Term
| What is the standard TB multi-drug Regimen, and duration? |
|
Definition
Standard TB Multi-Drug Regimen (RIPE)
->intensive phase of 2 months
->Isoniazid
->Rifampin
->Ethambutol
->Pyrazinamide |
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Term
| What is given for TB Prophylaxis |
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Definition
|
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Term
| What is given for the continuation phase of TB tx? |
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Definition
Continuation phase-
-4 months
-Isoniazid
-Rifampin |
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Term
| What is the method of action of Isoniazid (INH)? |
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Definition
MOA of INH
-a prodrug that requires activation by KatG.
-Activated INH complexes w/ acpM and kasA
-inhibits mycolic acid biosynthesis & prevents cell wall formation |
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Term
| How does Resistance occur in Isoniazid? |
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Definition
Resistance in Isoniazid
-Resistance due to katG deletion
-inhA overexpression-->cross resistance w/ ethionamde |
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Term
| Pharmacology of Isoniazid |
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Definition
• Pharmacology
– Well distributed, even in CNS
– Crosses cell membranes
• effective against intracellular mycobacteria
– Acylated in the liver
-->• Fast acylators t1/2 = 1.5 h
-->• Slow acylators t1/2 = 3 h |
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Term
| Adverse Reactions of Isoniazid? |
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Definition
Isoniazid- Adverse reactions
• Competition with pyridoxine phosphate (vitamin B6)
– Co- administer with pyridoxine hydrochloride (vitamin B6)
• Peripheral neuritis • Hepatotoxicity
• age dependent |
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Term
|
Definition
Rifamapin
MOA-inhibition of RNA polymearse |
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Term
|
Definition
Rimfampin
-Resistance-->altered RNA polymerase |
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Term
|
Definition
Ethambutol
• Inhibits cell wall biosynthesis
• arabinogalactan and lipoarabinomannan
• Bacteriocidal to proliferating mycobacteria
• Effective against M. tuberculosis and M. kansasii
• Included in standard TB regimen to prevent growth of isoniazid or rifampin resistant mycobacteria |
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Term
|
Definition
Ethambutol
• Resistance
– Overexpression of embB gene
• Encodes arabinosyl transferace
• Overexpression of drug target confers resistance
– No cross resistance |
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Term
|
Definition
Pyrazinamide
• Mechanism of Action
– Pyrazinamide is a prodrug
– Must be activated by pncA to active form pyrazinoic acid
– Active only at low pH (lysosomes)
• Use
– Treatment of typical TB
– Important part of initial therapy by killing intracellular pathogens |
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Term
| Resistance to Pyrazinamide? |
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Definition
Resistance
-pnc A mutations
-Reduced uptake |
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Term
|
Definition
Streptomycin
-first-choice drug if multidrug resistance is suspected
-must be administered iv or i.m. |
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Term
|
Definition
Streptomycin
-Broad spectrum aminoglycoside antibiotic
-inhibits mycobacterial protein synthesis
-bacteriocidal only aganist extracellular bacilli |
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Term
|
Definition
Streptomycin AE
-Ototoxicity, vestibular toxicity-can be permanent
-Nephotoxicity |
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Term
|
Definition
Amphotericin B• Mechanism of Action
– Fungicidal or fungistatic
– Binds to ergosterol in mycosal membranes
– Forms pores
– Binds with lower affinity to cholesterol |
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Term
| When is Amphotericin B Used? |
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Definition
Amphotericin B-Use
-Broad spectrum anti-fungal
-initiation of anti-fungal therapy
-Anti-fungal azoles used for maintenance |
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Term
| What are Amphotericin B Adverse Effects? |
|
Definition
Amphotericin B- Adverse effects
• “Ampho-terrible”
• Rapidly occurs in almost all patients
–Headache, chills, fever
• (1 - 4 hours after infusion)
• Late – Decreased renal function
• Incidence - 80%
– Phlebitis
– Hypochromic normocytic anemia • Incidence- 27% |
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Term
| How do you treat Aspergillus? |
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Definition
| give Echinocandins-Capsofungin |
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Term
| MOA of Echinocandins-Capsofungin |
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Definition
Echniocandins-Capsofungin
MOA
-inhibits glucan synthase
-blocks formation of 1-3 beta glucan
-Disrupts cell wall synthesis |
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Term
| Use of Anitfungal Azoles? |
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Definition
Antifungal azoles
– Broad fungistatic activity
– Fungicidal at higher doses
– Prophylaxis for immunocompromised patients
– Fluconazole • CNS infection |
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Term
| MOA of Antifungal Azoles? |
|
Definition
Antifungal azoles
• Mechanism of Action
– Blocks the yeast cytochrome P40 enzyme lanosterol 14␣- demethylase
– Inhibits ergosterol biosynthesis
• 14␣-methyl sterol accumulates
– Disrupts cell membrane function |
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Term
| What drugs are used to Tx. RSV? |
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Definition
Tx of RSV
1) Ribavirin
2)Palivizumab |
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Term
|
Definition
Ribavirin
-works at multiple sites due to lowered GTP levels |
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Term
| AE & Contraindications of Ribavirin |
|
Definition
Ribavirin- Pharmacology
• Aerosol administration
• Sequestered in erythrocytes
• Delayed adverse effects due to long half life
• Respiratory depression
• Teratogenic and potentially fatal to fetuses |
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Term
|
Definition
Palivizumab
␣ Antibody against the fusion protein of RSV
␣ Use- prophylaxis against RSV
␣ <2 years of age who have bronchopulmonary dysplasia or were premature |
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Term
| MOA of Albuterol, Metaproterenol, Pirbuterol, & Levalbuterol |
|
Definition
MOA
-activation of beta2-adrenergic receptors on airway smooth muscle
-acitvation of adenylate cyclase inc. cAMP
-activation of protein kinas A
-inhibition of phosphorylation of myosin and dec. intracellular calcium resulting in relaxation of the smooth muscle |
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Term
| Why is Pirbuterol preferred? |
|
Definition
Pibuterol
-preferred bc it is available as a breath activated "autohaler" |
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Term
| SE of Adrenergic Bronchodilators? |
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Definition
| SE: Common: Tremor as a result of stimulation of beta2-receptors in skeletal muscle; tachycardia and palpitations |
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Term
| What are the long-acting beta2 agnoist |
|
Definition
1) Samleterol
-->not effective for the tx of acute bronchospams
2)Formetoerl
-its onset of action is significantly faster than salmeterol |
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Term
| What are Methylxanthine Bronchodilators? |
|
Definition
| Theophylline and Aminophylline |
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Term
| MOA of Theophylline & Aminophylline |
|
Definition
MOA
-may function as an adenosine antagonist
-may inhibit the intracellular release of calcium
-may function as a phosphodiesterase inhibitor
-strengthens contraction of the diaphragm and may reverse fatige in pts w/ chronic obstructive lung diease |
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Term
| When is Thophylline and Aminophylline used? |
|
Definition
-not first line tx b/c of low therapeutic index
-commonly used in COPD maintenance therapy then in asthma |
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Term
| What are the SE of Theophylline and Aminophylline |
|
Definition
SE
-nausea, anorexia, vomiting ,headache, undesierable cardiac stimulation |
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Term
| What are the Antimuscarinic Bronchodilators and MOA |
|
Definition
1) Ipratropium Bromide
2) Tiotropium
MOA--> blocks muscarinic receptors in airway smooth muscle and thus inhibits vagal cholinergic tone resulting in bronchodilation
-->inhibits component of bronchodilation due to cholinergic nerves
--less effective in the tx of chronic asthma
--effective in the tx of COPD
-not affective aganist allergen challenge |
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Term
|
Definition
Tiotropium
-long acting
-only approved for COPD |
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Term
| What would you give a pt that is get tachycardia from albuterol? |
|
Definition
Ipratropium
-syntergistic w/ b-agonist
-sole bronchodilator in pts who get tachy from albuterol |
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Term
| List the Aerosol Preparations of Corticosteroids |
|
Definition
) Beclomethasone
2)Dipropionate
3) Triamcinolone acetonide
4) flunisolide
5) Budesonide
6) Fluticasone
7) Cicloseinde |
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Term
| List the oral and parenteral prepaations of Corticosteroids |
|
Definition
1) Prednisolone
2) Methylprednisoline
3) Triamcinoline |
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Term
|
Definition
MOA
-inhibition of the formation & release of certain mediators of inflammation inhibition of phopholipase A2
-block the late response and the subsequent bronchial hyperresponsiveness
-Bronchial hyperresponsiveness is reduced when they are given on a long-term basis
-Long-term adminstration also reduces the immediate resonse to allergens |
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Term
|
Definition
SE
-oropharyngeal candidiasis and dysphonia may occur w/ larger doses
-spacers may reduce SE
-high does
-->cause ocular catracts
-->effects on growth rate in children
Orally or parenteally Steroids
-osteoporosis, weight gain, hypertension, diabetes
-catracts, psychiatric disturbances, myopathy
-immunosuppression, and suppression of the HPA axis
-Edema, potassium wasting, hypertension and diabetes |
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Term
| What is special of Budesonide |
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Definition
| Budesonide is the ONLY steroid available as a nebulizer preparation |
|
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Term
|
Definition
MOA
-blocks delayed chloride channels
-inhibits release of mediators from mast cells
-immediate response to allergen and exercise
-prevents bronchoconstriction-some action on sensory nerve fibers |
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Term
| What drug is given to prevent exercise induced asthma? |
|
Definition
|
|
Term
|
Definition
SE of Cromolyn Sodium
-few
-throat irritation when the powder is inhaled |
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Term
|
Definition
Nedocromil
-effects on airway neuronal relfexes that cromolyn lacks
-inhibits reflex reactions to irritants and to exercise and cold |
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Term
| List the Drugs that interfere w/ Leukotrienes |
|
Definition
1) Zarfirlukast
2) Montelukast |
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Term
| MOA of Zafrilukas & Montelukast |
|
Definition
MOA
-oral
-Leukotriene D4 receptor ANTAGONIST
- inhbits bronchoconstriction
-rapidly absorbed from GI tract, take before or after meals |
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Term
| When is Zafirlukast or Montelukast used? |
|
Definition
Clinical Use:
-maintenance tx of mild to moderate asthma
-not recommended for acute asthma tx |
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Term
| SE of Zarfirlukast and Montelukast |
|
Definition
SE
-potential for many drug interactions
-Warfain levels inc. |
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Term
|
Definition
MOA
-5-lipoxygenase inhibitor
-reduces teh formation of leukotrines B4, C4, D4 |
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Term
| What drug is given for aspirin-sensitive asthmatics? |
|
Definition
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Term
|
Definition
SE
-can increase concen. of warfarin, propranolol, and theophylline |
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Term
| What do you give pts who are allergic to Monteleukast and Zafirleukast? |
|
Definition
|
|
Term
|
Definition
Omalizumab
-biological antibody to human IgE
-IM once or twice monthly
-indicated in pts w/ high IgE levels |
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