05- Adrenergics Flashcards
atenolol (Tenormin)
adrenergic antagonist that is B1 SELECTIVE (post-junctional inhibition)
- will decrease HR, force of contraction and result in dec. CO
- major clinical use: anti-hypertensive
- cardiac selective and does not block B2 receptors which is beneficial for those with asthma or COPD
- Half-Life: 6-9 hrs
- produces few CNS effects because does not cross BBB easily
- can induce cardiac failure in those with cardiac insufficiency
betaxolol (Betoptic, Kerlone)
adrenergic antagonist that is B1 SELECTIVE (post-junctional inhibition)
- will decrease HR, force of contraction and result in dec. CO
- major clinical use: treatment of glaucoma (given topically)
- cardiac selective and does not block B2 receptors which is beneficial for those with asthma or COPD
- Half-Life: 14-22 hrs
- can induce cardiac failure in those with cardiac insufficiency
metoprolol (Lopressor)
adrenergic antagonist that is B1 SELECTIVE (post-junctional inhibition)
- will decrease HR, force of contraction and result in dec. CO
- major clinical use: anti-hypertensive and angina pectoris
- effective prophylactic agent to prevent recurrence of myocardial infarction
- long-term use following MI prolongs survival (may suppress arrhythmias)
- cardiac selective and does not block B2 receptors which is beneficial for those with asthma or COPD
- Half-Life: 3-4 hrs
- ataxia and dizziness are common, esp. with initial therapy
- can induce cardiac failure in those with cardiac insufficiency
propranolol (Inderal)
adrenergic antagonist that is NON-SELECTIVE BETA BLOCKER (post-junctional inhibition)
- Major clinical use: anti-hypertensive, anti-arrhythmic, angina pectoris, and migraine headaches
- will cause B2 blockade my inhibit dilation of bronchioles, which may be significant for patients with asthma
- effective prophylactic agent to prevent recurrence of myocardial infarction
- Half-life: 3-6 hrs
pindolol (Visken)
adrenergic antagonist that is NON-SELECTIVE BETA BLOCKER (post-junctional inhibition)
- Major clinical use: anti-hypertensive
- will cause B2 blockade my inhibit dilation of bronchioles, which may be significant for patients with asthma
- Half-life: 3-4 hrs
nadolol (Corgard)
adrenergic antagonist that is NON-SELECTIVE BETA BLOCKER (post-junctional inhibition)
- Major clinical use: anti-hypertensive
- will cause B2 blockade my inhibit dilation of bronchioles, which may be significant for patients with asthma
- minimal CNS effect b/c cannot cross BBB
- Half-life: 14-24 hrs
timolol (Timoptic)
adrenergic antagonist that is NON-SELECTIVE BETA BLOCKER (post-junctional inhibition)
- Major clinical use: anti-hypertensive, angina pectoris, and decrease intraocular pressure
- will cause B2 blockade my inhibit dilation of bronchioles, which may be significant for patients with asthma
- effective prophylactic agent to prevent recurrence of myocardial infarction
- Half-life: 4-5 hrs
a-methldopa (Aldomet)
acts BOTH as an adrenergic agonist that is A2 SELECTIVE and as a MISC. PRE-JUNCTIONAL
- major use: anti-hypertensive
- stimulate pre-synaptic a2 receptors as well as post-synaptic a2 receptors on nerve terminals in CNS
- inhibits NE release by nerve terminal (feedback inhibition)
- able to enter both PNS and CNS adrenergic neurons
- partially replaces DOPA in synthetic pathway leading to NE synthesis
- synthesized and stored in vesicles (instead of NE)
- known as a false transmitter because after exocytosis from vesicles, its efficacy is greatly reduced as compared to NE as agonist
- hypotensive activity results from potent stimulation within the brainstem affecting vasomotor center
- decreases TPR, HR, CO; does not affect baroreceptor reflexes and rarely elicits orthostatic hypotension
- Adverse Effects: sedation , postural hypotension, dizziness, sleep disturbances, impotence, dry mouth, nasal congestion
guanethidine (Ismelin)
misc. PRE-JUNCTIONAL inhibition of NE release through synaptic vesicle depletion, and membrane stabilization
- orally effective anti-hypertensive usually reserved for therapy of most severely elevated arterial pressures
- transported into adrenergic neurons via NE transporter
- hypotensive activity elicited by reducing NE release
- agents that inhibit transport (cocaine, tricyclic antidepressants) will antagonize desired hypotensive activity
- stabilizes membranes, interfering with exocytosis
- chronic administration accompanied by depleting NE within synaptic vesicles
- minimal effects observed w/ other biologic amines (Epi, DA)
- minimal adverse effects in CNS since does not cross BBB
reserpine
misc. PRE-JUNCTIONAL inhibition of NE release through synaptic vesicle depletion (reduce concentrations of NE stored within synaptic vesicles, thus decreasing the overall amount of NE released into synapse)
- depletes stores of biogenic amines (Epi, NE, DA, serotonin) in both PNS and CNS by blocking transport into storage vesicles
- very potent, orally effective, long duration of action
- adverse effects are primarily in CNS (sedation, depression, Parkinsonian symptoms); inc. GI motility leads to ulcers
cocaine
AMINE I TRANSPORTER (NET) inhibitor
- prevents reuptake of NE from the synapse thus synaptic levels of NE rise allowing further sympathetic stimulation of target site (vasoconstriction, tachycardia, mydriasis)
- inhibitors of NET is important within PNS when considering drug interactions and potential toxicological problems
- can be used to achieve decreased blood flow such as hemostasis during surgery
DMI (desmethylimipramine)
AMINE I TRANSPORTER (NET) inhibitor
- a tricyclic anti-depressant
- prevents reuptake of NE from the synapse thus synaptic levels of NE rise allowing further sympathetic stimulation of target site (vasoconstriction, tachycardia, mydriasis)
- inhibitors of NET is important within PNS when considering drug interactions and potential toxicological problems
tyramine
RELEASING AGENT
- pre-junctional sympathetic stimulation
- enter nerve terminal via NET
- NE gets displaced from storage vesicles and released into synapse
- found in certain food products (cheddar, Guyere cheese, salami, yeast)
- may elicit side effects for individuals on MAO inhibitors through combination of dec. synaptic NE metabolism (MAO inhibitor) and inc. NE release (tyramine) elevates Art. pressure
pseudoephedrine (Sudafed)
RELEASING AGENT
- pre-junctional sympathetic stimulation
- enter nerve terminal via NET
- NE gets displaced from storage vesicles and released into synapse
- used to reduce congestion of mucous membranes
doxazosin (Cardura)
Competitive adrenergic antagonist.
- selective α1 antagonist/blocker
- -Use: HTN, urinary obstruction (BPH)
prazosin (Minipress)
Competitive adrenergic antagonist.
- selective α1 antagonist/blocker
- tachycardia is mild to none because there is no significant effect on α2 receptors.
- long DOA (12’).
- -Use: HTN, urinary obstruction (BPH)
tamsulosin (Flomax)
Competitive adrenergic antagonist.
- selective α1 antagonist/blocker
- Use: HTN, urinary obstruction (BPH)
terazosin (Hytrin)
Competitive adrenergic antagonist.
- selective α1 antagonist/blocker
- -Use: HTN, urinary obstruction (BPH)
phenoxybenzamine (Dibenzyline)
Non-competitive adrenergic antagonist.
- slightly more selective for α-1 vs α-2.
- alkylates α1 and α2 receptors.
- inhibits NET.
- no β1 inhibition, so may produce orthostatic HOTN and tachycardia.
- Use: pheochromocytoma
phentolamine (Vasomax)
Competitive adrenergic antagonist.
- equal selectivity for α1 and α2
- α1 blockade produces vasodilation
- α2 blockade inhibits NE negative feedback leading to increased release of NE. This can produce tachycardia (no blockade of β1).
- Considered “dirty” drug because it acts at multiple sites (i.e. α, muscarinic, histamine).
- Use: pheochromocytoma
labetelol (Trandate)
Mixed α and β antagonist.
- non-selective β blocker.
- displays antagonism of β1 and β2.
- β1 blockade reduces heart rate and contractility/CO. Caution in patients with severe LV dysfunction.
- β2 blockade can precipitate bronchoconstriction in asthmatic patients
dopamine
- dopamine receptor agonist released by renal and splanchnic vascular smooth muscle
- D1 binds Gs: vasodilation (renal, msenteric)
- D2 binds Gi: negative feedback to decrease NT release from terminals
- High doses have alpha 1 and beta 1 agonist effects
dobutamine
- Beta 1 selective agonist. B1>B2»»alpha
- drug of choice along with dopamine with cardiogenic shock following myocardial infarction
isoproterenol
- non selective beta agonist. B1=B2»»alpha
- potent vasodilator, decreased MAP due to B2 activity
- increased cardiac output due to B1 activity
albuterol
- B2 selective agonist. B2»B1»»alpha
- smooth muscle relaxation/dilation (e.g. myometrium, bronchial ree, GI tract)
- first line treatment for bronchial asthma attack
metaproterenol
- B2 selective agonist. B2»B1»»alpha
- smooth muscle relaxation/dilation (e.g. myometrium, bronchial ree, GI tract)
terbutaline
- B2 selective agonist. B2»B1»»alpha
- smooth muscle relaxation/dilation (e.g. myometrium, bronchial ree, GI tract)
- relax pregnant uterus
bromocriptine
- Dopamine D2 receptor agonist
- primarily used as an anti-parkinson agent w/ CNS activities
- peripheral side effects: postural hypotension during initial therapy and development of cardiac arrhythmia
- D2 receptors on post-synaptic effector sites in the CNS are not involved in feedback inhibition
fenoldopam
- dopamine receptor agonist. D1»D2
- D1 binds Gs: vasodilation (renal, msenteric)
- D2 binds Gi: negative feedback to decrease NT release from terminals
- High doses have alpha 1 and beta 1 agonist effects
metaraminol
Alpha-1 agonist
- substitution to benzene ring (decreases COMT metabolism)
- substitution to alpha carbon (block oxidation by MAO & displaces NE from vesicles)
methoxamine
Alpha-1 agonist
phenylephrine
Alpha-1 agonist
- substitution to benzene ring (decreases COMT metabolism)
- nasal decongestant
- mydriasis
- vasoconstricts (protects cerebral and coronary blood flow)
- reduces diffusion of local anesthetics from injection site
clonidine
Alpha-2 agonist presynaptic nerve terminal negative feedback to decrease NE release -decrease blood pressure -sedation is a side effect
guanabenz
Alpha-2 agonist presynaptic nerve terminal negative feedback to decrease NE release -decrease blood pressure -sedation is a side effect
amphetamine
- mixed Alpha-1 Beta-1 agonist
- releasing agent
- taken in via NET, block NE re-uptake and reverse transport to release intraneuronal NE
- CNS effects: alertness and mood
- depresses appetite
ephedrine
- mixed Alpha-Beat agonist
- releasing agent
- substitution to benzene ring (decreases COMT metabolism)
- substitution to alpha carbon (blocks oxidation by MAO, displaces NE from vesicles)
- elevates cardiac output & arterial pressure
- CNS stimulant
- Beta-2 activity to dilate bronchial smooth muscle
- nasal decongestant
epinephrine
Alpha-1 and Beta-1 agonist
- released from adrenal medulla
- low dose stimulates Beta only
- potent vasoconstrictor and cardiac stimulant
- vasodilation of vessels to skeletal muscles d/t B2 activity, may decrease TPR
- with bolus, sharp rise in MAP elicits baroreceptor response & vagal reflex to decrease MAP
- hemostasis during surgery
- reducing diffusion of local anesthetics from injection site
- cardiac arrest and heart block
- anaphylaxis
norepinephrine
Alpha and Beta-1 agonist
- primary NT of adrenergic nerves
- increase blood pressure
- reduces diffusion of local anesthetics from injection site
Alpha-1 receptor activation
- arterial and venous constriction
- vagal response leads to bradycardia
- pupillary dilator muscle contraction (mydriasis)
- myometrium muscle contraction
- urinary bladder sphincter contraction
- relaxation of intestinal smooth muscle
- increased glycogenolysis
- contraction of vas deferens
- increased secretions: salivary & sweat glands
Alpha-2 receptor activation
presynaptic nerve terminals
negative feedback to decrease NE release
Beta-1 receptor activation
- increase HR and contractile force
- directly activates SA node
- increase renin secretion
- increase lipolysis in fat cells
Beta-2 receptor activation
- vascular smooth muscle dilation
- bronchial tree relaxation
- GI tract and myometrium relaxation
- decreased intraocular pressure
Beta-3 receptor activation
- increased lipolysis in fat cells
- decreased micturition
Dopamine-1 receptor activation
- vasodilation (renal/splanchnic)
- increase blood flow
Dopamine-2 receptor activation
PNS: presynpatic nerve terminals, modulatory role to derease NT release from terminals
CNS: postsynaptic, NT
COMT
found in liver
transfers OH group with methyl group for catecholamine metabolism
MAO
found in adrenergic nerve terminals, liver, and brain
removes NH2 group
deamination
