🤷♀️🤷♀️사족: 중환자실에서 벤토린 네뷸을 사용하는 환자에서 tachycardia 발생하는 경우가 종종 있는데 흡입약/국소약이기 때문에 벤토린 네뷸의 가능성은 상대적으로 낮을 것으로 예상했는데 생각보다 beta-2 agonist로 인한 심혈관계 부작용이 뚜렷(?)하다는 문헌을 찾고 놀람!
SABA(short acting beta-2 agonist)
| Salbutamol(Albuterol) | |||
| 상품명 | 벤토린 에보할러 | 벤토린 네뷸 | 벤토린 흡입액 |
| 제형 | 흡입제(MDI) | 흡입액 | 흡입액 |
| 용량 단위 | 100 μg/puff 200 puffs/ea |
2.5 mg/2.5 mL 2.5 mL/Amp |
5 mg/mL 20 mL/병 |
| 사진 |  |
 |
 |
| 용법용량 | 1회 2 puffs씩 1일 4회 흡입 (1일 최대 8 puffs) |
1회 2.5~5 mL를 4~6 시간 간격으로 분무기를 이용하여 흡입 |
용액 0.5~1 mL를 최종 용적이 2~4 mL가 되도록 생리 식염수로 희석한 후, 1일 4회 분무기를 이용하여 흡입 |
| 부작용 | 구강·인후 자극감, 기침, 폐질환, 기관지염, 후두염, 천명, 쉰 목소리, 인두염, 비충혈, 구강 인두 건조감, 두통, 진전, 신경과민, 졸음, 어지러움, 불면, 불안, 흥분, 운동과잉, 심계항진, 빈맥, 혈압 변동, 협심증, 부정맥, 말초혈관이완, 식욕부진, 구역, 구토, 구갈, 구내염, 미각 이상, 설사, 두드러기, 발진, 혈관부종, 기관지 경련, 구강인두 부종, 저혈압, 허탈, 중증의 저칼륨혈증, 근육통, 근육 경련, 근육 경축, 드물게 근육 긴장감 |
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MDI: Metered Dose Inhaler (정량식분무흡입제)
LABA(long acting beta-2 agonist)
- Indacaterol
- Vilanterol
- Formoterol
- Olodaterol
- Salmeterol
In summary, the initiation of beta-2 agonist therapy was associated with significant increases in heart rate and reductions in potassium concentrations, which are known to be common systemic effects of beta-adrenergic stimulation, compared to placebo. With continued treatment, the rate of cardiovascular events was increased compared to placebo, with a significant increase in sinus tachycardia and a non-significant trend toward an increase in major cardiovascular events. It is possible that beta 2-agonists could precipitate arrhythmias, ischemia, and congestive heart failure through the activation of beta-adrenergic stimulation.
The beta-adrenergic system has a very tight negative feedback mechanism as an adaptive response to either stimulation or blockade of the receptors. Stimulation results in the uncoupling and internalization of the receptors, which is known as desensitization, and it can occur within a time range of minutes to hours.
This is followed by a decrease in receptor density and receptor gene expression, which is known as downregulation, and it develops within hours of stimulation.
This tolerance to adrenergic stimulation could explain why the highest risk for adverse cardiovascular events is seen during the initiation of beta 2-agonist therapy.
Conversely, when stimulation is stopped, the receptor begins to recover within a few hours, indicating that the risk for cardiac stimulation is present with continued beta 2-agonist use, even when used on a relatively regular basis.
🎶🎶 해당 meta 분석의 several limitation
A marked heterogeneity noted in the longer duration trials, despite the fact that no heterogeneity was seen in the results. For example, there was a wide range in study size and duration, the mean age of participants, medications used, and documentation of adverse events.
This analysis provides evidence that beta 2-agonists, when administered regularly for a few days or for up to 1 year, may increase the risk for adverse cardiovascular events compared to placebo. However, it is not possible to estimate the absolute risk attributed to treatment, as only those trials with at least one event were included in the analysis.
reference:
1) Salpeter, Shelley R., Thomas M. Ormiston, and Edwin E. Salpeter. "Cardiovascular effects of β-agonists in patients with asthma and COPD: a meta-analysis." Chest 125.6 (2004): 2309-2321.
2) KIMS
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