Side Effect Flashcards
Macrolides side effect
1) GIT disturbance
2) thrombophlebitis
3) ototoxicity
4) hepatotoxicity (c&a better tolerated)
5) QT prolongation
Allergic can cause fever rash eosinophilia
Beta lactam side effect
1) hypersensitivity
2) bone marrow suppression (reversible)
3) seizure
4) hepatotoxicity
5) GI disturbance
All reversible
Penicillin 2 DDI
W oral contraceptives (decrease contractive level)
- bacteria cannot hydrolyse conjugated hormones
W probenecid
( accumulate BL; block secretion at renal tubular cells)
Cephalosporin SE
Hypersensitivity: rash, pruritus, fever
Anorexia, nausea, flatulence
Supra infection: ceftriaxone, cefoperazone and cefotetan may cause bleeding tendencies
Taking cefotetan and alcohol may cause serious disulfiram like reaction
Cephalosporins DDI
Cephalosporins + warfarin can increase warfarin effects
l reduce the absorption of vitamin K in the body.
l Long-term use (more than 10 days) of antibiotics may result in vitamin K deficiency because these drugs kill not only harmful bacteria but also beneficial, vitamin K- activating bacteria
Increase the anticoagulant effect of warfarin
Monobactam se
Side effects of monobactams
1. Very well-tolerated
2. No IgE-mediated cross-allergenicity with penicillins
3. Hematologic, GI, nephrotoxic or neurotoxic reactions are rare
Carbapenam DDI
Valproate + Meropenem can decrease valproate levels (may apply to all carbapenems); AVOID CONCOMITANT USE
- Decreased absorption of VPA secondary to inhibition of intestinal transporters by carbapenems;
- Decreased enterohepatic recirculation of VPA due to decreased gut bacterial beta-glucuronidase, which may be disrupted due the broad-spectrum activity of carbapenems;
- Increased distribution of VPA into erythrocytes; and
- Disruption of the normal metabolism of VPA
Glycopeptide SE
- Dermatological rash; haemotologic (neutropenia and thrombocytopenia with prolonged therapy (reversible)
- Thrombophlebitis, fever, chills (10%)
- “Red-neck” or “Red man syndrome”
(rash above the nipple line due to histamine release when vancomycin is infused too rapidly). Give antihistamine or prolong infusion time. - Increased nephrotoxicity and ototoxicity when vancomycin is used with aminoglycoside
Glycopeptide DDI
Aminoglycoside
Polymyxin
Daptomycin SE
Myopathy (muscle weakness due to dysfunction of muscle fibre)
Monitoring of weekly creatinine phosphokinase levels recommended
Daotomycin DDI
Statin
Polymyxin SE
Adverse effects of Polymyxins
1. Polymyxin B applied to intact or denuded skin or mucous membranes produces no systemic reactions and almost complete lack of absorption.
2. Nephrotoxic: avoid aminoglycosides or other nephrotoxins.
3. Interfere with neurotransmission at the neuromuscular
junction, resulting in muscle weakness and apnea.
4. Other neurological reactions include paresthesias, vertigo, and slurred speech.
Polymyxin DDI
Avoid amioglycoside
Vancomycin
Not w neuromuscular blocker
Aminoglycoside SE
1) ototoxicity
Associated with excessively high peak concentration on in conventional onal dosing
• Auditory and vestibular damage – Auditory- High frequency hearing loss
first
– Vestibular – affect balance, nausea, vomiting ng, ver=go
• May be reversible/ irreversible
- Nephrotoxicity
• Reported up to 20%
• Due to uptake into proximal renal tubular epithelial cells • A saturable process
Risk factors:
Trough conc >2-3 mg/L for gentamicin, tobramycin, netilmicin and >10mg/L for amikacin
– Prolonged duration on of therapy (>10-14 days) – Advance age
– Concomitant nephrotoxins (vancomycin) – Sepsis
– Gentamicin/ Amikacin > tobramycin • Reversible
3) neuromuscular blockage
Reversible with calcium gluconate
4) risk factor
Myasthenia gravis
HypoCa
HypoMg
Aminoglycoside DDI
Avoid polymyxin
Vancomycin
Not w CCB
Tetracycline SE
GI disturbance Liver failure Vertigo Desorption in bone and teeth Photo toxicity
Avoid pregnancy
Drug to Avoid in pregnancy
Quinolones
Tetracycline
Metronidazole
Chloramphenicol
Aminoglycoside
Tetracycline
Aminoglycoside DDI
- amphotericin B,
- Vancomycin
- NSAIDs
Nephrotoxic
reduce renal blood flow by inhibiting prostaglandin production
Tetracycline DDI
- Phenytoin
- Carbamazepine
- Phenobarbitone
- Antacids
Hepatic enzyme inducers -shorten the plasma
half-life of doxycycline by 50%
Antacid Reduce absorption
Cations: Ca++, Fe++ and Al+++
- reduce the absorption of oral
tetracycline
Tigecycline SE
Side effects of Tigecycline
1. Nausea, vomiting (20-30%)
2. Photosensitivity (uncommon)
3. Superinfection
4. Increase risk of mortality and treatment failure
Tigecycline DDI
Warfarin increase R warfarin AUC 40% but don’t affect INR
Macrolide DDI
Erythromycin
Clarithromycin
- Simvastatin
- Carbamazepine
- Cyclosporine
Inhibition of CYP450 3A4
Lead to increase level of these drugs
*azithromycin: doesn’t inhibit CYP 450
Digoxin
By inactivating gastrointestinal bacteria thought to metabolize digoxin in the gut?
Increase digoxin conc by 2-4x can suffer digoxin-induced toxicity, including arrhythmias, anorexia, altered color vision, and mental change
Clindamycin SE
- Hypersensitivity
- Gastrointestinal (most common)
• Diarrhea and nausea
• C difficile Pseudomembranous colitis - Hepatotoxicity (rare)Are Adverse effects of Clindamycin
Lincosamide DDI
Neuromuscular blocking agents
Clindamycin can inhibit neuromuscular transmission; therefore potentiate effects
Linezolid SE
- GI intolerance (nausea, vomiting ng, diarrhoea)
- Myelosuppression (thrombocytopenia, anemia) Most oien with treatment duration of >2 weeks
Increase risk in patients with renal failure, pre-existing myelosuppression, on drugs that can cause myelosuppression
Reversible upon discontinuation - Monoamine oxidase inhibition (Serotonin Syndrome ) Additive with other agents (MAOI, SSRI, etc)
- Peripheral and optic neuropathy
- Lactic acidosis
Clinical implication linezolid
Weekly FBC, especially platelets
• BP
• Visual changes
Linezolid DDI
monoamine oxidase inhibitors
1. SSRI
2. tyramine rich
food
3. adrenergic
agents
Reason: Monoamine oxidase inhibition (Serotonin Syndrome )
- Rifampicin
Rifampicin induce CYP450 enzymes
decrease linezolid AUC by 32%
Macrolide clinical application
.1 Community-acquired pneumonia pertussis
2. Corynebacterial
3. chlamydial infection
Lincosamide clinical applications
- Skin and soft tissue infections; anaerobic infections
- Prophylaxis against endocarditis prior to dental procedures in patients with valvular heart disease.
- Treat Pneumocystis jaroveci infection in HIV patients
Oxazolidinone clinical application
Treatment of severe infections caused by Gram-positive bacteria that are resistant to other antibiotics.
Agst MRSA, VRE (equivalent to vancomycin but can be taken orally!)
Anti folate SE
- Gastrointestinal disturbances (common) - Nausea, vomiting, and diarrhea
- Hypersensitivity/ allergic reactions - due to the products of sulpha
- Photosensitivity
- Renal
– False increase in creatinine (ave 18%) (common) – Nephrotoxicity, allergic nephritis
– Crystalluria - Hyperkalemia (with higher doses +/‐ renal impairment)
- Bone marrow suppression
Megaloblastic anemia (Give folinic acid supplementation in special cases- pregnant, malnourished)
May cause hemolytic reactions in G6PD patients Thrombocytopenia in high doses
Sulphonamide clinical application
- Lower urinary tract infections
- Sulphadiazine+pyrimethamine: -1st line for toxoplasmosis
-2nd line for malaria.
Trimethoprim clinical application
- Lower urinary tract infection
- Prescribed to patients with sulfonamide allergy
Cotrimoxazole clinical application
- Urinary tract infections
- P jaroveci pneumonia
- Toxoplasmosis
- Nocardiosis
Cotrimoxazole DDI
Oral anticoagulants: Warfarin
Poss mechanisms: disrupts vitamin K synthesis; Enhance the antithrombotic effect
Methotrexate
Increase levels of methotrexate (by displacing warfarin/methotrexate from protein binding, decreased renal tubular elimination).
Hydantoin anticonvulsants: Phenytoin
Increase the half-life of phenytoin (by inhibiting its metabolism)
Sulfonylurea hypoglycemic agents
increase risk of hypoglycemia – monitor
– Poss mechanisms: protein binding displacement
2-4. Inhibit metabolism of drugs and displace bilirubin from albumin
Floroquinolone SE
- Gastrointestinal disturbances (common)
- Nausea, vomiting, diarrhea and dyspepsia - Central Nervous systems
- Headache, agitation, insomnia, dizziness, rarely, hallucinations and seizures (elderly) - Hypersensitivity
- Cardiac
QT interval prolongaJon; Moxi> cipro, levo - Articular Damage
Arthopathy including arJcular carJlage damage, arthralgias, and joint swelling - Tendinitis and tendon rupture (black box warning)
- Alterations in blood glucose
Nitrofurantoin SE
- GIT disturbances - the principal adverse effects
- Hypersensitivity reactions (occasional and reversible): skin rash, pneumonitis, chills and fever
- Pulmonary interstitial fibrosis with chronic use, especially in the elderly
- Blood dyscrasias – neutropenia; hemolysis in infants and G6PD-deficient subjects
**Best to avoid use in pregnancy and the elderly
Floroquinolone DDI
Divalent/trivalent cations (eg in antacid, enteral feeds, iron)
- Co‐administration reduce fluoroquinolone absorption
- Reduce fluoroquinolone conc > treatment failure
- Separate by at least 2‐4 hours
Warfarin:
increase anticoagulation effect
Drugs that can cause QTc prolongation (eg quinidine, procainamide, amiodarone
— increase QT risk
Nitrofurantoin DDI
Antacid—–Reduce nitrofurantoin conc.
Floroquinolone Clinical application
- Urinary tract infections
- Gastroenteritis
- Osteomyelitis
- Anthrax
- TB (2nd line)
Nitrofurantoin uses
- Acute UTI
- Prophylaxis of lower UTI
**Only approved for the treatment of urinary tract infections caused by microorganisms known to be susceptible to the drug
Fosfomycin Clinical application
- Uncomplicated lower UTI
- Safe for use in pregnancy
Metronidazole SE
- GI intolerance, metallic taste
- Headache
- Peripheral neuropathy
- Disulfiram-like reacJon with alcohol
- Encephalopathy, aseptic meningitis, optic neuropathy
Dry mouth
Metronidazole DDI
Warfarin
Potentiate anticoagulant effect
Ethanol
Disulfiram like reaction
Lithium
Reduced Li renal elimination –> concentration
Metronidazole clinical uses
Effective against amoebiasis, giardasis, anaerobic peritoneal infections (CDAD) and bacteremia, Helicobacter
pylori
Polymyxin causes _______
Muscles weakness
Nephrotoxic
Do not affect ECG
Fosfomycin SE
RHVIN
Rash HA Nausea Rhinitis Vaginalis
