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Foundations of Disease and Therapy > Clinical Pharmacology of Antivirals, Antifungals, and Antibiotics > Flashcards

Clinical Pharmacology of Antivirals, Antifungals, and Antibiotics Flashcards

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1
Q

Macrolides (Azithromycin)

ADME, Side Effects

A

Administered orally; food delays absorption

Diffuses into all fluids except CSF. Can cross placenta and enter fetal circulation; also enters breast milk

Excreted by kidney and liver

Large doeses cause epigastric distress. Inhibit CYPs and can have drug-drug interactions

Elevates QT interval and is associated with cardiovascular disease !!

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2
Q

Sulfonamides

Use, ADME, Side Effects

A

Highly concentrated in urine, good for treating UTI’s

May precipitate in acidic urine

Can cause acute hemolytic anemia in those with G6P Dehydrogenase Deficiency

Commonly cause rashes, ulceration on mucous membranes, and serum sickness

TOXIC EPIDERMAL NECROLYSIS - similar to Scarlet Skin Syndrome (Staph); skin loses glue that holds epidermis together and looks like second degree burn

CAN CAUSE ENCEPHALOPATHY AND BILIRUBIN DEPOSITS IN BRAIN OF FETUSES AND INFANTS - ABSOLUTE CONTRAINDICATION

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3
Q

Clindamycin

ADME, Side Effects

A

Can be given orally, parentally, or topically

Does not get into CSF, but crosses placenta

Accumulates in Neutrophils, Macrophages, and Pus - good for treating Staph and Strep

Excreted by liver and kidneys

Causes C. diff colitis and skin rash. Can lead to toxic megacolon

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4
Q

Cidofovir

Use, Pharmacokinetics, Side effects, Interactions

A

Nucleotide analog that does not require phosphorylation - activity against Herpes, Papilloma, Polyoma, Pox, and Adenovirus

IV formulation treats CMV Retinitis and Acyclovir-resistant HSV infections

Does not penetrate CSF

HIGHLY NEPHROTOXIC - Co-Administer with Probenecid and Saline to limit toxicity

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5
Q

Enfuvirtide:

Administration, Side Effects, Interactions

A

HIV Fusion inhibitor

only HIV drug given parenterally, route of elimination not known

Can cause cysts and reactions at site of injection

No interactions

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6
Q

Which B-Lactam does not cross-react with Penicillin?

A

Aztreonam (a Monobactam)

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7
Q

Carbapenems: Imipenem

Use, ADME, Side Effects

A

Broad-Spectrum with activity against Pseudomonas

Imipenem must be co-administered with cilastatin to inhibit its secretion in urine

Excreted by kidneys

Cause Nausea and Vomiting

Can cross-react with penicillins

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8
Q

(Anti-mitotic) Griseofulvin:

Distribution, Side Effects, Drug Interactions

A

Absorbed through GI

Deposited in keratin precursor cells where it persists and provides prolonged fungal resistance

Is Teratogenic (embryo deformation) and causes Confusion

Is a CYP 450 Inducer that Increases Warfarin metabolism

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9
Q

Side Effects and Interactions of Polyenes

A
  • High Nephrotoxicity - drug accumulates in kidney since it’s excreted in urine
  • Restriction of renal blood flow and toxic to distal tubules
  • Due to drug attacking cholesterol renal membranes at high concentrations
  • Drug-Drug interactions with Cyclosporine and Aminoglycosides (concurrent nephrotoxicity)
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10
Q

Toxicity of Penicillin (other than Hypersensitivity)

A
  • Pain at injection site (dose related)
  • large doses given to renal failure patients can cause confusion, twitching, and seizures
  • C. diff colitis
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11
Q

Tetracyclines

ADME, Side Effects

A

Given orally or parenterally

Divalent cations interfere with absorption (milk and antacids)

Wide distribution, including CSF

Minocycline is completely absorbed by stomach and excreted through bile

Causes nausea and vomiting. Hepatic toxicity in large doses. Renal Toxicity and Fanconi Syndrome if taking expired drug

COMMONLY CAUSES PHOTOSENSITIVITY AND GETS DEPOSITED IN BONES AND TEETH - contraindicated in Pregnant and Children

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12
Q

Administration of Polyenes

A

Amphotericin B comes in:

  1. Oral suspension
  2. 4 IV Lipid formulations (Lipid formulations reduce toxicity and side effects)
  3. Topical - Nystatin
  4. Opthalmic - Natamycin
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13
Q

Cross-Reactivity of Cephalosporins and Penicillins

A

6-10%

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14
Q

ADME of Polyenes

A
  • Polyene = Amphotericin B
  • Poor oral absorption - must be given IV
  • Does not penetrate CSF, eye, or amniotic fluid
  • Half life of 15 days
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15
Q

What drug needs to be co-administered with Cilistatin?

A

Imipenem

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16
Q

Cefazolin (First Gen)

What it’s good for, ADME

A

Good for susceptible Staph and Strep (surgery prophylaxis)

Given parentally (other 1st gens are given orally)

largely circulates bound to plasma proteins

excreted by kidneys

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17
Q

Adverse effects of Azoles

A

In general, they are well-tolerated

INHIBIT TESTOSTERONE SYNTHESIS (ketoconazole)

“Associated w/ endocrine dysfunction”

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18
Q

CYP Inducer

A

Rifampin

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19
Q

HIV Integrase Inhibitors:

Side effects, Interactions

A

Raltegravir

May cause Rhabdomylosis and Hypercholesterolemia

No interactions

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20
Q

Drugs to avoid during pregnancy and what they cause

A

“SAFe Children Take Really Good Care”

  • Sulfonamides - Kernicterus (bilirubin deposition in brain)
  • Aminoglycosides - Ototoxicity
  • Fluoroquinolones - Cartilage damage
  • Clarithromycin - Embryotoxic
  • Tetracyclines - Discolored Teeth, Inhibited Bone Growth
  • Ribavirin - Teratogenic
  • Griseofulvin - Teratogenic
  • Chloramphenicol - Gray Baby Syndrome
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21
Q

Cefoxitin (second generation)

what it’s good for, ADME

A

Good for RTI’s, intra-abdominal infections, pelvic inflammatory disease, and diabetic foot ulcers

Given Parentally (others in gen given orally)

excreted by kidneys

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22
Q

Ganciclovir:

Pharmacokinetics, Use, Side Effects, Interactions

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A

Monophosphorylated by Phosphotransferase in CMV

Commonly causes Neutropenia, Thrombocytopenia, Leukopenia, and is more toxic to host enzymes than Acyclovir

Do not give during pregnancy

Co-administration with nephrotoxic agents increases nephrotoxicity

23
Q

NNRTI’s

Side Effects and Interactions

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A
  • Non-competitive inhibitors of HIV Reverse Transcriptase*
  • Efavirenz, Nevirapine, Delaviridine*

May cause Rash and Hepatotoxicity

May also cause CNS side effects such as depression, hallucination, and mania

Eliminated by CYPs, so may interact with other drugs metabolized by CYPs

24
Q

Acyclovir and Valacyclovir:

Pharmacokinetics, Activity, Absorption, Distribution, Excretion

Study These Flashcards
A

Monophosphorylated by Thymidine Kinase in HSV/VZV

Used to treat HSV-1 and HSV-2 to reduce pain and improve recovery times

Can also treat VZV if used within 24 hours of rash onset

No activity in CMV, poor for EBV

Low oral bioavailability, Prodrug rapidly converted to ACV by liver

Widely distributed, including CSF

Excreted via kidney

25
Aminoglycosides Use, ADME, Side Effects
Parenteral Administration Poor penetration - **does not get inside cells, CSF, or Eye** **No activity against anaerobes** Excreted by kidneys - **Nephrotoxic** **Accumulates in Perilymph and Endolymph of Inner ear - Causes Dizziness and Ototoxicity** Can cause Neuromuscular Blockade - Contraindicated in Myasthenia Gravis
26
Which Penicillins are Oral vs IV?
Oral: Penicillin V, Amoxicillin IV: Penicillin G, Ampicillin, Nafcillin, Piperacillin-Tazobactam
27
Flucytosine: Distribution, Side Effects, Interactions
Well absorbed through GI tract - **Concentrates in CSF** May cause **Bone Marrow Suppression** No drug interactions
28
What determines what antibiotic to use?
Can the concentration of that antibiotic reach the minimum inhibitory concentration at the site of infection?
29
Echinocandins: Administration, Side Effects, Interactions
IV formulations only May cause GI upset and flushing due to histamine **Cyclosporine increases levels of caspofungin by 35%**
30
Type II Penicilin Allergy
Penicillin acts as a Hapten and binds to Erythrocytes This makes them antigenic, and it can result in lysis via complement or phagocytosis of RBC's
31
Metronidazole: Side Effects
**DO NOT MIX WITH ALCOHOL** Causes nausea, vomiting, skin flushing, tachycardia, and dyspnea Can also cause metallic taste (dysgeusia) and black urine
32
Rifamycin Side effects
Colors urine, saliva, and tears orange-red ## Footnote **Flu-like illness** **CYP Inducer; decreases half life of HIV drugs, contraceptives, and corticosteroids**
33
Allylamines: Side Effects and Interactions (terbinafine)
Can lead to **taste disturbances** and **hepatotoxicity** Metabolized by **Liver** **Rifampin** decreases plasma concentrations (CYP inducer) **Cimetidine** increases plasma concentratoins (increases stomach pH)
34
Cefepime (4th gen) Use, ADME
More resistant to Beta-Lactamases than Third Generation **Exellent CSF penetration** Given parentally Cleared by kidneys
35
Ethambutol Side Effects
Dose dependent **visual problems** ## Footnote **Red-Green Color Blindness**
36
Pyrazinamide Side Effects
Can cause hepatotoxicity, hyperuricemia, and **gout**
37
Vancomycin: Use, ADME, Side Effects
Use for MRSA, C. Diff, or for G+'s in Penicillin-allergic Given IV over an hour Secreted by kidneys **If infused too rapidly it can cause Red Man Syndrome - facial and neck flushing due to histamine release**
38
Isonazid Side effects
Penetrates into granulomas Causes **Rash and fever**
39
Imidazoles vs Triazoles
**Imidazoles** are an older class of Azole **Triazoles** are **metabolized more slowly** and have less effect on human sterol synthesis
40
Ceftriaxone What it's good for, ADME
**Broad-Spectrum**; good for serious infections like Bacterial Meningitis, Lyme Disease, and G- Sepsis **Not active** against **Listeria** and **Strep Pneumo** Given Parentally Good penetration in body tissues and fluids Excreted through **bile**
41
Acyclovir Resistance How it happens, What to use instead
Lack of Thymidine Kinase (usually) In this case, give drug that doesn't require phosphorylation such as **Cidofovir**
42
Fluoroquinolones (Ciprofloxacin) ADME and Side Effects
Orally administered - **divalent cations interfere with absorption (milk and antacids)** Gets inside cells Cleared by kidneys and is excreted in breast milk **Causes nausea, vomiting, and abdominal discomfort** Can cause C. diff colitis Causes **headache** and dizziness **Tendonopathy in adults and arthropy in children**
43
aDME of Penicillins
Widely distributed in tissues and secreations, EXCEPT: CNS, prostatic fluid, and eye Does not kill intracellular pathogens Rapid elimination through kidney (other compounds added to slow secretion) secreted in breast milk
44
Maraviroc: Side Effects, Drug Interactions
HIV Entry Inhibitor by preventing gp120 from binding CCR5 Can cause allergic reactions and hepatotoxicity **INHIBITOR OF CYP 450**
45
NRTI's Pharmacokinetics, Side Effects, Interactions
**The active triphosphates have 4x the half-lives of the parent compound - may accumulate in tissues to toxic levels** **Cause skeletal muscle myopathy due to depletion of mitochondrial DNA** Also cause Bone Marrow Suppression, Hypersensitivity, Peripheral Neuropathy, Lactic Acidosis Interacts with Stavudine and Zidovudine
46
CYP Inhibitors
Erythromycin, Clarithromycin, and Ketoconazole
47
Empiric Therapy vs Specific Therapy
Emperic Therapy - use of broad-spectrum drug Specific Therapy - use of narrower drug to target organism
48
Acyclovir and Valacyclovir: Side Effects and Interactions
Dose-limiting renal toxicity Interacts with Z**idovudine** (antiretroviral) and **Cyclosporine** (nephrotoxic)
49
Foscarnet Use, Mechanism, Side Effects, Interactions
Inhibits Viral DNA Polymerase but is **not a nucleoside analog** Used to treat CMV Retinitis and Acyclovir resistant HSV Causes **Nephrotoxicity** and **Hypocalcemia** **IV Pentamidine (anti-protozoal) increases hypocalcemia**
50
Aztreonam: Use
**Only works against G-**, incuding Pseudomonas Useful in patients with Penicillin allergy because it has **no cross-reactivity**
51
Drug interactions of Azoles
**INHIBITORS OF CYP 450 ENZYMES** Absorb better at low pH - don't take with antacids Can ketalate to metal cations in vitamins and slow absorption **Drugs that induce CYPs will significantly reduce serum concentratoins of Azoles**
52
Penciclovir Mechanism of Action and Use
Phosphorylated by TK in HSV and VZV, similar to Acyclovir ## Footnote **The major difference is that Penciclovir is less potent but the half life is 4x greater** **Used to treat Shingles (HZV)**
53
HIV Protease Inhibitors: Side Effects and Interactions
Commonly cause nausea, diarrhea, and vomiting. Can cause fatal hepatotoxicity. ## Footnote **Can cause crystalluria from poor drug solubility, along with nephropathy and hematuria** **Metabolized by CYP3A4 and may interact with other drugs metabolized by CYPs**
54
Toxic Epidermal Necrolysis
Rare side effect of Sulfa drugs Looks like Scarlet Skin Syndrome caused by Staph Layers of Epidermis become "unglued" and injury appears like a second degree burn

Foundations of Disease and Therapy (12 decks)

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