下列何藥物因為首渡效應(first-pass effect)高,而不適於口服用藥?
(a)Morphine
(b)Atropine
(c)Propranolol
(d)Benazepril

首先,我們要了解一下什麼叫做首渡效應

The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall. Notable drugs that experience a significant first-pass effect are imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine.

After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system. It is carried through the portal vein into the liver before it reaches the rest of the body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of the drug. Alternative routes of administration like suppository, intravenous, intramuscular, inhalational aerosol and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly into the systemic circulation.--wikipedia

Morphine oral Bioavailability:Oral: 20% to 40%

--CCIS

Peak levels after oral administration are much lower than after parenteral routes, since oral M undergoes extensive first-pass metabolism in the liver. With repeated administration, the oral-parenteral relative potency ratio is 1:3 M can be administered epidurally or intrathecally and has also been given intracerebroventricularly.

-- Therapeutic Drug Monitoring [1991, 13(1):1-23], Clinical pharmacokinetics of morphine.

Atropine oral Bioavailability:Oral Availability:50%

-- Applied Biopharmaceutics & Pharmacokinetics, table E.1

Propranolol:50% to 70% of an oral dose is metabolized in the liver during its first pass (Cleveland & Shand, 1972).

--CCIS

Benazepril: is unsuitable for oral administration due to poor absorption:Oral: 37%

--CCIS

所以從以上資料看來,其實會因為首渡代謝效應而無法做成口服的藥物,morphinepropranolol 是確定會遭到首渡代謝,其餘兩個藥物資料有限,只能說是口服吸收效果不佳。但是因為製劑學的進步,所以目前在臨床上使用的藥物,morphinepropranolol皆以口服居多,morphine有針劑,但是propranolol則少見。Atropine則多為針劑,少有口服劑型,多見於複方。Benazepril雖然不適合做口服,但是是因為口服吸收差而非遭首渡代謝。

答案是A或C

Atropine的口服製劑:

MOTOFEN(difenoxin hydrochloride and atropine sulfate) Tablet

Difenoxin (as the hydrochloride) . . .. . . . . . . . . . . . . . . . . . . .1.0 mg

Atropine Sulfate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .0.025 mg

藥物長相motofen

Difenoxin的結構:

motofen1  

整體藥物結構:

motofen2  

作用:

management of acute nonspecific diarrhea and acute exacerbations of chronic functional diarrhea.

不過台灣應該比較看不到這個藥物。

另外還有一個藥物:

541096_3114795550279_1570165299_n  

Belladonna Alkaloids with Phenobarbital

(phenobarbital/ hyoscyamine/ atropine/scopolamine) 0.0194 mg-0.1037 mg-16.2 mg-0.0065 mg)

用途:IBS、acute enterocolitis、duodenal ulcer。

說到Atropine就不能忘記有機磷中毒:

Protocol for Organophosphate Poisoning


文章標籤

快樂小藥師 發表在 痞客邦 留言(0) 人氣()