Opt 328 lecture note by Dr.(Mrs.

)Uwagboe

WHAT ARE ANTIBIOTICS?

Antibiotics are a group of medicines that are used to treat infections. Antibiotics are sometimes

called antibacterials or antimicrobials. Antibiotics can be taken by mouth as liquids, tablets, or

capsules, or they can be given by injection. Usually, people who need to have an antibiotic by

injection are in hospital because they have a severe infection. Antibiotics are also available as

creams, ointments, or lotions to apply to the skin to treat certain skin infections.

It is important to remember that antibiotics only work against infections that are caused by

bacteria and certain parasites. A parasite is a type of germ that needs to live on or in another

living being (host). Antibiotics do not work against infections that are caused by viruses (for

example, the common cold or flu), or fungi (for exampleu, thrush in the mouth or vagina),

or fungal infections of the skin

Occasionally, a viral infection or minor bacterial infection develops into a more serious

secondary bacterial infection. In this case, antibiotics would be needed.

There are various antibiotics available and they come in various different brand names.

Antibiotics are usually grouped together based on how they work. Each type of antibiotic only

works against certain types of bacteria or parasites. This is why different antibiotics are used to

treat different types of infection. The main types of antibiotics include:

 Penicillins - for example, phenoxymethylpenicillin, flucloxacillin and amoxicillin.

  Cephalosporins - for example, cefaclor, cefadroxil and cefalexin.

 Tetracyclines - for example, tetracycline, doxycycline and lymecycline.

 Aminoglycosides - for example, gentamicin and tobramycin.

 Macrolides - for example, erythromycin, azithromycin and clarithromycin.

Clindamycin.

 Sulfonamides and trimethoprim - for example, co-trimoxazole.

Metronidazole and tinidazole.

 Quinolones - for example, ciprofloxacin, levofloxacin and norfloxacin.

How do antibiotics work?

By interfering with the biosynthesis of the bacterial cell wall

Some inhibit protein synthesis

Change in cell membrane permeability

Inhibit DNA synthesis

Side effect of antibiotics

Antibiotics may have side effects. Some of the more common side effects may include:

 Soft stools or diarrhea

 Mild stomach upset

 Vomiting

 Severe watery diarrhea and abdominal cramps

 Allergic reaction (shortness of breath, hives, swelling of lips, face, or tongue, fainting)

 Rash

 Vaginal itching or discharge

 White patches on the tongue

A) THE PENICILLINS

Examples are phenoxymethylpenicillin, flucloxacillin ,amoxicillin, ampicillins.they are mostly

active against gram-positive organism. i.e Pneumococci Streptococci. Easily destroyed by

penicillinase.

When given orally, different Penicillin’s are absorbed to differing degrees depending on their

stability in acid and their absorption to food. penicillin can be given by intramuscular or

intravenous injection.
CLINICAL USE OF PENICILLIN

Penicillins are given by mouth or, in most severe infections, intravenously, and often in

combination with other antibiotics.

uses include

Bacterial meningitis (e.g.caused by Neisseria Meningitidis,streptococcus pneumonia)

Bone and joint infections (e.g staphylococcus aureus) flucloxacillins.

Pharyngitis (S.pyogenes.) phenoxymethylpenicillin

Pneumonia------------amoxicillins

Bronchitis--------------amoxicillins

Urinary tract infections------amoxicillins caused by E.coli

MECHANISM OF ACTIONS

Penicillin which is a B-lactam antibiotics interfere with the synthesis of the bacterial cell wall

peptidoglycan. After attachment to binding sits on bacteria they inhibit the transpeptidation

enzyme that cross links the peptide chains attached to the backbone of the peptidoglycan. The

final bactericidal event is the inactivation of an inhibitor of the autolytic enzymes in the cell wall:

this leads to lysis of the bacterium.

ADVERSE EFFECTS

penicillin are relatively free from direct toxic effect .the main unwanted effects are

hypersensitivity reactions caused by degradation products of penicillin, which combine with

the host protein and become antigenic. Skin rashes and fever are common also acute

anaphylactic shock which may in some cases be fatal but is fortunately very rare. Penicillin,

particularly the broad spectrum type given orally, alter the bacterial flora in the gut .this can be

associated with gastrointestinal disturbances and in some cases with suprainfection by

microorganism not sensitive to penicillin.

B) THE CEPHALOSPORINS

 Cephalosporins are a large group of antibiotic that belong to a class known as beta-

lactams.

These drugs are used to treat bacterial infections including:

 Ear infections

 pneumonia

 Skin infection

 Kidney infections

 Sexually transmitted infections such as gonorrhea

 Bone infections

 Strep throat and other throat infections

  Meningitis

Cephalosporins are bactericidal drugs, meaning they kill bacteria directly. They do this by

interfering with how bacteria build their cell walls.

Cephalosporins are grouped into five generations based on when the drugs were developed. In

general, each generation is effective against certain types of bacteria.

MECHANISM OF ACTION

Cephalosporins are bactericidal and have the same mode of action as other β-lactam antibiotics

(such as penicillins), but are less susceptible to β-lactamases. Cephalosporins disrupt the

synthesis of the peptidoglycan layer forming the bacterial cell wall. The peptidoglycan layer is

important for cell wall structural integrity.

ADVERSE REACTION

Common adverse drug reactions (ADRs) (≥ 1% of patients) associated with the cephalosporin

therapy include: diarrhea, nausea, rash, electrolyte disturbances, and pain and inflammation at

injection site. Infrequent ADRs (0.1–1% of patients) include vomiting, headache, dizziness, oral

and vaginal candidiasis, pseudomembranous colitis, superinfection, eosinophilia, nephrotoxicity,

neutropenia, thrombocytopenia, and fever.

Examples of cephalosporins

 Ancef and Kefazol (cefazolin)

 Ceclor and Cefaclor (cefaclor)

  Cefdinir

 Ceftin and Zinacef (cefuroxime)

 Duricef (cefadroxil)

 Keflex and Keftabs (cephalexin)

 Maxipime (cefepime)

 Rocephin (ceftriaxone)

 Suprax (cefixime)

 Teflaro (ceftaroline fosamil)

The AMINOGLYCANS

Aminoglycosides are a class of antibiotics used mainly in the treatment of aerobic gram-negative

bacilli infections, although they are also effective against other bacteria including Staphylococci

and Mycobacterium tuberculosis. They are often used in combination with other antibiotics.

Aminoglycosides are thought to work by inhibiting protein synthesis inside bacteria. Once inside

the bacterial cell, aminoglycosides bind to the 30s ribosomal sub-unit and cause a misreading of
the genetic code. This subsequently leads to the interruption of normal bacterial protein

synthesis. Kill rates of bacteria are increased when higher concentrations of aminoglycosides are

present; however, the margin between a safe and a toxic dose is narrow and monitoring is often

needed, although once daily dosing increases the safety window. Impairment of kidney function

and hearing loss are the most common side effects of aminoglycosides. Aminoglycosides tend to

be used when other less toxic antibiotics are contraindicated or ineffective.

Aminoglycosides are not well absorbed when given by mouth, so need to be given by injection

by healthcare personnel.

Examples of aminoglycosides include:

 Gentamicin (generic version is IV only)

 Amikacin (IV only)

 Tobramycin

 Gentak and Genoptic (eye drops)

 Kanamycin

 Streptomycin

 Neo-Fradin (oral)

 Neomycin (generic version is IV only)

C) THE MACROLIDES
Macrolide antibiotics such as erythromycin, clarithromycin, and azithromycin have been used

widely to combat primarily respiratory diseases caused by Gram-positive pathogens

and fastidious Gram-negative pathogens. The popularity of this class of antibiotics is largely due

to their spectrum of activity and their relative safety. The second-generation macrolides,

clarithromycin and azithromycin, are derived from erythromycin, and have a broader spectrum of

activity and improved pharmacokinetic properties. Macrolide antibiotics inhibit bacterial protein

synthesis by interfering with ribosome function, and details of the inhibitory mechanisms have

been clarified by recent advances in the x-ray structure of the ribosome–macrolide complexes.

The widespread use of these antibiotics had catalyzed the emergence of macrolide-

resistant strains, especially among Streptococcus pneumoniae, Streptococcus pyogenes,

and Staphylococcus aureus. In response to these resistant pathogens, third-generation macrolides,

represented by the ketolide telithromycin, are being developed. These derivatives have increased

affinity for the bacterial ribosome and a reduced propensity to be efflux pump substrates

compared with the first- and second-generation macrolides. Discovery of telithromycin and its

introduction into the market triggered a renewed interest in the chemistry of macrolide

antibiotics in recent years. As a result, a large number of novel and potent analogs were

synthesized and are under investigation.

The mechanism of action of macrolides has been studied for more than 30 years but is still

unclear. All macrolides inhibit bacterial protein synthesis to varying extents.

The macrolides bind to the 50S ribosomal subunit with a specific target in the 23S ribosomal

RNA molecule and various ribosomal proteins

Minor side effects of macrolides include nausea, vomiting, diarrhea, and ringing or buzzing in

the ears (tinnitus). Serious side effects, including allergic reaction andcholestatic hepatitis
(inflammation and congestion of bile ducts in the liver), are generally associated only with the

use of erythromycin

D) TETRACYCLINE

Examples are :Chlortetracycline, oxytetracycline, demethylchlortetracycline,

rolitetracycline, limecycline, clomocycline, methacycline, doxycycline, minocycline

Tetracycline are broad spectrum antibiotics that are polypeptide in nature and have a tetracene

ring structure. Tetracycline’s block bacterial cell growth by inhibiting the protein synthesis.

Tetracyclines are commonly used to treat acne and other skin infections. Tetracyclines have the

ability to chelate calcium and therefore prevent its absorption, therefore its use leads to calcium

deficiency. It is also capable of binding to the calcium in teeth thereby staining it. Tetracycline

drugs such as doxycycline has been used as a prophylactic drug for anthrax as well as for the

bubonic plague. Systemically, tetracyclines are useful for the treatment of infections of the

respiratory tract, urinary tract and the gastrointestinal tract. They are especially useful in patients

who are hypersensitive to β-lactams and macrolides.

Mechanism of Action of Tetracyclines

Tetracyclines act by binding to the 30S subunit of the ribosome at the A-site. During protein

biosynthesis, the new t-RNA with the amino acid attempts to bind to A-site of the ribosome.

However, since the A-site is blocked by the tetracycline, the aminoacyl-tRNA cannot bind to it.

Thus without the sequential attachment of the tRNA at the A-site, protein biosynthesis cannot

occur. By inhibiting protein biosynthesis tetracyclines cause cell death of the bacterial cell.
Adverse reaction

Side-effects from tetracyclines are not common, but of particular note is phototoxicity. It

increases the risk of sunburn under exposure to light from the sun or other sources. This may be

of particular importance for those intending to take on vacations long-term doxycycline as a

malaria prophylaxis.

They may cause stomach or bowel upsets, and, on rare occasions, allergic reactions. Very rarely,

severe headache and vision problems may be signs of dangerous secondary intracranial

hypertension, also known as idiopathic intracranial hypertension.

Tetracyclines are teratogens due to the likelihood of causing teeth discolouration in the fetus as

they develop in infancy. For this same reason, tetracyclines are contraindicated for use

in children under 8 years of age. Some adults also experience teeth discoloration (mild grey hue)

after use. They are, however, safe to use in the first 18 weeks of pregnancy.

Some patients taking tetracyclines require medical supervision because they can

cause steatosis and liver toxicity.

F) FLUROQUINOLONES

fluroquinolones and fluoroquinolones consists of drugs which act as chemotherapeutic agents

against bacteria consisting of drugs which generally contain the term “oxacin” in the end.
Fluoroquinolones and quinolones cause severe side effects in rare cases and are therefore not

used for regular treatment of bacterial infections. They are generally used for more resistant

strains of bacteria and are especially useful in genitourinary infections. Structurally these

drugs contain a quinoline ring system and hence given the name quinolones. After the first

generation of drugs were found to be active, it was noted that a fluorine atom at the 6-

position of the quinoline ring imparted greater potency, and hence the second generation of

drugs was called the fluoroquinolones.

Examples are nalidixic acid ,ciprofloxacin ,oxacillin,norfloxacin,levfofloxacin.

Mechanism of action

fluoroquinolones inhibit bacterial replication by blocking their DNA replication pathway.

DNA is the core genetic material of the cells, and is responsible for proper functioning of the

cell. During protein synthesis and DNA replication, the double-stranded DNA needs to

unwind into a single stranded structure, which allows for complementary base pairing to

occur and synthesis of mRNA to procede. This unwinding of DNA in the bacteria is done by

enzymes in the bacteria called DNA gyrase or DNA topoisomerase. DNA gyrase is a

topoisomerase II type enzyme that unwinds the DNA by introducing negative supercoils and

can also help relax positive supercoils. Quinolones and fluoroquinolones inhibit this enzyme

by binding to the A-subunit of the enzyme due to which the bacteria is unable to replicate or

even synthesize proteins.

Adverse effect
 CNS-dizziness,insomnia,headache,depression related to possible effects on the CNS

membrane.

G) SULFONAMIDES

Examples Sulfazalazine,sulfamethoxazole,sulfadiazine,

Sulfonamides, or sulfa drugs, are antibiotics that treat infections caused by bacteria. It is a

synthetic drug, meaning that it is manufactured and is not naturally occurring.

Sulfonamides are considered broad spectrum antibiotics. This means that they are able to

treat a large variety of bacteria that cause disease.

Some diuretics (a medication that increases the output of water and salt from the body)

also have sulfa in them. An allergy to a sulfa containing antibiotic does not necessarily

mean that there will be an allergy to a diuretic that contains sulfa. This is because the two

types of medications have different chemical make-ups.

Mechanism of action

Folic acid is a vitamin that helps make DNA and red blood cells. A person has to ingest folic

acid through their diet or supplements because the body cannot make it. On the other hand,

bacteria can make their own folic acid which it uses to multiply and grow more bacteria . A

sulfonamide interferes with the ability of bacteria to use folic acid to grow by stopping the

metabolic process. Therefore, the bacteria are unable to reproduce. Sulfonamide is considered

a bacteriostatic because it is able to stop bacteria growth, but it is not able to kill the bacteria.

The white blood cells in the body are usually able to do that. Sometimes a different type of

antibiotic is used along with a sulfonamide called trimethoprim. Trimethoprim is

a bactericidal because it is able to kill the bacteria. The combination of the medications stops

bacteria from multiplying and destroys them.

Sulfonamides: Uses

One use of sulfonamides is to treat bacterial infections. Sulfonamide antibiotics may be

prescribed for infections including:

 Urinary tract infections

 Pneumonia

 Ear infections

 Diarrhea

 Bronchitis

 Bacterial meningitis

 Eye infections

 Severe burns

Adverse reaction

Nausea vomiting diarrhea abdominal pain,etc.

ANTIFUNGAL DRUGS
 Fungal infections are termed mycoses and, in general ,can be divided into superficial

infections(affecting skin, nails, scalp or mucous membrane) and systemic infections(affecting

deeper tissues and organs.) superficial fungal infections can be classified into dermatomycoses

and candidiasis .Dermatomycoses are infections of the skin, hair and nails most commonly

caused by Trichophyton, Microsporum and Epidemophyton spp., which cause various type of

“ring worm” or tinea. Tinea capitis affects the scalp ,Tinea cruis, the groin, Tinea pedis, the

feet(causing athlete’s foot)

Antifungal medicines are used to treat fungal infections, which most commonly affect your skin,

hair and nails. Fungal infections commonly treated with antifungals include:

ringworm

 athlete's foot

 fungal nail infection

 vaginal thrush

 some kinds of severe dandruff

Less commonly, there are also more serious fungal infections that develop deep inside the body

tissues, which may need to be treated in hospital.

Examples include:

 aspergillosis, which affects the lungs

 fungal meningitis, which affects the brain

 Antifungal medicines are available as:

 topical antifungals – a cream, gel, ointment or spray you can apply directly to your skin, hair or

nails

 oral antifungals – a capsule, tablet or liquid medicine that you swallow

 intravenous antifungals – an injection into a vein in your arm, usually given in hospital

 intravaginal antifungal pessaries – small, soft tablets you can insert into the vagina

some common names for antifungal medicines include:

 clotrimazole

 econazole

 miconazole

 terbinafine

 fluconazole

 ketoconazole

 amphotericin

HOW ANTIFUNGAL MEDICINES WORK

Antifungal medicines work by either:

 killing the fungal cells – for example, by affecting a substance in the cell walls, causing the

contents of the fungal cells to leak out and the cells to die

 preventing the fungal cells growing and reproducing

SIDE EFFECTS OF ANTIFUNGAL MEDICINES

Your antifungal medicine may cause side effects. These are usually mild and only last for a short

period of time.

They can include:

 itching or burning

 redness

 feeling sick

 tummy (abdominal) pain

 diarrhoea

 a rash

CLASSIFICATION OF ANTI FUNGAL

A) ANTIBIOTICS examples polyenes: Amphotercin B (AMB), Nystatin, Hamycin.

Ecohinocandins: caspofungin, micafungin ,Anidulafungin

Heteriocyclin benzofuran:Griseofulvin
B) ANTIMETABOLITE: Flucytosine(5-fc)

C) AZOLEs : Imidazoles

Topical: clotrimazole, econazole, miconazoles, oxiconazoles

Synthetic: ketoconazole

Triazoles(systemic):Fluconazoles, ltraconazoles ,voriconazole,posaconazoles.

D) Allylamine: Terbinafine

E) Other topical agents: Tolnaftate, undercylenic acid, Benozoic acid, quiniodochlur,

ciclopirox olamine ,Butenafine, SOD. thiosulficate.

AMPHOTERICIN

Is a macrolide antibiotics of complex structure, characterized by mainly membered ring of

carbon atoms.
MECHANISM OF ACTION

Amphotericin binds to cell membrane and interferes with permeability .it forms a pore in the

membrane and causes the loss of intracellular K +. Amphotericin has a selective action, binding

avidly to the membranes of fungi and some protozoa .It is nearly insoluble in water and is

therefore prepared as a colloidal suspension of amphotericin B and sodium desoxycholate for

intravenous injection. Several new formulations have been developed in which amphotericin B is

packaged in a lipid-associated delivery system (Liposomal Amphotericin B It has high affinity

for ergosterol present in fungal cell membrane. • This Polyenes are combine with membrane

protein and form a 'micropore‘ and increase the cell permeability (ions, amino acids and other

water soluble substances move out through hydrophilic side forms) allowing leakage of a variety

of small molecules • Cholesterol, present in host cell membranes, closely resembles ergosterol;

the polyenes bind to it as well, though with lesser affinity.

. ANTIFUNGAL SPECTRUM/ ACTIVITY:

Active against a wide range of yeasts and fungi .It is fungicidal at high and static at low

concentrations Amphotericin B has clinical activity against Candida spp., Cryptococcus

neoformans, Blastomyces dermatitidis, Histoplasma capsulatum, Sporothrix schenckii,

Coccidioides immitis, Paracoccidioides braziliensis, Aspergillus spp., Penicillium marneffei, and

the agents of mucormycosis. .

PHARMACOKINETICS •
Given orally amphotericin is poorly absorbed:it is therefore only given by this route for fungal

infections of the gastrointestinal tract.it can also be given topically.for systemic infections,it is

complex with sodium deoxycholate and given as a suspension by slow intravenous injection.

THERAPEUTIC USES:

• Broad spectrum of activity and fungicidal action

• Used as the initial induction regimen for serious fungal infections and is then replaced by one

of the newer azole drugs for chronic therapy or prevention of relapse (important for

immunosuppressed patients and those with severe fungal pneumonia, cryptococcal meningitis). •

For treatment of systemic fungal disease, amphotericin B is given by slow intravenous infusion

at a dosage of 0.5-1 mg/kg/d

• Mycotic corneal ulcers and keratitis can be cured with topical drops as well as by direct

Subconjunctival injection

• Amphotericin B given once weekly has been used to prevent relapse in patients with AIDS who

have been treated successfully for cryptococcosis or histoplasmosis.

• Amphotericin B is most effective drug for resistant cases of kala azar and mucocutaneous

leishmaniasis

ADVERSE EFFECTS: Chills, fever, aches, pain all over, nausea, vomiting Nephrotoxicity

(renal toxicity) is the most common (it occurs fairly uniformly and is dose related) –

manifestations are--azotemia, reduced, acidosis, hypokalemia and inability to concentrate urine.

It reverses slowly and often incompletely after stopping of therapy. – Anaemia: Most patients
develop slowly progressing anaemia which is due to bone marrow depression. It is largely

reversible. – CNS toxicity: occurs only on intrathecal injection-headache, vomiting, nerve

palsies, etc.

SYNTHETIC ANTIFUNGAL DRUGS(AZOLES)

The azoles are a group of synthetic fungistatic agents with a broad spectrum of activity.the main

drugs available are fluconazoles, itraconazole, ketoconazole.

MECHANISM OF ACTION : they inhibit the fungal cytochrome p450 3A (CYP3A)enzyme

which is responsible for converting lantosterol to ergosterol, the main sterol in the fungal cell

membrane. The resulting depletion of ergosterol alters the fluidity of the membrane and this

interfers with the action of membrane-associated enyzmes.

ANTIVIRAL DRUGS

Viruses are small infective agents consisting essentially of nucleic acid (RNA AND DNA)

enclosed in a protein coat or capsid. Certain viruses also contain enzymes that initiate their

replication in the host cell. In order to replicate, they have to attach to and enter a living host-

animal, plant, bacterial and use it metabolic processes

EXAMPLES OF VIRUSES AND THEIR DISEASES

Because viruses share many of the metabolic processes of the host cell, it is difficult to find

drugs that are selective for the pathogen. However, there are some enzyme that are virus specific

and these are potential targets for drugs. Most currently available antiviral agents are only

effective while the virus is replicating.

DNA viruses :poxviruses (smallpox), herpes-viruses (chickenpox, cold

sores),adenoviruses(sore throat, conjunctivitis) and papillomaviruses(wart)

RNA

VIRUSES:orthomyxoviruses(influenza).paramyxoviruses(measles.mumps,lassa

fever ),rubella viruses(German

measles),rhabdoviruses(rabies),picornaviruses(colds,meningitis,poliomyelitis)retr

oviruses(acquired immunodeficiency syndrome(AIDS),Tcell leukaemia).

HIV DRUGS

There are of two main classes.

-Reverse transcriptase inhibitors

-Protease inhibitors

The reverse transcriptase inhibitors are divided into two

A) Nucleoside reverse transcriptase inhibitors

B) Non-nucleoside reverse transcriptase inhibitors.

A combination of both form highly active antiretroviral therapy (HARRT).with HARRT regimen

HIV replication is inhibited, the presence in the plasma if HIV RNA is reduced to undetectable

levels and patient survival is prolonged. But the regimen is complex, has many unwanted effects,

is difficult to adhere to and may well have to be lifelong because HIV will not have been

eradicated. The virus will be lying latent in memory T cells, integrated into host genome and

forming a source for potential reactivation if the drugs are stopped.

 Nucleoside reverse transcriptase inhibitors: Example are Zidovudine, (AZT) didanosine

(ddI) ,zalcitabine(ddC), lamivudine(3TC),stavudine,(d4T) abacavir(ABC).

ZIDOVUDINE

Unwanted effect could include: Anemia, GIT disturbances, skin rash, mouth ulcer,

headaches .etc.

Mechanism of Action: All are phosphorylated by host cell enzymes to give 5’-

triphoshosphate.The 5’-triphosphate moiety competes with the equivalent host cellular

triphosphates, which are essential substrates for the formation of proviral DNA by viral reverse

transcriptase, the incorporation of the 5’triphosphate moiety into growing viral DNA chain

results in chain termination.

It is administered orally twice a day but can.; also be given by intravenous infusion. The

bioavailability is 60-80% and the peak plasma concentration is 30 minutes. Its half-life is 1 hour,

and the intracellular half- life of the active triphosphate is 3 hours.

  Non-nucleoside reverse transcriptase inhibitors: Non-nucleoside reverse transcriptase

inhibitors are chemically diverse compounds that binds to reverse transcriptase near the

catalytic site and denature it. Most non-nucleoside reverse transcriptase inhibitors are

inducers, substrates or inhibitors to varying degrees of the liver cytochrome enzymes.

Examples are: neviaprine,(NVP) efavirenz(EFZ). The adverse effect are often mild and consist

of CNS symptoms which is dizziness, confusion), skin rash, GIT disturbances.

NEVIRAPINE

Nevarapine is given orally,its bioavailability is ¿ 90% and its CSF levels is 45% of that in the

plama.it is metabolized in the liver and the metabolite is excreted in the urine.Nevarapine can

prevent mother-baby transmission of HIV if given to the mother and the neonate.

 Protease inhibitors :Examples Aciclovir, Gangciclovir ,ribavirin .they are all given

orally.

Unwanted effect: GIT disturbances, high blood sugar and hyperlipidemia .long term

effect use may lead to an unusual redistribution of cutaneous fat:less subcutaneous fat,

increased abdominal fat ,breast enlargement etc

Mechanism of action; they binds to the site where cleavage occur ,and their use, in

combination with reverse transcriptase inhibitor ,has transformed the therapy of AIDS.
 OTHER ANTIVIRAL DRUGS

Drugs that affect viruse other than HIV act by inbition of viral DNA polymerase or

inhibition of attachment to the host cell

Aciclovir(acyclovir)

The era of effective selective antiviral therapy began with acyclovir.This agent is a

guanosine derivatives with a high specificity for herpes simplex and varicella-zoster

viruses. Herpes simplex can cause cold sores, conjunctivitis, mouth ulcers, genital

infection and, rarely but seriously encephalitis. In immunocompromised patients it is

much more aggressive. Varicella-Zoster virus cause shingles and chickenpox.

Aciclovir can be given orally, intravenously or topically.

Unwanted effect are minimal,nausea and headache

CORTICIOSTERIODAL DRUGS

Commonly referred to as steroids, corticosteroids are a type of anti-inflammatory drug. They are

typically used to treat rheumatologic diseases, like rheumatoid arthritis, lupus or vasculitis

(inflammation of the blood vessels). Specific corticosteroids include the medications cortisone

and prednisone

SIDE EhFFECT

corticosteroids can:

 cause sodium (salt) and fluid to be retained in the body and cause weight gain or

swelling of the legs (edema)

  High blood pressure

 Loss of potassium

 Headache

 Muscle weakness

 Puffiness of the face (moon face)

 Facial hair growth

 Thinning and easy bruising of the skin

 Slow wound healing

 Glaucoma

 Cataracts

 Ulcers in the stomach and duodenum

 Loss of diabetes control

 Menstrual irregularity

 "Buffalo hump," a condition described as a rounding of the upper back

The prolonged use of corticosteroids can cause obesity, growth retardation in children, and even

lead to convulsions and psychiatric disturbances. Reported psychiatric disturbances

include depression, euphoria, insomnia, mood swings, and personality changes. Psychotic

behaviors also have been reported.

Corticosteroids, since they suppress the immune system, can lead to an increase in the rate of

infections and reduce the effectiveness of vaccines and antibiotics.

The long term use of corticosteroids may cause osteoporosis which can result in bone fractures.
Shrinking (atrophy) of the adrenal glands can be caused by the long term use of corticosteroids

resulting in the body's inability to produce cortisol, the body's natural corticosteroid, when the

systemic corticosteroids are discontinued.

Another condition which can result from the long term use of corticosteroids is adrenal necrosis

of the hip joints, a very painful and serious condition that may require surgery. Any symptoms of

hip or knee pain in people taking corticosteroids require prompt medical attention.

Corticosteroids should not be stopped suddenly after prolonged use as this can result in adrenal

crisis because of the body's inability to secrete enough cortisol to make up for the

withdrawal. Nausea, vomiting, and shock are the reported side effects of adrenal crisis.

Corticosteroids are steroid hormones that are either produced by the body or are man-

made.Systemic corticosteroids refer to corticosteroids that are given orally or by injection and

distribute throughout the body. It does not include corticosteroids used in the eyes, ears, or nose,

on the skin or that are inhaled, although small amounts of these corticosteroids can be absorbed

into the body. Naturally occurring corticosteroids, hydrocortisone (Cortef) and cortisone, are

produced by the outer portion of the adrenal gland known as the cortex (hence the name,

corticosteroid). Corticosteroids are classified as either:

-glucocorticoids (anti-inflammatory) which suppress inflammation and immunity and assist in

the breakdown of fats, carbohydrates, and proteins, or as

-mineralocorticoids (salt retaining) that regulate the balance of salt and water in the body.
Synthetic corticosteroids mimic the actions of naturally occurring corticosteroids and may be

used to replace corticosteroids in people with adrenal glands that are unable to produce adequate

amounts of corticosteroids, however, they more often are used in higher-than-replacement doses

to treat diseases of immunity, inflammation or salt and water balance. Examples of synthetic

corticosteroids include:

bethamethasone, (Celestone) ,prednisone ,triamcinolone (Aristospan Intra-Articular, Aristospan

Intralesional, Kenalog) ,methylprednisolone (Medrol, Depo-Medrol, Solu-

Medrol) ,dexamethasone (Dexamethasone Intensol, DexPak 10 Day, DexPak 13 Day, DexPak 6

Day).

Some glucocorticoids also in addition to their anti-inflammatory actions have salt retaining

properties but they are used mostly for their anti-inflammatory effects. Fludrocortisone

(Florinef), a synthetic mineralocorticoid has strong salt retaining effects with significant anti-

inflammatory actions, and is used mostly for it's salt retaining capabilities

HOW DO STEROIDS WORK?

Steroids work by decreasing inflammation and reducing the activity of the immune system.

Inflammation is a process in which the body's white blood cells and chemicals can protect

against infection and foreign substances such as bacteria and viruses. In certain diseases,

however, the body's defense system (immune system) doesn't function properly. This might

cause inflammation to work against the body's tissues and cause damage. Signs of inflammation

include:

 Redness.
  Warmth.

 Swelling.

 Pain.

Steroids reduce the production of chemicals that cause inflammation. This helps keep tissue

damage as low as possible. Steroids also reduce the activity of the immune system by affecting

the way white blood cells work.

WHEN ARE STEROIDS GIVEN?

Steroids are used to treat many conditions in which the body’s defense system doesn’t work

properly and causes tissue damage. Steroids may be the main therapy for certain diseases. For

other conditions, steroids might only be used sparingly or when other measures have not been

successful.

Steroids are used in the treatment for certain rheumatologic inflammatory conditions, such as:

 Systemic vasculitis (inflammation of blood vessels).

 Myositis (inflammation of muscle).

 Rheumatoid arthritis (chronic inflammatory arthritis).

 Systemic lupus erythematosus (a generalized disease caused by abnormal immune system

function).

HOW CAN THE SIDE EFFECTS OF STEROIDS BE MINIMIZED?

To minimize the side effects of steroids, healthcare providers follow several guidelines:
  Use steroids only when necessary.

 Watch the patient closely to detect early signs of serious side effects.

 If possible, use local steroids for local problems.

 Use the smallest dose needed to control the disease.

 Reduce the dose gradually as long as the disease remains under control.

 Monitor blood pressure and blood sugar often and treat if necessary.

 Monitor bone density and prescribe medications and supplements to help bone health.

NON-STERIODAL ANTINFLAMATORY DRUGS

Non -steroidal anti-inflammatory drugs are medications that relieve or reduce pain. The most

popular examples of this group of drugs are aspirin and ibuprofen

HOW DO NSAIDS WORK?

NSAIDs block the production of certain body chemicals that cause inflammation. NSAIDs are

good at treating pain caused by slow tissue damage, such as arthritis pain. NSAIDs also work

well fighting back pain, menstrual cramps and headaches.

NSAIDs work like corticosteroids (also called steroids), without many of the side effects of

steroids. Steroids are man-made drugs that are similar to cortisone, a naturally-occurring

hormone. Like cortisone, NSAIDs reduce pain and inflammation that often come with joint and

muscle diseases and injuries

SIDE EFFECT
The most frequently reported side effects of NSAIDs are gastrointestinal (stomach and gut)

symptoms, such as:

 Gas.

 Feeling bloated.

 Heartburn.

 Stomach pain.

 Nausea.

 Vomiting.

 Diarrhea and/or constipation.

These gastrointestinal symptoms can generally be prevented by taking the drug with food, milk

or antacids (such as Maalox® or Mylanta®).

 Dizziness.

 Feeling lightheaded.

 Problems with balance.

 Difficulty concentrating.

 Mild headaches.

Can I take NSAIDs if I'm being treated for high blood pressure?

NSAIDs can cause high blood pressure (hypertension) in some people. You may have to stop

taking NSAIDs if you notice your blood pressure increases even if you’re taking your blood

pressure medications and following your diet. Ask your doctor about this before you start taking

NSAIDs.
In what cases should I check with my doctor before taking NSAIDs?

If you have any of the following conditions or circumstances please check with your doctor

before you take NSAIDs:

 Pregnancy (NSAIDs should be avoided in the third trimester. Consult with your provider

about use in the first or second trimester).

 Children and teenagers with viral infections (with or without fever) should not receive

aspirin or aspirin-containing products due to the risk of Reye's syndrome (a rare but

deadly illness that can affect the brain and liver).Reye syndrome is a rare condition that

causes confusion, swelling in the brain and liver damage. Children recovering from a

viral infection such as chickenpox or Flu or who have a metabolic disorder are most at

risk, especially if they have been taking aspirin

 Those who have an upcoming surgical procedure, including dental surgery.

 People who have three or more alcoholic beverages per day.

 Asthma that gets worse when taking aspirin.

 If you are 65 years of age or older.

Disease states

 Diabetes that is difficult to control.

 Known kidney disease.

 Known liver disease.

  Gastroesophageal reflux disease, also known as GERD.

 Crohn’s disease or ulcerative colitis.

 Active peptic ulcer disease (stomach ulcers or previous history of stomach ulcer

bleeding).

Heart and bleeding conditions

 Bleeding problems (people who have a history of prolonged bleeding time or who bruise

easily).

 High blood pressure that is difficult to control.

 Active congestive heart failure.

 History of stroke or heart attack.

Allergic and drug interactions

 Known allergies to medications, especially aspirin, other NSAIDs and sulfa drugs.

 Nasal polyps (linked to a greater chance of NSAID allergy).

 Please check with your pharmacist or healthcare provider before starting an NSAID to

determine if your current medications, both prescription and OTC, and also your

dietary/herbal supplements, are compatible with the NSAID. Do this especially if you are

on warfarin (Coumadin®), clopidogrel (Plavix®), corticosteroids (for example,

prednisone), phenytoin (Dilantin®), cyclosporine (Neoral®, Sandimmune®), probenecid

and lithium (Lithobid®).

 If you take diuretics (also known as water pills) to control your blood pressure, you may

be at greater risk of kidney problems if you take an NSAID.

  Phenylketonuria (PKU). Some nonprescription NSAIDs are sweetened with aspartame, a

source of phenylalanine.

Can NSAIDs cause allergic reactions?

Rarely, an NSAID can cause a generalized allergic reaction known as anaphylactic shock. If this

happens, it usually occurs soon after the person starts taking the NSAID. The symptoms of this

reaction include:

 Swollen eyes, lips or tongue.

 Difficulty swallowing.

 Shortness of breath.

 Rapid heart rate.

 Chest pain or tightness.

If any of these symptoms occur, call 9-1-1 or have someone drive you to the nearest emergency

room immediately.

Remember, before any medication is prescribed, tell your doctor:

 If you are allergic to any medications, foods or other substances.

  If you currently take any other medications (including over-the-counter medications)

and/or herbal or dietary supplements.

 If you are pregnant, planning to become pregnant, or are breast-feeding.

 If you have problems taking any medications.

 If you have anemia, kidney or liver disease, stomach or peptic ulcers, heart disease, high

blood pressure, bleeding or clotting problems, asthma or growth in the nose (nasal

polyps).

Examples of NSAIDs

OTC NSAIDs include:

 Ibuprofen

 Aspirin

 Naproxen Sodium

Prescription NSAIDs include:

 Oxaprozin

 Etodolac

 Indomethacin

 Naproxen

 Nabumetone

 Diclofenac

 Vimovo (Naproxen/Esomeprazole
What are NSAIDs used to treat?

NSAIDs are used for three broad symptom types that occur in a range of conditions:

 high temperature or fever

 inflammation

 pain

NSAIDs are used to ease pain in a number of conditions, including:

 arthritis

 backache – particularly long-term pain in the lower back

 cold or flu

 headaches

 period pains

 joint or bone injuries, sprains, and strains

 muscle or joint complaints

 toothache
In low doses, aspirin is used to help prevent artery disease that can lead to heart attack or stroke.

It may also be used to reduce the risk of some types of colorectal cancer.

Headache and lower back pain are two of the more common reasons for using NSAIDs. If these

problems become long-term issues, patients should consider the safety of using NSAIDs.

Using NSAIDs for cold and flu

For more than 100 years, NSAIDs have been taken to treat symptoms of the common cold.

However, these drugs do not kill the virus or improve the course of the illness. NSAIDs simply

relieve some of the symptoms, including fever and pain.

A systematic review of the best available evidence for treating a common cold with NSAIDs

shows that they produce significant results against headache, ear pain, and muscle and joint pain.