11 04 2014 Adrenergic Agonists and Antagonists Flashcards
Name of drugs that mimic SNS response vs. drugs that go against SNS response
Agonists: Sympathomimetics, adrenomimetics
Antagonists: Sympatholytics
Epinephrine
Adrenergic Agonist
alpha 1 = alpha 2 , Beta 1= B2
Norepinephrine
Adrenergic Agonist
Alpha 1= alpha 2; Beta 1»» B2
Used (uncommonly) for pressor effects
Isoproterenol
Adrenergic Agonist
Beta 1 = Beta 2»_space;»> alpha
Used mostly for heart stimulation in bradycardia or heart block (direct and reflex from beta 2 effects)
Dobutamine
Adrenergic Agonist
Beta 1 > Beta 2»_space;»»> alpha
(+) inotropic effects more prominent than (+) chronotropic effects ( HR)
- used in congestive heart failure
Dopamine
Adrenergic Agonist
D1 = D2»_space;»> beta 1» alpha
Vasodilation of renal, mesenteric, and coronary beds
* dose dependent. If go too high you can cause severe vasoconstriction = ischemia of peripheral tissues
Use: heart stimulation with positive effects on renal output
Who are the catecholamines
Epinephrine, Norepinephrine, Isoproterenol, Dobutamine, Dopamine
All work directly on receptor
Who are the direct noncatecholamines?
Phenylephrine
Clonidine
Albuterol, ritodrine
Phenylephrine
Noncatecholamine– Direct
Alpha 1 > Alpha 2»_space;» Beta
Vasoconstrictive effects used to treat hypo tensions, shock
nasal decongestion (topical), ophthalmic effect (topical) - mydriasis (dilation of pupil)
Clonidine
Noncatecholamine– Direct
Alpha 2 > alpha 1»_space;»» Beta
Penetrates CNS, inhibits SNS output
= Hypotension, bradycardia, sedation
Used in hypertension
Also used in deminish craving in narcotic, alcohol, and nicotine withdrawal
Albuterol, ritodrine
Noncatecholamine– Direct
Beta 2»_space; Beta 1»_space;»» alpha
- Asthma, COPD for bronchodilation
- Inhalers minimize systemic effects
- uterine muscle relaxant to delay preterm labor (benefits?)
Who are the Noncatecholamine– Indirect ??
Amphetamine, methylphenidate
Tyramine (when MAO inhibitor present)
Cocaine
( alpha and beta, typically like NE)
Who are the mixed Noncatecholamines
Ephedrine
Pseudeoephedrine
(indirect plus direct alpha and beta)
Therapeutic uses of Epinephrine
- Anaphylactic shock ( bronchioconstriction, hypotensions and vasucular collapse, angioedema) ( via alpha and beta)
- Acute asthmatic attacks (not really anymore because of beta -2 specific agonists)
- Prolonged action of local anesthetics (alpha)
- Topical hemostatic agent (alpha)
- Cardiac arrest ( alpha – increase diastolic pressure)
Adverse effects of Epinephrine
** DO NOT USE ON HYPERTHYROID PATIENTS because increase in thyroid hormone increases epinephrine receptors = crisis
- Marked HYPERTENSION
- Arrhythmias
- Angina
- Necrosis following extravasiation
Amphetamine, methylphenidate
Noncatecholamine, indirect (alpha and beta, typically like NE)
Readily enters CNS, releasess catecholamines (including DA)
CNS: elevates mood, alterness, suppresses appetite
used in narcolepsy, weight loss, and ADHD
Cocaine
Noncatecholamine, indirect (alpha and beta, typically like NE)
Vasoconstrictive
Local anesthetic
Abuse side effects–> hypertensive response
Tyramine
Noncatecholamine, indirect (alpha and beta, typically like NE)
Found in FOOD: cured meats, smoked fish, cheese
produces NE-like Hypertensive crisis if paired with MAO inhibitor.
- inhibits VMAT on vesicle membrane in pre-synaptic cell and NET at cell membrane of presynaptic cell reverses–> into synapse
Ephedrine, pseudoephedrine
Noncatecholamine, mixed
Orally available, excreted unchanged (kidneys), long duration of action, some CNS penetration, mild stimulant
Used as nasal decongestant, bronchodilator (cold medications)
Pharmacology of non-specific alpha blockers (antagonists)
Alpha 1 and alpha 2 targeted
Predominant effect = vasodilation
- reflex tachycardia because alpha 2 receptors mediate a negative feedback role and
-hypotensive response is blunted by increased CO.
BP = CO x PVR
What are some of non-specific alpha blockers Adverse effects?
orthostatic hypotension, nasal stuffiness, tachycardia
Phenoxybenzamine
nonspecific alpha blocker
- requires bioactivation (lag in onset)
- Covalent, irreversible modification
used for treatment of pheochromocytoma (tumor of the medulla = increase in catecholamine synthesis ex. NE)
Phentolamine
Nonspecific (alpha 1 + alpha 2) blocker
used for short term treatment of phenochormocytoma because shorter duration and for hypertensive crisis.
-alpha agonist reversal for hypertensive crisis
Alpha 1 blockers Pharmacology
Decrease blood pressure with less reflex stimulation of heart rate
Decreases preload and after load
Used to treat hypertension, relaxes smooth muscle in prostate, urethra, and bladder neck
= promotes urine flow (benign prostatic hyperplasia)
Prazosin, terazosin
Alpha 1 blockers
used for hypertension and BPH
Tamsulosin
Primarily alpha 1 blocker, but is somewhat selective for alpha 2 as well
- promote urine flow in BPH with little effects on blood pressure.
Effects of beta blockers?
- CV: decrease HR and contractility
- short term = decrease CO, increase Peripheral resistance
- long term: peripheral resistance normalizes, decrease myocardial O2 consumption - BP –no effects on blood pressure if normal but will decrease hypertension in hypertensive patients
- LUNGS– Bronchoconstriction (antagonism of B2) Dangerous in COPD and asthma
- EYE– Decreases aqueous humor production from ciliary epithelium
- METABOLIC: blocks glucose mobilization ( B2 antagonism); slows lipolysis, increases vLDL, and lowers HDL (mechanism unclear)
Pharmacokinetics of Beta blockers
- well absorbed orally
- bioavailbity – 1st pass metabolism and clearance dependent on agent
- lasts for hours, exception is Esmolol (10 min half-life) - used IV
- partial agonist activity
Therapeutic uses of beta blockers
- Angina
- Hypertension
- Supraventricular and ventricular arrythmias
- Myocardial infarction
- Hyperthyroidism
- glaucoma
- Neurological: migraine; tremor
- heart failure
Adverse effects/ constraints of beta blockers
- Heart Failure – acute treatment
- Bradycardia
- COPD and asthma
- Abrupt withdrawal = angina, sudden death
- Blunt recovery from hypoglycemia (also mask symptoms of concern in insulin-dependent diabetics)
- Adverse plasma lipoprotien profiles
- CNS : sleep disturbances, depression
Propanol
Beta-blocker
no selectivity
no intrinsic sympathomimetic activity (partial agonist)
- membrane stabilizing activity ( local anesthetic properties)
- High lipid solubility
- Prototypic agent
Esmolol
Beta 1 selectivity
- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
- low lipid solubility
- half-life = 10 min, IV administration
Acebutolol
Beta 1 selectivity
- intrinsic sympathomimetic activity
- membrane stabilizing activity
- low lipid solubility
Carvedilol
No selectivity
- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
- lipid solubility unknown
- SOME alpha 1 blockage
Pindolol
No selectivity
- intrinsic sympathomimetic activity
- membrane stabilizing activity
- moderate lipid solubility
Atenolol
Beta 1 selective
- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
- low lipid solubility
Timolol
No selectivity beta antagonist
- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
- moderate lipid solubility
Who are the beta 1 selective beta blockers?
Esmolol, Acebutolol, and atenolol
Metoprolol, Bisoprolol, Nebivolol
