B9 Flashcards
Paracetamol
Indirect COX inhibitor.
Effect it has:
- Analgesic.
- Antipyretic. (effects the hypothalamus, resulting in peripheral vasodilation and sweating)
Effects it doesn’t have:
- Antiplatelet.
- Anti-inflammatory.
- Gastric ulcerative.
Amoxicillin
Beta-lactam antibiotic.
MoA: Amoxicillin binds to PBP-1A and facilitates its inactivation. Penicillin-binding protein 1A (PBP-1A) is located inside the bacterial cell well. Inactivation of PBP-1A prevents the cross-linking of two linear peptidoglycan strands, inhibiting bacterial cell wall synthesis.
Use: Against wide range of gram-positive, limited range of gram-negative organisms.
Note: Amoxicillin (a beta-lactam antibiotic) combined with Clavulanic acid - a β-lactamase inhibitor to overcome bacterial antibiotic resistance mediated through β-lactamase production.
Methicillin
A transpeptidase inhibitor.
Narrow spectrum beta-lactam antibiotic.
MoA: It inhibits bacterial cell wall synthesis, via inhibition of transpeptidase enzyme used by bacteria to cross-link the peptide (D-alanyl-alanine) used in peptidogylcan synthesis in the cell wall of Gram-positive bacteria.
What does MRSA stand for?
Methicillin-resistant Staphylococcus aureus.
MRSA describes Staphylococcus aureus strains resistant to all penicillins.
Cefuroxime
Transpeptidase inhibitor (2nd gen cephaosporin) Bactericidal
Unlike most other second-generation cephalosporins, cefuroxime can cross the blood-brain barrier.
Listeria and MRSA bacterial classes are resistant to cefuroxime.
HMG-CoA-Reductase inhibitors also known as?
Statins
Competitive inhibitor of HMG-CoA-Reductase reduce hepatic synthesis of cholesterol and clearance of LDL from the blood plasma.
Fibrates
PPAR nuclear receptor agonists
Amphipathic carboxylic acids
MoA: Binding to ‘peroxisome proliferator-activated receptors’ (PPAR) and increasing lipoprotein lipase transcription, hence facilitating lipid metabolism.
PPAR = intracellular receptors that modulate carbohydrate and fat metabolism and adipose tissue differentiation.
Use: range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore hypolipidemic agents.
Note: Fibrates are structurally and pharmacologically related to Thiazolidinediones. A novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ).
Benzylpenicillin (Penicillin G)
Transpeptidase inhibitor
Penicillin G is a beta-lactam antibiotic used to target usually gram-positive organisms
MoA: Via binding to penicillin binding proteins. That then causes the inhibition of cell wall synthesis. In addition it may inhibit the action of bacterial autolysin inhibitor
Penicillin G is stable against hydrolysis by these beta-lactamases:
- Penicillinases
- Cephalosporinases
- Extended spectrum beta-lactamases
List 3 transpeptidase inhibitors.
Methicillin
Cefuroxime
Benzylpenicillin
Oxytetracycline
30s inhibitor
Broad-spectrum antibiotic
MoA: Inhibition of bacterial cell growth by binding to the 30S ribosomal subunit. This prevents the amino-acyl tRNA from binding to the A site of the ribosome, causing inhibition of translation. It’s lipophilic so diffuses through porin channels in the bacterial.
Use: Treat many infections, including acne
Erythromycin
50S inhibitor
Macrolide group of antibiotic
It is effective only against actively dividing organisms
MoA: Reversibly binds to the 50S subunit of bacterial ribosomes, at the donor binding site. This binding blocks the translocation of peptides from the acceptor site to the donor site, inhibiting protein synthesis.
Use: Infections including: respiratory infections, syphilis, skin infections, chronic prostatitis.
Pregnancy: After absorption, erythromycin diffuses readily into most body fluids and will pass into both breast milk and placental barrier.
Gentamicin
30S/50S inhibitor
Broad spectrium aminoglycoside antibiotic
MoA: Active against gram-negative bacteria, E.g. pseudomonas, acinetobacter, enterobacter. Aminoglycosides can be used to treat mycobacteria (TB) and gram-positive infections. Bind to bacterial 30S ribosomal subunit –> inhibiting protein synthesis
SE: Significant ear and kidney damage (just like other aminoglycosides)
Rifampicin
RNA/DNA polymerase inhibitor
Broad spectrum antibiotic (targets gram-positive and gram-negative organisms).
Easily absorbed and distributed within the body.
MoA: Via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death
Use: Rifampicin can target bacterial but not mammalian versions of the enzyme - DNA-dependent RNA polymerase. The use of rifampicin been restricted to mainly mycobacterial infections due to emergence of resistant bacteria.
Trimethoprim
Folate antagonist
MoA: Binds to (bacterial) dihydrofolate reductase
This inhibits the reduction of dihydrofolic acid to tetrahydrofolic acid (THF). THF is an essential precursor in the thymidine synthesis pathway. Interference with this pathway inhibits bacterial DNA synthesis.
Use: UTIs, acute and chronic bronchitis
Note: Trimethoprim’s affinity for bacterial dihydrofolate reductase is greater than its affinity for the human version of dihydrofolate reductase.
Sulfamethoxazole
A sulfonamide drug (PABA analogue)
PABA - para-aminobenzoic acid
MoA: It competes with para-aminobenzoic acid (PABA) in binding to dihydrofolate synthase. It can therefore cause the inhibition of dihydrofolate synthetase, inhibiting the synthesis of tetrahydrofolic acid (THF) synthesis. THF is required for the synthesis of purines and dTMP and inhibition of its synthesis inhibits bacterial growth.
Use: Bronchitis, prostatitis, UTIs
Note: Trimethoprim and sulfamethoxazole are commonly used in combination because they target the same pathway and their synergistic effects reduce the development of bacterial resistance
Vancomycin
Peptidoglycan inhibitor
MoA: Via inhibition of incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. In addition, vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between vancomycin and other antibiotics.
Use: Used only after other antibiotics have failed. It’s active against Listeria monocytogenes, Streptococcus pyogenes, Streptococcus pneumoniae (indlucing penicillin-resistant strains), Streptococcus agalactiae, Actinomyces species, and Lactobacillus species.
Note: Inactive against gram-negative bacilli, mycobacteria, or fungi.
Colistin
Polymyxin antibiotic agent - A phospholipid detergent
MoA: To distrub bacterial cell membrane, changing its permeability. In addition colistins can enter the bacteria and precipitate cytoplasmic components, mainly ribosomes.
Use: Colistin is used to treat acute or chronic infections due to sensitive strains of certain gram-negative bacilli, particularly - Pseudomonas aeruginosa.
Ciprofloxacin
A broad spectrum quinolone antibiotic (Topoisomerase II inhibitor)
MoA: Inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination.
Use: Used against a wide range of gram-negative and gram-positive microorganisms.
What is fusidic acid?
A translocation inhibitor - a bacteriostatic antibiotic typically used in creams and eyedrops.
MoA: Inhibition of the translocation of the elongation factor G (EF-G) from the ribosome, leading to inhibition of protein synthesis.
In addition it also can inhibit chloramphenicol acetyltransferase enzymes.
NSAIDs
Inhibition of cyclooxygenase activity.
The constitutive cyclooxygenase, COX-1, synthesizes prostaglandins necessary for normal gastrointestinal and renal function.
The inducible cyclooxygenase, COX-2, generates prostaglandins involved in inflammation.
Inhibition of COX-1 is thought to be associated with gastrointestinal and renal toxicity while inhibition of COX-2 provides anti-inflammatory activity, reduced pain, fever and swelling.
Note: Paracetamol (acetaminophen) is generally not considered an NSAID because it has only little anti-inflammatory activity
Examples:
Aspirin - irreversible
Ibuprofen - reversible
Naproxen
Acetylsalicylic acid’s antirheumatic actions are a result of what?
Its analgesic and anti-inflammatory mechanisms.
Irreversible inhibition of COX prevents the formation of the aggregating agent thromboxane A2 in platelets.
Platelets cannot produce more COX enzyme and thus, the effects of aspirin persist for the life of the exposed platelets (7-10 days).
Aciclovir
DNA polymerase inhibitor
MoA: Aciclovir in an antiviral agent activated by viral thymidine kinase.
Aciclovir –> (alot of steps) –> aciclovir triphosphate.
Aciclovir triphosphate competitively inhibits viral DNA polymerase and competes with the natural deoxyguanosine triphosphate, for incorporation into viral DNA. Once incorporated into DNA, aciclovir acts as a termination signal.
Note: Aciclovir is selective and low in cytotoxicity as the cellular thymidine kinase of normal, uninfected cells does not use aciclovir effectively as a substrate