Antibiotics , Protein Synthsis ,DNA Inhibtor , Cell Metabolism ,Metabolits Inhibtors , TB , Others Flashcards
classification of protines synthisis antibiotics
a) Antibiotics targeting the 50S ribosomal subunit
macrolides
lincosamides
chloramphenicol
б) Antibiotics targeting the 30S ribosomal subunit
aminoglycosides
tetracyclines
Explain The Proteins synthesis Inhibitors ( Aminoglycosieds ) Drugs , chemistry , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
-Drugs :
1-Streptomycin Pwdr 1st gen
2-Gentamicin amp 2gen
3-Amikacin pwdr 3 gen ( synthetic drug)
-Chemistry : Consists of NH2+ amino group and glycoside : sugar , And hydroxyle group which is mean ita water sulable
-Pharmacokinetics:
1-Absorption: not orally duo to inozed charge
2-Distribution:
2-1 Not Pass BBB , but pass placenta and its tetaroginic , breast milk Pass ( and its not tetarogenic ) bcs its not absorbed orally
3-Metabolism: in liver
4-Excretion : kidney, high concentration and unchanged and increases alkalinity of urine , Normally Ph of urine is 5.8 so the drug are more used in alklain urine which is needed to treat UTI
—Mechanism of action :
-its inhibit the protein synthesis by binding irriverasbly in the 30s subunit ribosome , which lead to error in the mRNA reaching and formation of functional abnormal proteins
-In details it consists of 3 phases :
1-Attachment: which the amino group NH2+ have positive charge , there will be attraction (Electrostatic Attraction ) bcs the outer membrane of the gram - its consist of negative charge
2-open pores : the outer membrane pores will open only incase of needed of nutrients and the aminoglycosides are similar to the nutrients so the pores will open and the drug molecules will enter
3-irreversible bond : once the drug reached the nucleus there is the ribosomes 30s subunit and it will bind to it irreversibly and inhibit mRNA translation
-Spectrum: they are bactriocidal ( broad spectrum shifted towards Gram -) duo to :
1-Mainly gram - : Entrobactria , Pusdomonas (2gen ,3gen ) , mycobacteria ( 1gen , amikacin )
2- few gram + : staphylococcus
3-TB
-Resistant:
1-P,Coccai
2- Anearobic and intercellular pathogen such as. (Calm my leg )
3-Cant be used for acquired
resp infection
-Uses :
1-Gram - infection: E coli UTI
3-Resp infection
4-Gram - spetecymi
5-TB : Streptomycin , Amikacin
-Side effect :
1-Neohrotoxcity : duo to exacration of this drug in renal , and bcs has + charge and can bind to Kidneys proteins
2-Nerve toxicity 8th cranial : the molecule of this drug enters the inner ear and cause toxicity to the 8th cranial nerve ( vitebular and auditory ) and cause deafness duo to accumulate in the endolymph of the inner ear
3-NMB : muscle weakness, we can reverse it with Neostagmine
—Dosage : 5mg per kg and its concentration killing dependent
Explain The Proteins synthesis Inhibitors ( macrolides ) Drugs , chemistry , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
-Drugs :
1-Erythromycin tab/pwdr 1gen
2-Clarithromycin tab/pwdr 2gen
3-Azithromycin tab 2gen
—Chemistry : consists of macrolacton ring , and sugar and its MW more then 500
-Pharmcokintics:
1-Absorpation : poor and deceased by food
2-Distribution:
2.1 BBB : not pass
2.2 Placenta / breast milk : pass and they are not teratogenic
2.3 body fluids : they reach most body fluids with good concentration ( they have selective distribution to neutrophils and phagocytes
3-metabolism: in liver
4-Execration : they are execrated through liver billary and entrohepatic circulation, thats why they are heptao toxic,
-NB! 1gen is not stable in acid stomach so low bioavailability and short half life , 2nd generation is the opposite
-mechanism of action : they bind reversible to 50s subunits of the ribosomes and inhibit peptide transferase , and inhibit elongation of proteins, which block the translocation of ribosomes to the next Codon on the mRNA
-Spectrum: Bacteriostatic / Concentration dependent, Spectrum:
1-Mainly G +
2-Intercellular pathogens: Calm my leg
3-H.Pylori : Clarithromycin
-Resistant: in the case id macrolides the bacteria becomes resistant in approximately 10 days by changing the 50s binding site
-uses :
1- Gram +
2-Atypical organisms
3-otaits media
4-sinuses
-Advera effect :
1-GIT upset
2-Cholistatic hepatitis: duo to accumulation in liver entrohepatic circulation, inhibitory of CYP450
3- Ototoxcity
4-Prolongation of QT interval : which could cause a ventricular arrhythmia
-C.I : combination of macrolides and penicillins
Explain The Proteins synthesis Inhibitors ( Lincosamides ) Drugs , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
-Drugs :
1-Lincomycin Tab/amp ( prototype)
2-Clindamycin tab/amp (synthetic drug )
-Pharmcokintics:
1-Absorpation : complete
2-Distribution:
2.1 BBB : yes / Can treat CNSI
2.2 Placenta / breast milk :pass but mo teratogenic
2.3 body fluids :reach , and has selective distribution on bone and joints ( osteomyelitis)
3-metabolism: liver
4-Execration : through bile
-mechanism of action : its bind in the same site of microlieds in the 50s subunits and inhibits piptiedly transferase which is lead to decrease peptide elongation
-spectrum: bacteriostatic
1-gram + Aerobic bacteria : strepto , stephy , P.cocci
2-gram - Anearobic
3-Protosa : malria , Toxoplasma
-Resistant: easy and rapid and if the bacteria get resistant from macrolids it will be resistant to lincosamides also
-uses :
1-Dental infection: because most of oral infections its Anearobic bacteria and duo to selectively bone and joints
2-Osteomyelitis
3-Toxic shock syndrome : such as staphylococcus produce Exotoxins, we cant use bactriocidal bcs it will spread the Exotoxins
-Advera effect :
1-Clostridium defissil
Explain The Proteins synthesis Inhibitors ( tetracycline) Drugs , chemistry , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
-Drugs :
1-Tetracycline Tab
2-Doxycycline tab/pwder
—Chemistry : there MW less then 500 , and they consist of hydroxyl group which is mean they are water sulable
-Pharmcokintics:
1-Absorpation : incomplete duo to water sulablety , food decrease teh absorption and they are make complex with the metals ( doxycycline is more absorbed)
2-Distribution:
2.1 BBB : not pass
2.2 Placenta / breast milk :pass and its teratogenic
2.3 body fluids :reach
3-metabolism: liver , and exctinssive metabolism , duo to entrohepato circulation
4-Execration : mainly kidney , but they cant Treat UTI duo to extansive metabolism in liver and the drug becomes inactive , but doxycycline’s 50% renal and 50% bilary which can use with patient with renal impairment, but in the same time they are hepatotoxic duo to entroheptaic circulation
-mechanism of action :they are binding reversiblly to 30s subunyand inhibiting the binding of Aminoacyl-tRNA to The Aminoacyl-Centre which is lead to disrupting the early stage of translocation-imitation
-spectrum: broad spectrum/ bacteriostatic
1-most G+ but not Staph
2-most G- but not pausdomonas
3-most of Anearobic bacteria ( CL difesil )
4-Atypical organisms ( Calm my leg ) + borrlia , Reckissia , Coxilla
5-Protozoa : malaria , Toxoplasma ( bind to 40s )
-Resistant: Cross resistant easily and rapid
-uses :
1-Sexual transmitted infections : in patients who has tolerance to B lactamse
2-Pneumophil ( Ligunla )
3-peptic ulcer
4-dangerous infection; Plague , cholera , Antha
4-Zoomases ( loptosorosis , bracellosis )
5-Intracellular pathogens: such as lyma disease, Ricksosis , Q fever )
6-Acne
-Advera effect :
1-GIT upset
2-teeth and bone : ditrubunce of skeleton formation deposition in bone and teeth leading leading to ( Colouring the enamel in yellow-Brown color )
3-Cholistatic hepatitis: liver cell injury, hepatotoxic, Hypertophy of the hepatocyte
4-Photosensitivity
-C.I :
1-Allergies from tetracycline
2-Children under 8 years
3-Pregnancy
4-Liver impairment
Explain The Proteins synthesis Inhibitors ( chloramphenicol ) Drugs , chemistry , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
-Drugs :
1-Chloramphenicol
—Chemistry :consist of OH group which mean its very lipid suable, also its MW its less then 500 , Consist of 2 Molecules of Chloride which increase the activity against bacteria and increase toxicity
-Pharmcokintics:
1-Absorpation : Complete and the food doesn’t effect
2-Distribution:
2.1 BBB : Pass and can treat CNSI
2.2 Placenta / breast milk :pass and teratogenic ( gray beby syndrome)
2.3 body fluids :reach with high concentrations
3-metabolism: in liver by Glucronic transferase , Cant be given to child under 2 years bcs unwill development of Glucrinc transferase enzyme
4-Execration : bilary 90%
-mechanism of action :bind to 50s subunit and inhibit peptidyl transferase enzymes and decrease peptides elongation
-Resistant: cross resistant duo to modifications or blocking proteins which synthesis by bacteria in the binding site or by synthesis of CAT ( Chloramphenicol acetyl transferase ) and bind to the drug which change its structure and cannot bind to the binding site of the ribosomes 50s
-spectrum: bactriostatic ( Braod spectrum)
1-Gram +
2-Gram -
3-Anaerobic bacteria
4-Atypical organisms: calm my leg , BCR
-uses : its only used as 3rd choice
1-atypical organisms
2-typhoid fever
3-meningitis
-Advera effect :
1-BM suppression :sever irreversible ( Aplastic anaemia : complete BM failure)
2-grey baby syndrome : duo to immaturity of glucronic transferase and the first 2-4 weeks of life and , also functional immaturity of renal tubules impaired execration
3-Dermatitis
4-Neurotoxicity : Paychosis , prephrial neuropathy
-C.I :
Explain The DNA-RNA Inhibitors ( Quinolons and floraquinolons ) Drugs , chemistry , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
-Drugs :
1gen-Nalidixic acid tab ( prototype ) -ve
2gen-Ciprofloxacin tab/amp 8h , -ve
3gen-Levofloxacin Tab/amp -ve,+ve,Atypical 12h
4gen-Moxifloxacin tab -ve,+ve,atypical,anaerobic
—Chemistry : consist of Floride , and MW its more then 500 , lipid sulable
-Pharmcokintics:
1-Absorpation : Complete, make complex with metals but not like Tetracycline
2-Distribution:
2.1 BBB : Pass and can treat CNSI
2.2 Placenta / breast milk :pass and teratogenic
2.3 body fluids :good accumulation of phagocytes
3-metabolism: liver
4-Execration : renal and unchanged so are capable of treating UTI except Moxifloxacin
-mechanism of action : its inhibit the bacterial Topisomarse which is required for relaxation of The DNA to form a RNA masenger to form a new DNA , we have 4 type of topisomarse 1,2,3,4 these drugs inhibit 2nd ( gyrse ) and 4th especially in :
1-Gram - : gyrase
2-Gram + : topisomarse 4th
-spectrum: bactericidal ( broad spectrum)
1-Nalidixic acid : mainly G-
2-Ciprofloxacin : Mainly G- , few G+
3-Levofloxacin : G-,G+ , Atypical
4-Moxifloxacin : G-,G+,atypical,Anearobic
-resistant: Cross resistant but not raoid duo to point mutation in the gyrase and topisomarese
-uses :
1-UTI
2-Resp infection
3-osteomyelitis
4-meningitis
4–Atypical
-Advera effect :
1-Muscloskletal adverse effect : cause arthropathy in the growing cartilage
2-CNS : increase seizures, duo to inhibation of GABA Receptor
3-prolangtion of QT interval : leading to fetal ventricular tachy arrhythmias
-C.I :
2-Pregnancy
2-children under 18
Explain The Bacterial metabolites Inhibitors ( Sulfonamides , Trimethroprim ) Drugs , chemistry , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
-Drugs :
1-Trimethoprim/sulfamethoxazole tab ( Bactriocidal )
2-Sulfadiazine argentum oint 1%-50ml
—Chemistry : they consist of sulfer group and amino acid group ( So2NH2) this what is responsible for the effect but the R chain is only for pharmcokintics
-NB!
1-individual drug : bacteriostatic
2-Combined drug : bactriocidial
-Pharmcokintics:
1-Absorpation :good
2-Distribution:
2.1 BBB : pass and can treat CNSI
2.2 Placenta / breast milk :pass and its tertaoginic
2.3 body fluids :good reach
3-metabolism: liver
4-Execration : renal in acetylation metabolite with good concentration and can treat UTI , but we should alklain the urin first or it will lead to crystallurea
-mechanism of action :they are bacterial metabolites inhibitors of folic acid which us essential for DNA synthesis , in the norm , the bectrai synthesis the folic acid by this pathway :
-Paraaminobenzonic acid with help of Dihydroprotrate synthase transfer into dihydrofolic acid then with help of Dihydrofolate reducatse transfer into tetrahydrofolic acid then to purines then to DNA
- so the sulfa interfers with the first dihydroprotrate synthase but bacteria with time can modify it , but the Trimethoprim interferes with dinydrofolate reductase
- So now we useing the combination called Co-trimoxazol = Trimethoprim +Sulfamathoxazol to interfere the both phases
-spectrum: wide spectrum ( narrow )
1-few G+
2-Few G-
3-Atypical organisms
-uses :
1-UTI
2-Streptococcal
3-Puemocystis carinii ( PCP )
4-Toxoplasma
-Advera effect :
1-Allergy skin rash : Steven Johnson syndrome
2-Crystallurea
3-Kernectrus : displacement of billerubin in the albumen and can pass CNS in childrenunder 2 years the BBB not will developed and can cause permanent brain damage
4-BM suppression
-C.I :
1-Children under 2 years
2-Pregnancy
Explain The Bacterial metabolites Inhibitors ( metronidazole ) Drugs , chemistry , Pharmcokintics, Mechanism of Action , resistance, Spectrum, Uses , adverse effects
Drugs : Metronidazole tab/Amp
—Chemistry :consist of Nitro group and Mw its 137 ( prodrug )
-Pharmcokintics:
1-Absorpation :Complete
2-Distribution:
2.1 BBB : Pass and can treat CNSI
2.2 Placenta / breast milk :pass and not teratogenic
2.3 body fluids :reach
3-metabolism: liver
4-Execration : renal unchanged but cant treat UTI bcs its spectrum only anaerobic bacteria and the UTI its gram - , but can discolour the urin dark brown and its not harmful
-mechanism of action :
NB! :
1-OIL : oxidation is lose of electrons
2-RIG : redaction is gain of electrons
—- the metronidazole uptake by all type of bacteria but its only effect the anaerobic bacteria bcs its mechanism works on PFOR
Pyruvate:ferrodoxine oxido reductase
Which is responsible for generation kf the ATP in the anaerobic bacteria by oxidation and reduction so as we know metronidazole consist of Nitro group so the PFOR reduction the oxygen in the Nitro group and becomes free radical compounds and unstable which is cytotoxic free radical and bind to DNA and damage the DNA
-Resistant: its very slow or by efflux ( pumping out )
-spectrum: bactericidal
1-All Anaerobic bacteria
2-Protozoa :Entomoab hustolytica
3-Tricomons viginitis
-uses :
1-Anaerobic bacteria
2-Clustridum defesil
-Advera effect :
1-GIT upset
2-Metallic taste
3-CNS toxicity : headech , increase seizures in epileptic patients
4-Steven jhonsn syndrome
5- Sever BM suppression
-
explain Nitrofurans
- bactericidal
- broad antibacterial spectrum including some protozoa
- Oral drug forms
- ## Uses is limited-Drugs :
1. Non-absorbable from GIT : Nifuroxazide tab
Is used in acute bacterial diarrhea
2.Systemic use
-Furazolidone - intestinal and biliary infections
-Nitrofurantoin - urinary tract infections
-Nifuratel
explain Oxazolidinones , mechansim , spectrum , C.I
-Drug : Linezolid (T 0,6; A 0,2% - 100 ml)
-mechansim :. inhibits protein synthesis (binding to the P site of the 50S ribosomal subunit and preventing formation ribosomal
complex)
-Spectrum : is effective against Gr(+) bacteria including MRSA,
Vancomycin resistant enterococci (VRE), Gr(+) anaerobes
* Linezolid is bactericidal against streptococci, pneumococci and B. fragilis and bacteriostatic against enterococci and
staphylococci.
-C.I :is a weak reversible MAO inhibitor. Linezolid is contraindicated in patients taking any drug which inhibits MAO A or B, in patients with uncontrolled hypertension
explain the Isoniazid for treatment of TB , mechansim ,spectrum , advers effect ,
-drug : Isoniazid Tab 0.3 Amp
-mechansim : Mechanism of action
* It is a prodrug activated by a mycobacterial catalase–peroxidase.
* It targets the enzymes which are essential for synthesis of mycolic acid.
* Inhibiting mycolic acid leads to a disruption in the bacterial cell wall.
-Antibacterial spectrum: M. tuberculosis
-Side effect :
1.Hepatitis
2.Neurotoxicity (Due to a relative pyridoxine deficiency. This can be avoided by supplementation of 25-50 mg per day of pyridoxine).
* Peripheral neuropathy
* Convulsions in patients prone to seizures.
