Adrenergics - Antagonists Flashcards
What is the general mechanism for an adrenergic neuron blocker?
Disrupts the synthesis, storage, or release of NE (does not block receptor)
What is the mechanism of action of guanethidine?
Taken into adrenergic nerves via NET -> ultmately causes decrease of NE via unknown mechanism
What is guanethidine used to treat?
Severe hypertension
What are the side effects of guanethidine?
Many side effects -> orthostatic hypotension, interfere with sexual function, diarrhea, muscle weakness, edema
What is significant about the chemical structure of guanethidine?
It is polar -> doesn’t enter the CNS
What is the site of action of guanethidine?
PNS
What is Guanadrel?
Drug very similar to Guanethidine
What is the mechanism of action of Reserpine?
Diffuses into adrenergic nerves -> inhibits VMAT2 -> prevents NE uptake into granules -> prevents NE release
What are the effects of Reserpine?
prevent release of NE
What is the significance of reserpine being lipophilic (2)?
Gets into CNS -> acts on CNS
diffuses into nerves, doesn’t need transporter, has no effect on NET
What is the route of administration of Reserpine?
orally
What are the therapeutic uses of reserpine?
essential hypertention -> decreases BP
What are the side effects of reserpine?
Sedation, diarrhea, orthostatic hypotention, increased gastric acid secretion, depression, suicidal tendencies
What is the relative half life and onset of reserpine?
Long-acting, slow onset
What is an adrenergic receptor blocker?
agent that produces its major action by inhibiting A and B receptors
What is the mechanism of action of Phenoxybenzamine?
block A1 and A2 receptors
How does phenoxybenzamine block receptors?
Irreversible antagonist - binds covalently to A1 and A2 receptors
What is the route of administration and duration of action of phenoxybenzamine?
orally, long duration of action b/c of irreversible binding -> new receptors have to be synthesized
What are the effects of phenoxybenzamine and phentolamine?
vasodilation (blocking A1 prevents binding of NE to smooth muscle receptors, preventing contraction, blocking A2 on pre-synaptic nerve terminals causes increase NE release b/c loss of negative feedback)
What are the side effects of phenoxybenzamine and phentolamine?
With non selective alpha blockers when the antagonist binds A2 on the pre-synaptic nerve terminal, loss of negative feedback occurs. This causes the cell to release lots of NE, and since it has nowhere to bind it binds B1 receptor on cardiac muscle. -> tachycardia, edema, orthostatic hypotention
What are the clinical uses of phenoxybenzamine?
Phenochromocytoma, to reverse or shorten the effects of soft-tussue anesthesia from a local anesthetic
What is the mechanism of action of phentolamine?
Competitive reversable antagonist to A1 and A2 recpetors
What is the route of administration and duration of action of phentolamine?
orally active, shorter duration (2-4 hours)
What are the clinical uses of phentolamine?
hypertension - in combination with other agents, pheochromocytoma, reduce the effects of local anesthetic
What is the mechanism of action of prazosin?
Selectively blocks A1 receptors, competitive antagonist
What are the effects of Prazosin?
Decreases vascular tone (dec BP), favorable lipid profile -> low LDL and high HDL
Why is Prazosin preferred over phentolamine or phenoxybenzamine for treating HTN?
Fewer side effects. A1 selective blockers (prazosin) has little effect on A2 blockers leading to less side effects of reflex tachycardia
What are the therapeutic uses of prazosin?
HTN, short term treatment of CHF -> preload and afterload reducing agent, BPH -> relaxes A1 mediated contraction of prostate and bladeder neck that contributes to resistance in urine flow meaning it makes it easier to pee
What are the side effects of prazosin? How are some of them counteracted?
First dose phenomenon -> hypotention and syncope 30-90 min after first dose -> give first dose at bedtime
persistent orthostatic hypotention
edema (salt and water retention)
What is the mechanism of action of tamsulosin?
A1 receptor antagonist (some selectivity of A1a over A1b
What are the effects of tamsulosin?
blocks A1a receptors (prostate) which decreases tone in prostate and neck of bladder -> easier to urinate
Has little effect on hypertension b/c A1b receptors aren’t generally blocked
What are the clinical uses of tamsulosin?
Benisn Prostatic Hyperplasia (BPH)
What is the mechanism of action of propranolol?
competitive reversible block of B1 and B2 receptors
What are the therapeutic uses of propranolol? (6)
Hypertension - block b receptors in hear and kidney
Angina -> decrease work of heart and energy demand
Cardiac arrhythmia due to excess catecholamines or that respond do a reduction in HR/AV conduction velocity
Acute MI
Pheochromocytoma
Migrane prophylaxis
What are the side effects of propranolol?
Cardiac depression, heart block
increased airway resistance (b/c blockage of B2)
Can mask symptoms of hypoglycemia
Sedation, impotence, nightmares
Can have withdrawl syndrome with can cause arrhythmias or infarction
What conditions should be considered before prescribing propranolol?
Asthma Congestive heart failure bradyarrhythmias, AV block insulin-dependent diabetes prone to hypoglycemic episodes hypotention vasospactiv angina
What is the route of administration of propranolol?
orally available, but lg first pass effect so need to give in high doses
What is the route of administration of timolol?
orally active
What are the therapeutic uses of timolol?
Same as propranolol
Additional use for acute wide angle glaucoma
What is the mechanism of action of timolol?
Non selective beta receptor antagonist - competitive, reversable
Explain how timolol can treat glaucoma.
What will timolol do to pupil size and accommodation?
With opthalmic administration -> beta blocker decreases aqueous humor formation (b/c b2 antagonist) by the cillary epithelium -> less fluid -> less interocular pressure
No effect on pupil size or accommodation -> no blurred vision, no night blindness
What are the potential side effects of ophthalmic timolol adminstration>
Small amounts can be absorbed into the system leading to other non-selective beta blocking effects -> care with pts with cardiac diseases
What is the mechanism of action of metoprolol?
B1 selective reversible antagonist, competitive
What is the selectivity of metoprolol? Which dose (high vs low) has better selectivity?
Selective to B1, but will bind B2 1/10
More selective at low doses
What are the major therapeutic uses of metoprolol?
Same as propronol
Heart Failure
What is the reasoning behind using metoprolol as heart failure treatment?
By blocking B1 receptors selectively there is less stress on the heart. Been proven that continuous sympathetic activation of beta receptors will cause progression of the disease
What are the side effects of metoprolol?
Same as propranolol
Less bronchioconstriction at lower doses
What is the mechanism of action of atenolol?
B1 receptor antagonist
What are the therapeutic uses of atenolol?
Similar to propranolol, except for migraine prophylaxis
How is atenolol different than propranolol? Significance?
Atenolol does not penetrate into CNS -> restricted to periphery
Fewer side effects (especially drowsiness) and longer duration of action
What is the mechanism of action of Labetaolol?
Competitive antagonist of A1 and B1, and B2 receptors. (non-selective)
What are the therapeutic uses of labetanol, and for each what is the route of administration?
Essential hypertension - oral
hypertensive emergencies -> IV
What is the mechanism of action of carvedilol?
Non selective beta blocker, A1 antagonist too -> all competitive
What are some additional effects of carvedilol?
anti-oxidant properties
anti-inflammatory efects
blocks L-type Ca++ channels at higher doses
What are the therapeutic uses of carvedilol?
Chronic heart failure, hypertension, acute MI
