Helicobacter pylori eradication

Question 1

Proton pump inhibitors

Common indications

Answer 1

1. Prevention and treatment of peptic ulcer disease, including NSAID-associated ulcers
2. Symptomatic relief of dyspepsia and GORD
3. Eradication of H.pylori

Question 2

Proton pump inhibitors

MOA

Answer 2

• PPI reduces gastric acid secretion
• They act by irreversibly inhibiting H+/K+-ATPase in gastric parietal cells
• This is acid
• An advantage of targeting the final stage of gastric acid production is that they are able to suppress gastric acid production almost completely
• In this respect they differ from H2-receptor antagonist

Question 3

Proton pump inhibitors

Adverse effects

Answer 3

• Common side effects of PPI include GI disturbance and headache
• By increasing the gastric pH, PPI may reduce the body’s host defence against infections- there is some evidence of increased C.dif infection in patients taking PPIs
• Prolonged treatment with PPIs can cause hypomagnesaemia, which if severe can lead to tetany and ventricular arrhthmias

Question 4

Proton pump inhibitors

Warnings

Answer 4

• PPIs may disguise symptoms of gastric cancer, so prescribers should enquire about alarm symptoms before and during treatment
• Increase the risk of fractures
• Osteoporosis

Question 5

Proton pump inhibitors

Interactions

Answer 5

• Reduce the antiplatelet effect of clopidogrel by decreasing its activation by CYP P450

Question 6

Penicillins

(Amoxicillin)

Common indications

Answer 6

• Streptococcal infection, including tonsillitis, pneumonia (in combination with a macrolide if severe), endocarditis and skin and soft tissue infection
• Clostridial infection e.g. tetanus
• Meningococcal infection e.g. meningitis, septicaemia

Question 7

Penicillin

(Amoxicillin)

MOA

Answer 7

• Penicillins inhibit the enzymes responsible for cross-linking peptidoglycans in bacterial cell walls
• This weakens cell walls, preventing them from maintaining an osmotic gradient
• The uncontrolled entry of water into bacteria causes cell swelling, lysis and death
• Penicillins contain B-lactam ring, which is responsible for their antimicrobial activity
• B-lactamase is an enzyme bacteria use to inactivate penicillin
• Other mechanisms include reduced bacterial permeability or increased extrusion)

Question 8

Penicillin

(Amoxicillin)

Adverse effects

Answer 8

• Allergy- 1-10% usually a skin rash
  
  • Less common is anaphylaxis
• CNS toxicity- high doses of penicillin or where severe renal impairment delays excretion

Question 9

Penicillin

(Amoxicillin)

Warnings

Answer 9

• Penicillin can gernerally be used safely in most clinical situation although a dose reduction is required for patients with renal impairment
• The main contraindication to penicillin use is a history of penicillin allergy
• Penicillins reduce renal excretion of MTX, increasing the risk of toxicity

Question 10

Macrolide (Clarithromycin)

Common indications

Answer 10

1. Respiratory and skin and soft tissue infections
2. Severe pneumonia
3. H.pylori

Question 11

Macrolide (Clarithromycin)

MOA

Answer 11

• Macrolides inhibit bacterial protein synthesis
• They bind to 50S subunit of the bacterial ribosome and block translocation, a process of required for elongation of the polypeptide chain
• Inhibition of protein synthesis is bacteriostatic (stops bacteria growth), which assists the immune system in killing bacteria
• Erythromycin, first macrolide, was isolated from streptomycetes in the ’50s
• It has a relatively broad spectrum of activity against G+, G-ve
• Mutations in ribosome a mechanism of resistance

Question 12

Macrolide (Clarithromycin)

Adverse effects

Answer 12

• Macrolides are irritant, causing nausea, vomiting and ab pain
• Allergies
• Antibiotic-associated colitis
• Liver abnormalities- choleostatic jaundice, QT interval prolongation, ototoxicity
  *

Question 13

Macrolide (Clarithromycin)

Warnings

Answer 13

• Macrolide hypersensitivity
• Severe hepatic impairment
• Dose reduction in severe renal failure

Question 14

Macrolide (Clarithromycin)

Interactions

Answer 14

• Erythromycin and clarithromycin are both CYP P450 enzymes
• This increases plasma concentrations and risk of adverse effects with drugs metabolism by CYP P450 enzymes
• For example with warfarin there is an increased risk of bleeding
• Drugs that prolong QT interval- or cause arrhythmias such as amiodarone, antipsychotics, SSRIs

Question 15

Metronidazole

Common indications

Answer 15

• Antibiotic-associated colitis caused by Clostridium difficile
• Oral infections
• Surgical and gynaecological infections
• Protozoal infections

Question 16

Metronidazole

MOA

Answer 16

• Metronidazole enters bacterial cells by passive diffusion. In anaerobic bacteria, reduction of metronidazole generates a nitroso free radical.
• This binds to DNA, reducing the synthesis and causing widespread damage, DNA degradation and cell death. As aerobic bacteria are not able to reduce metronidazole in this manner, the spectrum of action of metronidazole is restricted to anaerobic bacteria (and protozoa).
• Bacterial resistance to metronidazole is generally low but is increasing in prevalence. Mechanisms include reduced uptake of metronidazole and reduced generation of nitroso free radicals.

Question 17

Metronidazole

Adverse effects

Answer 17

• GIT upset
• Hypersensitivity
• Peripheral and optic neuropathy
• Seizures
• Encephalopathy

Question 18

Metronidazole

Warnings

Answer 18

• Metabolised by CYP enzymes therefore reduced dose should be used in severe liver disease
• No alcohol- due to inhibition of alcohol dehydrogenase

Question 19

Metronidazole

Interactions

Answer 19

• metronidazole inhibits CYP P450- reducing metabolism of drugs e.g. warfarin and phenytoin
• CYP inducers- results in lower plasma concentrations and lack of efficacy
• Increase risk of toxicity with Li