chemotherapy

Chemotherapy .. (1 / 5 )

Drugs that kill bacteria Drugs that kill viruses Drugs that kill fungus Drugs that kill cancer cell

You can kill bacteria by : NPC N = Destruction of the nucleic acid of bacteria . P = prevent the protein synthesis of bacteria or interfere with the metabolic pathway of this Bactria . C = inhibit the formation of cell wall of the bacteria or interfere with integrity of cell membrane . * Antibiotics drugs are categorized as bacterioStatic and bactericiDal : Q : what the different between the bacteristatic and bactericidal ? BacterioStatic = Stop growth and wait for immune system to finish the process . BactericiDal = kill bacteria Directly without immune system .

Cell wall inhibiters

-lactam antibiotic Vancomycin Bacitracin Penicillin cephalosporin carbapenems monobactoms

MODE OF ACTION: It is act on cell wall via : 1) distraction the wall already synthesis : through activation autolysin ( an enzyme found inside the bacteria that lead to cell wall distraction , cause its inside the cell , the penicillin must get into the cell ) . 2) inhibit forming of new cell wall : by inhibit the last step of cell wall formation "transpeptidation"** , through binding protein PBP cell wall loose allowing water to reabsorb swelling rupture death , So Penicillin is consider as BACTIROCAIDAL . ** "Cell wall synthesis of peptaidoglaycan linked to each other by cross linkage or transpeptidation "

)antibacterial ( antivirus ) ( (anticancer cell ) ( cytotoxic)

)antifungal (

(antibacterial )

(PREPARATION OF PENICILLIN )

1-natural 2-anti-staph 3-extended spectrum 4-anti-pseudomonas

* The natural and anti-staph penicillin are considered narrow spectrum antibiotics, cues they don't act

on gram ve bacilli , So the broad spectrum antibiotics are extended spectrum and anti-pseudomonas . * generally all penicillin depend on KIDNEY execration . * all penicillin groups can be taken orally except : 1-penicillin G 2- anti-pseudomonas can take parentally cues they are unstable with high gastric acidity . # Bacteria succeeded in inhibiting all group of -lactam antibiotics except : Anti-staph penicillin ( by secreting -lactemase) , so it is considered (-lactemase resistant group) . *To overcome the effect of -lactemase , -lactemase inhibitors must be added to the antibiotics Eg : Augmantine = Amoxicillin + Clavulanic acid .

anti-pseudomonas extended spectrum anti-staph natural Ticarcillin

Carpencillin Pipercillin

Ampicillin Amoxicillin

Cloxacillin Flucloxacillin

Nafcillin

Penicillin G Penicillin V

members

Resistant gram ve bactiria

Mainly ve BACILLI also +ve BACILLI & cover all previous

one .

Gram +ve & -ve COCCI, only +ve BACILLI

"narrow spectrum"

spectrum

Unstable So should taking

parenteral

Stable So it can take it oral

Stable So it can be

oral taking

G unstable V stable

GIT stability

Yes LLLL Yes LLLL NO Yes LLLL Affect by lactan enzyme

Chemotherapy .. ( 2 / 5 ) CLINICAL USES OF PENCILLIN:

Therapeutic uses:

1-tretment of Meningococcal meningitis "penicillin can't cross BBB in normal states, it can cross inflamed BBB as in case of meningitis" 2-tretment of streptococcal infection "in form of sore throat, sub acute bacterial endocardaitis

""SABE" 3-tretment of typhoid fever "a fever affecting stomach & GIT" 4-tretment of pneumococcal pneumonia 5- treatment of syphilis and gonorrhea 6-tretment of Tetanus and gas gangrene PROPHYLACTIC USESE: 1-prevent Recurrence of rheumatic fever 2-prevent occurrence of SABE "sub acute bacterial endocarditis"

*Why should an inflamed tonsil "in form of tonsillitis" more than 3 times per Year , must be removed? CAUSE Streptococcal bacteria has protein in its wall called M protein which is similar to a protein in the heart , so the immune system is attacking at the same time the infected pharynx and the heart , and with the recurrence of infection many times 'SABE' might develop . *IF Penicillin is used as prophylaxis, a new preparation of penicillin must be used which is (long acting penicillin) Long acting penicillin eg : Benzathine given : once per month for people up to 18-20 years IM "the muscle act as reservoir, releasing the drug gradually" 1.2 million units used as prophylaxis taken since childhood to high risk individual till age of 18 or 20 years .

If the patient already have sub acut bacterial endocarditis ? Amino glycosides can be used (used and reserved for serious cases as sub acute bacterial endocarditis , septicemia , Bacteremia , peritonitis, recurrent UTI ,etc) but not used in mild infectious a pharyngitis or mild UTI, but it might lead to dangerous side effects as deafness and renal failure .

* Amino glycosides when used to treat SABE it needs the presence of peincillin, cause penicillin act on distruction of cell wall and inhibit it synthesis and Amino glycosides act on inhibition of protein synthesis, so as if penicillin is opening the way for Amino glycosides to act inside the streptococcus bacteria . *Is it allowed to mix both penicillin and Amino glycosides in the same syringe and give it to patient? NO, its not allowed to avoid precipitation which affect the concentration of the drug, so the solution for this is by giving the penicillin in one syringe then after 2-3min give the Amino glycosides in another syringe .

Adverse effect of penicillin: P E N I C I L N 1-Platlet dysfunction thrombocytopenia increase bleeding tendency . SO dont give it with other drugs that bleeding tendency as warfarin . 2-Edema, rash, bronchial asthma, anaphylactic shock hypersensitivity "because of the present of -lactam group which is might be considered by some individual immune system as hatpin which can cause activation of the immune system so avoid injection of penicillin till after an allergy test " 3-Nephrotoxicity up to renal stones 4-Injection pain, so add procaine to penicillin "local anesthesia" to decrease pain 5-Cation disorder with ticarcillin 6-Loss of stool "Diarrhea" 7-Super infection with extended spectrum "kills also normal flora" 8-Neurotoxicity

Cephalosporin "cell wall inhibitor from -lactan group :

4th 3rd 2nd 1st cefepime Ceftriaxone cephamycins cefazolin

cephalexin #Cef tri axone: can pass through BBB , bone and bile We can use it with patient with renal failure pass with bile We can use it with osteomyelitis pass bone We can use it with meningococcal meningitis pass through BBB Clinical uses OF cephalosporin: Clinical uses of cefatoriaxon are just like penicillin With the addition of Bone infection due to its ability to pass the bone , Bilary infection due to its ability to pass through the bile unlike penicillin . The same as penicillin + biliary tract infection + bone infection Adverse effect cephalosporin: 1-Platelet dysfunction"thrombocytopenia" 2- Edema, rach, bronchial asthma, anaphylactic shock hypersensetivity due to the presence of -lactam . 3- Nephrotoxicity up to stones 4- Injection pain "I.M" 5-Thrombophelebitis (inflammation of the vain when given I.V), causing the walls of the veins to stick causing thrombus so to avoid this problem by injection saline after cephalosporin injection .

Chemotherapy .. (3 / 5 )

Carbapenems monobactams Brood spectrum Narrow spectrum

Given : IV IV , IM Act on : GRAM +VE / - VE GRAM - VE Effect : Aerobic / Anaerobic Aerobic

* when he mention this drugs can effect on anaerobic bacteria that mean can use it for treatment of dental and bone infection eg : Carbapenems .

Cell wall inhibiters

-lactam antibiotic Vancomycin Bacitracin MODE OF ACTION : inhibites cell wall formation , used for treatment of : A substitute for -lactam in case allergy . B severe staph infection especially : osteomyelitis , carditis . C pseudo membranous colitis . * clindamycin = for dental infection ( anaerobic infection ) like Carbapenems , if taken more 10 days or one week it will kill normal flora and other organism ( clostridium difficult ) take upper hand and prduce toxins = ulcers . Treatment pseudo membranous colitis : 1) Vancomycin : kills the source of toxins . 2) cholestyramine : bind toxins and release it out of the body . Adverse effect of Vancomycin : 1) red man syndrome : Vancomycin release histamine in huge amount causing rash , urticaria , redness , so before use Vancomycin use : antihistamine drugs . 2) ototoxicity : Vancomycin can destroy the vestibule ocular nerve 3) fever , rigors , chills : when we injected Vancomycin IV : cuz an allergic reaction + its taking only IV not absorbed orally exept in : pseudo membranous colitis . 3) Bacitracin : stable nowadays as cream of skin infection . If given in systematic routs renal failure .

Drugs dealing with proteins

Tetracycline : 4 memrane : ( tetra- , mino- , dexy- , demeclo- ) -cycline : Clinical uses of Tetracycline : Acne , ameba . Brucella , biliary infection . Cholera , clylamedia Mycoplasma , meningococol carrier . * meningocovocal carrier = the organism is present in the nasal secretion and sliva . * meningocococal meningitis = the organism is present in brain so tetracycline cant cress the BBB . * minocyclin is the treatment of choice for menococal carrier Pharmacokinetics of Tetracycline : 1) absorption : its absorption is incomplete if taken orally it absorption is zero if given with food containing ca , Fe , AL , Mg . 2) distribution : crated in bone and teeth can cross the placenta , secreted with milk . 3) metabolism : in liver 4) excretion : in kidney expect doxycycline , doxycycline: renal impairment and biliary infection ( excreted in urine , bile ) Adverse effect of Tetracycline : 1) epigastric pain : if taken with milk forming unabsorpable chelate causing pain . 2) teeth discoloration : bone hypoplesia : no Tetracycline in pregnant or less than 8 years . 3) phototoxicity 4) hepatotoxicity . 5) fanconi's syndrome : renal tubular dysfunctional , glucosuric , renal failure , when happened ? if we take autodated Tetracycline .

Tetracycline

clindamycin chloramphenicol aminoglycoside

macroclines

Chemotherapy .. ( 4 / 5 ) Drugs dealing with proteins

2) aminoglycoside is group of drugs : members are : ( streptomycin , gentamicin , nathamycin , neomycin , amikacin) . * spectrum = gram ve ( aerobic ) , aminoglycoside : must enter the body of bacteria by carrier and this carrier depend on oxygen . Pharmacokinetics of aminoglycoside : 1) absorption : not absorbed orally ( injected better ) . 2) distribution : cant cross BBB , EVEN if inflammed , its concentrated in endolymph and perilymph of inner ear and renal cortex . 3) metabolic : in liver . 4) exaction in : kidney . Clinical uses of aminoglycoside : 1- SABE with penicillin 2 peritonitis 3- septicemia 4 hepatic coma

Adverse effect of aminoglycoside : 1) nephrotoxicity : large dose , long duration , old age , dehydration , concomitant with other nephrotoxic drugs . 2) ototoxicity : compilations with frusemide . 3) neuromuscular paralysis : it inhibits Ca+2 entry into nerve terminal .


microclines : (clairthromycin , azithromycin , roxythromcin , erthromycin ) Clinical uses of microclines : 1- Chylamedial infection in pregnancy 2- Allergy with B-lactam 3- Mycoplasma in child < 8 years

Tetracycline


microclines

Tetracycline


microclines

Adverse effect of microclines : 1-thrombophelebitis 2- ototoxicity 3- epigastric pain 4- cholestatic jaundice 5-drug interaction : erthromycin + warfrin :bleeding tendency . And digoxin + erthromycin : kill the patient by killing the flora and the digoxin will be absorbed completely .


Clindarycin: use mainly in anaerobic infection (dental - leg )infection adverse effect : pseudo-membranous colitis .


Chloramphenicol Clinical uses : 1) anaerobic brain abseess 2) Haemophilus influenzae meningitis 3) Typhoid 4) Eye infection Adverse effect of chloramphenical: 1) grey baby syndrome : with baby : hypothermia hypotension renal failure 2) Bone marrow suppression 3) Optic neuritis 4) GIT upset 5) enzyme inhibition.

Tetracycline


microclines

Tetracycline


microclines

Chemotherapy .. ( 5 / 5 )

Drugs that dealing with nucleic acid : 1- DNA inhibitors Quinolone 2-RNA inhibitors Rifampicine (Quinolone) , Mechanism of Quinolone : quinolones inhibit gyrase enzyme ,which is responsible for unwinding of the double strand DNA allowing replication to occur. First generation of Quinolone (non flurinated Quinolone): Naldixic acid not used nowadays , only used in UTI , It is not used much cause it`s highly bound to plasma proteins Up to 90 to 95% meaning that it has slow release allowing new resistant strain To bacteria develop ( cause in such case almost 90% Naldixic acid is inactive and just 10% is active . Second generation Quinolone : ( flurinated Quinolone ) : The fluorine inhibit plasma protein binding to drug . All the flurinated quinolone end with the suffex (floxacin) .

4th generation 3rd generation 2nd generation

Clinafloxacin Levofloxacin Ciprofloxacin

------------ ------------- Ofloxacin ------------ ------------- Pefloxacin ------------ ------------- Norfloxacin

Mainly Gram + / less - Anaerobic

Equal Gram -/+ Aerobic

Mainly Gram -/ less + Aerobic

Drug used in anaerobic infection : 1-carbapeniem 2-clindamycin 3-chloramprencol 4-clinafloxacin * Clinical uses of Quinolone : TRUST 1- typhoid fever : 1st choice , Ciprofloxacin . 2- respiratory tract infection : pneumonia caused by mycoplasma . 3- UTI , prostatitis , gonorrhea : only 1st choice injection of ofloxacin . 4- soft tissue , bone infection . 5- T.B resistant type .

Adverse effect of Quinolone : 1) artrpathy : if given below 18 years , quinalone will convert one part of the cartilage into bone leading to redundancy in the ligaments and pain in the joints . 2) nausea , vomiting , diarrhea ( GIT upset ) . 3 ) headache , dizziness . 4) hepatotoxicity . 5) drugs interaction : its an inhibitor drugs its also need acidic media to be absorbed . so dont give it with antacid .

RNA inhibitors: ( Rifampicin ) .. ( rifampicin , rimactane , rifadin) -Rna inhibitor -high bacterial Resistantwas used in TB treatment but not anymore due to resistant . -Red color of sweat ,urine ,tears ,saliva&lens coleration. - flue like syndrome (sneezing) .. REMMEBER ALL PREVIOUS SYNDROMES : *red man syndrome by vancomycin *gray baby syndrome by chloramprenicol *flue like syndrome by rifampicin *fanconi's syndrome by outdated tetracyclic -Rash -BRucella infection (1st choice in brucella infection) -enzyme induceR (the only inducer antibiotic is rifampcin,all other are inhibitors) . -main drug in meningitis prophylaxis. * If rifampicin is given with contraceptive drug , explain what will happen? Rifampicin is an enzyme inducer causing increase in the activity of liver enzyme , the contraceptive drug will be distracted so pregnancy might happen. * Antibiotics inhibiting metabolic pathways: Antimetabolites : acting on folic acid (sulfonamides) PABA folic acid folinic DNA & RNA * what are the antimetabolite so for: 1-sulfonamides EX : sulfamethoxazole : inhibit DHPS 2-trimethoprim : inhibit DHFR * if either (sulfamethoxazole or trimethoprim) used alone it will be narrow spectrum , less potent , high resistance and static . * so a combination of both ( sulfamethoxazole + trimethoprim ) will be used in drug Called : cotrimoxazole , MEANS : CO : Combination , TRI : trimethoprime , MAXAZOLE : sulfamethoxazole . * sulfamethoxazole : safe , becomes its selective for bacteria . * trimethoprime : toxic , because it's not selective .

Sulfonamides : * clinical uses of sulfonamides: 1- eye infection sulfacetamides 2-burnssulfadiazine 3-colitissulfasalazine 4-malaria sulfadoxine & sulfamethoxazole. Adverse effects of sulfonamides : CHHIK 1-crystaluria sulfonamideshould be taken with high amount of 2 liter of water 1 day to avoid sulfonamide deposition . 2-hemolytic anemia in case of G-6P dehydrogenese deficiency . 3- hypersensitivity (due to sulfer group) 4-drug interation (high drug interaction) *it's an enzyme inhibitor. *it displace other drugs ( eg :if taken with warfarin it will cause cerebral hemorrhage). 5-kernictrus (which is preventable mental retardation &deafness) . *drug related to age : 1-sulfonamides forbidden completely in new borns 2-chlorapheicol forbidden completely in new borns 3- tetracycline forbidden below 8 4-ciprofluxacin forbidden

chemotherapy

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