DPP4 inhibitors (gliptins), Tetracyclines and glycylcyclines, Aminoglycosides

Sitagliptin, linagliptin and alogliptin are all examples of ...?

Dipeptidylpeptidase-4 inhibitors.

When are DPP-4 inhibitors used in type 2 diabetes?

1) As add-on therapy with metformin (± other agents) if glycaemic control is inadequate,

2) Monotherapy if metformin is contraindicated or not tolerated.

How do DPP-4 inhibitors lower blood glucose?

By inhibiting DPP-4, preventing incretin degradation and increasing active incretin levels.

Why do DPP-4 inhibitors have a low risk of hypoglycaemia?

Incretin effects are glucose-dependent and do not act at normal or low glucose levels.

How do DPP-4 inhibitors differ from sulphonylureas?

They do not stimulate insulin secretion regardless of glucose level.

What are the common side effects of DPP-4 inhibitors?

GI upset, headache, nasopharyngitis and peripheral oedema.

When is hypoglycaemia more likely with DPP-4 inhibitors?

When combined with insulin or sulfonylureas.

What serious but rare adverse effect is associated with DPP-4 inhibitors?

Acute pancreatitis (0.1–1%).

How should suspected pancreatitis be managed in a patient on a DPP-4 inhibitor?

STOP the drug; symptoms should resolve.

In which conditions are DPP-4 inhibitors contraindicated?

Hypersensitivity, type 1 diabetes, ketoacidosis, pregnancy, and breastfeeding.

In which patients should DPP-4 inhibitors be used with caution?

Older adults (>80 years) and those with a history of pancreatitis.

How does renal impairment affect DPP-4 inhibitor use?

Dose reduction may be required in moderate-severe renal impairment.

Which DPP-4 inhibitor should be avoided in hepatic impairment?

Saxagliptin

Which drugs can reduce the effectiveness of DPP-4 inhibitors?

Prednisolone, thiazide and loop diuretics.

Which drugs increase the risk of hypoglycaemia with DPP-4 inhibitors?

Insulin, sulphonylureas, and alcohol.

Why can β-blockers be problematic with DPP-4 inhibitors?

They may mask symptoms of hypoglycaemia.

Can DPP-4 inhibitors be taken with food?

Yes, with or without food.

How is treatment response to DPP-4 inhibitors monitored?

HbA1c measurement.

What HbA1c target is used for DPP-4 inhibitor monotherapy?

<48 mmol/mol.

What HbA1c target is used for DPP-4 inhibitor combination therapy?

<53 mmol/mol.

When should DPP-4 inhibitor therapy usually be intensified (with another agent)?

HbA1c >58 mmol/mol.

What important limitation of DPP-4 inhibitors should be remembered?

No proven reduction in vascular complications and no weight-loss benefit - unlike SGLT-2s and GLP-1s.

Doxycycline and lymecycline are examples of what class antibiotic?

Tetracyclines

What are the common indications for tetracyclines?

1) Acne vulgaris.

2) LRTIs- incl. infective exacerbation of COPD and pneumonia

3) Chlamydial infection- incl. pelvic inflammatory disease.

4) Other- typhoid, malaria and Lyme disease.

When is tigecycline used?

Severe skin, soft-tissue, or abdominal infections where other options are limited.

What is the antimicrobial spectrum of tetracyclines?

Broad spectrum against Gram-positive and Gram-negative organisms.

How does resistance differ between tetracyclines and tigecycline?

Resistance is common with tetracyclines but less problematic with tigecycline.

Are tetracyclines bactericidal or bacteriostatic?

Bacteriostatic.

How do tetracyclines inhibit bacterial growth?

By inhibiting protein synthesis at the 30S ribosomal subunit.

What specific step in protein synthesis is blocked by tetracyclines?

Binding of tRNA to mRNA, preventing amino acid addition.

What is a common mechanism of resistance to tetracyclines?

Efflux pumps that remove the drug from the bacterial cell.

Why is tigecycline less affected by resistance?

It is structurally modified and less susceptible to efflux mechanisms.

Which class of broad-spectrum antibiotic have a lower risk of C. Difficile infection with use?

Tetracyclines.

Is there cross-reactivity between tetracyclines and β-lactam antibiotics?

No.

Name rare but serious adverse effects of tetracyclines.

Hepatotoxicity and intracranial hypertension.

What tetracycline side effects affect the oesophagus and skin?

Oesophageal ulceration/dysphagia and photosensitivity.

What dental effect can tetracyclines cause in children?

Tooth discolouration and enamel hypoplasia.

In which groups are tetracyclines contraindicated?

Pregnancy, breastfeeding, and children ≤12 years.

Why should tetracyclines be used cautiously in renal impairment?

Reduced excretion increases adverse effect risk and anti-anabolic effects raise serum urea.

Which substances reduce tetracycline absorption? What action should be taken when these are co-prescribed?

Calcium, antacids, and iron (divalent cations).

They should therefore not be given within 2 hours of each other.

How do tetracyclines interact with warfarin?

They enhance anticoagulant effect by reducing vitamin K-producing gut bacteria.

How should oral tetracyclines be taken to prevent oesophageal injury?

Swallowed whole with plenty of water while sitting or standing.

What medicines should patients avoid around tetracycline dosing?

Antacids and supplements containing iron or zinc.

What sun-related advice should be given to patients on tetracyclines?

Protect skin from sunlight due to photosensitivity.

How is response to tetracycline therapy monitored?

Resolution of symptoms, signs, and inflammatory markers where appropriate.

What are the main systemic uses of aminoglycosides?

Severe gram -ve infections, incl. sepsis, pyelonephritis/ complicated UTI, intra-abdominal infection, and endocarditis.

Which aminoglycoside is used topically for otitis externa?

Neomycin

Name two commonly used systemic aminoglycosides.

Gentamicin and amikacin.

Against which organisms are aminoglycosides most active?

Gram -ve aerobic bacteria, including Pseudomonas aeruginosa.

Which organisms are aminoglycosides ineffective against?

Streptococci and anaerobes.

Which ribosomal subunit do aminoglycosides bind to?

30S.

Are aminoglycosides bactericidal or bacteriostatic?

Bactericidal.

Why are streptococci and anaerobes intrinsically resistant to aminoglycosides?

They lack the oxygen-dependent transport system needed for drug entry.

How do penicillins enhance aminoglycoside activity?

By weakening the bacterial cell wall and increasing drug penetration.

What are the two most important toxicities of aminoglycosides?

Nephrotoxicity and ototoxicity.

How does aminoglycoside nephrotoxicity present?

Reduced urine output and rising serum creatinine (often reversible).

What symptoms are associated with aminoglycoside ototoxicity?

Hearing loss, tinnitus (cochlear damage), and vertigo (vestibular damage).

Is aminoglycoside-induced ototoxicity reversible?

Often irreversible.

Why must aminoglycoside doses be adjusted carefully?

They are renally excreted and have a narrow therapeutic index.

Which patient groups are at higher risk of aminoglycoside toxicity?

Neonates, older people, and those with renal impairment.

In which neuromuscular condition should aminoglycosides be avoided if possible?

Myasthenia gravis.

Which drugs increase the risk of ototoxicity with aminoglycosides?

Loop diuretics and glycopeptide antibiotics.

Which drugs increase the risk of nephrotoxicity with aminoglycosides?

Cephalosporins, NSAIDs, and other nephrotoxic drugs.

Why must systemic aminoglycosides be given parenterally?

They are NOT absorbed from the GI tract.

What determines aminoglycoside dose and dosing interval?

Body weight, renal function, and plasma drug concentration monitoring.

What trough level is generally considered safe for gentamicin before redosing?

<1 mg/mL.

How long should aminoglycoside treatment usually last?

As short as possible, typically <7 days and often a single dose.

Why is adjusted body weight used for aminoglycoside dosing in obesity?

Aminoglycosides distribute in body water, not fat.

Why should aminoglycosides be infused slowly IV?

To limit high peak concentrations that increase ototoxicity risk.