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65 Cards in this Set

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Beta-1 Agonist Effects
+ chronotropic (heart rate)
+ ionotropic (contractility)
+ dromotropic (conduction velocity)
+ lustitropy (relaxation rate)
bronchodialation
smooth muscle relaxation (vascular)
hepatic glycogenolysis
Release of renin and glucagon
arrythmogenesis ( increased automaticity)
Epinephrine b1 = b2 > a1 = a2
Norepinephrine b1 = a1 > b2 = a2
Dopamine b1 = b2 > a1
Dobutamine b1 > b2 > a1
Isoproterenol b1 = b2
xxx
Beta 1 antagonist effects
- chronotropic (heart rate)
- ionotropic (contractility)
- dromotropic (conduction velocity)
- lustitropy (relaxation rate)
smooth muscle relaxation (vascular)
inhibition of hepatic glycogenolysis
inhibition of release of renin and glucagon
antiarrythmic (sympathetic nervous system blockade)
antianginal (decreased cardiac workload/MvO2)
antihypertensive (decreased CO from -chronotropy, -ionotropy, -renin release)
Beta-1 selective antagonist side effects/contraindications
bradycardia
bronchospasm (use with caution -asthmatics!!)
dyspnea (secondary to bronchospasm)
nausea/vomiting
hypotension (especially with mixed therapy)
heart block
heart failure
fatigue
Dizziness (secondary to hypotension)
insomnia
exacerbation of Reynaud’s syndrome
ISA (intrinsic sympathomimetic activity)
“Some agents are capable of exerting low level agonist activity at the beta-adrenergic receptor while simultaneously acting as a receptor site antagonist. These agents, therefore, may be useful in individuals exhibiting excessive bradycardia with sustained beta blocker therapy” (Wikipedia).
Atenolol (Tenormin) only beta-1 specific with ISA
Acebutolol (Sectral, Prent)
Beta 1 selective antagonist drugs
Acebutolol
Atenolol(Tenormin)
Esmolol (Brevibloc)
Metoprolol(Lopressor)
Betaxolol
Bisoprolol
Nebivolol
Acebutolol (Sectral, Prent)
cardioselective
ISA (intrinsic sympathomimetic activity)
more suitable for patients with Asthma or chronic obstructive lung disease.
indications: HTN, angina, arrhythmias

hydrophilic
bioavailability 35-40%
hepatic metabolism
active metabolite increases duration to 8-13 hours
oral prep only
Atenolol (Tenormin)
cardioselective
Similar to propranolol but without negative ionotropic effects
PO prep only
indications: HTN, CAD, arrhythmias, AMI after event
hydrophilic
bioavailability 40-50%
hepatic metabolism (10%<)
renal excretion
half life 6-7 hours
Nebivolol
cardioselective
arterial vasodilator
increases nitric oxide levels
indications: HTN
PO oral
bioavailability ?
hepatic metabolism
renal excretion
half life 10 hours
Metoprolol (Lopressor)
cardioselective
PO and IV preps
Indications: HTN, CAD, arrhythmias, AMI after event, migraine prophylaxis
lipophilic
bioavailability 12%
hepatic metabolism
renal excretion
half life 3-7 hours
Esmolol (Brevibloc)
cardioselective
rapid onset
prevents the action of epinephrine and norepinephrine.
Indications: treatment for tachycardia and SVT
IV prep only
bioavailability ?
plasma esterase metabolism
renal excretion
half life 9 minutes
Bisoprolol (Ziac)
cardioselective
Combined with HCTZ
Indications: HTN, CAD, arrhythmias, AMI after event, CHF, angina
PO prep only
bioavailability > 90%
hepatic metabolism
renal excretion
half life 9-12 hours
Betaxolol (Betoptic)
bioavailability 89%
? metabolism
renal excretion
half life 14-22 hours
cardioselective
ophthalmic use common
Indications: HTN, Glaucoma
CARBACHOL
Carbachol is sometimes used to constrict the pupils during cataract surgery. Intraocular (eyedrop) administration is used to produce miosis during cataract surgery, either topically or with intraoccular injection

Carbachol is a parasympathomimetic that stimulates both muscarinic (primarily) and nicotinic receptors (mimincs the effects of acetylcholine). Carboachol is not easily metabolized by chollinesterse. Duration of action is 4-8 hours for topical administration and 24 hours for intraoccular administration. Principal effects are miosis and increased aqueous humor outflow. Side effects are blurred vision, abdominal cramps, bradycardia, N/V, and diaphoresis. Carbachol is contraindicated, for patients with asthma, CAD, GI ulcers.obstruction, urinary incontinence, epilepsy, Parkinson’s disease, recent MI, pregnancy and hyperthyroidism. Carbachol reduces the effects of non-depolarizing muscle relaxants.
Raymond Ahlquist (1948) rationalized that catecholamines acted via two principal receptors.
these receptors where termed Alpha & Beta
Nonselective beta antagonist Agents
Propanolol (Inderal) PO: 40-360 mg
IV: 1-10 mg
Timolol (Timoptic) PO: 10-30 mg
IV: 0.4-1mg
Pindolol (Visken) PO: 5-20 mg
IV: 0.4-2 mg
Nadolol (Corgard)
PO: 40-320 mg
IV: none
Addition of alkyl groups at nitrogen increases selectivity for _ receptor
Beta 2
Albuterol
Bitolterol
Mesylate
Formoterol
Isoproterenol
Levabuterol
Metaproterenol
Salmeterol
Terbutaline
Presence of 3,5 di-hydroxy on phenyl with longer chain give _2 specificity
Beta 1
Norepinephrin
Isoproterenol
dobutamine
Epinephrine
Pharmacokinetics of non-selective beta adrenergics blockers
Structural analogues of beta-adrenergic receptor agonists
all of them can be given PO
all but nadolol can be given IV
Agonist Mechanism of Action
Beta-adrenoceptors are coupled to a Gs-proteins, which activate adenylyl cyclase to form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A) that phosphorylates L-type calcium channels, which causes increased calcium entry into the cell. Increased calcium entry during action potentials leads to enhanced release of calcium by the sarcoplasmic reticulum in the heart; these actions increase inotropy (contractility). Gs-protein activation also increases heart rate (chronotropy). PK-A also phosphorylates sites on the sarcoplasmic reticulum, which lead to enhanced release of calcium through the ryanodine receptors (ryanodine-sensitive, calcium-release channels) associated with the sarcoplasmic reticulum. This provides more calcium for binding the troponin-C, which enhances inotropy. Finally, PK-A can phosphorylate myosin light chains, which may contribute to the positive inotropic effect of beta-adrenoceptor stimulation.
Because there is generally some level of sympathetic tone on the heart, beta-blockers are able to reduce sympathetic influences that normally stimulate chronotropy (heart rate), inotropy (contractility), dromotropy (electrical conduction) and lusitropy (relaxation). Therefore, beta-blockers cause decreases in heart rate, contractility, conduction velocity, and relaxation rate. These drugs have an even greater effect when there is elevated sympathetic activity.
Antagonist Mechanism of Action

Nonselective Beta Adrenergic Receptor Antagonists
Selective for beta receptors
Beta1= Heart tissue
Beta2= Smooth muscle, liver, other tissues
Competitive inhibition
Reversible
Chronic use increases # of beta-adrenergic receptors
Propranolol (Inderal)

Nonselective Beta Adrenergic Receptor Antagonist
Use:
HTN
angina
IV for life threatening arrhythmias or pts. under anesthesia
migraine HA
acute myocardial infarction
acute thyrotoxicosis
pheochromocytoma
MOA:
interacts with B1 and B2 receptors equally.
lacks intrinsic sympathomimetic activity. (pure antagonist)
most important activity is on the heart (B1 receptors) leading to _HR, _myocardial contractility = _CO
B2 receptor activity on the vasculature = increased peripheral vascular resistance (vasoconstriction)
does not block alpha-adrenergic receptors.
high membrane stabilizing activity (local anesthetic)

propranolol and pindolol are the only two that have membrane stabilizing activity or local anesthetic activity. They are able to block sodium channels in nerves and heart tissue and thereby slow conduction velocity.
Propranolol ADME

Nonselective Beta Adrenergic Receptor Antagonists
Absorption:
rapid and almost complete absorption in the GI
Distribution:
lipophilic(high Vd) readily enters the CNS
approximately 90-95% protein bound
Metabolism:
high first pass hepatic metabolism
4-hydroxypropranolol is active metabolite. (equal to parent in activity)
Elimination:
elimination half-time is 2-3 hours
Timolol (Timoptic)

Nonselective Beta Adrenergic Receptor Antagonists
Use:
glaucoma (_ intraocular pressures)****************
HTN
angina
IV for life threatening arrhythmias or pts. under anesthesia
migraine HA
acute MI
MOA:
interacts with B1 and B2 receptors equally.
lacks intrinsic sympathomimetic activity. (pure antagonist)
no membrane stabilizing activity (no local anesthetic activity)
Nonselective Beta Adrenergic Receptor Antagonists

Timolol ADME
Absorption
rapid and almost complete absorption in the GI
Distribution
lipophilic(high Vd) readily enters the CNS
protein binding is not extensive
Metabolism
high first pass hepatic metabolism
Elimination
elimination half-time about 4 hours
Nonselective Beta Adrenergic Receptor Antagonists

Pindolol (Visken)
Use:
HTN
angina
MOA:
interacts with B1 and B2 receptors equally.
has intrinsic sympathomimetic activity. (partial agonist activity on beta receptors)
low membrane stabilizing activity (local anesthetic activity)
most important activity is on the heart (B1 receptors) leading to _HR, _myocardial contractility = _CO
Nonselective Beta Adrenergic Receptor Antagonists

Pindolol (Visken) ADME
Absorption
rapid and almost complete absorption in the GI
Distribution
moderately lipid soluble
Metabolism
approximately 50% metabolized by liver.
Elimination
remaining 50% excreted unchanged in the urine.
elimination half-life is 3-4 hours
Absorption
rapid and almost complete absorption in the GI
Distribution
moderately lipid soluble
Metabolism
approximately 50% metabolized by liver.
Elimination
remaining 50% excreted unchanged in the urine.
elimination half-life is 3-4 hours
Nonselective Beta Adrenergic Receptor Antagonists

Nadolol (Corgard)
Use
HTN
migraine HA
angina pectoris
MOA
interacts with B1 and B2 receptors equally.
no intrinsic sympathomimetic activity.
no membrane stabilizing activity
Nonselective Beta Adrenergic Receptor Antagonists

Nadolol (Corgard) ADME
Absorption
water soluble
slow and incomplete absorption in the GI (35% bioavailable)
Distribution
not well distributed due to water solubility
Metabolism
does not occur with 75% of drug excreted unchanged in the urine and the remainder in the bile.
Elimination
elimination half-time is 20-40 hours********************
Nonselective beta-adrenergic blocker Side Effects
Cardiovascular
bradycardia
hypotension
Pulmonary
airway resistance
bronchospasm
GI
NV
abdominal cramping
diarrhea
CNS
lethargy
lightheadedness
fatigue
Other
agranulocytosis
Contraindications of Nonselective beta-adrenergic antagonist
Heart block
Sinus bradycardia
Bronchial asthma
CHF
COPD
pilocarpine
Pilocarpine is a muscarinic alkaloid obtained from the leaves of tropical American shrubs from the genus Pilocarpus. It acts as a muscarinic receptor agonist in the parasympathetic nervous system.
pilocarpine primary use
Pilocarpine (pye-loe-KAR-peen) is used to treat glaucoma and other eye conditions.
Pilocarpine has been used in the treatment of chronic open-angle glaucoma and acute angle-closure glaucoma for over 100 years
It acts on a subtype of muscarinic receptor (M3) found on the iris sphincter muscle, causing the muscle to contract and produce miosis. This opens the trabecular meshwork through increased tension on the scleral spur. This action facilitates the rate that aqueous humor leaves the eye to decrease intraocular pressure
pilocarpine other uses
Pilocarpine is also used to treat dry mouth (xerostomia). Pilocarpine stimulates the secretion of large amounts of saliva and sweat. Pilocarpine is used to stimulate sweat glands in a sweat test to measure the concentration of chloride and sodium that is excreted in sweat. It is used to diagnose cystic fibrosis (CF).
Anesthesia Considerations for pilocarpine
Use of pilocarpine may result in a range of adverse effects, most of them related to its action as a muscarinic receptor agonist. Pilocarpine has been known to cause excessive sweating (it is important that you drink extra liquids to offset this sweating so you do not lose too much fluid and become dehydrated), excessive salivation, bronchospasm, increased bronchial mucus secretion, bradycardia, hypotension, bronchospasm, and diarrhea.
Asthma exacerbation
Eye disease or problem exacerbation
Other Considerations for pilocarpiine
Symptoms of too much medicine being absorbed into the body
Increased sweating; muscle tremors; nausea, vomiting, or diarrhea; troubled breathing or wheezing; watering of mouth. --Chest pain; confusion; diarrhea (continuing or severe); fainting; fast, slow, or irregular heartbeat (continuing or severe); headache (continuing or severe); nausea or vomiting (continuing or severe); shortness of breath or troubled breathing; stomach cramps or pain; tiredness or weakness (continuing or severe); trembling or shaking (continuing or severe); trouble seeing (continuing or severe)

More common
Blurred vision or change in near or far vision; decrease in night vision.

Less common
Eye irritation; headache or browache.
metacholine
Methacholine Chloride is a parasympathomimetic (cholinergic)
Synthetic choline ester that acts as a non-selective muscarinic receptor agonist
Methacholine has a charged quaternary amine structure, rendering it insoluble to lipid cell membranes. Clinically, this means that it will not cross the blood-brain barrier and has poor absorption from the gastrointestinal tract.
It is broken down at a relatively slow rate within the body, due to its resistance to acetylcholinesterase.
metacholine uses
The primary clinical use of methacholine is to diagnose bronchial hyperreactivity, which occurs in asthma
It is a bronchoconstrictor agent to be administered ... by inhalation, for diagnostic purposes,it is FOR DIAGNOSTIC PURPOSES ONLY AND SHOULD NOT BE USED AS A THERAPEUTIC AGENT.
The methacholine challenge test is one method of assessing airway responsiveness. In this test, the patient inhales an aerosol of one or more concentrations of methacholine. Results of pulmonary function tests (eg, spirometry, specific conductance) performed before and after the inhalations are used to quantitate response. This guideline applies to adults and children capable of adequately performing spirometry or body plethysmography and of cooperating during the course of the challenge.

may be a good test to discover the patients pulmonary function.
does the patient have asthma?
or how severe there asthsma may be.
Contraindications for metacholine
SIDE EFFECTS: Headaches, throat irritation, lightheadedness, and itching may occur. If any of these effects persist or worsen, notify your doctor. Tell your doctor immediately if any of these serious side effects occur: chest tightness, trouble breathing, cough, wheezing. If you notice other effects not listed above, contact your doctor or pharmacist.
PRECAUTIONS: Tell your doctor your medical history, especially of: epilepsy, heart disease, thyroid disease, trouble urinating (urinary obstruction), stomach ulcers, any allergies. This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor. It is not known whether this drug passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Tell your doctor of all prescription and nonprescription medication you may use, especially of: beta- blockers (e.g., nadolol, propranolol), asthma medications. Do not start or stop any medicine without doctor or pharmacist approval.
Alpha-adrenergic receptor antagonists
bind selectively to alpha-adrenergic receptors and interfere with the ability of catecholamines or other sympathomimetics to provoke alpha responses.

Nonselective _-antagonists act at both postsynaptic _-1 and presynaptic _-2 receptors.

Not used for chronic hypertension (reflex tachycardia)
Alpha-adrenergic receptor antagonists

Phenoxybenzamine
In the body forms an electrophilic carbonium ion.
The ion forms a stable covalent bond with the alpha adrenergic receptor.
This bond results in the noncompetitive antagonism of adrenergic agents.

Because of it’s noncompetitive and relatively irreversible blockade of alpha adrenergic receptors it produces what has been called a Chemical Sympathectomy
Alpha-adrenergic receptor antagonists

Phenoxybenzamine notes
Used to treat hypertensive episodes in patients with pheochromocytoma.

A pheochromocytoma is an adrenal medulla tumor that secretes large amounts of catecholamines causing patients to have extremely high blood pressure.

Treated with phenoxybenzamine until surgical removal of tumor.
Raynaud’s

Excessive peripheral vasoconstriction associated with hemorrhagic shock after intravascular fluid replacement

pupil constriction
increase in GI tract motility and secretions
glycogen synthesis (prevents the inhibitory action of epi on the secretion of insulin)
relaxes smooth muscle in bladder neck and prostate.
Alpha-adrenergic receptor antagonists

Phentolamine (Regitine)
Produces a competitive (reversible) blockade of alpha receptors.
Alpha1 antagonism and direct smooth muscle relaxation are responsible for peripheral vasodilation and drop in arterial pressure.
Local infiltration with phentolamine- containing solution is appropriate when a sympathomimetic is accidentally administered extravascularly.

Local injection of catecholamines can cause tissue necrosis and sloughing.

Norepinephrine usually more damaging than Epinephrine but effect is dose dependent.
Alpha-adrenergic receptor antagonists

Tolazoline
An alpha adrenergic blocking agent, tolazoline HCl is structurally related to phentolamine.
By directly relaxing vascular smooth muscle, tolazoline has peripheral vasodilating effects and decreases total peripheral resistance.
It is a vasodilator that is used to treat spasms of peripheral blood vessels (as in acrocyanosis).
Was used for the treatment of persistent pulmonary hypertension in a new born – not clinically used due to replacement by nitrous oxide.
Alpha and Beta Adrenergic Antagonists

Primary Agents
Carvedilol (Coreg)
Labetalol (Normodyne, Trandate)
Alpha and Beta Adrenergic Antagonists

Labetolol
Treatment of hypertension (decreases HR, CO, & PVR). Dose- 0.1-0.5mg/ kg (usually 20-80mg), can repeat Q 10min until desired BP or can give short term as a continuous IV infusion. Can also give orally for chronic HTN.

Extensive first-pass metabolism
Rapidly and extensively metabolized in the liver by oxidation and conjugation with glucuronic acid. There is only 5% of drug eliminated unchanged in urine.
Elimination half-time is 5 to 8 hours
longer with liver disease (no effect with renal disease)
Alpha and Beta Adrenergic Antagonists

Carvedilol
Treatment of hypertension (decreases PVR, HR & BP). Dose- 6.25mg BID to max of 25mg BID.
CHF/MI (increases CO, is an antioxidant, and has antiapoptotic properties-prevents myocyte death and decreases infarct size). Dose- 3.125mg BID and can increase with caution over time.

Alpha:Beta activity is 1:10 (compared to 1:
Antioxidant properties (Sengal, 2000).
“Antiapoptitic” (Kawai, 2004).4 for labetalol)

Extensive first-pass metabolism
Metabolized in liver to active metabolites.
Active metabolites have weak vasodilator actions.
Elimination half time is 6 to 10 hours.
Alpha and Beta Adrenergic Antagonists

The normal process of norepi neurotransmission
When a nerve impulse arrives at a norepi nerve terminal, norepi is released from synaptic vesicles into the synaptic cleft. Norepi molecules bind to their receptors on the post-synaptic membrane and the nerve impulse is propagated or inhibited, depending on the specific receptor. Noradrenaline molecules are then released from their receptors and taken back into the nerve terminal via the noradrenaline re-uptake transporter. Noradrenaline is degraded by MAO and COMT, these are found in both the synaptic cleft and in the nerve terminal.
Alpha and Beta Adrenergic Antagonists

Side Effects
Hypotension
Can cause or exacerbate CHF
Bradycardia and syncope
Peripheral Vascular Disease
Bronchospasm
Paradoxical hypertension
Fatigue, weakness, drowsiness, headache, sleep disturbances, and depression. Seizures with OD.
Sexual dysfunction
Nausea, Hypoglycemia is rare.
If discontinue suddenly after long-term use can cause angina and sudden death.
Edema with Carvedilol use

CHF- mostly exacerbates it in pts with compensated failure, MI, or cardiomegaly
Bradycardia- or life-threatening bradyarrhythmias in pts with AV blocks
PVD- cold extremities, Raynaud’s phenomenon
Bronchospasm- usually only in pts with pulmonary diseases like COPD or asthma
Drug Interactions of alpha/beta antagonists
Labetalol with TCA’s can cause tremors
With Labetalol, may need higher doses of Beta agonists in pts with pulmonary diseases
Labetalol has synergistic effects with Halothane (severe decrease in CO with >3% Halo)
Cimetadine with either drug will cause increased concentrations of both drugs
Ca++ channel blockers may cause rhythm disturbances with either drug
Labetalol with Nitroglycerine= severely decreased HR & BP
Carvedilol with cause Digoxin levels to increase by as much as 15%
Carvedilol with MAOIs or Clonidine will see even lower HR & BP
Insulin or oral hypoglycemics with Carvedilol will cause increased incidence of hypoglycemia.
Cyclosporin levels will increase with Carvedilol
Quinidine will increase dizziness with Carvedilol
Rifampin will cause increased concentrations of Carvedilol
Selective Alpha Blockers (Antagonists)
Cardura – HTN and BPH (Benign Prostatic Hypertrophy)
Flomax- BPH
Uroxatral- BPH
Minipress- HTN and unapproved in adult but has been shown to decrease symptoms of PTSD – and I have seen it used for other psych Dx’s such as chronic depression and psychosis.
Hytrin- HTN and BPH
Alpha 1 & 2 Receptors
Alpha receptors mediate many important actions of endogenous catecholamines including:

a. Alpha 1 mediated vasoconstriction in smooth muscle of the GI tract, eyes, lungs, uterus, blood vessels of the skin, and skeletal muscle, and direct constriction of nonvascular smooth muscle in the genitourinary tract

b. Alpha 2 receptor mediated inhibition of the release of NE and ACh

c. Alpha 2 mediated inhibition of insulin secretion and inhibition of lipolysis

d. Alpha 2 mediated contraction of blood vessels in skin and mucosa (these receptors are preferentially activated by circulating catecholamines, whereas alpha 1 receptors are activated by NE released at sympathetic nerve terminals)

e. Alpha 2 mediated central inhibition of sympathetic tone

Alpha receptors are G coupled-protein post synaptic receptors located in smooth muscle throughout the body. Activation of these receptors increases intracellular calcium ion concentration, which leads to muscle contraction.
The most important effects of alpha 1 & 2 adrenergic antagonists are on the cardiovascular system. These cardiovascular effects are mediated in large part by the effects of the antagonists on sympathetic nerve endings, and by effects on the CNS. Alpha 1 antagonists are competitive in nature.
Cardiovascular & Other Effects of Alpha 1 Antagonists
Alpha 1 selective antagonists block vasoconstriction induced by endogenous catecholamines (Norepinephrine, Epinephrine)
They also block the vasoconstriction and hypertensive effects of exogenous sympathomimetics (Phenylephrine)
Other – They can also block Alpha 1 receptors that mediate contraction of nonvascular smooth muscle.

Block vasoconstriction endogenous catecholamines - The resulting fall in peripheral vascular resistance, cardiac preload, left ventricular afterload, and arterial blood pressure leads to a fall in mean blood pressure and CO. The decrease in blood pressure leads to a reflex tachycardia. The reflex effects are exaggerated if the drug also has alpha 2 antagonist effects because antagonism of alpha 2 receptors facilitates release of NE, presynaptically, to cause a further tachycardic effect. Usually these side effects prevent the use of nonselective alpha-adrenergic antagonists in the management of ambulatory essential HTN because they can stimulate alpha 1 and alpha 2.
Side Effects and Cautions pf alpha blockers
Alpha blockers may have what's called a “First-Dose Effect."
Other side effects include headache, dizziness, drowsiness, heart palpitations, nausea, weakness, weight gain and small decreases in low-density lipoprotein cholesterol (the "bad" cholesterol).
The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).
first dose effect with alpha blockers
First dose effect - When a person first starts taking an alpha blocker they may experience orthostatic hypotension related to differences in sympathetic tone when lying down compared to when standing and a decrease response to the baroreceptor reflex, this may be minimized by taking the alpha blocker at bedtime and starting with lower doses and working up to an effective dose.
Pharmacokinetics of Selective Alpha-Adrenergics

Doxazosin (Cardura)
Peak plasma levels occur at about 2-3 hours.
Bioavailability is approximately 65%, reflecting first pass metabolism by the liver.
Extensively metabolized in the liver, mainly by O-demethylation of the quinazoline nucleus or hydroxylation of the benzodioxan moiety
Several active metabolites of doxazosin have been identified, the pharmacokinetics of these metabolites have not been characterized
Approximately 63% of the dose was eliminated in the feces and 9% of the dose was found in the urine
Approximately 98% of the circulating drug is bound to plasma
Plasma elimination of doxazosin is biphasic, with a terminal elimination half-life of about 22 hours
Pharmacokinetics of Selective Alpha-Adrenergics

Tamsulosin (Flomax)
Absorption is essentially complete (>90%)
Distributed to most tissues including kidney, prostate, liver, gall bladder, heart, aorta, and brown fat, and minimally distributed to the brain, spinal cord, and testes.
extensively bound to human plasma proteins (94% to 99%).
Extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged.
97% of the dose was recovered, with urine representing the primary route of excretion compared to feces (3%)
half-life of tamsulosin HCI is approximately 9 to 13 hours in healthy
Pharmacokinetics of Selective Alpha-Adrenergics

Alfluzosin (Uroxatral)
Bioavailability of is 49%
Volume of distribution following intravenous administration in 3.2 L/kg.
Moderately bound to human plasma proteins (82% to 90%),
Extensively metabolized by the liver by three metabolic pathways: oxidation, O-demethylation, and N-dealkylation.
The metabolite is not pharmacologically active. CYP3A4 is the principal hepatic enzyme involved in its metabolism.
Elimination: 69% in feces and 24% in urine
Pharmacokinetics of Selective Alpha-Adrenergics

Terazosin (Hytrin)
Essentially completely absorbed in man.
Minimal hepatic first-pass metabolism
Half-life of approximately 12 hours.
90-94% bound to plasma protein
Approximately 40% of the dose is excreted in the urine and approximately 60% in the feces.
alpha blockers Uses Prozosin (Minipress)
Originally designed and used for treatment of hypertension
Almost exclusively used for treatment of
urinary retention in men with BPH (benign prostatic hypertrophy).
Originally designed and used for treatment of hypertension
CHF, vasospastic disorders, ventricular arrhythmias related to coronary artery ligation, mitral and aortic valve insufficiency G and G
alpha blockers Uses Terazosin (Hytrin)
Originally designed and used for treatment of hypertension
Almost exclusively used for treatment of
urinary retention in men with BPH (benign prostatic hypertrophy). G and G
CHF, vasospastic disorders, ventricular arrhythmias related to coronary artery ligation, mitral and aortic valve insufficiency G and G
alpha blockers Uses Doxazosin (Cardura)
Originally designed and used for treatment of hypertension
Almost exclusively used for treatment of
urinary retention in men with BPH (benign prostatic hypertrophy). G and G
CHF, vasospastic disorders, ventricular arrhythmias related to coronary artery ligation, mitral and aortic valve insufficiency G and G
alpha blockers

Uses Tamsulosin (Flomax)
Originally designed and used for treatment of hypertension
Almost exclusively used for treatment of
urinary retention in men with BPH (benign prostatic hypertrophy). G and G
CHF, vasospastic disorders, ventricular arrhythmias related to coronary artery ligation, mitral and aortic valve insufficiency G and G
alpha blockers
Uses Uses Alfuzosin (Uroxatral)
Originally designed and used for treatment of hypertension
Almost exclusively used for treatment of
urinary retention in men with BPH (benign prostatic hypertrophy). G and G
CHF, vasospastic disorders, ventricular arrhythmias related to coronary artery ligation, mitral and aortic valve insufficiency G and G
Precautions/Contraindications for alpha blockers
Cardiomyopathy
Depresses barareceptor reflex
Postural hypotension
Start with low doses and add if needed
HA, dizziness, drowsiness, and nausea
G and G.