This document discusses the basic principles of chemotherapy. It provides a history of chemotherapy beginning in the 19th century with Pasteur and Koch's germ theory of disease. Early developments included Ehrlich's discovery of arsphenamine to treat syphilis. Later discoveries included sulfa drugs, penicillin, streptomycin, and other antibiotics produced by soil microbes. The document discusses the mechanisms of several classes of antimicrobial drugs including those that inhibit cell wall synthesis, protein synthesis, and nucleic acid synthesis. It also covers the desirable properties of chemotherapeutic agents and issues like resistance.
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
synthetic antimicrobials having a quinolone structure that are active primarily against gram-negative bacteria, though newer fluorinated compounds also inhibit gram-positive ones.
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
Basic principles of chemotherapy/ AMAs covers definition, history of AMAs development, principles of AMAs, problems associated with AMAs, failure of therapy with examples.
synthetic antimicrobials having a quinolone structure that are active primarily against gram-negative bacteria, though newer fluorinated compounds also inhibit gram-positive ones.
Malignancy is most familiar as a characterization of cancer.Chemotherapy is a category of cancer treatment that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
My all and slides mostly try to simplify pharmacy knowledge. Any time you are free to connect me. It's my pleasure to help you to get simplified pharmacy concepts. You may suggest topics needs to simplify the terminolog
Anthelmintics | B.Pharm 3rd year 2nd Sem | Medicinal Chemistry-III | History, Classification, Structures & Synthesis of anthelmintics, Synthesis of Diethylcarbamazine citrate, Synthesis of Mebendazole
My all and slides mostly try to simplify pharmacy knowledge. Any time you are free to connect me. It's my pleasure to help you to get simplified pharmacy concepts. You may suggest topics needs to simplify the terminolog
1. chemotherapy principles and problems JagirPatel3
The objective of chemotherapy is to study and to apply the drugs that have highly selective toxicity to the pathogenic microorganisms in the host body and have no or less toxicity to the host, so as to prevent and cure infective diseases caused by pathogens
Bacteria have their own enzymes for
1. Cell wall formation
2. Protein synthesis
3. DNA replication
4. RNA synthesis
5. Synthesis of essential metabolites
Relative or complete lack of effect of antimicrobial agent against a previously susceptible microbe/pathogen.
It is an evolutionary principal that organism adopt genetically to change in their environment.
since the doubling time of bacteria can be as short as 20 mnt, there may be many generations in even a few hours, providing ample opportunity for evolutionary adaptation.
The phenomenon of resistance imposes serious constraints on the options available for the treatment of many bacterial infections.
The resistance to chemotherapeutic agents can also develop in protozoa, in multicellular parasites and in population of malignant cells.
Today there are different strains of S. aureus resistant to almost every form of antibiotic in use.
The Pharmacovigilance Programme of India is an Indian government organization which identifies and responds to drug safety problems. Its activities include receiving reports of adverse drug events and taking necessary action to remedy problems.
Human ear, organ of hearing and equilibrium that detects and analyzes sound by transduction (or the conversion of sound waves into electrochemical impulses) and maintains the sense of balance (equilibrium).
A disorder of the central nervous system that affects movement, often including tremors.
Nerve cell damage in the brain causes dopamine levels to drop, leading to the symptoms of Parkinson's.
Parkinson's often starts with a tremor in one hand. Other symptoms are slow movement, stiffness and loss of balance.
Treatment consists of medications to increase dopamine.
Neurotransmitters are chemical messengers that your body can't function without. Their job is to carry chemical signals (“messages”) from one neuron (nerve cell) to the next target cell. The next target cell can be another nerve cell, a muscle cell or a gland.
Hallucinogens are a type of drug that changes a person's perception of reality. Also known as 'psychedelic drugs', hallucinogens make a person see, feel and hear things that aren't real, or distort their interpretation of what's going on around them
endocrine system is made up of several organs called glands. These glands, located all over your body, create and secrete (release) hormones. Hormones are chemicals that coordinate different functions in your body by carrying messages through your blood to your organs, skin, muscles and other tissues
Stimulants work by acting on the central nervous system (CNS) to increase alertness and cognitive function. Stimulants can be prescription medications or illicit substances, such as Cocaine. Stimulants may be taken orally, snorted, or injected. If you have a Stimulant addiction, seek help today.
Local anaesthesia involves numbing an area of the body using a type of medicine called a local anaesthetic. These medicines can be used to treat painful conditions, prevent pain during a procedure or operation, or relieve pain after surgery
Myasthenia gravis is a chronic autoimmune, neuromuscular disease that causes weakness in the skeletal muscles (the muscles that connect to your bones and contract to allow body movement in the arms and legs, and allow for breathing).
Skeletal muscle relaxants are drugs that act peripherally at neuromuscular junction/ muscle fibre itself or centrally in the cerebrospinal axis to reduce muscle tone and/or cause paralysis. • A muscle relaxants is a drug that affects skeletal muscle function and decreases the muscle tone
A joint is a point where two bones make contact. Joints can be classified either histologically on the dominant type of connective tissue functionally based on the amount of movement permitted. Histologically the three joints in the body are fibrous, cartilaginous, and synovial.
DNA Gyrase Inhibitors -quinolones and Fluoroquinolones.pptxVijay Salvekar
DNA gyrase inhibitors of synthetic origin. Fluoroquinolones have been the most successful antibacterial agents targeting DNA gyrase. These compounds have been extensively explored and researched to improve spectrum of activity, potency and bacterial resistance.
biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems
Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain.
Anatomy refers to the internal and external structures of the body and their physical relationships, whereas physiology refers to the study of the functions of those structures.
Alzheimer's disease is a progressive neurologic disorder that causes the brain to shrink (atrophy) and brain cells to die. Alzheimer's disease is the most common cause of dementia — a continuous decline in thinking, behavioral and social skills that affects a person's ability to function independently.
Anti-anxiety medications help reduce the symptoms of anxiety, such as panic attacks or extreme fear and worry. The most common anti-anxiety medications are called benzodiazepines. Benzodiazepines are a group of medications that can help reduce anxiety and make it easier to sleep.
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells.
Neurons (also called neurones or nerve cells) are the fundamental units of the brain and nervous system, the cells responsible for receiving sensory input from the external world, for sending motor commands to our muscles, and for transforming and relaying the electrical signals at every step in between.and A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Skeletal muscle is one of the three significant muscle tissues in the human body. Each skeletal muscle consists of thousands of muscle fibers wrapped together by connective tissue sheaths. The individual bundles of muscle fibers in a skeletal muscle are known as fasciculi.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. CHEMOTHERAPY:
Is a term that applies to the use of both natural
and synthetic chemicals to interfere with the
functioning of the foreign cell population.
The Synthetic chemical substances used to
inhibit or destroy microorganisms. (ie bacteria).
The term is used for both treatment of cancer
and treatment of Infection.
3. 19th Century
LOUIS PASTEUR & ROBERT KOCH: Identified
bacteria as causative agent of disease. (Germ theory)
(Now know what is causing disease, need to find out how
to stop it)
1877 Pasteur: Soil bacteria injected into animals
made Anthrax harmless
1888 de Freudenreich: Isolated product from bacteria with
antibacterial properties. Toxic and
The Development of Chemotherapy
4. Early 20th century
1904: Paul Ehrlich is pioneer researcher found that
the dye trypan red was effective against Trypanosoma
(sleeping sickness)
Arspheniamine against syphilis
1st antibacterial, only cured syphilis.
Systemic infection : Blood stream
Enunciated : 1906 Therapia Sterilizans Magna
Published :Magic Bullet
5. Paul Ehrlich:
Quinine : Malaria
Various Dyes (Gentian Violet); Disinfectants
Heavy Metals : Antimicrobial Agents
Fight against systemic infection and acknowledged
as the Father Of Chemotherapy
6. Sulfa drugs:
1927: Domagk discovered that the dye Prontosil
Red was effective against staphlococcal and
streptococcal infections; later in 1935 it was found
that Protonsil red was converted to sulfonamide in
the body
Penicillin
Produced by Penicillium notatum
Discovered in 1928 by Fleming
Method of mass production developed in late 1930s
- early 1940s by Chain and Florey
7. Streptomycin
Produced by Streptomycin griseous
Discovered in 1944 by Waksman after screening
10,000 soil isolates
Following its discovery was the discovery of other
antibiotics produced by soil microbes, including
chloramphenicol, neomycin, terramycin, and
tetracyclin by the early 1950s
8. •Selective toxicity
•Ability of chemical strike selectively at
foreign cell and harm them without
causing significance damage to host
cells.
•Drug must inhibit microorganism at
lower concentrations than those that
produce toxic effects in humans
•No Chemotherapy is completely safe
10. Antibiotic : A chemical that is produced by one
microorganism and has the ability to harm other
microbes.
Bacteriostatic activity: Ability of compound to
inhibit the growth and multiplication of organism.
Bacteriocidal activity: Actually killing effect on
the microorganism
Antibiotic spectrum:
Broad
Narrow
12. 1- Wrong Diagnosis
2- Wrong Choice Of Drug
3- Wrong Dose
4- Development Of Resistance
5- Infections With More Than One Organism
6- Presence of Pus ,Blood ,Necrotic Tissues .
13. Microbs: Bacteria, viruses, fungi,
Parasites: Protozoa, helminths
Living Organism Are Classified :
Prokaryotic : Cell Without Nuclei. Ex. Bacteria
Eukaryotic : Cell With Nuclei ex. Protozoa,
fungi,helminths
14. Bacteria cause more infectious disease than any other parasites.
Simplicity well-developed cell structure .
16. BIOCHEMICAL REACTION AS POTENT TARGETS
Class I reaction: Not Promising Targets : 2 Reason
1st :- No Diffence b/w Bacteria And Human Cell
Mechanism for Obtaining Energy {Glucose}
ex. By EMP Pathway And TCA Cycle
2nd :- Glucose Pathway Blocked and Other Coumpound
Used By Bacteria{ AA , Lactate}
17. Class II Reaction : Better / Potent Target
• Essential Amino Acid Responsible For Growth
Ex. Synthesis Of Folate : Required For DNA Synthesis
In Human: Obtain From Diet/Not Sythesise
In Bacteria: Synthesis Own Folate
18. CLASS III REACTION :
Good Target { Macromolecules }With Selective Toxicity
Formation of skeleton ,
Protect from osmotic disruption{3 to 5 times}
23. Cell Membrane semipermiable Function With Very
Selective Permiability
{ Tripple Layered Lipoprotien Structure }
Locate: b/w cytoplasm and cell wall
Function:maintain Osmotic Pressure And Barrier
Rapid Release Of Small Molecules From Interior Barrier
b/w External ATM
Increase Permiability :Result Cell {Disorganizing Cell
Function}
24. Protein synthesis
DNA mRNA Protein
transcription translation
Ribosome is a protein factory in bacteria takes mRNA
in and produces proteins from them.
Bacterial ribosome has 2 parts:
30S binds to mRNA to translate mRNA into amino
acids, which form Proteins
50S required for Peptide Elongation
25. • 3 phases from mRNA to protein
Initiation
Elongation
Termination
Disruptive effect on many essential bacterial functions
leading to cell death
26.
27. 1. Inhibition The Synthesis of The Nucleotides:
for class II reaction
2.Altering The Base Pairing Properties of The Templet:
Framshaft mutation= misreading addition of extra base
28. 3.Inhibiting Either DNA or RNA Polymerase:
Drugs bind to Guanine in DNA and block the movement of
RNA polymerase prevent transcription leads to inhibit
protein synthesis
4.Inhibition Of DNA Gyrase:
chromosome fold around RNA core
Supercoiling by DNA gyrase {Topoisomerase II}
29. 5.Direct Effect On DNA Itself:
covalent bond with base{Prevent Replication}
Only for cancer chemo. Not for antibacterial agents
30. Ability of the drug to reach the site of infection
Route of administration
Rate at which the drug is eliminated from the
body
Susceptibility of the pathegen to the drug
Level of the drug must exceed the pathogen’s
MIC value at the site of infection
31. 1. Allergic Reactions: some people develop
hypersensitivities to antimicrobials
2. Toxic Effects: some antimicrobials toxic at
high concentrations or cause adverse effects
3. Suppression of normal flora: when normal
flora killed, other pathogens may be able to
grow to high numbers
32. Selectively toxic to microbe but nontoxic to host.
Soluble in body- tissue distribution .
Remains in body long enough to be effective -
resists excretion and breakdown.
Shelf life.
Does not lead to resistance.
Cost not excessive.
Hypoallergenic.
Microbiocidal rather than microbiostatic.
33. Mechanisms of Drug resistance
Origin of Drug Resistance in a microbial population
Drug resistance genes on chromosomes and plasmids
Transmission of resistance genes between bacteria
34.
35. 30S
1 3
2 GTP
1 2 3 GTP
Initiation
Factors
mRNA
3
1
2 GTP
30S
Initiation
Complex
f-met-
tRNA
Spectinomyci
n
Aminoglycoside
s
1
2
GDP + Pi
50S
70S
Initiation
Complex
AP
36. GTP
AP
Tu GTP Tu GDP
Ts
Ts
Tu
+
GDP
Ts
Pi
P A
Tetracycline
AP
Erythromyci
n
Fusidic Acid
Chloramphenico
l
G GTP
G GDP + Pi
G
GDP
AP
+
GTP
37.
38.
39. Chemicals used to treat microbial infections
Before antimicrobials, large number of people died
from common illnesses
Now many illnesses easily treated with antimicrobials
However, many antimicrobial drugs are becoming less
useful
42. Most modern antibiotics come from species of
microorganisms that live in the soil
To commercially produce antibiotic:
1. Select strain and grow in broth
2. When maximum antibiotic concentration reached,
extract from medium
3. Purify
4. Chemical alter to make it more stable
43. Cause greater harm to microorganisms than to host
Chemotherapeutic index: lowest dose toxic to patient
divided by dose typically used for therapy
45. Antimicrobial medications vary with respect to the
range of microorganisms they kill or inhibit
Some kill only limited range : Narrow-spectrum
antimicrobial
While others kill wide range of microorganisms:
Broad-spectrum antimicrobial
46.
47. Combinations are sometimes used to fight infections
Synergistic: action of one drug enhances the activity of
another or vice versa.
Antagonistic: activity of one drug interferes with the
action of another.
48. 1. Allergic Reactions: some people develop
hypersensitivities to antimicrobials
2. Toxic Effects: some antimicrobials toxic at high
concentrations or cause adverse effects
3. Suppression of normal flora: when normal flora
killed, other pathogens may be able to grow to high
numbers
49. Some microorganisms inherently resistant to effects of
a particular drug
Other previously sensitive microorganisms can
develop resistance through spontaneous mutations or
acquisition of new genes (more later).
50. Selectively toxic to microbe but nontoxic to host.
Soluble in body- tissue distribution – BBB.
Remains in body long enough to be effective -
resists excretion and breakdown.
Shelf life.
Does not lead to resistance.
Cost not excessive.
Hypoallergenic.
Microbiocidal rather than microbiostatic.
Concerns suppression of normal flora - antibiotic
associated colitis with Clostridium difficule and it’s
toxins or Candida albicans.
51. 1. Inhibit cell wall synthesis
2. Inhibit protein synthesis
3. Inhibit nucleic acid synthesis
4. Injury to plasma membrane
5. Inhibit synthesis of essential metabolites
52.
53. Irreversibly inhibit enzymes involved in the final steps
of cell wall synthesis
These enzymes mediate formation of peptide bridges
between adjacent stands of peptidoglycan
b-lactam ring similar in structure to normal substrate
of enzyme
Drug binds to enzyme, competitively inhibit
enzymatic activity
54. Some bacteria produce b-lactamase- enzyme that
breaks the critical b-lactam ring
b-lactam drugs include: penicillins and
cephalosporins
55.
56. Acid-labile.
Gram+ bacteria.
So, take phenoxymethylpenicillin.
Large Vd, but penetration into brain: poor, except when
the meninges are inflammed.
Broad spectrum penicillins: amoxicillin and ampicillin
are more hydrophillic and therefore, are active against
gram- bacteria.
57. Penicillinase-resistant penicillins – Flucloxacillin
Indicated in infections caused by penicillinase-
producing pen-resistant staphlococci.
Has an isoxazolyl group at R1 sterically hinders
access of the enzyme to the β-lactam ring.
Less effective than benzylpen.
So, should be used only for pen-resistant infections.
Well-absorbed orally, but in severe infections,
should be i.v. and not alone.
Staphlococci aureas-resistant strains to flucloxicillin
and MRSA (methicillin-resistant Staph aureas) –
increasing problem.
58. Ampicillin and amoxicillin – very active against non-β-
lactamase-producing gram+ bacteria.
Because they diffuse readily into Gram- bacteria, also very
active against many strains of E. coli, H. influenzae, and
Salmonella typhimurium.
Orally, amoxicillin is better because absorption is better.
Ineffective against penicillinase-producing bacteria (e.g., S.
aureus, 50% of E. coli strains, and up to 15 % of H.
influenzae strains.
Many baterial β-lactamases are inhibited by clavulaic acid
± amoxicillin (co-amoxiclav) antibiotic is effective
against penicillinase-producing organisms.
Co-amoxiclav indicated in resp and UT infections, which
are confirmed to be resistant to amoxicillin.
59. Used for treatment of meningitis, pneumonia, and
septicemia.
Same mech and p’col as that of pens.
May allergic rxn and cross-reactivity to pen.
Similar to pens in broad-spectrum antibacterial activity.
Cedadroxil (for UTI) in case of antibact resist.
Cefuroxime (prophylactic in surgery) – Resistant to
inactivation by β-lactamases and used in severe infections
(others ineffective).
Ceftazidine – wide range of activity against gram- including
Pseudomonas aeruginosa), but is less active than
cefurozime against gram+ bact (S aureus).
Used in meningitis (CNS-accessible) caused by gram-
bacteria.
60. Not well absorbed orally.
Inhibits peptidoglycan formation.
Active against most gram+ organisms.
I.v. treatment for septicemia or endocarditis caused by
MRSA.
Used for pseudomembranous colitis (superinfection of
the bowel by Clostridium difficile – produces a toxin
that damages the colon mucosa)
62. Target ribosomes of bacteria
Aminoglycosides: bind to 30S subunit causing it to
distort and malfunction; blocks initiation of
translation
Tetracyclines: bind to 30S subunit blocking
attachment of tRNA.
Macrolides: bind 50S subunit and prevents protein
synthesis from continuing.
63. Against many gram- and some gram+.
Narrow TI – very potentially toxic.
Most important adverse side-effect: VIIIth cranial n.
(ototoxicity) and kidney damage.
Resistance – several mechs: inactivation of the drug
by acetylation, phos, or adenylation, Δ envellope to
prevent drug access, and Δ the binding site of the 30S
subunit (streptomycin only).
64. Gentamicin – used for acute, life-thretening gram-
infections. Has synergism with pen and van and combo.
Amikacin – used for bact that are gent-resistant.
Netilmicin – less toxic than gentamicin.
Neomycin – too toxic for parenteral use. Used for topically
for skin infections and orally for sterilizing bowel before
surgery.
Streptomycin – active against Mycobacterium tuberculosis.
But bec of its ototoxicity, rifampicin replaces.
Rifampicin – resistance develops quickly alone; so, with TB,
combine with isoniazid, ethambutol, and pyrazinamide for
the 1st 2 mos of treatment, followed by another 4 mos with
rifampicin and isoniazid.
65. Very safe drugs.
Ususally given orally.
Erythromycin and clarithomycin
Effective against gram- bact and can be used as an alt to
pen-sensitive patients, esp in infections caused by
streptococci, staphylococci, pneumococci, and clostridia.
Don’t cross the BBB – ineffective against meningitis.
Resistance- occurs bec of plasmid-controlled Δ of their
receptor on the 50S subunit.
Erythromycin – in high doses, may cause nausea and
vomiting (less so with clarithromycin and azithromycin).
Azithromycin – very long t1/2 (~40-60 hr) and a single dose
is as effective in treating chlamydial non-specific urethritis
as tretracycline admin over 7 days,
66. Broad-spectrum.
Penetrate microorganisms well.
Sensitive organisms accumulate it through partly passive
diffusion and partly through active transport.
Resistant organisms develop an efflux pump and do not
accumulate the drug.
Genes for tet-resistance transmitted by plasmids.
Closely assoc with those for other drugs to which the
organisms will also be resistant (e.g., sulphonamides,
aminoglycosides, chloramphenicol).
Tets bind to Ca in growing bones and teeth can discolor
teeth. So, should be avoided in children < 8 yrs old.
67. Broad-spectrum.
Serious side-effects: bone marrow aplasia,
suppression of RBCs, WBCs, encephalopathy, optic
neuritis.
So, periodic blood counts required, esp in high
doses.
Large Vd, including CNS.
Inhibits the actions of other drugs and may incr
the actions of phenytoin, sulphonlureas, and
warfarin.
Neonates cannot met the drug rapidly accum
‘grey baby’ syndrome (pallor, abdominal
distension, vomiting, and collapse).
70. Target enzymes required for nucleic acid synthesis
Fluoroquinolones: inhibit enzymes that maintain the
supercoiling of closed circular DNA
Rifamycins: block prokaryotic DNA-dependent RNA
polymerase from initiating transcription
71. Sulfadiazine well-absorbed orally. Used to treat
UTIs.
But many strains of E. coli are resistant.
So, use less toxic drugs instead.
Adverse effects: allergic rxns, skin rashes, fever.
Trimethoprin – used for UTIs and Resp TIs
Co-trimoxazole (trimethoprin +
sulfamethoxazole) – used mostly for pneumonia,
neocarditis, and toxoplasmosis.
74. Inhibit DNA gyrase.
Nalidixic acid – used only for UTIs.
Ciprofloxin (6-fluoro substituent) that greatly
enhances its effectiveness against both gram- and
gram+ bacteria.
Well-absorbed both orally and i.v.
Eliminated largely unchanged by the kidneys.
Side-effects (headache, vomiting, nausea) are rare;
but convulsions may occur.
75. Wide-spectrum
Metronidazole – against anaerobic bacteria and
protozoan infections.
Tinidazole – longer duration of action.
Diffuses into the organism where the nitro group is
reduced chemically reactive intermediates are
formed that inhibit DNA synthesis and/or damage
DNA.
76.
77. Polymyxin B: binds to membrane of G- bacteria and
alters permeability
This leads to leakage of cellular contents and cell death
These drugs also bind to eukaryotic cells to some
extent, which limits their use to topical applications
79. Very few antiviral drugs approved for use in US
Effective against a very limited group of diseases
Targets for antiviral drugs are various points of viral
reproduction
80. Amantadine – interferes with replication of influenza A by
inhibiting the transmembrane M2 protein that is essential
for uncoating the virus.
- Has a narrow spectrum; so, flu vaccine is usually
preferable.
Zanamivir – inhibits both influenza A and B
neuraminadase. Decr duration of symptoms if given
within 48 hr of the onset of symptoms. Prophylactic in
healthy adults.
Immunoglobulins – Human Ig contains specific Abs
against superficial Ags of viruses can interfere with their
entry into host cells. Protection against hepA, measles, and
rubellla (German measles).
81. Acyclovir- used to treat genital herpes
Cidofovir- used for treatment of cytomegaloviral
infections of the eye
Lamivudine- used to treat Hepatitis B
82. HSV and VZV contain a thymidine kinase (TK)
that acyclovir to a monophosphate
phosphorylated by host cell enzymes to
acycloguanosine triphosphate, which inhibits viral
DNA pol and viral DNA synthesis.
Selectively toxic (TK of uninfected host cells
activates only a little of the drug).
Viral enzymes have a much higher affinity than the
host enzymes for the drug.
Effective against HSV, but does not eradicate them.
Need high doses to treat shingles.
83.
84.
85. Quite toxic (neutropenia) –so, given only for severe
CMV infections in immunosuppressed patients.
CMV is resistant to acyclovir because it does not code
for TK.
86. Currently implies a drug used to treat HIV
Tenofovir- nucleotide reverse transcriptase inhibitor
Zidovudine- nucleoside analog – inhibits RT of HIV and is
only used orally for AIDS.
- Activated by triple phosphorylation and then binds RT
(with100X affinity than for cellular DNA pols).
- Incorporated into the DNA chain, but lacks a 3’OH; so
another nucleoside cannot form a 3’-5’-phosphodiester
bond DNA chain elongation is terminated.
-Severe adverse effects: anemia, neutropenia, myalgia,
nausea, and headaches.
Stavudine, didanosine, zalcitabine – among other NRTIs.
Nevirapine, efavirenz – Non nucleoside RTIs - denature RT.
89. Zanamivir (Relenza) and Oseltamivir phosphate
(Tamiflu)- inhibitors of the enzyme neuominidase
Used to treat influenza
Indinavir- protease inhibitors. Inhibit the synthesis of
essential viral proteins (e.g., RT) by viral-specific
proteases.
90. Cells infected by a virus often produce interferon,
which inhibits further spread of the infection
Alpha-interferon - drug for treatment of viral hepatitis
infections
91. 1. Bacteria spread on surface of agar plate
2. 12 disks, each with different antimicrobial drug,
placed on agar plate
3. Incubated- drugs diffuse outward and kill
susceptible bacteria
4. Zone of inhibition around each disk
5. Compare size of zone to chart
92.
93. Drug resistance limits use of ALL known
antimicrobials
Penicillin G: first introduced, only 3% of bacteria
resistant
Now, over 90% are resistant
94. 1. Inactivating enzymes that destroy the drug (e.g., β-
lactamases).
2. Decreased drug accumulation (e.g., tet).
3. Altering the binding sites (e.g., aminoglycosides and
erythromycin).
4. Development of alternative metabolic pathways
(sulphonamides ( dihydropteroate synthease) and
trimethoprim (dihydrofolate reductase).
95.
96. 1. Spontaneous Mutation: happen as cells replicate –
Within a pop, there will be some bact with acquired
resistance. The drug then elim the sensitive
organisms, while the resistant ones proliferate.
2. Gene Transfer or Transferred resistance: Usually
spread through conjugative transfer of R plasmid (
may be virally mediated).
97.
98. 1. Responsibilities of Physicians: must work to identify
microbe and prescribe suitable antimicrobials, must
educate patients
2. Responsibilities of Patients: need to carefully follow
instructions
99. 3. Educate Public: must understand appropriateness and
limitations of antibiotics; antibiotics not effective
against viruses
4. Global Impacts: organism that is resistant can quickly
travel to another country
- in some countries antibiotics available on non-
prescription basis
- antibiotics fed to animals can select for drug-
resistant organisms
100. Scientists work to find new antibiotic targets in
pathogens
Discovery of new and unique antibiotics is necessary