Block 9 Pharmacology Flashcards
Paracetamol
Analgesic and Anti-pyretic with some anti-inflammatory efffect
- Used when NSAIDs can’t be.
MOA Inhibition of COX-1,2,3 > inhibition of prostaglandin synthesis
S/E - toxic dose cause nausea and vomiting then 24hrs later potentially fatal liver toxicity
Amoxicillin
Beta-lactam antibiotic (bactericidal) -> interferes with bacterial cell wall synthesis
Uses: Active against wide range of Gram+, and a limited range of Gram-bacteria
MOA: inhibit enzymes that crosslinks peptidoglycan within cell wall -> inhibits cell wall synthesis -> causes cell lysis
Resistance - Not effective against staph (due to β-lactamase- resistant bacterial enzyme) and streptococci (have impaired β-lactam binding) -> Amoxicillin can be combined with clavulanic acid (β-lactamase inhibitor) to overcome resistance mediated through β-lactamase production -> Co-amoxiclav
Methicillin
Beta lactam antibiotic - A transpeptidase inhibitor
Uses: Narrow spectrum beta-lactam antibiotic against gram+ bacteria
MOA: Inhibits bacterial cell wall synthesis, via inhibition of transpeptidase enzyme used for cross-linking peptidoglycan
-Flucloxacillin and Dicloxacillin used in clinic.
Cefuroxime
Cephalosporin (type of beta-lactam antibiotic) -> Transpeptidase inhibitor (Bactericidal)
Uses: Highly active against gram- cocci/ bacilli, anaerobes more than gram+ cocci/bacilli
Uses: sinusitis, ear infections, lower respiratory tract infections, urinary infections and gonorrhea
MOA: inhibits cell wall synthesis, leading to bacterial lysis (similar to penicillin)
-Can cross the blood brain barrier.
-There is resistance to Cefuroxime in Listeria and MRSA
Benzylpenicillin
Beta lactam antibiotic - A transpeptidase inhibitor (bactericidal)
Uses: target usually gram+ organisms but can target gram-aerobic and anaerobic bacteria
Uses: streptococcal, gonococcal, meningococcal infections; also anthrax, dipththeria, gas gangrene
MOA: binds penicillin proteins that then causes the inhibition of cell wall synthesis -> cell lysis
Oxytetracycline
A 30s inhibitor ( tetracycline antibiotic) - bacteriostatic
-A broad-spectrum antibiotic
Uses: infections caused by a variety of Gram positive and Gram negative microorganisms including M. pneumoniae, Pasteurella pestis,E. coli, H. influenzae (respiratory infections), and Diplococcus pneumoniae.
Uses: Used to treat many infections, including acne.
- MOA inhibition of cell growth by binding to the 30S ribosomal subunit -> Prevents tRNA from binding ribosome site -> INHIBITS translation
- Lipophilic = can pass through the cell membrane or passively diffuse through porin channels in the bacterial membrane.
Erythromycin
A 50s inhibitor (Macrolide Antibiotic) -> bacteriostatic/bacteriocidal
Uses: to treat multiple infections (respiratory infections, syphillis, skin infections, whooping cough and chronic prostatitis) in pts allergic to penicillin
- Effective ONLY against actively dividing organisms.
MOA: reversibly binds to the 50S subunit of ribosomes -> blocks the translocation of peptides from the acceptor site to the donor site -> INHIBITS PROTEIN SYNTHESIS
Gentamicin
A 30S inhibitor (aminoglycoside antibiotic)
Uses: A broad spectrum antibiotic
Uses: infections involving Gram- bacteria (such as Pseudomonas, Acinetobacter, and Enterobacter)
- septicaemia, meningitis, pyelonephritis, endocarditis and pneumonia
- can be used to treat mycobacteria (TB) and gram+ infections.
MOA: bind to the bacterial 30S ribosomal subunit, INHIBITS PROTEIN SYNTHESIS
- NOTE: aminoglycosides can cause ototoxicity and nephrotoxicity
Rifampicin
A RNA/DNA polymerase inhibitor (Ansamycin antibiotic) -> Bactericidal
Uses: A broad spectrum antibiotic (targets both gram+ and gram- bacteria)
Uses: TB, Leprosy. Prophylaxis for meningococcal meningitis, and H. influenzae. Also used for brucellosis, endocarditis, legionnaires’ disease, serious staphylococcal infections
MOA: inhibition of DNA-dependent RNA polymerase -> prevents RNA synthesis -> cell death
NOTE: Due to increased resistance Rifampicin is restricted to mainly mycobacterial infections.
Trimethoprim
Folate antagonist (Antibiotic)
Uses: UTIs, acute and chronic bronchitis, prostatitis
MOA: binds to DHF synthetase enzyme -> prevents formation of tetrahydrofolate-> less thymidine synthesis -> INHIBITION OF BACTERIAL DNA SYNTHESIS
-Trimethoprim has higher affinity for bacterial dihydrofolate reductase that human form of the enzyme
Sulfamethoxazole
A sulfonamide antibiotic (PABA analogue)
Uses: to treat bronchitis, prostatitis and urinary tract infections and combined with trimethoprim to treat pneumocystis pneumonia, toxoplasmosis & nocardiosis
MOA: Competitively inhibits DHF synthetase -> inhibits tetrahydrofolate synthesis -> less thymidine synthesis -> INHIBITION OF BACTERIAL DNA SYNTHESIS
Trimethoprim and sulfamethoxazole are commonly used in combination -> they target the same pathway and their synergistic effects reduce the development of bacterial resistance
Vancomycin
Glycopeptide antibiotic -> affects cell wall synthesis
Uses: Listeria monocytogenes, Strep. pyogenes, Strep. pneumoniae (including penicillin-resistant strains) BUT NOT active against gram negative bacilli, mycobacteria, or fungi
MOA: incorporation of NAM and NAG subunits into peptidoglycan cell wall matrix -> affects cell wall permeability -> cell lysis
NOTE used as a ‘last resort drug’ after other antibiotics have failed as no cross-resistance with other ABs
Colistin
A polymyxin polypeptide antibiotic -> bactericidal
Uses: acute or chronic infections due to sensitive strains of certain gram-negative bacilli (Particularly) Pseudomonas aeruginosa)
MOA: Polymyxins are polypeptides that disrupt bacterial cell membrane -> changes cell permeability -> cell lysis
The use of polymyxins is coming back after multi-drug resistance gram- bacteria against penicillins and cephalosporins
Ciprofloxacin
Quinolone antibiotic (Topoisomerase II inhibitor) -> bactericidal
Uses: Broad spectrum AB used against a wide range of gram- and gram+ bacteria. Infections of the urinary tract/ GIT and bones & joints. Also resp. infections not caused by pneumococci and for gonorrhoea and septicaemia
MOA inhibits topoisomerase II (DNA gyrase) which produce supercoils in DNA that is needed for replication -> INHIBITS DNA SYNTHESIS
Fusidic acid
Translocation inhibitor (antibiotic) -> Bacteriostatic
Uses: to treat staphylococcal bacterial skin and eye infections (used as cream/eyedrops)
MOA inhibits translocation during protein synthesis
Aspirin
NSAID
Uses: Analgesic, antipyretic and anti-inflammatory effects. anti-platelet -> inhibits platelet aggregation
MOA: Irreversibly inhibits COX 1 and COX2 enzymes to decrease formation of prostaglandins and thromboxanes from arachidonic acid
Ibuprofen
NSAID
Uses: Infammatory conditions (e.g. rheumatoid disease, osteoarthritis, musculo-skeletal disorders); dysmenorrhoea
MOA Reversible inhibition of COX1 and weak inhibition of COX2 -> decreasing prostaglandin synthesis -> reduced inflammation, pain, fever and swelling. Anti-pyretic effect possibly due to effect on hypoT - > leading to increased peripheral blood flow, vasodilation which allows for heat dissipation
Aciclovir
Antiviral drug
Uses: Herpes simplex infections (cold sores, mouth ulcers, conjunctivitis, genital infections and more seriously, encephalitis). Herpes zoster infections (shingles, chickenpox)
MOA: Interferes with viral nucleic acid synthesis. Converted by viral and host cell kinases to aciclovir triphosphate which selectively inhibits viral DNA polymerase.
Aciclovir is selective and has low cytotoxicity as uninfected cells dont incorporate aciclovir successfully as a substrate.
Amantadine
Anti-viral drug (also anti-parkinson agent)
Uses: prophylactic/symptomatic treatment of Influenza infection and Parkinson’s disease ( less effective than levodopa, dopamine agonists or MAOB inhibitors)
MOA (as antiviral) inhibition of viral M2 ion channel found on viral envelope-> This is usually needed for the viral particle to become “uncoated” once it is taken inside the cell by endocytosis -> INHIBITS VIRULENCE
MOA (in parkinson’s) increases dopamine release, and blocks dopamine reuptake in striatal neurons
Diamorphine (heroin)
Analgesic (Mu-opioid receptor agonist)
Uses: Moderate to severe chronic and post-operative pain. Epidural anaesthesia. Neuropathic pain.
MOA: bind mu-opioid receptors (MOR) in the brain, spinal cord causing an analgesic/sedative effect
note: Diamorphine still used clinically but morphine more common. Repeated use of drug results in upregulation of MOR (desensitisation)
Amprenavir
Protease inhibitor (used for HIV-1 treatment)
Uses: HIV ( in combination with other anti-HIV drugs)
MOA: inhibits HIV-1 protease which is normally needed for proteolytic cleavage of viral proteins -> inhibition leads to immature non-infectious viral particles
Phenoxymethylpenicillin (Penicillin V)
Narrow spectrum Beta lactam antibiotic -> Bacteriocidal
Uses: Commonly used to treat bacterial infections caused by gram+ bacteria (Strep. pneumoniae, Staphylococcus)
MOA: bactericidal. Inhibits bacterial cell wall synthesis by binding to specific penicillin-binding proteins (PBPs) located inside the cell wall -> Cell lysis
Zidovudine
NRTI (nucleoside reverse transcriptase inhibitor).
Use: HIV in combo with other drugs (slows progression)
MOA: It is a prodrug that is converted into a structural analog of thymidine -> gets incorporated into viral DNA and inhibits HIV-1 reverse transcriptase via DNA chain termination -> INHIBITS VIRAL DNA GROWTH
Also weak inhibitor of DNA polymerase
Clotrimazole
Anti-fungal aka Canesten -> Fungistatic
Uses: Broad spectrum antimyotic for vaginal yeast infections, oral thrush, diaper rash etc.
MOA inhibits inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes -> increased membrane permeability -> leakage of intracellular constituents -> cell death
MOA same as Fluconazole
Fluconazole
Antifungal
Uses: to treat vaginal candidiasis
MOA inhibits inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes -> increased membrane permeability -> leakage of intracellular constituents -> cell death
MOA same as Clotrimazole
Nystatin
Antifungal
Uses: a wide variety of yeast/fungal infections: such as candida albicans
MOA: binds ergosterol in fungal cell membranes -> formation of pores in membrane causing leakage of cell constituents -> leads to cell death
MOA same as Amphotericin
Amphotericin
Antifungal
Uses: for serious fungal infections and leishmaniasis
MOA: binds ergosterol in fungal cell membranes -> formation of pores in membrane causing leakage of cell constituents -> leads to cell death
MOA same as Nystatin
Pyrimethamine
Antimalarial/ antiparasitic drug
Uses: to treat uncomplicated, chloroquine resistant, P. falciparum malaria and toxoplasmosis
MOA folate antagonist. Inhibits dihydrofolate reductase -> blocks biosynthesis of pyrimidines -> INHIBITS DNA SYNTHESIS
Used in combination tablet with sulfadoxine for the treatment of falciparum malaria.
Quinine
Antimalarial drug (Quinoline- shizonticidal)
Uses: to treat infections caused by chloroquine-resistant P.falciparun malaria or acute attacks of malignant malaria (P. falciparum)
MOA:
It is thought to inhibit breakdown heme used for digestion -> lack of breakdown = parasite starves and toxic levels hemoglobin builds up -> PARASITIC death
NOTE: more toxic and less effective than chloroquine
Often given in combination with (or followed by) doxycycline, clindamycin or pyrimethamine + sulfadoxine
Artemether
Antimalarial drug (A peroxide antimalarial)
Use: Malaria - Reduces the number of malarial parasites and provides rapid relief of symptoms
MOA interacts with heme in the parasite and leads to the production of toxic oxygen and carbon radicals.
Note: usually administered with lumefantrine (which has a much longer half-life and clears residual parasites quicker)
Griseofulvin
Narrow spectrum anti-fungal
Use - Fungal infections of skin, hair and scalp (ringworm); trichophyton infections in children.
MOA unclear: Interacts with microtubules inhibiting spindle formation -> prevents synthesis
Clobetasone
Topical corticosteroid (A glucocorticoid nuclear receptor agonist)
Uses: skin inflammation as seen in eczema, psoriasis and dermatitis -> reduces
MOA: Binds nuclear glucocorticoid receptor -> inhibit expression of prostaglandins, kinins, histamine and other inflammatory mediators
Dacarbazine
Alkylating agent (Chemotherapy)
Uses: chemotherapy cancer treatment
MOA: attaches alkyl groups to DNA base
- form cross-bridges between base pairs in DNA
- cell tries to repair or divide causing breaks leading to apoptosis/CELL DEATH
Same MOA as cyclophosphamide
Cyclophosphamide
Alkylating agent (chemotherapy)
Use: Chronic lymphocytic leukemia, soft tissue sarcoma, osteogenic sarcoma, ovarian & breast cancers.
MOA: -attaches alkyl groups to DNA base
- form cross-bridges between base pairs in DNA
- cell tries to repair or divide causing breaks leading to apoptosis
Same MOA as Dacarbazine
Rituximab
Monoclonal antibody (chemotherapy)
Uses: Non-Hodgkins lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
MOA: acting as marker for immune system to destroy them (APCs)
-mediates cell lysis
Doxorubicin
Cytotoxic anthracycline antibiotic (chemotherapy)
Uses: Hodgkin’s lymphoma, gastric and ovarian cancers
MOA: intercalate DNA BPs, inhibit topo II, generate ROS, can cause alkylation of DNA
Paclitaxal
Antimicrotubule agent: Mitotic inhibitor (Chemotherapy)
Uses: Kaposi’s sarcoma, lung, ovarian and breast cancer
MOA: inhibit mitosis (M phase) by inhibiting normal microtubule function => induces apoptosis
Tamoxifen
Oestrogen receptor agonist (Chemotherapy)
Uses: Breast cancer (ER positive)
MOA: Tamoxifen competes with endogenous oestrogen for the oestrogen receptors and therefore inhibits the transcription of oestrogen-responsive genes
5-Fluorouracil
Anti-metabolite/Antipyrimidine (Chemotherapy)
Uses: GIT cancers, pancreas, breast and malignant skin
MOA: inhibits thymidylate synthetase needed for thymidine synthesis
Etoposide
Topoisomerase II inhibitor (Chemotherapy)
Uses: Small cell lung cancer
MOA: Normally Topo II relieves supercoiling that can occur in DNA by creating double strand breaks in DNA and religating it together. Etoposide inhibits this preventing cell division
Imatinib
Protein kinase inhibitor (Chemotherapy)
Uses: Chronic myeloid leukemia, acute lymphoblastic leukemia, GIT stromal tumours, chronic eosinophilic leukemia, myeloproliferative diseases
MOA: Bcr/Abl kinase normally binds ATP to transfer phosphate group to target protein. Imatinib mimics ATP and binds to ATP site on kinase -> competitively inhibits enzyme activity
Tretinoin
Vitamin A derivative (retinol)
Uses: Acne, promyelocytic leukaemia (subtype of acute myeloid leukaemia AML)
MOA: Binds to alpha, beta, and gamma retinoic acid receptors (RARs). RARs have been associated with the development of acute promyelocytic leukemia and squamous cell cancers
Vinblastine
Antimicrotubule agent: Vinca alkaloids
Uses: Breast cancer, testicular cancer, lymphomas, neuroblastoma, Hodgkin’s and non-Hodgkin’s lymphomas, mycosis fungoides, histiocytosis, and Kaposi’s sarcoma.
MOA: bind to tubulin and inhibit its polymerisation into microtubules causes cell arrest and apoptosis
