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Assalamualaikum my friends.

Before you started reading this lecture I wanted to emphasise on few things.

1) This lecture is not complete because Dr Ahmad stopped in the middle ofthe lecture to give chances for students who have their Prostodontics

exam.

2) The record was really bad and there were some points that I could not jotdown in this lecture

3) Dr was reading from the slides so I have included most of the slides in hereand not much explanation is given by the Dr. so this lecture will be boring

4) The DR also said something about endocarditis and he said that that therewill be question from the article he had given to Hutheifa and now its

available on elearning.

5) I will only say the most important points but its your responsible to knowall the points , Dr Ahmad said meaning that we still need to memorize

everything though.

6) The points that I could not hear clearly from the doctor I have triedsearching it on the net

7) Dont be sad if you dont have time to finish all these because Allah isalways planning the best for you.

8) Pearl RULES!!

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Protein and NA synthesis INHIBITOR

Protein synthesis inhibitor

Aminoglycosides Macrolides Clindamycin Cloramphinicol Tetracycline

AMINOGLYCOSIDES

a)Streptomycina prototype of this class

b)Gentamicinwidely used in clinic

c)Neomycinvery toxic and that why its used for skin lesion and eye problems

d)Amikacin

MOAof aminoglycosides in general : Bactericidal, Bind to 30S subunit of the ribosomes It has to get into the cell through channels Inhibit the intiation of peptide formationincorrect AA sequence

into peptide chain>Production of non-functional or toxic proteinwhich is fatal to the bacteria

Synergize with B-lactam antibiotics How- ??

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Ive tried searching the net but I couldnt find any so I will have to letyou guys do the searching.

Pharmacokinetics

Water soluble, do not easily cross cell membranes Poorly absorbed from GITthus all of these drugs given by either

topically @parenterally

( IV,IM) Neomycin used topically ONLY Distributed to ECF mainly (no fat) Poor transfer to CSF ,even in inflamed meninges Eliminated unchanged in the urine ,mainly by GF,may accumulate at renal

cortex causing toxicities to the kidney ( most significant side effects of

these drugs), dose reduction in renal impairment

These drugs are active against: Aerobic Gram (-) bacilli

P. aerogenosa Streptomycinis used in TB

In combination with other drugs because TB cannot be treated by asingle drug

Usually through multiple therapy

Therapeutic uses

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A lot of them will be combined with betaLactams because of synergic effect

together for eg.

Gramve bacillary infectionsspecially septicemia and pelvic abdominalsepsis

Gentamicin + Beta lactam and or metronidazole

Bacterial endocarditis:Gentamicin+ benzyl penicillinStrept.& enterococci

Gentamicin + cloxacillin (B-lactamase resistant)Staph

Other infections as TB, tularemia, plague and brucellosis-Streptomycin Neomycin- Topical use (sorry but the record up to here was very bad)

Very toxic systemically an you dont swallowit

Used as eye & ear drops or orally and to sterilize bowel

Side effects

The most important , the ones that limits their use and the ones that will be in the

exam!

And even the dr doesnt know why the accumulate in the hair cells and kidney

cortex.

Ototoxicity - means has problems in ears where he stops hearing and sometimesit will be irreversible

The same thing as kidney these aminoglycosides precipitate in the hair cells

present in the ear ( they are sentitive to different frequencies) producing

otototoxicity and the

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Nephrotoxicity- the moa as I mentioned before the aminoglycosides they are

acumulated in the kidney cortex

Paralysis- impair conductance of acetylcoline which is important for movements

and neuro muscular junctions

Rash and ??? ( sorry but I cant hear clearly due to the echo)

Macrolides

MOA: They bind to 50S subunits of ribosomes, bacteriostaticsand

interfere with the protein synthesis

Antibacterial spectrum: Erythromycin: as penicillin G,

It is used in patients who are allergic to penicillins. Used to be given now develop a lot of resisistance Clarithromycin and azethromycin

Clarthromycin: as erythromycin plus: (improved for of Erythromycin) H. influenzae,Erythromycin H. pylori.-( responsible for gastric ulcer)

Azethromycin less active against strept and Staph than erythromycin. More active against H.influenzae and Chlamydia

Pharmacokinetics

Erythromycin:

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Very well absorbed orally (but still destroyed by gastric juice) butsometimes parenterally given

Distributed readily to most tissues (not CSF) Eliminated through the bile Liver microsomal enzyme inhibitorSo drug that is metabolized by the microsomal enzyme in the liver will

have increased concentration , thus we must reduce the drugs dose

that is known to be metabolized by the liver microsomal enzyme .

Otherwise it will cause toxic effect of these drugs.

Illustration are clearer in the next picture:

Clarthromycin: More absorbable than erythromycin, longer half life

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Azthromycin,-once daily, do not affact MES (Microsomal Enzyme System)

Side Effects of these drugs

GIT disturbancesNausea and vomiting, diarrhea Allergy Interference with other drugs because of metabolism through the liver Cholestatic jaundice

Jaundice is yellowish pigmentation of the skin due to not enough

excretion of bile from the gall bladder and as we know that erythromycin

is eliminated through bile (from the previous points)

Ototoxicity: Transient deafness with high doses of erythromycin. reversible

Contraindicated with hepatic dysfunction

Clindamycin

-very widely used in dentistry

Binds to 50S subunits of bacterialribosomes then inhibits proteinsynthesis

Has similar spectrum as erythromycin+ B.fragilis and anaerobes in GITassociated sepsis.

Used in :

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Bone and joint infectionbecause teeth are located in the bone so they are preffered to

fight formation of dental infections

Intra abdominal sepsis Anaerobic infection

Adverse reaction:

It is a broad spectrum drug( means that it attcks both gram +ve and gramve

bacteria)

Also inhibiting normal flora

Pseudomembranous colitis, ( due to inhibition of normal flora whichis C.difficile)

Management ? - vancomycin( cell wall synthesis inhibitor ) andmetronidazole

Chloramphenicol

Bacteriostatic Interferes with protein synthesisby the ribosomes through binding to 50S

subunit.

Mammalian ribosomes = bacterial ribosomesSo sometimes they cannot differentiate between good ribosomes and bad

ribosomes

Antibacterial spectrum: Broad spectrum antibiotic -

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P. aerogenosa and Chlamydia are not affected. It has excellent activity against anaerobes.

What you need to know from it , that it is not commonly used due to lots of side

effect

Therapeutic uses

Used when other antimicrobials are ineffectiveEg . Bacterial meningitisyoull first give amoxicillin and other drugs.If they

proved to be ineffective then you switch to chloramphenicol

Other drugs proved to be ineffectiveeg benzyl penicillin

Brain abscess + penicillin

Typhoid, paratyphoid and salmonella septicemia. Ocular infection (topical and systemic)

The doctor voice was not clear but I think at this point he was talking about how

a cell could develop resistance to Cloramphenicol by blocked channels for drugs

to enter the cell.

Adverse Effect

Chloramphenicol use is limited for life threatening infections.1. GIT upset

2. Broad spectrum-induced effect

Similar to all broad spectrum antibiotics Opportunistic infections and Candida growth(fungal infection).

3. Aplastic anemia:

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Irreversible: Risk continues after you had stop taking drugs4. Bone marrow suppression:

Reversible, dose-dependent.5. Hemolytic anemia in pts with G6PD deficiency .

6. Gray baby syndrome:

In neonates(newborn) lack the necessaryliverenzymes to metabolize this drug. Due to failure of conjugation and renal excretion of the drug Presence of bluish or purple colour on the face Accumulation of metabolites, leading to shock ,depressed

breathing and cyanotic gray skin.

Some other drugs ,(eg . aminoglycosides has their effect stay inside the body for along period of time even after you stop giving the drugs.) same as

Chloramphenicol

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Tetracycline

Broad spectrum antibiotics , Bacteriostatic MOA:

Enter susceptible bacteria through passive AND by energy-dependent transport protein

Interfere with protein synthesis by binding to 30S subunit.( samewith aminoglycosides

Resistance: Decrease activity of transport system Active extrusion of tetracyclines out of the bacterial cells. Cross-tolerance between drugs in the same family

It really loves Love Ca+-If we take these drugs with calcium , the drug will not be absorbed in the GI

Tract because chelation will occur between Tetracycline and calcium thus

binding to calcium in manner that they

cannot be absorbed by the GI tract thus drug effect would be less.

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*Teeth and bone had lots of calcium so tetracycline goes to

this places and precipitate there producing Tetracyline

staining (Teeth)

As you can see , all teeth has almost one line of the tetracyline staining and this

occur due to precipitation during growth

They are also C/I inpregnant woman because it will precipitate in te primary

teeth if the newbornand also cannot be given when a kid is growing due to

growth of primary teeth

Bone -Sometime we can see some yellow fluorescence spots due to

precipitation

Pharmacokinetics

Partially absorbed from GIT. Unabsorbed amount may change bacterial flora pseudomembranous

colitis

Dairy products, antacids and iron reduce absorption by chelation Distributed through the body and can cross the placenta and

CSF(minocycline)

metabolized to glucuronides and excreted in urine and bile Most TCs are reabsorbed from the bile,

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Therapeutic uses

Broad SPectrum in:1. Chlamydia infection-psticosis ,trachoma

and lymph granuloma venerium

2. Mycoplasma pneumonia

3. Rickettsia (Q fever and typus)

4. V.Cholera and brucella

5. Borrelia (relapsing fever)

6. Acne, for monthes

7. Anaerobes (chlosterdia), and democycline in:

8. TT of hyponatremia due to inappropriate secretion of ADH

Adverse Effect

1. Gastric irritationnon-compliance, reduced by food other than dairyproducts

Diarrhea- change in bacterial flora Superinfections

2. Effects on calcified tissues:

deposition in bone and teeth in growing children

discoloration and hypoplasia of teeth and stunting of growth. from pregnancy12 years. ( To Prevent Tetracyline staining.)

3. Fatal hepatotoxicity:

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Especially in pregnant women4. Vestibular problems:

Dizziness, nausia and vomiting Due to accumulation in endolymph More with minocycline

5. Photosensitivity

Increased sensitivity to the sun and causes reddening of the parts ofbody tus exposure to intense light is not recommended

INHIBITOR OF NUCLEIC ACID

Fluoroquinolones - Sulphonamides and trimethoprim Azoles (Metronidazole)

Floroquinolonesare grouped to families, other drugs grouped to families are the

Cephalosporinswich are classified according to increased susceptibility to Gram

ve Bacteria

Lets continue to the family of Floroquinolones

Quinolones

Broad-spectrum antibiotics1stgeneration: Nalidixic acid

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Mainly gram (-)2ndgeneration: Ciprofloxacin

Gram (+) and (-), mycoplasma, and chlamydia Good in treating travelers diarrhea and P. aeruginosa infections Not good for MRSA(metycillin resistant Staph Aureus

3rdgeneration: Levofloxacin Enhanced gram (-), (+), and others

4thgeneration: Moxifloxacin Include anaerobes

Pharmacokinetics

Well absorbed orally, or IVWidely distributed in the body

Bone, urine, kidneyMoxifloxacine metabolized by the liver and Most quinolones eliminated by

renal excretion

.

Levo- and moxifloxacin have a long t1/2

once daily.

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Adverse Effect

Peripheral neuropathy GIT upset CNS effects: dizziness, headache, tremors and rare convulsions. Photosensitivity. Arthropathy and tendon sensitivity Contraindicated in pregnancy Drug Interactions: antiacids and cations decrease absorption. Ciprofloxacine inhibit P450 liver enzymes.

Sulfonamides & trimethoprim

*Folic Acid synthesis inhibitor

Folic acid is is an important precursor for Purine and Pyrimidine synthesis which

is the classes for DNA bases (guanine, cytosine etc)

Mechanism of action

Sulphonamides (SA) form an effective combination with trimethoprim(TM)

PABA * DiHydroFA TetraHydroFA FA synthetase, inhibited by SA ( PABA to DiHydroFA) DHF reductase, inhibited by TM (DiHydroFA to TetraHydroFA)

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If you guys remember PABA they come from ester LA PABA and Sulphonamides looks alike, so enzyme is confused between

which one they should take

PABA will be competing with SA for the production of FOLIC ACID , but aswe all know PABA loses the Fight leading to accumulation of PABA and

causing the less production of FOLIC ACID.

Accumulation of PABA in the end will still force the production of DiHydroFolic Acid and that is where is Trimetophrim comes in blocking the

production of TetraHydro Folic ACID

So these drugs are not given alone

Other Drugs :

Sulphamethaxozole and Trimethoprim (5:1)Well absorbed, mainly excreted by the kidney (80%) ?dose in renal

disease

Therapeutic Uses: DOC in pneumonia due to pneumocystis carinii Chronic urinary tract infection Typhoid fever CiprofloxacinPatient with infectious diarrhea eg. E Coli

*Other uses of SA :

1.Topical, silver sulphadiazine in prophylaxis and TT of burns, leg

ulcer and pressure ulcer.

2. Sulphacetamide eye drops

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3. sulphasalazine in ulcerative colitis

Adverse Reactions

SA: Crystalurea Hypersensitivity Hemolytic anemia

Especially with G6PD deficiency Displacement bilirubin from serum albumin

Kernicterus: (brain dysfunction); C.I. newborn and pregnancy Potentiation of warfarin

TM: Folic acid deficiency: megaloplastic

Folinic acid administration Cotrimoxazole: Same as above

Drug Interaction :

On the basis of protein binding displacement Warfarin

And on the basis of Inhibition of metabolism Phenytoin

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Metronidazole

Bactericidal

Only anaerobs and some protozoa contain the nitroreductase thatconverts the drug

to intermediate toxic metabolites which have antibacterial activity:

i: Inhibit bacterial enzymes

ii: Break down existing DNA

Pharmacokinetics

Well absorbed after oral and rectal routes Can also be given IV and vaginal pessaries. Well distributed to all tissues Excreted in urine unchanged and as metabolites Tinidazole is similar to metronidazole but with long duration of action

Therapeutic Uses

TT of sepsis- bacteroids & anaerobic cocci Prevention of postoperative infection-after bowel surgery

Pseudomembranous colitis- C. difficile (DOC)

Name another drug ( Clindamycin) Trichomoniasis of UG tract Amebiasisintestinal & extra intestinal

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Giardiasis Anaerobic vaginitis Acute ulcerative gingivitis and dental infection

Adverse Reaction

Nausea, vomiting and diarrhea Furred tongue Metallic taste Headache, dizziness and ataxia Disulfiram-like action with alcohol

Done by Abdullah Wafi Bizami