Exam 6 - Adrenergic Agonists & Antagonists Flashcards
Characteristics of adrenergic agonists
- Derivatives of B-phenylethylamine
- stimulate fight/flight
Catecholamines
- 2 OH groups on ring
- potent at B receptors
- rapid inactivation by MAO/COMT
- cannot give orally (too much COMT/MAO in gut)
- do not enter CNS…too polar
Noncatecholamines
- only 1 or no OH groups
- longer duration of action
- only MAO breaks it down…not very well
- greater access to CNS….less polar
Substitutions on amine Nitrogen
- more subs….more affinity for B receptors
Epinephrine
- Adrenalin
- endogenous neurotransmitter/hormone
- released by adrenal medulla (80%….NE 20%)
- BOTH alpha and beta
- Increases HR/contractility/renin/CO
- constricts skin/viscera vessels
- dilates liver/skeletal muscle vessels
- high dose = constrict (alpha)…low dose = dilate (B2)
- HR up / systolic up…diastolic down / PVR down
- bronchodilation / allergy inhibition
- hyperglycemia (increase glucagon / decrease insulin..alpha)
- Lipolysis (B3)
Epinephrine therapeutic uses
- Cardiac arrest
- Anaphylactic shock
- Acute asthma attack / bronchospasm
- With local anesthetics….to keep local
Epi CPR dose
1 mg IV/IO every 3-5 min
Epi bradycardia dose
2-10 ug/min IV to effect
Epinephrine pharmacokinetics
- Rapid onset, short duration
- due to MAO/COMT….is a catecholamine
- IM/IV/IO/SQ/inhalation/endotracheal….NOT orally
- excreted by kidney
Norepinephrine
- Levophed (leave em dead)
- endogenous neurotransmitter of adrenergic nerves
- Alpha and B1
- Intense vasoconstriction
- Increase contractility BUT barrorecpetor reflex….so HR down
- HR down / systolic up…diastolic up / PVR up
NE therapeutic uses
- Vasodilatory shock
- Hypotension
NE dose
0.5-12 ug/min to titrated to effect
NE pharmacokinetics
- lasts 1-2 minutes
- rapidly metabolized by MAO/COMT
- excreted via kidney
- IV ONLY…extravasation cause necrosis…no peripheral veins
Dopamine
- endogenous precursor to NE…neurotransmitter and hormone
- CNS/adrenal medulla
- D (low= 1-2 ug/kg/min) > B (medium= 2-10) > alpha (high= >10)
- HR up / contractility up
- contracts at HIGH doses
- dilates renal/splanchnic arteries
Dopamine therapeutic uses
- MAIN drug for cardiogenic/septic shock
- Renal failure…increases renal flow
- Hypotension/heart failure…especially if with renal failure
- NE will decrease renal flow even more
Dobutamine
- Dobutrex
- synthetic, direct catecholamine
- B1
- Increases CO/HR ( < dopamine)/Contractility ( >dopamine)
- NO PVR effect
- Less increase in O2 consumption
Dobutamine therapeutic uses
- Increase CO in acute heart failure
- short term “failure to wean” drug
Isoproterenol
- Isuprel
- synthetic catecholamine
- Nonselective B1 and B2
- Increase contractility/HR
- potent vaso/bronchodilator
- Up HR / zero-little up systolic…down diastolic / down PVR
Isoproterenol therapeutic uses
- Second choice for cardiac emergency
- bronchospasms during anesthesia
- cardiac stimulant
Phenylephrine
- Neo-Synephrine
- synthetic Alpha 1
- lasts 20 min (longer than epi/NE)
- constriction
- Up systolic….up diastolic
- Drops HR….due to reflex bradycardia…like NE
Phenylephrine theraputic uses
- Hypotension
- Tachycardia
- Nasal decongestant if topical/oral
- VERY common to increase SVR and MAP
Neo dosing
- Start with test dose (50-100 ug/ml)
- LD = 50-500 ug
- IV = 10-15 in 250 ml fluid (40-60 ug/ml)
Indirect adrenergic agonists
- increase endogenous levels of Epi/NE
- cause release / inhibit reuptake / inhibit degradation
- Amphetamine / Tyramine / Cocaine
Amphetamine
- reverse NE reuptake channels on presynaptic terminal
- more release of NE
Cocaine
- binds and blocks reuptake NE receptors
Mixed action adrenergic agonists
Ephedrine (if no epi) > Pseudoephedrine (decongestant)
- release stored NE…AND
- directly stimulate alpha/beta
- Like epi…less potent….longer duration
- vasoconstriction / cardiac stimulation / Up systolic AND diastolic
- Mild CNS
Side effects of adrenergic agonists
- arrhythmia
- headache
- hyperactivity
- insomnia
- nausea
- tremors
Dopaminergic agonists
- Levodopa
- goes into CNS…turns into dopamine…stays in CNS
- useful for Parkinson’s
Direct Adrenergic Agonist Drugs
- Epinephrine (Adrenalin)
- NE (Levophed)
- Dopamine
- Dobutamine (Dobutrex)
- Isoproterenol (Isuprel)
- Phenylephrine (Neo-Synephrine)
Indirect Adrenergic Agonist Drugs
- Amphetamine
- Tyramine
- Cocaine
Mixed Action Adrenergic Drugs
- Ephedrine
- Pseudoephedrine
Dopaminergic Agonist Drugs
- Levodopa
Adrenergic Antagonists
- no need to use on B2
- sympatholytics
- alpha and beta blockers
Alpha blockers
- vasodilates
- severely drops BP
- causes reflex tachycardia
Alpha 1 receptors
- increase vascular tone
- smooth muscle vasculature
- on effector organ
- constricts when stimulated
Alpha 2 receptors
- presynaptic
- control release of NE
- inhibitory autoreceptors
- stimulation blocks NE release
Phenoxybenzamine
- Dibenzyline
- Nonselective alpha blocker
- Noncompetitive….covalently bonds
- irreversible…long lasting
- vasodilates / reflex tachycardia
- blocks inhibitory alpha2 receptors on heart…more NE…up CO
Uses:
- Pheochromocytoma: too much adrenaline from adrenal gland
- DONT use for hypertension…it increases CO
Phentolamine
- Regitine
- Nonselective alpha blocker
- competitive
- short lasting…4 hours
Uses:
- short term pheochromocytoma
- locally to prevent dermal necrosis…NE extravasation
- Epi reversal… blocks alpha effects of Epi
Nonspecific alpha blocker side effects
- orthostatic hypotension
- tachycardia
- dizzy/headache
- sexual dysfunction
Selective Alpha 1 blockers
- Prazosin (minipress)
- Terazosin (Hytrin)
- Doxazosin (Cardura)
- used for hypertension w/ other things…also BPH
- competitive
- decrease PVR and lower BP
- minimal changes to CO (no B)
- first dose may cause orthostatic hypotension
Selective alpha 2 blockers
- Yohimbine
- competitive
- more sympathetic to periphery
- treats impotence/aphrodisiac
Beta blockers
- think -olol
- competitive
- widely used
- patient specific dosing (usually judge via HR)
Beta blocker uses
- hypertension
- angina
- arrhythmias
- MI
- heart failure
- hyperthyroidism
- glaucoma
- migraine prophylaxis
Propranolol
- Inderal
- Gold standard
- blocks B1 and B2 equally
- down HR / contractility / CO / oxygen consumption
- PVR up initially…but normal or decrease with long term use
- due to reflex peripheral constriction
Propranolol bronchial effects
- constriction
- DON’T use for COPD
Propranolol glucose effects
- Hypoglycemia
- decrease glucagon secretion
- careful with diabetic patients
Propranolol drug interactions
- blocks isoproterenol (B agonist)
- no cardiac stimulation (B1)
- no drop in MAP and diastolic BP (B2)
- blocks SOME Epi
- leaves alpha 1 alone…. vasoconstriction action unimpaired
Propranolol therapeutic uses
- hypertension (drops work of heart and PVR over time)
- angina (less O2 used)
- MI (better recovery and preventative for future MI)
- migraine (prophylactically)
- hyperthyroidism
- stage fright / anxiety
Propranolol adverse effects
- bronchoconstriction
- arrhythmias (receptor upregulation / DO NOT stop abrupt)
- sexual dysfunction
- metabolic disturbance (high LDL / low HDL / more fat…B3)
- CNS effects:
- depression / dizzy / weak / tired / hallucination / STML
Nadolol
- Corgard
- blocks B1 and B2 equal
- nonselective
- similar to propranolol but MORE potent
- longer duration….12-24 hours
Uses:
-Hypertension
Selective B1 blockers
- can effect B2 with high dose…still careful w/ COPD
- less bronchoconstriction at low dose
Uses:
- lower BP in hypertension…especially w/ impaired pulmonary
- increase exercise in angina
- chronic angina therapy
- chronic heart failure
- Bisoprolol / Metoprolol (extd. release)
Esmolol
- Brevibloc
- B1 blocker
- very short half life
- IV
- used for BP or rhythm in surgery
Selective B1 blocker w/ partial agonist activity
- Acebutolol (Sectral)
- ISA - Intrinsic sympathomimetic activity
- weakly activates AND blocks from other potent binding
- leads to decrease in cell activity…not total block
- less effect on CO/HR but minimal lipid/carb disturbance
Uses:
- hypertension w/ bradycardia …drop in HR is less
Nonselective B block w/ alpha-1 blocking actions
- Labetalol (Trandate)
- Carvedilol (Coreg)
- peripheral dilation (block alpha 1)
- reduce BP
Uses: - Hypertensive emergency (IV)
- Pregnancy hypertension
Non Selective alpha blockers
“-amine”
- Phenooxybenzamine (Dibenzyline)
- Phentolamine (Regitine)
Selective alpha 1 blockers
“-azosin”
- Prazosin (Minipress)
- Terazosin (Hytrin)
- Doxazosin (Cardura)
Selective alpha 2 blocker
- Yohimbine
Non Selective B blockers
- Propranolol (Inderal)
- Nadolol (Corgard)
Selective B1 Blockers
- Esmolol (Brevibloc)
- Atenolol (Tenormin)
- Metoprolol (Lopressor)
- Bisoprolol (Zebeta)
Selective B1 blockers w/ partial agonist activity
- Acebutolol (Sectral)
Non Selective B Blockers w/ Alpha-1 block activity
- Labetalol (Trandate)
- Carvedilol (Coreg)
