Clinical Pharmacology of Antivirals, Antifungals, and Antibiotics Flashcards Preview

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

Flashcards in Clinical Pharmacology of Antivirals, Antifungals, and Antibiotics Deck (54):
1

Macrolides (Azithromycin)

ADME, Side Effects

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 !!

2

Sulfonamides

Use, ADME, Side Effects 

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

3

Clindamycin 

ADME, Side Effects

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 

4

Cidofovir

Use, Pharmacokinetics, Side effects, Interactions 

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 

5

Enfuvirtide:

Administration, Side Effects, Interactions

HIV Fusion inhibitor

only HIV drug given parenterally, route of elimination not known 

Can cause cysts and reactions at site of injection

No interactions  

6

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

Aztreonam (a Monobactam)

7

Carbapenems: Imipenem

Use, ADME, Side Effects 

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

8

(Anti-mitotic) Griseofulvin:

Distribution, Side Effects, Drug Interactions 

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 

9

Side Effects and Interactions of Polyenes

  • 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) 

10

Toxicity of Penicillin (other than Hypersensitivity)

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

11

Tetracyclines

ADME, Side Effects

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 

12

Administration of Polyenes 

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 

13

Cross-Reactivity of Cephalosporins and Penicillins

6-10%

14

ADME of Polyenes 

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

15

What drug needs to be co-administered with Cilistatin?

Imipenem

16

Cefazolin (First Gen)

What it's good for, ADME

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 

17

Adverse effects of Azoles

In general, they are well-tolerated 

INHIBIT TESTOSTERONE SYNTHESIS (ketoconazole)

"Associated w/ endocrine dysfunction"

 

18

CYP Inducer

Rifampin

19

HIV Integrase Inhibitors:

Side effects, Interactions

Raltegravir 

May cause Rhabdomylosis and Hypercholesterolemia 

No interactions 

20

Drugs to avoid during pregnancy and what they cause

"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 

21

Cefoxitin (second generation)

what it's good for, ADME

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

Given Parentally (others in gen given orally)

excreted by kidneys 

22

Ganciclovir:

Pharmacokinetics, Use, Side Effects, Interactions

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

NNRTI's

Side Effects and Interactions 

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

Acyclovir and Valacyclovir:

Pharmacokinetics, Activity, Absorption, Distribution, Excretion

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

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 

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 Zidovudine (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

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.

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