Understanding Prazosin: A Pharmacological Case Study

Case Study

Michael Hanson is a 77-year-old Caucasian male with a 60 year history of smoking. He has severe hypertension and benign prostatic hypertrophy. He has been prescribed Prazosin (Minipress) starting with 1 mg at bedtime and then increasing the dose to 10 mg BID in 2 weeks.

Pharmacokinetics, Pharmacodynamics and Pharmacotherapeutics

The mechanism of action for Alpha 1 Antagonists is to inhibit postsynaptic alpha-adrenergic receptors which causes vasodilation of vessels and in turn causes an overall decrease in blood pressure and peripheral resistance (Prazosin Lexicomp, 2015). The primary purpose of this drug or drug class is to treat hypertension but off label uses include use with regards to post-traumatic stress disorder (PTSD) related sleep disturbances as a sleep aid, as well as treatment of Raynaud’s disease (Prazosin Lexicomp, 2015). Prazosin (Minipress) is an oral medication and is highly protein binding at 97% of molecules that bind to receptors after dosing (Prazosin Lexicomp, 2015). This alpha 1 antagonist is metabolized in the liver and has immediate bioavailability at 60-86% of the drug left to bind after first pass metabolism in the liver (Prazosin Lexicomp, 2015). Prazosin (Minipress) has a half-life of 2-3 hours

which requires total adult dosing 2-3 times a daily (Prazosin Lexicomp, 2015). This drug is excreted through bile and feces (Prazosin Lexicomp, 2015).
Mr. Hanson, is a 77 year old male who was prescribed Prazosin (Minipress) with the instructions to start at 1 mg at bedtime but to increase the dose to 10 mg BID in 2 week (Prazosin Lexicomp, 2015). The first dose must be taken immediately before bed in order to avoid issues with first dose syncope phenomenon and may cause loss of consciousness (Prazosin Lexicomp, 2015). Recommendations for initial adult dosing are, 1 mg, 2 to 3 times daily with a recommended slow increase to a standard dosage of 6 to 15 mg/day in divided doses or alternatively (Prazosin Lexicomp, 2015). The dose may be increased to 20/mg per day in divided doses which is exactly the dose Mr. Hanson will graduate to; in some circumstances it is recommended to increase the dosage to 40mg/day in divided doses (Prazosin Lexicomp, 2015).
Contraindications for Prozasin (Minipress) include a sensitivity to quinazolines, prazosin, or any other product of this formulation (Prazosin Lexicomp, 2015).

Severe adverse effects that have been reported in 5% or more patients taking the Prazosin (Minipress) include: heart palpitations, dizziness, headache, drowsiness, decreased energy, weakness and nausea (Prazosin Lexicomp, 2015). Other adverse effects that were not as common include: edema, orthostatic hypotension, syncope, exacerbation of existing mental depression, dysphoria, nervousness, vertigo, constipation, liver toxicity, diarrhea, vomiting, urinary frequency, blurred vision, reddened sclera, dyspnea, epistasis and nasal congestion (Prazosin Lexicomp,

2015).
There is a significant list of drug to drug interactions, however most were a risk C interaction which means to monitor therapy (Prazosin Lexicomp, 2015). The risk C interaction can potentially increase hypotension or exacerbate the effect of the hypertension medication; some of these C medications include barbiturates, MAO inhibitors, levodopa and risperidone (Prazosin Lexicomp, 2015). Alpha 1 blockers are considered a risk X which means the patient should avoid therapy with these drugs all together (Prazosin Lexicomp, 2015). The only other risk noted was D, which means to consider therapy modification; some of these medications include, amifostine, beta blockers and rituximab (Prazosin Lexicomp, 2015). This drug Prozasin (Minipress), is recommended to take without food because food affects the metabolism and absorption of the drug.
Teaching for this drug includes that it is a class C for pregnancy, which is not recommended for pregnant women and trace amounts were detected in excretion of breast milk (Prazosin Lexicomp, 2015). Teach the patient the importance and action of monitoring orthostatic blood pressure at home with an automatic blood pressure machine as well as watching for symptoms of angina, which would cause discontinuation of the drug (Prazosin Lexicomp, 2015). If the patient must have cataract surgery while taking this drug, it could cause “floppy iris syndrome,” which can be avoided by using a different technique during cataract surgery (Prazosin Lexicomp, 2015).
First Pass Reaction
The exclusive metabolism of prazosin in the liver results in a significant risk of orthostatic hypotension within 30 to 90 minutes after administration of the initial dose (Woo & Wynn, 2011). Although this reaction decreases with subsequent doses, it can cause syncope making it necessary to take precautions to ensure patients safety when administering the initial dose (Woo & Wynn, 2011). Syncope is a loss of consciousness resulting from the reduction of blood flow to the brain which, in the case of alpha blockers, is caused by arterial and venous vasodilation (Lewis et al., 2012 & Woo & Wynn, 2011). Syncope carries an especially high risk of injury if it occurs upon standing, as is the case with orthostatic hypotension, due to the risk of falling (Lewis et al., 2012).
In order to reduce the potential for falls related to first dose orthostatic hypotension it is advised to administer the first dose of prazosin in the office where the patient can be monitored for possible hypotensive syncope or advise patients to take the medication once they have retired to bed for the night (Woo & Wynn, 2011). Additionally, patients should be advised that first dose orthostatic hypotension will reoccur upon resuming if therapy is stopped, even temporarily, therefore the suggested first dose precautions should be taken when the medication is restarted (Woo & Wynn, 2011).
Minimization of First Pass Reaction
First pass orthostatic hypotensive reactions can be minimized by beginning Prazosin therapy with low dosages, 1 mg, and increasing slowly over a two week period until therapeutic effects are obtained (Woo & Wynn, 2011). Although orthostatic hypotensive risk is greatest with initiation of prazosin therapy, the risk of hypotensive episodes with alpha blockers remains a risk with subsequent doses, with research revealing an elevated risk when they are taken in the morning (Lewis et al., 2012). Given this finding, it is appropriate to advise patients to continue bedtime medication administration of Prazosin beyond the initial phase in order to ensure maximum patient safety from falls related to the inherent risk of hypotension associated with alpha blocker therapies (Lewis et al., 2012).
Tamsulosin, Alfuzosin, Silodosin BPH Treatment
Benign prostatic hypertrophy (BPH) is the obstruction of urine outflow due to an enlarged prostate gland. Tamsulosin, Alfuzosin, and Silodosin are alpha antagonists with increased specificity for the alpha 1 receptors concentrated in the bladder neck and prostate gland allowing for the relaxation of the bladder neck and prostate gland with very little effect on the receptors related to blood pressure. This specificity makes these drugs especially useful in relieving the outflow obstruction caused by BPH with less risk of the adverse effects such as reflex tachycardia and orthostatic hypotension that are associated with less selective alpha blockers (Woo & Wynn, 2011).

Patient Teaching
It is vital that the nurse practitioner ensure that the patient truly understand Prazosin including both the good that it can do as well as the potential bad. A patient must be fully educated on a new medication that they are to begin taking so that they understand what the goals are as well as what to watch out for. They need to be aware to always tell their doctors that they are taking this medication prior to any procedure. The goals of taking Prazosin are to keep high blood pressure in check and to not suffer from any adverse effects of the drug including injury related to low blood pressure, urinary issues, depression, syncope, dizziness, or potential CNS changes (Prazosin Lexicomp, 2015).
It is important to teach the patient to check his vital signs with regular home monitoring for orthostatic hypotension as well as watching for symptoms of angina (Prazosin Lexicomp, 2015). The patient needs to know what range he needs to be in as well as what vital signs should be reported to their health care professional. The patient needs to understand that the first dose of medication must be taken right before bed in order to curtail the potential effects of first dose phenomenon, the side effects do diminish with continued therapy but reoccur with any start or stop of the medication (Prazosin Lexicomp, 2015). As syncope is a side effect of Prazosin it is important that the patient remember to always rise slowly and avoid sudden changes in movement and to not drive or operate heavy machinery until the patient is sure of how they function on the medication. Prazosin can provoke existing mental conditions as a result of its depressant action on the central nervous system, the patient needs to be aware of this and report any feelings of dysphoria, suicidal feelings or depression immediately (Prazosin Lexicomp, 2015). Other neurological signs to be aware of include blurred vision, tinnitus, edema and epistaxis (Prazosin Lexicomp, 2015). Over the counter nasal decongestants, cough medicines and cold medicines, stimulants and NSAIDs should not be taken until cleared by a health care provider (Prazosin Lexicomp, 2015). Due to a potential for liver toxicity lab testing may be required, carefully monitor for liver issues and report them immediately such as nausea and vomiting, diarrhea or changes in stool color, rash, jaundice and abdominal pain tenderness or distension.