Nifedipine (Adalat, Procardia)
Nifedipine, a calcium ion influx inhibitor (Ca-channel blocker), selectively inhibits calcium ion influx across the cell membrane of cardiac muscle and vascular smooth muscle while maintaining serum calcium concentrations. In humans, Nifedipine decreases peripheral vascular resistance and creates a modest fall in systolic and diastolic pressure (5-10mm Hg systolic although sometimes larger). Nifedipine is generally given using the “bite and swallow” method, in a dose of 10 mg.
| Author Year; Country Score Research Design Sample Size |
Methods | Outcome |
| Thyberg et al. 1994; Sweden
Pre-post N=10 |
Population: 10 subjects with cervical or high thoracic SCI.
Treatment: 10 mg nifedipine sublingually during cystometry. Outcome Measures: blood pressure and heart rate. |
1. Patients demonstrated decreased maximum SBP and DBP after the administration of nifedipine.
2. Maximum SBP decreased from 147 mmHg to 118 mmHg. 3. The decrease in BP was due to a decrease in baseline pressure and BP response during cystometry. |
| Kabalin et al. 1993; USA
Case series N=20 |
Population: 10 subjects with tetraplegia, 10 with paraplegia.
Treatment: 10-30 mg nifedipine sublingually during Estracorporal shock wave lithotripsy (ESWL) for kidney stone treatment. Outcome Measures: electrocardiogram, blood pressure, pulse rate, peripheral oxygen saturation. |
1. All but one SCI patient demonstrated AD during ESWL with maximal increase in systolic BP of 74 mmHg.
2. Nifedipine was administered sublingually and controlled BP elevation. 3. For severe, acute increases in BP, ESWL stimulation was momentarily discontinued until pharmacological control of the BP was achieved, after which treatment was continued. |
| Steinberger et al. 1990;
USA Prospective controlled trial N=10 |
Population: All subjects with injury levels above T5; mean 9 years post-injury (range 3-21 years).
Treatment: 10-30 mg nifedipine sublingually 15 min prior to electroejaculation or no nifedipine. Outcome Measures: blood pressure, voltage and current delivered during electroejaculation. |
1. In 9/10 patients, blood pressures were markedly lower after nifedipine pretreatment.
2. Compared with no treatment, SBP during electroejaculation was lower with nifedipine pretreatment (168 mmHg vs. 196 mmHg). 3. In 9/10 patients, tolerance to electrical stimulation was ≥ post nifedipine pretreatment. |
| Dykstra et al. 1987;
USA Pre-post N=7 |
Population: Subjects with complete, cervical injuries.
Treatment: 10 mg nifedipine during cystosopy procedure. Outcome measures: blood pressure, presence of AD. |
1. Nifedipine alleviated AD when given sublingually during cystoscopy and prevented autonomic hyperreflexia when given orally 30 minutes before cystoscopy.
2. No adverse drug effects were observed. |
| Lindan et al. 1985;
USA Prospective controlled trial N=12 |
Population: 12 subjects with tetraplegia.
Treatment: phenoxybenzamine (10mg bid) versus nifedipine (20mg bid) administration at least 4 days prior cystometry. 11 patients were also tested for the efficacy of 10 mg nifedipine (sublingually or by mouth) for controlling AD symptoms. Outcome Measures: blood pressure. |
1. Neither drug prevented AD secondary to bladder filling, and a significant number of patients developed hypotension.
2. Sublingual dose of nifedipine (10 mg) was effective in managing acute attacks of AD. |
Discussion
Five studies (n=59) (Steinberger et al. 1990; Lindan et al. 1985; Thyberg et al. 1994; Kabalin et al. 1993; Dykstra et al. 1987) have evaluated the effects of Nifedipine; two level 2 controlled but not randomized trials (Steinberger et al. 1990; Lindan et al. 1985), and three level 4 studies (Thyberg et al. 1994; Kabalin et al. 1993; Dykstra et al. 1987). Four of these five studies saw a reduction or alleviation of AD with nifedipine (Steinberger et al. 1990; Thyberg et al. 1994; Kabalin et al. 1993; Dykstra et al. 1987). In their non-randomized control trial, Steinberger and co-investigators (1990) reported that sublingual nifedipine decreased peak systolic, diastolic, and mean blood pressure in SCI individuals undergoing electroejaculation. Braddom and Rocco (1991) surveyed 86 physicians with an average of 16.8 years of experience in managing AD in patients with SCI. While pharmacologic treatment of AD varied greatly from physician to physician, antihypertensive medications were the most frequently used medications with Nifedipine being a drug of choice for 48% of physicians for minor AD cases and for 58% of physicians for severe symptomatic AD cases. Although nifedipine has been the most commonly used agent for management of AD in individuals with SCI (Thyberg et al. 1994; Dykstra et al. 1987; Esmail et al. 2002; Braddom & Rocco 1991), its use has declined recently (Frost 2002; Anton & Townson 2004). There have been no reported adverse events from the use of nifedipine in the treatment of AD (Blackmer 2003), although all studies had a very small sample size. However, a review of nifedipine for the management of hypertensive emergencies not specific to SCI found serious adverse effects such as stroke, acute myocardial infarction, death and numerous instances of severe hypotension (Grossman et al. 1996). Due to several reports of serious adverse reactions occurring after administration of immediate-release nifedipine, the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (1997) has discouraged use of this drug.
Conclusion
There is level 2 evidence (from 2 prospective controlled trials: Steinberger et al. 1990; Lindan et al. 1985) that Nifedipine may be useful to prevent dangerous blood pressure reactions, e.g. during cystoscopy and other diagnostic or therapeutic procedures in SCI injured patients with AD.
There is level 5 evidence (from clinical consensus: Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure 1997), that serious adverse effects from Nifedipine may occur and these have been reported in other populations.
