Adrenergic Agonists and Antagonists Flashcards
Adrenergic receptor subtypes
Alpha 1 and 2, Beta 1 and 2, dopamine
Adrenergic neurotransmitters
Norepinephrine, Epinephrine, Dopamine
Alpha-1 receptor function
ocular: mydriasis
Blood vessels: vasoconstriction
male genitals: ejaculation
Bladder: neck (sphincter) and prostate constrict while detrusor relaxes
Alpha-2 receptor function
located on presynaptic cell
minimal clinical significance
inhibits release of NE
Located in PNS and CNS
Beta-1 receptor function
we have one heart so “one=heart”
increases force of contraction
increases heart rate
increases velocity of conduction in AV node
kidneys: stimulates release of renin
Beta-2 receptor function
bronchial dilation
vasodilation in heart, lungs, liver, and skeletal muscles
relaxation of uterine smooth muscle
glycogenolysis in liver and skeletal muscle
enhanced contraction of skeletal muscle
Dopamine receptor function
Primarily in CNS
Only known function:
dilation of renal arteries - enhanced renal perfusion
Epinephrine
activates alpha 1, alpha 2, beta 1, beta 2
released from adrenal medulla
Norephinephrine
activates alpha 1, alpha 2, beta 1
released from post-ganglionic neurons in SNS
Dopamine
activates alpha 1, beta 1, and dopamine
Lifecycle of NE
synthesized in presynaptic terminal from a series of precursors
Stored in vesicles, released by action potential
Transmission by NE is terminated by dissociation from receptor and reuptake into presynaptic neuron terminal
- recycled or
- broken down by MAO
Lifecyle of Epinephrine
synthesized in adrenal medulla (NE –> Epinephrine)
Stored in vesicles in chromaffin cells of adrenal medulla –> activation of Nicotinic n receptors causes release of Epinephrine by adrenal medulla
travels in bloodstream to all parts of body
transmission terminated by hepatic metabolism (half life only 2-3 minutes)
Direct activation
receptor binding
most common
mimic natural transmitter
Indirect activation
mostly used for CNS effects
promotes NE release
inhibits NE uptake
inhibits NE inactivation
Catecholamines
endogenously produced
have a polar moeity which makes it hard to cross blood brain barrier
examples: epinephrine, NE, dopamine, dobutamine
Non-catecholamines
lack catechol group = much less polar
examples: ephedrine, phenylephrine, terbutaline
more CNS effects
Implications of catecholamines
cannot be used orally
rapidly metabolized by MAO and COMT (enzymes in intestinal wall and liver)
must be administered by continuous infusion
duration of action is BRIEF
cannot cross BBB –> minimal use in CNS
Implications of non-catecholamines
can be used orally
slowly metabolized by MAO
not degraded by COMT
duration of action is LONGER
Better at crossing BBB –> can cause CNS effects
Receptor specificity is…
relative (NOT absolute)
LOW doses are best to be MORE selective for specific receptors
Alpha 1 therapeutic applications
Hemostasis (via vasoconstriction, helpful during sutures)
Elevation of BP (ICU)
Mydriasis (eye drops for ophthalmic exam)
Nasal decongestion (constricts vessels in mucous membrane = reduced swelling; doesn’t have effect on nasal secretions)
Alpha 1 receptor for local anesthetics
vasoconstriction is induced and allows:
- decreased in anesthetic dosage
- prolongs anesthesia
- decreases systemic effects
- Epi is mostly commonly used
- Lidocaine + epi can be contained in same vial
Alpha 1 receptor activation
3 ADVERSE EFFECTS
HTN (hypertension)
Bradycardia (reflex bradycardia): an increased BP can signal cardiac inhibitory signal in medulla = stimulates lower HR
-risk of local cell death (necrosis) when used with anesthesia or if IV extravasates; cause: prolonged vasoconstriction
Beta 1 Therapeutic Applications
cardiac arrest
acute heart failure
shock
AV block
Beta 1
3 ADVERSE EFFECTS
tachycardia
angina/chest pain
dysrhythmia
Beta 2 therapeutic applications
relax smooth muscle of bronchi (Asthma, albuterol)
Relax uterine smooth muscle (delay preterm labor)
Beta 2
2 ADVERSE EFFECTS
Hyperglycemia (in diabetics)
Tremor
Dopamine therapeutic applications
at low doses –> dilates renal vasculature
at high doses –> enhances cardiac performance; will activate all adrenergic receptors (ICU drug)
Anaphylactic shock:
Cause? S/S? Treatment?
Cause : Severe Allergy
S/S: HTN, bronchial constriction, edema of glottis
Treatment: Epinephrine (IM; fewer ADE than IV)
Adrenalin uses
mimic epinephrine
IM, SQ, IV, topically (catecholamine, cannot be taken orally)
used in anaphylaxis, cardiac arrest, increase BP in shock
used for local vasoconstriction
inhaled for treat croup symptoms and for asthma if other treatments ineffective
Adrenalin
ADVERSE EFFECTS
shakiness, anxiety, sweating, tachycardia, HTN
Levophed
mimics NE
activates A1, A2, B1
Isoproterenol
potent nonselective beta-adrenergic agonist
low affinity for alpha-adrenergic receptors. Systemic effects:
lowering of peripheral vascular resistance and diastolic pressure
positive inotropic and chronotropic effects
prevention of bronchoconstriction
Phenylephrine
alpha 1 agonist
newest product
only activates A1
Alpha Blockers
Therapeutic Applications
BPH: allows PSNS to take over = increased urination
Pheochromocytoma: catecholamine secreting tumor of adrenal medulla = excessive secretion of epinephrine; blockers serve to lessen the symptoms by blocking receptors
Raynaud’s disease: prevents vasoconstriction of fingertips and toes
Reverse toxicity caused by alpha 1 agonists
Phentolamine
Non-selective alpha blocker
blocks A1 an A2
uses:
hypertensive crisis
treats pheochromocytoma, given IV or IM
Prazosin
alpha 1 BLOCKER
uses:
BPH
Nightmares from PTSD (CNS effect)
Alpha Blockers
4 ADVERSE EFFECTS
Orthostatic hypotension
Reflex tachycardia
Nasal congestion
Inhibition of ejaculation
Propranolol
Non-selective BETA blocker
Blocks Beta 1 and Beta 2
contraindicated in asthma, COPD, SOB
overt cardiac failure, severe bradycardia
Metoprolol
Blocks Beta 1 receptors (cardioselective)
Used for HTN, heart failure
Beta blockers
Therapeutic applications
Angina Pectoris HTN Cardiac dysrhythmias (by slowing down HR) MI (during rehab and thereafter) HF (useful much of time but not all the time) Migraine Hyperthyroidism Stage fright Glaucoma
Beta 1 blockage
Therapeutic consequences
Reduced HR
Reduced force of contraction
Reduced velocity of impulse conduction
Beta Blockers
ADVERSE EFFECTS
Bradycardia AV heart block Reduced CO (cardiac output) HF, symptoms of CHF Hypotension Inhibition of glycogenolysis Bronchial constriction Drowsiness, depression
Albuterol
Beta 2 agonist
Dobutamine
Beta 1 agonist
