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65 Cards in this Set
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Beta-1 Agonist Effects
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+ 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) |
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Epinephrine b1 = b2 > a1 = a2
Norepinephrine b1 = a1 > b2 = a2 Dopamine b1 = b2 > a1 Dobutamine b1 > b2 > a1 Isoproterenol b1 = b2 |
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Beta 1 antagonist effects
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- 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) |
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Beta-1 selective antagonist side effects/contraindications
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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 |
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ISA (intrinsic sympathomimetic activity)
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“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) |
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Beta 1 selective antagonist drugs
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Acebutolol
Atenolol(Tenormin) Esmolol (Brevibloc) Metoprolol(Lopressor) Betaxolol Bisoprolol Nebivolol |
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Acebutolol (Sectral, Prent)
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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 |
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Atenolol (Tenormin)
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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 |
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Nebivolol
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cardioselective
arterial vasodilator increases nitric oxide levels indications: HTN PO oral bioavailability ? hepatic metabolism renal excretion half life 10 hours |
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Metoprolol (Lopressor)
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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 |
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Esmolol (Brevibloc)
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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 |
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Bisoprolol (Ziac)
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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 |
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Betaxolol (Betoptic)
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bioavailability 89%
? metabolism renal excretion half life 14-22 hours cardioselective ophthalmic use common Indications: HTN, Glaucoma |
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CARBACHOL
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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. |
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Raymond Ahlquist (1948) rationalized that catecholamines acted via two principal receptors.
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these receptors where termed Alpha & Beta
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Nonselective beta antagonist Agents
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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 |
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Addition of alkyl groups at nitrogen increases selectivity for _ receptor
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Beta 2
Albuterol Bitolterol Mesylate Formoterol Isoproterenol Levabuterol Metaproterenol Salmeterol Terbutaline |
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Presence of 3,5 di-hydroxy on phenyl with longer chain give _2 specificity
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Beta 1
Norepinephrin Isoproterenol dobutamine Epinephrine |
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Pharmacokinetics of non-selective beta adrenergics blockers
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Structural analogues of beta-adrenergic receptor agonists
all of them can be given PO all but nadolol can be given IV |
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Agonist Mechanism of Action
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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. |
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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 |
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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. |
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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 |
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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) |
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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 |
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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 |
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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 |
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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 |
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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******************** |
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Nonselective beta-adrenergic blocker Side Effects
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Cardiovascular
bradycardia hypotension Pulmonary airway resistance bronchospasm GI NV abdominal cramping diarrhea CNS lethargy lightheadedness fatigue Other agranulocytosis |
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Contraindications of Nonselective beta-adrenergic antagonist
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Heart block
Sinus bradycardia Bronchial asthma CHF COPD |
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pilocarpine
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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.
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pilocarpine primary use
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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 |
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pilocarpine other uses
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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).
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Anesthesia Considerations for pilocarpine
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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 |
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Other Considerations for pilocarpiine
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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. |
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metacholine
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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. |
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metacholine uses
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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. |
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Contraindications for metacholine
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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. |
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Alpha-adrenergic receptor antagonists
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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) |
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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 |
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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. |
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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. |
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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. |
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Alpha and Beta Adrenergic Antagonists
Primary Agents |
Carvedilol (Coreg)
Labetalol (Normodyne, Trandate) |
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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) |
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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. |
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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.
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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 |
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Drug Interactions of alpha/beta antagonists
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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 |
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Selective Alpha Blockers (Antagonists)
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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 |
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Alpha 1 & 2 Receptors
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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. |
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Cardiovascular & Other Effects of Alpha 1 Antagonists
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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. |
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Side Effects and Cautions pf alpha blockers
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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). |
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first dose effect with alpha blockers
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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.
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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 |
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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 |
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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 |
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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. |
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alpha blockers Uses Prozosin (Minipress)
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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 |
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alpha blockers Uses Terazosin (Hytrin)
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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 |
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alpha blockers Uses Doxazosin (Cardura)
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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 |
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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 |
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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 |
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Precautions/Contraindications for alpha blockers
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Cardiomyopathy
Depresses barareceptor reflex Postural hypotension Start with low doses and add if needed HA, dizziness, drowsiness, and nausea G and G. |
