Pharmacology, TB, Parasitic, Sepsis EXAM 1

Multiple drug regimens

At least 6 months

Resistance is a problem

Multidrug-resistant TB (MDR-TB)

Extensively drug-resistant TB (XDR-TB)- MDR-TB plus resistance to FQ's and additional second-line drugs.

Tuberculosis Therapy

Isoniazid (INH)

Ethambutol (EMB)

Pyrazinamide (PZA)

Rifampin (RIF)

Rifabutin

Rifapentine (RPT)

Tuberculosis 1st line drugs

Fluoroquinolones- Levofloxacin, Moxifloxacin

Cycloserine

Amikacin

Ethionamide

Streptomycin

Tuberculosis 2nd line drugs- Reserved for patients with resistant organism or HIV co-infected

Inhibits synthesis of mycolic acid

Activated by mycobacterial catalase-peroxidase (katG) forming a complex with reduced NADH.

Usually given Orally

Well absorbed in gut and widely distributed

WARNING:

Contraindications:

Drug-induced hepatitis: within first 3 months (Monitor LFTS at baseline and throughout treatment)

Acute liver disease

Peripheral neuritis: Pyridoxine inhibition

Isoniazid

Butanol derivative that has bacteriostatic activity against mycobacteria.

Warnings:

Optic neuritis (typically reversible)

Color blindness

Hyperuricemia

Not recommended in children <13 years old.

Ethambutol

Coverted to pyranzinoic acid which lowers pH of the environment resulting in rapid bacteriocidal acitivity.

Used to shorten initial treatment from 9-12 months to 6 months

Warnings:

Arthralgia

Hyperuricemia

Fever

Hepatitis

Increased serum iron concentrations

Pyrazinamide

Rifampicin

Inhibits bacterial RNA synthesis by binding to the beta subunit of DNA-dependent RNA polymerase, blocking RNA transcription (Does not bind RNA polymerase of eukaryotic cells)

Resistance is a problem---NEVER USE ALONE to treat active infections.

Warnings:

Food decreases absorption

STRONG inducer of metabolism--LOTS of drug interactions

Hepatitis-Monitor LFTs every 2-4 weeks

Hypersensitivity reactions (flu-like)

Discoloration of saliva, tears, and urine (permanent staining of contacts)

Rifampin

2 months

INH + RIF + PZA + EMB

Daily or 5d/week or 3x/week

Initial Phase of TB treatment

4 months

INH + RIF + OR INH + RPT

Initiation phase dosing dictates option for continuation phase.

RPT given weekly

Extended to 7 months if: initial chest x-ray shows a cavitary lesion, culture is positive at 2 months, you use ONLY INH/RIF/EMB in initial phase, and potentially in patients with HIV.

Continuation Phase of TB treatment

INH X 9 months

Monthly follow-up visits for pill count, symptoms for hepatitis, neurotoxicity

Latent TB

RIF X 4 months (6 months in children)

RIF + PZA X 2 months

Alternative TX for Latent TB

Usually PO

IV available in severe infections

Active against ANAEROBIC bacteria

Renal secretion

Disrupts DNA's helical structure

Eradication of H. pylori

Adverse RXNS:

Nausea/vomiting

Xerostomia (dry mouth)

Dysgeusia (metallic taste)

Metronidazole

Metronidazole (Flagyl)

Drug of choice for Amebiasis, giardiasis, and trichomoniasis

Metronidazole

Drug of choice for enterocolitis caused by C. difficile

Metronidazole

is available in gel or cream for topical treatment of rosacea (acne with persistent erythema)

GI discomfort

N/V

Metallic taste

transient leukopenia

thrombocytopenia

TAKE WITH FOOD

Disulfiram-like reaction with ethanol: Avoid drinking

DO NOT prescribe drug to women during 1st trimester.

Metronidazole Side effect

2nd gen nitroimidazole

ACTIVE AGAINST Metronidazole-resistant strains of Trichomonas vaginalis

Tinidazole

Chloroquine -Resistance!

Quinine (being used instead of Chloroquine)

Quinidine

1st line treatment for Malaria

Primaquine (to eradicate vivax or ovale malaria)

What drug is chloroquine combined with (because of resistance) in areas where Malaria is still big

GI distress

N/V

Toxic doses can cause retinal damage and even blindness.

Pregnant: CAUTION

Adverse effects of Chloroquine

quinine sulfate plus either doxycycline or pyrimethamine-sulfadoxine

Atovaquoneproguianil (Malarone)

Artersunate plus mefloquine (Lariam)

Patients with chloroquine-resistant malaria are usually treated with a combination of

Mefloquine (Lariam)

antimalarial drug that is used for both prevention and treatment of chloroquine-resistant malaria

Neuropsychiatric syndrome

-Hallucinations

-Anxiety

-Confusion

-Seizures

-Coma

Mefloquine can cause

Malarone

Proguanil is a biguanide derivative that acts as a folate reductase inhibitor. Sometimes combined with atovaquone to treat Chloroquine resistant malaria, it is available as a fixed-dose combo product called

Trimethroprim-sulfamethoxazole (Bactrim)

Alternatives:

Atovaquone

Pentamidine

Pneumocystis jiroveci treatment.

Benzimidazoles

Albendazole (Albenza)

Mebendazole (Vermox)

Side effects:

Mild GI discomfort and constipation or diarrhea

High dose of albendazole for echinococcosis can cause hepatitis or hematologic toxicity

Contraindicated in pregnancy

Drugs for Nematodes

Ascariasis

Capillariasis

Hookworm

Pinworm

Whipworm

Pyrimidine derivative

Activates nicotinic acetylcholine receptors in somatic muscles of nematodes and causes depolarizing neuromuscular blockade.

Poorly absorbed from the gut and acts primarily within the intestinal tract

Pyrantel (Pin-x)

Pyrantel

Liquid suspension of _________ for children and adults who have ascariasis, hookworm infection, or pinworm infection.

Permethrin (causes paralysis of the organisms)

Pediculosis: Liquid prep for HAIR AND SCALP

Permethrin cream: Scabies

Ectoparasite treatment

LICE AND MITES

Prompt broad-spectrum antibiotics within 1 hour of recognizing sepsis.

Double coverage for gram-negative organisms

Duration 7-10 days (immunocompromised-->longer duration)

Consider antifungals!!!

SEPSIS TX

Rifampin

a 22-year old female IV drug user was admitted to the hospital with a 4-week hx of cough and fever. A chest radiograph showed left upper lobe cavitary infiltrates. Culture of sputum yielded M. Tuberculosis susceptible to all antimycobacterial drugs. The patient received self-administered isoniazid, rifampin, pyrazinamide, and ethambutol. Two weeks following initiation of therapy, the patient is concerned that her urine is a "funny looking reddish color" which drug is the most likely cause?

Isoniazid

Rifampin

Pyrazinamide

Ethambutol

Isoniazid

Can cause peripheral neuropathy with paresthesias and numbness

A 32-year old man has been on standard four-drug therapy for active pulmonary tuberculosis for the past 2 months. He has no other comorbid conditions. At his regular clinic visit, he complains of a "pins and needles" sensation in his feet. Which drug is most likely causing this?

Isoniazid

Rifampin

Pyrazinamide

Ethambutol

Pyridoxine (Vitamin B6)

a 32-year old man who takes standard four-drug therapy for active pulmonary TB complains about a "pins and needles" feeling in his feet. He is diagnosed with peripheral neuropathy. Which vitamin should have been included in the regimen for this patient to reduce the risk of neuropathy?

Niacin

Pyridoxine

Thiamine

Ascorbic Acid

Rifampin

Potent inducer of cytochrome P450-dependent drug-metabolizing enzymes.

A 23-year old man was started on standard four-drug therapy for tx of Active TB. He has epilepsy, which is controlled with carbamazepine. He has had no seizures in 5 years; however, upon return to clinic at 1 month, he reports having two seizures since his last visit. Which drug may be the reason his carbamazepine is less effective?

Isoniazid

Rifampin

Pyrazinamide

Ethambutol

Rifabutin + others.

This should replace Rifampin in patients with HIV because it is a less potent inducer of CYP enzymes.

a 26-year old female HIV patient was recently diagnosed with active TB. Currently, she is on a stable HIV regimen consisting of two protease inhibitors and two nucleoside reverse transcriptase inhibitors. Which is the most appropriate regimen for treatment of her tuberculosis?

Rifampin + Iso + Pyra + etha

Rifabutin + iso + Pyra + etha

Rifapentine + iso + Pyra +etha

Rifampin + moxifloxacin + pyra + etha

Moxifloxacin

QT interval is associated with the fluoroquinolones.

a 28-year old man with MDR-TB is receiving the following medications for treatment: Pyrazinamide, ethionamide, moxifloxacin, streptomycin, and para-aminosalicyclic acid. Which drug in his regimen requires monitoring for QT prolongation?

Pyrazinamide

Ethionamide

Moxifloxacin

Streptomycin

Ethambutol + Pyrazinamide

Both may increase uric acid concentrations and have the potential to precipitate gouty attacks.

a 46-year old male patient with active tuberculosis is to be initiated on the four-drug regimen of isoniazid, rifampin, pyrazinamide, and ethambutol. The patient reports no other conditions except gout. Which pair of antituberculosis drugs has the potential to worsen his gout?

Rifampin + isoniazid

Ethambutol + Pyrazinamide

Rifampin + Ethambutol

Isoniazid + ethambutol

Iodoquinol

After the acute infection, which medication is given to treat the asymptomatic colonization state of E. histolytica?

Chloroquine

Iodoquinol

Metronidazole

Primaquine

Atovaquone-proguanil

A group of college students are traveling to a chloroquine-resistant malaria area for a mission trip. Which medication can be used to both prevent and treat malaria in these students?

Pyrimethamine

Artemisinin

Atovaquone-proguanil

Hydroxychloroquine

Metronidazole (Flagyl)

A 42-year old man returned from a camping trip and is diagnosed with Giardia Lamblia. Which medication would be considered the treatment of choice?

Chloroquine

Nifurtimox

Paromomycin

Metronidazole

Chloroquine + primaquine.

Which treatment option is most appropriate for a patient diagnosed with uncomplicated malaria due to P. ovale?

-Artesunate plus mefloquine

-Doxycycline

-Chloroquine

-Chloroquine + primaquine

Pyrimethamine

(In combination with sulfadiazine is treatment of choice for toxoplasmosis)

Which antiprotozoal agent is active against Toxoplasma Gondii

Metronidazole

Pyrimethamine

Leucovorin

Miltefosine

Mefloquine

Preferred regimens for prophylaxis in pregnant women.

a 32-year old pregnant woman is traveling abroad to a malaria-endemic country with known chloroquine resistance. Which prophylactic regimen is MOST appropriate?

-Doxycycline

-Mefloquine

-Primaquine

-Artemether-lumefantrine

Mebendazole

a 32-year old man is diagnosed with whipworm disease after he spent the summer working outside without shoes. Which would be the best treatment option?

Pyrantel pamoate

Mebendazole

Thiabendazole

Diethylcarbamazine