
• Seizures, fits or convulsions

Side effects

The side effects of amoxicillin are as follows:

Common side effects

Some common side effects of amoxicillin are:

• Nausea, vomiting, diarrhea, stomach pain and discomfort.
• Headache
• Dizziness or confusion
• Vaginal itching or thrush
• Skin itching or rashes
• Insomnia and agitation
• Black hairy tongue

Rare or serious side effects

Below are specified the serious side effects of amoxicillin:

• Fever and flu like symptoms
• Swollen or bleeding gums
• Skin bruises, hives, bleeding or peeling
• Breathing difficulty
• Joint pain or ache
• Reduced urine output
• Tingling sensation in the body
• Seizures and convulsions
• Raised liver enzymes

Drug interactions

Amoxicillin shows following drug interactions:

• Probenecid reduces the urinary excretion of amoxicillin, retaining the higher concentration in the body that leads to increase risk of side effects.
• Allopurinol when taken along with amoxicillin, increases the tendency of skin rashes and itching.
• Other antibiotics like tetracyclines and sulphonamides also interfere with the action of Amoxicillin.ü  Amoxicillin was found to reduce the effect of oral contraceptive. Therefore, alternative method of contraception is advised for ladies taking penicillin.
• Herbal and vitamin supplements should not be used without doctor’s consultation as they affect the action of amoxicillin.

Conclusion

When it comes to penicillin vs amoxicillin comparison, amoxicillin is preferred as it is more effective than penicillin and has a wider antibacterial coverage. Both drugs have got their own medical uses but amoxicillin is better than penicillin in terms of efficacy, antibiotic coverage, absorption and plasma half life.