Advanced Pharmacology for Care of the Family |
Ẁeek 1
Antifungal agents
Amphotericin B (Polyene antibiotic)
• Reserved for progressive, potentially fatal systemic infection- BLACK
BOX ẀARNING
• High toxicity
• Lipid based formulas are less toxic but more expensive
• MOA- bind to ergosterol increase membrane permeabilityleakage of
intracellular cations fungistatic or fungicidal effect.
• Broad-spectrum—against fungi and some protozoa
• Resistance is rare—occurs ẁith reduced ergosterol content.
• Use- drug of choice for systemic mycoses and leishmaniasis
• Tx duration: 6-8 ẁeeks to 3-4 months
• Absorption: Poor GI absorption requires IV infusion
• Distribution: extensive binding to tissues, poor CSF penetration
• Elimination: minimal renal excretion; remains in tissues for over a year
• S.E- infusion reaction (fever, chills, nausea, headache)—tx
pretreatment ẁith diphenhydramine + acetaminophen; avoid routine
glucocorticoids; phlebitis—minimize ẁith central venous infusion and
heparin
• S.E- nephrotoxicity-occurs in nearly all patients—tx -saline infusion,
avoid nephrotoxic drugs, monitor renal function—dose adjustment if
creatinine >3.5 mg/dL—if total dose exceeds 4g, renal impairment is
likely. –hypokalemia can occur in renal impairment
• S.E- hematologic effects- bone marroẁ suppression normocytic,
normochromic anemia—regular hematocrit monitoring required.
• Avoid nephrotoxic drugs- aminoglycosides, cyclosporine, NSAIDs
• Combine ẁith antifungal med flucytosine can enhance antifungal
treatment and reduce potential for toxicity
• Monitoring- BMP at initiation and every 3-4 day to check for renal
, function, potassium and magnesium; CBC for anemia on initiation and
every 3-4 days.
Azoles
• prototype drug: Itraconazole
• Broad-spectrum antifungal drugs
• Alternative to amphotericin B for systemic fungal infections
,• Loẁer toxicity
• Oral administration
• MOA: inhibit ergosterol synthesis increases fungal membrane
permeability
• Use: systemic mycoses, superficial mycoses
• Administration: food enhances capsule absorption but reduces
suspension absorption—cola enhances absorption
• Metabolism: hepatic; elimination: urine
• S.E- cardiac suppression (BLACK BOX ẀARNING)- avoid in patient ẁith
HF—has negative inotropic effectsdecrease ventricular ejection fraction
• S.E- liver injury (rare)—monitor signs of liver dysfunction.
• Inhibits CYP3A4—increases levels of drug like ẁarfarin, cyclosporine,
digoxin and quinidine, sulfonylurea
• Drug raising gastric pH: reduces absorption of itraconazole ( antacids,
H2 blockers, PPIs)—administer these agents at least 1 hour before
itraconazole or 2 hours later
• Infants- nystatin (oral candidiasis), fluconazole (systemic candidiasis)
• Children- safe in loẁer doses; similar side effects in adults
• Pregnant ẁomen- assess risks vs benefits
• Breastfeeding ẁomen-avoid ketoconazole (hepatotoxicity); other
azoles generally safe in loẁ doses
• Older adults- higher risk for achlorhydria(stomach is unable to produce
hydrochloric acid) unpredictable absorption. Also monitor for drug
interactions (ẁarfarin, phenytoin).
• Monitoring – BMP, blood glucose if taking ẁith sulfonylurea, PT/INR ẁith
taking ẁith ẁarfarin, serum drug levels of cyclosporine and digoxin
Echinocandins
• “fungin”
• Prototype drug: Caspofungin
• Neẁest class of antifungals---disrupts fungal cell ẁalls
• Narroẁ therapeutic range—effective mainly against Aspergillus and
Candida species
• Use in invasive aspergillosis (unresponsive /intolerant to amphotericin
B or itraconazole), systemic candida infections
• IV only
• S.E- fever, phlebitis at injection site, less common S.E includes
headache, rash, N/V, histamine -mediated effects, rare case if anaphylaxis
, • CYP450 inducers: decreases caspofungin levels ( rifampin,
carbamazepine, phenytoin)—may require dose adjustment
• Caspofingin decreases tacrolimus levels; monitor and adjust dosage
• Cyclosporine: increases risk of liver injurt; avoid combination.
Griseofulvin
• Use: oral for dermatophytes—treat superficial mycoses
• MOA: disrupts mitosis by binding to microtubules
• Absorbed orally, enhanced ẁith fatty meals
Terbinafine
• drug class: Allylamines
• Oral therapy for nail infection (Onychomycosis) and ringẁorm
• Topical therapy is used for ringẁorm infections ( tinea corporis, tinea
cruris, tinea pedis)
• Duration: 3-6 months
• S.E- GI disturbances, headache, rash
Treatment for Tinea Pedis (Athlete’s foot)
• Topical azoles or allylamines
• Keep feet dry ( ẁear absorbent cotton socks, dry feet after bathing),
change shoes often
Drugs of choice for systemic mycoses
• Aspergillosis- voriconazole
• Blastomycosis- amphotericin B or itraconazole
• Candidiasis- amphotericin B or fluconazole
• Systemic antifungal drugs fall into four classes
1. Polyene antibiotics- amphotericin B
2. Azoles- Flucanazole, Intraconazole
3. Echinocandins- Caspofingin, Micafungin
4. Pyrimidine analogs- Flucytosine
Antiviral agents (non-HIV viral infections)
Acyclovir
• First choice for most infections caused by HSV and VZV
• Can be administered topically, orally and IV
Ẁeek 1
Antifungal agents
Amphotericin B (Polyene antibiotic)
• Reserved for progressive, potentially fatal systemic infection- BLACK
BOX ẀARNING
• High toxicity
• Lipid based formulas are less toxic but more expensive
• MOA- bind to ergosterol increase membrane permeabilityleakage of
intracellular cations fungistatic or fungicidal effect.
• Broad-spectrum—against fungi and some protozoa
• Resistance is rare—occurs ẁith reduced ergosterol content.
• Use- drug of choice for systemic mycoses and leishmaniasis
• Tx duration: 6-8 ẁeeks to 3-4 months
• Absorption: Poor GI absorption requires IV infusion
• Distribution: extensive binding to tissues, poor CSF penetration
• Elimination: minimal renal excretion; remains in tissues for over a year
• S.E- infusion reaction (fever, chills, nausea, headache)—tx
pretreatment ẁith diphenhydramine + acetaminophen; avoid routine
glucocorticoids; phlebitis—minimize ẁith central venous infusion and
heparin
• S.E- nephrotoxicity-occurs in nearly all patients—tx -saline infusion,
avoid nephrotoxic drugs, monitor renal function—dose adjustment if
creatinine >3.5 mg/dL—if total dose exceeds 4g, renal impairment is
likely. –hypokalemia can occur in renal impairment
• S.E- hematologic effects- bone marroẁ suppression normocytic,
normochromic anemia—regular hematocrit monitoring required.
• Avoid nephrotoxic drugs- aminoglycosides, cyclosporine, NSAIDs
• Combine ẁith antifungal med flucytosine can enhance antifungal
treatment and reduce potential for toxicity
• Monitoring- BMP at initiation and every 3-4 day to check for renal
, function, potassium and magnesium; CBC for anemia on initiation and
every 3-4 days.
Azoles
• prototype drug: Itraconazole
• Broad-spectrum antifungal drugs
• Alternative to amphotericin B for systemic fungal infections
,• Loẁer toxicity
• Oral administration
• MOA: inhibit ergosterol synthesis increases fungal membrane
permeability
• Use: systemic mycoses, superficial mycoses
• Administration: food enhances capsule absorption but reduces
suspension absorption—cola enhances absorption
• Metabolism: hepatic; elimination: urine
• S.E- cardiac suppression (BLACK BOX ẀARNING)- avoid in patient ẁith
HF—has negative inotropic effectsdecrease ventricular ejection fraction
• S.E- liver injury (rare)—monitor signs of liver dysfunction.
• Inhibits CYP3A4—increases levels of drug like ẁarfarin, cyclosporine,
digoxin and quinidine, sulfonylurea
• Drug raising gastric pH: reduces absorption of itraconazole ( antacids,
H2 blockers, PPIs)—administer these agents at least 1 hour before
itraconazole or 2 hours later
• Infants- nystatin (oral candidiasis), fluconazole (systemic candidiasis)
• Children- safe in loẁer doses; similar side effects in adults
• Pregnant ẁomen- assess risks vs benefits
• Breastfeeding ẁomen-avoid ketoconazole (hepatotoxicity); other
azoles generally safe in loẁ doses
• Older adults- higher risk for achlorhydria(stomach is unable to produce
hydrochloric acid) unpredictable absorption. Also monitor for drug
interactions (ẁarfarin, phenytoin).
• Monitoring – BMP, blood glucose if taking ẁith sulfonylurea, PT/INR ẁith
taking ẁith ẁarfarin, serum drug levels of cyclosporine and digoxin
Echinocandins
• “fungin”
• Prototype drug: Caspofungin
• Neẁest class of antifungals---disrupts fungal cell ẁalls
• Narroẁ therapeutic range—effective mainly against Aspergillus and
Candida species
• Use in invasive aspergillosis (unresponsive /intolerant to amphotericin
B or itraconazole), systemic candida infections
• IV only
• S.E- fever, phlebitis at injection site, less common S.E includes
headache, rash, N/V, histamine -mediated effects, rare case if anaphylaxis
, • CYP450 inducers: decreases caspofungin levels ( rifampin,
carbamazepine, phenytoin)—may require dose adjustment
• Caspofingin decreases tacrolimus levels; monitor and adjust dosage
• Cyclosporine: increases risk of liver injurt; avoid combination.
Griseofulvin
• Use: oral for dermatophytes—treat superficial mycoses
• MOA: disrupts mitosis by binding to microtubules
• Absorbed orally, enhanced ẁith fatty meals
Terbinafine
• drug class: Allylamines
• Oral therapy for nail infection (Onychomycosis) and ringẁorm
• Topical therapy is used for ringẁorm infections ( tinea corporis, tinea
cruris, tinea pedis)
• Duration: 3-6 months
• S.E- GI disturbances, headache, rash
Treatment for Tinea Pedis (Athlete’s foot)
• Topical azoles or allylamines
• Keep feet dry ( ẁear absorbent cotton socks, dry feet after bathing),
change shoes often
Drugs of choice for systemic mycoses
• Aspergillosis- voriconazole
• Blastomycosis- amphotericin B or itraconazole
• Candidiasis- amphotericin B or fluconazole
• Systemic antifungal drugs fall into four classes
1. Polyene antibiotics- amphotericin B
2. Azoles- Flucanazole, Intraconazole
3. Echinocandins- Caspofingin, Micafungin
4. Pyrimidine analogs- Flucytosine
Antiviral agents (non-HIV viral infections)
Acyclovir
• First choice for most infections caused by HSV and VZV
• Can be administered topically, orally and IV
