Drugs for GI infections Flashcards
1) Name the antifungal P drugs.
2) Name the anti protozoan P drugs for C. difficile.
3) Name the antihelminthic P drugs.
1) Nystatin and fluconazole.
2) Metronidazole and Vancomycin.
3) Ivermectin and Albendazole.
Give the 2 main clinical indications for the use of anti fungal medications.
1) Treatment of local fungal infections including of the oropharynx, vagina or skin. Can be applied topically (nystatin/ clotrimazole) or taken orally (fluconazole).
2) Systemic treatment of disseminated or invasive fungal infections. Specialist treatment is required for these infections.
1) Which substance is used as a main target for anti fungal medications and why is this?
2) Describe how nystatin works.
1) Ergosterol because it is unique to fungal cells.
2) It is a polyene anti fungal which vends to ergosterol, creating a polar pore which allows intracellular ions to leak out of the cell. This kills or slows the growth of the fungi.
1) How do Imidazole (e.g. Clotrimazole) and triazole antifungals such as Fluconazole work?
2) When might resistance to antifungals occur, even though it is rare.
3) Describe 3 way that anti fungal resistance might happen.
1) Inhibit ergosterol synthesis, impairing cell membrane synthesis, cell synthesis and replication.
2) During long term treatment in immunosuppressed patients.
3) Alteration of membrane synthesis to exclude ergosterol, changes in target enzymes, increased drug efflux.
1) Give the main adverse reaction of topical nystatin and clotrimazole.
2) Name the 4 most common side effects of fluconazole.
3) Give 3 more serious adverse reactions to fluconazole.
1) Local irritation.
2) GI disturbance (N+V+D and abdo. pain), headache, hepatitis and hypersensitivity (causing a rash).
3) Severe hepatic toxicity, prolonged QT interval predisposing to arrhythmias and severe hypersensitivity including cutaneous reactions and anaphylaxis,
1) In what patients should fluconazole be prescribed with caution in?
2) In what patients is a dose reduction of fluconazole required?
3) In which types of patients should fluconazole be avoided?
4) Do nystatin and clotrimazole have any contraindications?
1) Patients with liver disease due to the risk of hepatotoxicity.
2) Patients with moderate renal impairment.
3) Pregnant women due to the risk of foetal malformation.
4) None.
1) What types of drugs does Fluconazole interact with and why?
2) List 3 of these drugs.
3) What is the potential interaction between clopidogrel and fluconazole?
4) Which drugs combined with fluconazole might cause an increase in risk of serious arrhythmias?
5) List 3 of these drugs.
1) Drugs that are metabolised by CYP450 enzymes as Fluconazole inhibits CYP450 enzymes, causing increases in plasma concentrations and risk of adverse events.
2) Phenytoin, carbamazepine, Warfarin, diazepam, simvastatin and sulfonylureas.
3) May reduce anti platelet effect of clopidogrel which is a prodrug and rewires activation through metabolism in the liver.
4) Drugs that prolong the QT interval.
5) Amiodarone, antipsychotics, quinine, quinolone, macrolides and SSRIs.
1) How is nyastatin usually administered?
2) How is clotrimazole usually administered?
3) How is fluconazole usually administered?
1) Topically
2) Topically
3) Orally.
What should be measured before and during long courses of Fluconazole and why?
Liver enzymes to monitor for hepatic toxicity.
1) Which group of people are particularly susceptible to oral candida infection?
2) Why is this?
1) Elderly hospital inpatients.
2) They are commonly treated with antibiotics and corticosteroids which predispose to oral candidiasis and with antimuscarinic drugs which reduce saliva.
Give the 4 main clinical indications for the use of Metronidazole.
1) Antibiotic associated colitis caused by C. Diff which is a gram positive anaerobe.
2) Oral infections (dental abscesses, etc) or aspiration pneumonia caused by gram negative anaerobes from the mouth.
3) Surgical and gynaecological infections caused by gram negative anaerobes from the colon (Bacteroides fragilis)
4) Protozoal infections (Trichomal vagina infection, amoebic dysentry, giardiasis).
1) How does Metronidazole enter bacterial cells?
2) What happens to Metronidazole in anaerobic bacteria?
3) Why can Metronidazole not be used for aerobic bacteria?
4) Give 2 reasons for the increasing prevalence of resistance to Metronidazole.
1) Passive diffusion.
2) Metronidazole reduced to Nitroso free radical > binds to DNA > reduction in synthesis > widespread damage, DNA degradation and cell death.
3) Because aerobic bacteria are not able to reduce metronidazole (only effective for anaerobic bacteria and protozoa)
4) Reduced uptake of metronidazole, reduced generation of Nitroso free radicals.
1) Give 2 common adverse reactions to Metronidazole.
2) Give 4 adverse effects of metronidazole when used at high doses for longer time periods.
1) GI upset (nausea and vomiting) and delayed and immediate hypersensitivity reactions.
2) Peripheral ans optic neuropathy, seizures and encephalopathy.
1) Why should the dose of Metronidazole be reduced in people with severe liver disease?
2) Why should alcohol NOT be consumed when taking Metronidazole?
3) Describe the reaction that may happen when Metronidazole and alcohol are combined.
1) Because Metronidazole is metabolised by hepatic CYP450 enzymes.
2) Because Metronidazole inhibits acetaldehyde dehydrogenase which is responsible for clearing the intermediate alcohol metabolite acetaldehyde from the body.
3) Disulfiram like reaction: flushing, headache, nausea and vomiting.
1) What effect does Metronidazole have on CYP450 enzymes?
2) What is the effect of metronidazole on Warfarin?
3) What is the effect of Metronidazole on Phenytoin?
4) Describe the interaction between Metronidazole and lithium.
5) Describe the interactions between Phenytoin/ Rifampicin and Metronidazole.
1) Inhibitory effect.
2) Reduces metabolism of warfarin, increasing the risk of bleeding.
3) Reduced metabolism of Phenytoin, increasing the risk of toxicity, including impairment of cerebellar function.
4) Metronidazole increases the risk of toxicity with lithium.
5) They are CYP450 inducers, and so can reduce plasma concentrations of metronidazole, leading to impaired antimicrobial efficiency.
