9) Adrenoreceptor antagonists Flashcards
Adrenergic agonist effect on smooth muscle (all)
- Alpha-1 agonist = increase calcium, and contraction
- Alpha-2 agonist = decrease in cAMP and contraction
- Beta-2 agonist = increase cAMP and dilation
The vasomotor center in the brainstem regulates
- Systemic Vascular Resistance (SVR) or Total Peripheral Resistance
- Causes arterioles to constrict via α-1 or dilate via β-2
The major role of arterioles
- Constrict or dilate to control the resistance to blood flow in the body
Alpha-2 pre-synaptic receptors
- Help neurotransmitter reuptake (which prevent their release)
- Example: Norepinephrine (NE) is reuptaken by the alpha-2 pre-synaptic receptor
Alpha-1 adrenergic receptors act on
- Blood vessels
- Sphincters of the GI
- Eye
- Genitourinary (uterus)
Alpha-2 adrenergic receptors act on
- Pre-synaptic
- Decrease release rate of NE, insulin, and ACh
Beta-1 receptors act on
- Heart
- Lipolysis
- Kidneys (release renin)
Beta-2 receptors act on
- Blood vessels
- Smooth muscle (lungs, uterine)
- Muscle, liver (glycogenolysis, gluconeogenesis)
Alpha-1 adrenergic receptor effects
- Vasoconstriction
- Increase peripheral resistance
- Increase blood pressure
- Mydriasis
- Increase closure of bladder sphincters
Alpha-2 adrenergic receptor effects
- Inhibits norepinephrine release
- Inhibits acetylcholine release
- Inhibits insulin release
Beta-1 adrenergic receptor effects
- Increase heart rate
- Increase lipolysis
- Increase myocardial contractility
- Increase renin
Beta-1 adrenergic receptor effects
- Vasodilation
- Decrease peripheral resistance
- Bronchodilation
- Increase glycogenolysis (muscle, liver)
- Increase glucagon release
- Relaxes uterine smooth muscle
Subdivisions of α blockers are based on
- Selective affinity for α1 versus α2
- Irreversible means they bind covalently to the α-receptors
Effects of non-selective blockers
- Blockade of α-1 and 2 mediated responses to sympathetic nervous system
- Reduction in vascular tone with a reduction of both arterial and venous pressures
- Baroreceptor reflex-mediated tachycardia as a result of the drop in mean arterial pressure
- Epinephrine reversal manifested as orthostatic hypotension
Orthostatic hypotension
- Decrease in systolic or diastolic blood pressure upon standing from the sitting or supine position
Prazosin
- Selective α1-inhibitor adrenergic receptor
- Lowers arterial blood pressure by blocking post-synaptic α1 receptors on arterial smooth muscle
Prazosin does NOT cause reflex tachycardia because
- It has no effect on the presynaptic α2 receptors in sympathetic nerve endings that innervate the heart
Non-selective alpha blockers, such as phentolamine, are associated with
- Marked reflex tachycardia due to blunting of inhibitory presynaptic α2 receptor that suppresses the uptake of norepinephrine at the synapse
Alpha-blocking drugs: epinephrine reversal
- Manifests as orthostatic hypotension
- Occurs when adding alpha- blockers
- Reveals the effects of β2 vasodilation (which drops blood pressure)
Normally epinephrine will
- Increase blood pressure through alpha-1 (vasoconstriction by decreasing the diameter of the blood vessels)
- Increase heart contractility by acting on beta-1 receptors
The epinephrine (alpha and beta agonist) response exhibits
- Net increase in blood pressure (the α response) to a net decrease (the β2 response) when alpha blockade is added
The response to phenylephrine (alpha-1 agonist)
- Increases blood pressure through α response
- Suppressed but not reversed, because phenylephrine lacks β2 action
α1 blockers reduce blood pressure with no
- Reflex tachycardia (compared to nonselective)
- Useful in relaxing effects on smooth muscle in the prostate
Clinical use of selective alpha-1 blockers
- Prazosin, terazosin for hypertension
- Tamsulosin to reduce urinary hesitancy and retention in men with benign prostatic
hyperplasia
Clinical use of alpha-2 blockers
- Yohimbine (not a drug) used for erectile dysfunction
Clinical use for non-selective alpha blockers
- Limited use
Selective alpha-1 blockers (generic names)
- Doxazosin
- Prazosin
- Tamulosin
- Terazosin
- Alfuzosin
Selective alpha-2 blocker
- Yohimbine (natural product)
Non-selective reversible alpha blockers
- Phentolamine (Oraverse)
Non-selective irreversible alpha blockers
- Phenoxybenzamine (Dibenzyline)
Doxazosin
- Brand = Cardura
- DOA = 24h
- Metabolism = hepatic
Prazosin
- Brand = Minipress
- DOA = 10-24h
- Metabolism = hepatic
Tamsulosin
- Brand = Flomax
- DOA = ?
- Metabolism = hepatic
Terazosin
- Brand = ?
- DOA = 24h
- Metabolism = hepatic
Alfuzosin
- Brand = Uroxatral
- DOA = 12h
- Metabolism = hepatic
Phentolamine
- Brand = Oraverse
- DOA = 30min (IM/IV)
- Metabolism = hepatic
Phenoxybenzamine
- Brand = Dibenzyline
- DOA = 24h (IV)
- Metabolism = ?
Side effects of alpha-adrenergic blockers
- Dizziness, headaches
- Shortness of breath
- Swelling of arms and legs, edema
- Erection
- Hypotension
Beta-blockers (subdivisions based on selective affinity for β-1 and β-2 receptors)
- First generation non-selective β-blockers
- Second generation cardio-selective β-1 blocker
- Third generation vasodilating β-2 blocker
Beta-blocker heart effects
- Decreased HR
- Decreased force of contraction
- Decreased rate of atrioventricular (AV) conduction
Beta-blocker side effects in the heart
- Bradycardia
- Lethargy
- GI disturbance
- Congestive heart failure (CHF)
- Decreased BP
- Depression
Beta1-receptor selectivity is needed to treat patients with
- Hypertension
- Asthmatic
Since β2 receptors exist in the lungs, using a non-selective β- blocker can cause
- Bronchospasm
Partial agonists (intrinsic sympathomimetic action/ISA)
- Effective in treating patients with asthma (less likely to cause bronchospasm)
- Labetalol
- Pindolol
- Acebutolol
Local anesthetic activity (“membrane-stabilizing activity”) is a disadvantage when β blockers are used topically in the eye because
- Decreases protective reflexes
- Increases the risk of corneal ulceration
Shortest acting beta-blocker
- Esmolol
Longest acting beta-blocker
- Nadolol
Beta-blockers that are less lipid-soluble and enter the central nervous system (CNS) to a lesser extent
- Atenolol
- Acebutolol
- Esmolol
- Labetalol
- Nadolol
- Nebivolol
Clinical usage of beta-blockers
- Open angle glaucoma
- Hypertension, angina, and arrhythmias
- Chronic heart failure
Beta-blocker side effects
- Slow SA node (which initiates heartbeat)
- Slow heart rate (allows LV to fill completely and lowers heart workload)
- Dilate arteries (lowering BP)
Due to the high penetration across the blood–brain barrier, lipophilic beta blockers, such as propranolol and metoprolol, cause
- Sleep disturbances (such as insomnia, vivid dreams and nightmares)
Adverse effects associated with β2-adrenergic receptor antagonist activity
- Bronchospasm
- Peripheral
vasoconstriction - Alteration of glucose and lipid metabolism
Hypoglycemia can occur with β2-blockers because
- They inhibit glycogenolysis and gluconeogenesis that form glucose
- Blocking β2-adrenoceptors lowers plasma glucose
