Q11

What are the organ system effects of theophylline?
Prompt: both the therapeutic and the toxic.

  • CNS: Mild cortical arousal with increased alertness and deferral of fatigue. Bronchodilation. Nervousness and tremor. Overdose causes medullary stimulation, convulsions and death.
  • CVS: Positive chronotropic and inotropic effects by inhibiting presynaptic adenosine receptors in sympathetic nerves and increasing catecholamine release at nerve endings. Produces tachycardia, increased cardiac output and BP. May cause arrhythmias.
  • GIT: Stimulates gastric acid and digestive enzymes secretion.
  • Kidney: Weak diuretic from increased glomerular filtration and reduced tubular sodium reabsorption.
  • Lung: Bronchodilation by relaxing airway smooth muscle and inhibits antigen-induced release of histamine from lung tissue

Pass: CVS and Resp effects

How do these effects of theophylline correlate to its serum concentrations?

  • Theophylline has a narrow therapeutic window, and its therapeutic and toxic effects are related to its blood level:
  • 5–20 mg/L: Improvement in pulmonary function. Anorexia, nausea, 15-20 mg/L: vomiting, abdominal discomfort, headache, and anxiety occur at concentrations of in some patients: >40 mg/L: Cause seizures or arrhythmias

Pass: Narrow therapeutic window


Q12

How does Penicillin exert its action?

  • Interferes in bacterial cell wall synthesis by binding to penicillin-binding-protein and preventing removal of terminal d-alanyl-d-alanine from peptides preventing crosslinking and formation of peptidoglycan

Pass: Inhibits bacterial cell wall synthesis

What are the mechanisms of resistance to B Lactam antibiotics?

  • (1)  Inactivation by B-lactamase
  • (2)  Modification of target PBPs
  • (3)  Impaired penetration of drug to target PBPs
  • (4) Presence of efflux pumps

Pass: Inactivation of B-lactamase, AND 1 other


Q13

Why is once-daily dosing advocated for gentamicin?
Prompt (if needed): What are the toxic effects of gentamicin (ototoxic and nephrotoxic)?

  • Concentration-dependent killing  + post-antibiotic effect  vs toxicity proportional to time over threshold concentration
  • Practical advantages.

Why is gentamicin usually used in combination with another antibiotic?

  • Usually combined with a cell-wall active drug that enhances gentamicin transport into the cell, e.g. beta-lactam or vancomycin

What is the mechanisms of action of gentamicin and how does resistance develop?
Prompt (if needed): What are the toxic effects of gentamicin (ototoxic and nephrotoxic)?

  • Aminoglycoside that binds to specific ribosomal proteins and inhibits protein synthesis
  • Resistance by
    • i) transferase that inactivates drug, carried by plasmids
    • ii) impaired cell entry (cell wall)
    • iii) altering ribosomal receptor protein

Pass: At least 1


Q14

What are the adverse effects of chloramphenicol?

  • GIT: nausea, vomiting and diarrhoea
  • Bone marrow suppression: reversible RBC suppression, idiosyncratic aplastic anaemia: 1/24000 – 1/40000
  • Newborn: gray baby syndrome
  • Drug interaction: Phenytoin, chlorpropamide ,warfarin prolongs half life and raises concentration

Pass: At least 2

Which bacteria does it affect?

  • Aerobic and anaerobic
  • Gram pos and negative
  • Rickettsia but not Chlamydia

What is mechanism of action?

  • Potent inhibitor of microbial protein synthesis
  • Binds to 50S subunit of bacterial ribosome by inhibiting peptidyl transferase.
  • Bacteriostatic

Q15

Describe the mechanism of action of Penicillin?

  • PBP binding, block peptidoglycan / cell wall synthesis

What are the important mechanisms of resistance to pencillins?

  • B-lactamase
  • Altered PBPs
  • Reduce penetration
  • Efflux pump

Describe the pharmacokinetics of penicillin?

  • Oral absorption food impaired, wide distribution, renal excretion and tubal secretion

Q16

What is the mechanism of action of trimethoprim?

  • Inhibits bacterial dihydrofolic acid reductase
  • Converts dihydrofolic acid to tetrahydrofolic acid (à purine synthesis & DNA)

Why are sulphonamides synergistic with trimethoprim?

  • Sulphonamides are a structural analog of p-aminobenzoic acid (PABA)
  • Inhibit synthesis of dihydrofolic acid therefore sequential blocking of sequence

What are mechanisms of bacterial resistance to trimethoprim?

  • Reduced cell permeability, increased production of dihydrofolic reductase or alteration in dihydrofolic acid reductase with reducing binding

Q17

What is the mechanism of action of the tetracyclines?

  1. Bacteriostatic drug
  2. Inhibits protein synthesis
  3. Enters bacteria by passive diffusion and active transport. Once inside, binds reversibly to 30S subunit of ribosome, blocking the binding of aminoacyl-tRNA to the acceptor site on mRNA ribosome complex, preventing the addition of a.acids to growing peptide

Pass: 2

What mechanisms of resistance affect the tetracyclines?

  1. Decreased intracellular accumulation due to impaired influx or increased efflux by an active transport protein pump
  2. Production of proteins that interfere with the tetracycline binding to the ribosome
  3. Enzymatic inactivation with production of efflux pump
  4. Resistance is plasmid mediated


Pass: 2

What are their adverse reactions?

  1. GIT: N,V,D due to local irritation
  2. Enamel dysplasia, bony deformity and growth retardation due to deposition in children < 8 yr and pregnancy
  3. Liver toxicity
  4. RTA if medicine is outdated
  5. Venous thrombosis is given IV
  6. Photosensitisation
  7. Vertigo from vestibular dysfunction

Pass: 3


Q18

What is the mechanism of action of ciprofloxacin?

  • Synthetic fluorinated analogs of nalidixic acid
    • Earlier forms not systemic antibacterial levels
    • Fluorinated derivates improved serum activity
  • Block bacterial DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) (prevent relaxation of positively supercoiled DNA needed for normal transcription and replication)  and topoisomerase IV (interferes with separation of replicated chromosomal DNA into daughter cells during cell division)

What are the uses of ciprofloxacin?

  • UTIs – norflox, cipro, oflox
  • Bactreial diarrhea –shigella, salmonella, Ecoli, Campyl
  • ST,bone, joint, intra-abdom, respiratory infection
  • GC (cipro, oxflox), chlamydia (cipro)

What are the adverse effects of ciprofloxacin?

  • Nausea, vomiting, diarrhea> h/ache, dizzy, insomnia, rash, LFT abnormalities
  • May damage growing cartilage, cause arthropathy not <18 yrs
  • Tendinitis in adults – risk of tendon rupture
  • Avoid during pregnancy and lactation

Q19

What is an antiseptic?

  • chemical disinfectant applied to living tissue (skin, mucous membranes and wounds) which decreases the number of organisms by killing, removing, diluting and has generally low toxicity to tissues

Pass: 2/3 mechanisms

Describe the actions and uses of chlorhexidine?

  • Low skin sensitising or irritating capacity; oral toxicity low (poorly absorbed from the alimentary tract)
  • Active against bacteria (most effective against G pos cocci), mycobacteria, moderate against fungi & viruses
  • Not inhibited by blood or organic products

When is chlorhexidine contraindicated?

  • Middle ear surgery (causes sensorineural deafness),
  • Neurosurgery as neural toxicity
  • Allergy

Q20

Name some macrolide antibiotics?

Erythromycin, azithromycin ,clarithromycin, roxithromycin

Pass: 2 examples

What is their mechanism of action?

Inhibits protein synthesis via binding to SOS ribosomal RNA and blocks aminoacyl translocation and the formation of initiation complexes

Pass: Protein synthesis and ribosomes

What organisms are usually sensitive to macrolides?

Gram positive: eg pneumococci, staphylococcus Mycoplasma, legionella, chyamydia and some mycobacteria Gram negative : neisseria, bordatella pertussis, bartonella, campylobacter
Treponema pallidum

Pass: At least 3


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