книга / 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Section VI λ Drugs for Inflammatory and Related Disorders

–↑ gastrointestinal acid and pepsin release → ulcers, gastrointestinal bleeding

–Electrolyte imbalance: Na+/water retention → edema and hypertension, hypokalemic alkalosis, hypocalcemia

–↓ skeletal growth in children

–↓ wound healing, ↑ infections (e.g., thrush)

–↑ glaucoma, ↑ cataracts (via ↑ sorbitol)

–↑ mental dysfunction

Chapter Summary

λSynthetic derivatives of cortisol are often used to manage inflammatory conditions or to promote immunosuppression. This chapter discusses the duration of action of several antiinflammatory steroids, their cellular effects and biochemical actions, as well as the many and severe adverse effects.

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Learning Objectives

Describe the mechanism of action of beta-receptor agonists, muscarinicreceptor blockers, glucocorticoids, and anti-leukotrienes in asthma

Compare the uses and side-effects of theophylline, cromolyn, and nedocromil

λAsthma is an inflammatory disease associated with bronchial hyperreactivity (BHR), bronchospasm, ↑ mucus secretion, edema, and cellular infiltration.

λEarly asthmatic responses (EAR) lasting from 30 to 60 minutes are associated with bronchospasm from the actions of released histamine and leukotrienes.

λLate asthmatic responses (LAR) involve infiltration of eosinophils and lymphocytes into airways → bronchoconstriction and inflammation with mucous plugging.

λManagement of asthma includes bronchodilators to provide short-term relief and antiinflammatory agents that reduce bronchial hyperactivity and protect against cellular infiltration.

Bronchoconstriction

++ +

Acetylcholine Adenosine Leukotrienes

AMP

ATP +

Beta Agonists

Figure VI-8-1. Drug Actions on Bronchiolar Smooth Muscle

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Section VI λ Drugs for Inflammatory and Related Disorders

BETA-RECEPTOR AGONISTS

λBeta-2 selective drugs (albuterol, metaproterenol, terbutaline) are widely used for relief of acute bronchoconstriction and in prophylaxis of exer- cise-induced asthma (see Figure VI-8-1).

λLonger-acting drugs (e.g., salmeterol) may decrease nighttime attacks (prophylaxis only) and permit dosage reduction of other agents.

λAerosolic forms have low potential for systemic toxicity but may cause anxiety, muscle tremors, and cardiovascular toxicity with overuse.

MUSCARINIC-RECEPTOR BLOCKERS

λIpratropium and tiotropium used via inhalation cause bronchodilation

in acute asthma, especially in COPD patients, and they may be safer than β agonists are in patients with cardiovascular disease.

λThey are the drugs of choice in bronchospasm caused by β blockers.

λThere are minor atropine-like effects.

THEOPHYLLINE

λBronchodilates via inhibition of phosphodiesterase (PDE) →↑ cAMP and also by antagonism of adenosine (a bronchoconstrictor)

λMainly adjunctive; regular use may decrease symptoms, but narrow therapeutic window predisposes to toxicity → nausea, diarrhea, CV (↑ HR, arrhythmias) and CNS excitation

λMany drug interactions; toxicity ↑ by erythromycin, cimetidine, and fluoroquinolones

λAminophylline IV sometimes used in bronchospasm or status asthmaticus

CROMOLYN AND NEDOCROMIL

λPrevent degranulation of pulmonary mast cells and ↓ release of histamine, PAF, and LTC4 from inflammatory cells

λProphylactic use:

–↓ symptoms and bronchial hyperactivity (BHR), especially responses to allergens

–Minimal systemic toxicity but may cause throat irritation and cough

–Relieved by a β2 agonist

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Section VI λ Drugs for Inflammatory and Related Disorders

Glucocorticoids

λ Prednisone, triamcinolone, dexamethasone, hydrocortisone

Drugs Used for Treatment of Gout

λAcute: colchicine, indomethacin

λChronic: allopurinol, probenecid, febuxostat, pegloticase

Drugs Used for Treatment of RA

λNSAIDs

λDMARDs: methotrexate, etanercept, infliximab, anakinra, and others

Drugs Used for Treatment of Asthma

λβ2 agonists: albuterol, terbutaline

λM-blocker: ipratropium, tiotropium

λMethylxanthine: theophylline

λMast-cell stabilizer: cromolyn

λSteroids: flunisolide

λLT modifiers: montelukast, zafirlukast, zileuton

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Chapter 9 λ Inflammatory Disorder Drug List and Practice Questions

1.A patient using NSAIDs for chronic pain develops a bleeding ulcer. What drug is designed to selectively treat ulcers of this type?

A.Famotidine

B.Bismuth

C.Aluminum hydroxide

D.Misoprostol

E.Muscarinic antagonists

2.Acute poisoning with acetaminophen often requires the use of a specific antidote. The beneficial property of this antidote is that it

A.supplies sulfhydryl groups to detoxify a reactive metabolite

B.induces P450 enzymes to enhance elimination

C.blocks the metabolism of acetaminophen

D.enhances renal clearance of acetaminophen

E.chelates acetaminophen

3.Which glucocorticoid is most likely to cause sodium and water retention?

A.dexamethasone

B.betamethasone

C.cortisol

D.celecoxib

E.desmopressin

4.A patient with RA is being treated with ibuprofen, but joint pain and stiffness are increasing. His physician prescribes another drug to be used with ibuprofen that may slow progression of the disease. Unfortunately, side effects develop, including dizziness, tinnitus, blurred vision, and pruritus. Ocular examination reveals corneal deposits and slight retinal pigmentation. What is the drug?

A.Gold salts

B.Etanercept

C.Hydroxychloroquine

D.Methotrexate

E.Thioridazine

5.A patient suffers from troublesome allergic rhinitis due to pollen, and you want to prescribe a drug for her that is least likely to cause sedation. What would your best choice be?

A.Betamethasone

B.Cimetidine

C.Hydroxyzine

D.Loratadine

E.Metoclopramide

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Section VI λ Drugs for Inflammatory and Related Disorders

6.The widely used anticoagulant warfarin is often implicated in drug interactions. If a patient takes warfarin but later begins self-medicating for ulcer pain, what drug useful for ulcers would increase the risk for bleeding?

A.Ranitidine

B.Sucralfate

C.Misoprostol

D.Cimetidine

E.Μetoclopramide

7.A patient with a migraine headache is treated with sumatriptan. This drug is beneficial because it

A.blocks 5HT3 receptors

B.stimulates 5HT1D receptors

C.blocks 5HT4 receptors

D.stimulates 5HT2 receptors

E.blocks muscarinic receptors

8.A child suffering from asthma is to be treated with a drug that blocks the synthesis of leukotrienes. What drug would be an appropriate choice?

A.Cromolyn

B.Montelukast

C.Ipratropium

D.Zileuton

E.Theophylline

9.Which one of the following is likely to be used in motion sickness, and nausea and vomiting of pregnancy?

A.Loratidine

B.Ondansetron

C.Meclizine

D.Fexofenadine

E.Cimetidine

10.For temporary maintenance of a patent ductus arteriosus prior to cardiac surgery in an infant, what is the drug of choice?

A.Alprostadil

B.Indomethacin

C.Epoprostenol

D.Celecoxib

E.Zileuton

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