Beta blockers, Alpha blockers and stimulants, direct, emergencies Flashcards
What are the Sympathetic effects of Alpha 1?
- Vasoconstriction
- Increased peripheral resistance
- Increased BP
- Mydriasis (dilate pupils)
- Increased closure of internal sphincter of the bladder
What are the Sympathetic effects of Alpha 2?
- Inhibition of norepinephrine release
- Inhibition of acetylcholine release
- Inhibition of insulin release
What are the Sympathetic effects of Beta 1?
- Tachycardia
- Increased lipolysis
- Increased myocardial contractility
- Increased release of renin
What are the Sympathetic effects of Beta 2?
- Vasodilation
- Slightly decreased peripheral resistance
- Bronchodilation
- Increased muscle and liver glycogenolysis
- Increased release of glucagon
- Relaxed uterine smooth muscle
Within the sympathetic system we can affect blood pressure by doing what?
- Blocking the beta-1 receptors
- Blocking peripheral alpha-1 receptors
- Trigger central alpha-2 receptors
What does Blocking the beta-1 receptors do?
- Reduce heart rate
- Reduce renin release
What does Blocking peripheral alpha-1 receptors do?
- Vasodilation
- Decreased peripheral resistance
What does Triggering the central alpha-2 receptors do?
Reduce sympathetic outflow to the heart
What are the 3 main Beta Blockers we need to know?
- Carvedilol (CoregTM)
- Metoprolol (LopressorTM, Toprol XL)
- Nebivolol (Bystolic)
What is the prescription for Metoprolol Ext. Rel.?
100 mg
One tablet daily
- Max dose = 400 mg
What is the prescription for Carvedilol?
12.5 mg
One tablet twice a day
What is the prescription for Bystolic™?
20 mg
One tablet daily
- May start at 5 mg and titrate up
What are the differences based on for the Beta Blockers?
Selectivity
What are the 3 categories of Selectivity for the Beta Blockers?
- ) Non-selective beta-blocker:
- Block both beta-1 and beta-2 receptor sites
- Example: propranolol - ) Selective beta-blockers
- Specifically block beta-1 receptors
- Example: metoprolol - ) Beta-blockers with peripheral vasodilatory effects
- Adds in an alpha-1 blockade effect –> Example: labetolol, carvedilol
- Affects nitric oxide levels –> Example: nebivolol
What is Atenolol indicated for?
- Treatment of hypertension, alone or in combination with other agents
- Management of angina pectoris
- Secondary prevention postmyocardial infarction
What is Carvedilol (Coreg™, Coreg CR™)
indicated for?
Management of hypertension
Mild-to-severe heart failure of ischemic or cardiomyopathic origin
Left ventricular dysfunction following myocardial infarction (clinically stable with LVEF ≤40%)
What is Metoprolol succinate (Toprol XL™) indicated for?
Treatment of hypertension
Treatment of angina pectoris
To reduce mortality/hospitalization in patients with heart failure (stable NYHA Class II or III) already receiving ACE inhibitors, diuretics, and/or digoxin
What is Nebivolol (Bystolic™) indicated for?
Treatment of hypertension, alone or in combination with other agents
What is the candidate for use of Beta Blockers?
Younger patients rather than older patients
What is the effectiveness of Beta Blockers?
- No evidence for primary prevention of hypertension
- Preferred agents for patients with cardiac disease
What Agents would require dose adjustments in patients with renal impairment?
Atenolol
What drugs have Hepatic metabolism and need no renal dose adjustment but have first pass effect issues?
Metoprolol, carvedilol
So oral is higher dose than IV
Because of lipid and water solubility and possible penetration of blood brain barrier, Beta Blockers could cause?
Theoretically beta blockers in the CNS would cause effects such as: Lethargy, Nightmares, Confusion, Depression
Beta Blockers that are water soluble have?
- Less tissue penetration
- Longer biological half-lives
Ex: atenolol
What are the Adverse effects of Beta Blockers?
- Many side effects related to effects on cardiac tissue: Bradycardia, Hypotension, Atrioventricular nodal conduction block
- Bronchoconstriction
- Hypoglycemia
What are the Alpha Blockers?
- **Doxazosin (Cardura)
- Prazosin (Minipress)
- Terazosin (Hytrin)
What is the prescription for Doxazosin?
8 mg
One capsule daily
How do the Alpha Blockers work?
o Blockade of alpha-1 receptors
Affect both arteriolar and venous resistance vessels
• Magnitude based on sympathetic system activity
• Body response to fall in blood pressure can be
o Increase in heart rate
o Increase in cardiac output
o Increased fluid retention
What are the Adverse Drug Reactions of the Alpha Blockers?
o Orthostatic hypotension
Increased fall risk
Easing into therapy or dose changes (First dose syncope)
o Aggravators
Nasal congestion, headache, reflex tachycardia, peripheral edema (B/c good at opening up blood vessels)
o Non-selective alpha blockade
Smooth muscles of the base of the urinary bladder
What are the differences between the alpha blockers?
o Biological half life –> Doxazosin has longest half life
What is Prazosin (Minipress) indicated for?
Treatment of hypertension
What is Terazosin (Hytrin) indicated for?
- Management of mild-to-moderate hypertension; alone or in combination with other agents such as diuretics or beta-blockers
- Benign prostate hyperplasia
What is Doxazosin (Cardura) indicated for?
Treatment of hypertension as monotherapy or in conjunction with diuretics, ACE inhibitors, beta-blockers, or calcium antagonists
Treatment of urinary outflow obstruction and/or obstructive and irritative symptoms associated with benign prostatic hyperplasia
What is a positive effect of the alpha blockers?
- Favorable effect on lipid profile?
- Diminish risk of atherosclerosis by this mechanism and reduction of effect of cathecholamines in stimulation of vascular smooth muscle hypertrophy
What are the Alpha Stimulants?
- Clonidine (Catapres™)
- Methyldopa (Aldomet™)
- Guanfacine (Tenex™)
- Guanabenz
Prescription for Clonidine?
200 mcg
One tablet twice a day
Prescription for Catapres TTS™?
0.2 mg/24 hrs
Apply one patch once every 7 days
Prescription for Methyldopa ?
500 mg
One tablet twice a day
Initial dose is 4 times a day, 2 times a day is maintenance dose
Mainly used in pregnancy
How do the Alpha Stimulants work?
No one knows?
Theory = brain with drug doesn’t let vessels clamp down
What is the difference between the Alpha Stimulants?
Pharmacokinetics
What is Methyldopa indicated for?
Management of moderate-to-severe hypertension
What is Clonidine indicated for?
Management of hypertension (monotherapy or as adjunctive therapy)
Tablets or patch
- Can be used to treat pain syndrome or heroine addicts going through withdrawal
What is Guanfacine indicated for?
- Management of hypertension
- May be used in extended release form to treat ADHD
What is Guanabenz indicated for?
Used alone or in combination with other classes of antihypertensive agents in the management of hypertension.
NOT available in US
What are the Adverse Drug Reactions of the Alpha Stimulants?
o Dry mouth
o Bradycardia
o Orthostatic hypotension
o Sedation
o Problem with abrupt withdrawal
Life-threatening hypertensive crisis
What are the Direct Vasodilators?
- Minoxidil
* Hydralazine
What is the Prescription for Minoxidil?
5 mg
One tablet daily
How does Minoxidil work?
Increase in nitric oxide levels
• Increase in nitric oxide equals vasodilation (both arterial and venous)
• Vasodilation equals drop in blood pressure
What are the Adverse Drug Reactions for Minoxidil?
Standard side effects for an antihypertensive and then…
• Oops!
o Pericarditis and pericardial effusion that could progress to tamponade
o Increase oxygen demand and exacerbate angina
o Some sodium and water retention leading to…
• Grow hair (used in Rogaine)
What is the prescription for Hydralazine?
50 mg
One tablet twice a day (maintenance dose)
Initial dose = 4 times a day
How does Hydralazine work?
Opening up potassium channels in vascular smooth muscle
Increased nitric oxide levels
You got me!
- is effective at vasodilating
What are the Adverse Drug Reactions for Hydralazine?
Blood pressure drop significant enough to cause reflex tachycardia • Give with beta blocker to blunt effect Adverse drug reactions • Headache • Lupus-like syndrome o Inflammation, fatigue, more in women
What is a Hypertensive Emergency?
o Severe elevations in blood pressure
o Often higher than 220/140 mm Hg
o Requires immediate attention and blood pressure reduction
What is a Hypertensive Urgency?
o Marked elevation in blood pressure
o Usually higher than 180/110 mm Hg
o S/S headache, shortness of breath, pedal edema
o Management with oral agents may be appropriate
What are the oral agents you can use in an Hypertensive Urgency?
o Captopril
o ***Clonidine
o Labetalol
o Amlodipine
What is the Dosage for Captopril?
- 25 mg PO, repeat as needed,
* SL- 25 mg
What is the Onset/duration for Captopril?
- PO:15-30 min/6-8 hrs
- SL: 10-20 min/2-6 hrs
What are the Adverse Drug Reactions for Captopril?
Hypotension, renal failure, bilateral renal stenosis
What is the Dosage for Clonidine?
0.1-0.2 mg PO, repeat hourly as required to total dosage of 0.6 mg
What is the Onset/duration for Clonidine?
30-60 min/8-16 hrs
What are the Adverse Drug Reactions for Clonidine?
Hypotension, drowsiness, dry mouth
What is the Dosage for Labetalol?
200-400 mg PO, repeat every 2-3 hours
What is the Onset/duration for Labetalol?
1-2 hr/2-12 hrs
What are the Adverse Drug Reactions for Labetalol?
Bronchoconstriction, heart block, orthostatic hypotension
What is the Dosage for Amlodipine?
2.5-5 mg PO
What is the Onset/duration for Amlodipine?
1-2 hr/12-18 hr
What are the Adverse Drug Reactions for Amlodipine?
Tachycardia, hypotension
What are some of the major Hypertensive Emergency Injectables?
o Sodium Nitroprusside
o Nitroglycerin
o Nicardipine
What is the Dosage for Sodium Nitroprusside?
0.25-10 mcg/kg/min IV infusion
What is the Onset/Duration for Sodium Nitroprusside?
Immediate/2-3 min after infusion stop
What are the Adverse Drug Reactions for Sodium Nitroprusside?
- TOXIC!!!
* Nausea, vomiting, cyanide poisoning, metabolic acidosis, arrhythmias, death
What is the Dosage for Nitroglycerin?
• 5-100 mcg IV infusion
What is the Onset/Duration for Nitroglycerin?
2-5 min/5-10 min after infusion stop
What are the Adverse Drug Reactions for Nitroglycerin?
Headache, tachycardia
What is Sodium Nitroprusside used for in special cases?
• Acute Coronary Syndrome, Heart failure, Acute or Chronic Renal Failure, Ischemic Stroke
What is Nitroglycerin used for in special cases?
Acute Coronary Syndrome, Heart failure
What is the Dosage for Nicardipine?
5-15 mg/hr IV infusion
What is the Onset/Duration for Nicardipine?
1-5 min/15-30 min*
What are the Adverse Drug Reactions for Nicardipine?
Tachycardia, nausea, increased intracranial pressure
What is Nicardipine used for in special cases?
• Acute Coronary Syndrome, Acute or Chronic Renal Failure, Ischemic Stroke
How might you be limited by laws in your state in prescribing meds for hypertensive urgencies or emergencies?
- You may be limited by state laws, regulations, etc., as to the extent of your ability to prescribe injectable vasoactive products
- You are likely not limited by state laws, regulations, etc as to the extent of your ability to prescribe oral vasoactive agents
- Familiarize yourself with oral options for hypertensive urgencies
- Know the IV approaches to hypertensive emergencies so you can guide others
- Be careful!
