Endogenous/Drug effects on receptor Flashcards
Norepinephrine has a low affinity/efficacy at what two receptors?
B2 & B3
EPI binds to what receptor causing bronchodilation?
B2
At low concentrations, epinephrine binds to what receptor?
What is the effect?
B2
vasodilation
At high concentrations, epinephrine binds to what receptor?
What is the effect?
A1
vasoconstriction
List 3 bronchodilators?
Epi
isoproterenol
albuterol
What can block NET? What is the result?
Cocaine and TCA(amitriptyline)
increased available Norepi
Methylxanthines (caffeine)
bronchodilation
Phenylephrine cause increase myocardial contractility by 2-3x WHY?
post junctional A1 receptors on heart
more prominent in failure or ischemia due to receptor upregulation
Sympathomimetic drugs such as ephedrine do what?
act using endogenous NT
Sympathomimetic drugs act primarily on what receptors
A1 and B1
Epi (agonist) primarily stimulates what receptors?
B1,2,3
Norepi stimulates_____, but minimal______ receptor activity?
B1
B2
Dopamine is a ____receptor agonist?
Beta
Stimulation of SNS causes 80% release of____from adrenal medulla.
Epi
Catecholamines are?
sympathetic amines with hydroxy substitutions 3 and 4 of benzene ring
Cocaine does what?
blocks reuptake of NE
Tyramine is
from fermented food, contraindicated with mao inhibitor
Tyramine, amphetamine, ephedrine cause what?
increase available nor epi, reuptake inhibition
Epinephrine in large doses may cause
PVC, tachycardia, fibrillation
The negative SE of EPI may exacerbated in
MI and anesthetic agents
In the presence of a beta blocker EPI will act as
vasoconstriction
EPI causes increased coronary blood flow via
metabolic adenosine
EPI via A1 causes high vasoconstriction where?
skin vasculature
Epinephrine indirectly increase blood pressure why?
Positive inotropic and chronotropic
Place in order affinity for A1&A2
Isoprotenrol
epi
norepi
epi
norepi
isoproterenol
epi>=NE»i
Place in order affinity for B1
Isoprotenrol
epi
norepi
B1 Isoprotenrol epi norepi i>epi=NE
Place in order affinity for B2&B3
Isoprotenrol
epi
norepi
Isoprotenrol
epi
norepi
i>=epi»NE
Dobutamine would be a good choice for what patient?
Short term cardiac decompensation states(post CT surg, acute MI, CHF
In severe CHF dobutamine would be a shit choice. Why?
down regulation of b adrenergic receptors would decrease its effectiveness.
Dobutamine facilitates AV conduction and may cause
ventricular ectopy.
Dobutamine predominantly simulates which receptor
B1
Dobutamine is more prominent inotrope or chronotrope?
inotrope
Pheonochromocytoma will cause an increase of ______release by the _____of _______%?
norepi
adrenal medulla
97%
A low dose of epi 2-10mcg will cause
B3 lipolysis
Epi can cause an increase in this electrolyte______. Why?
Potassium
Increased Na-K pump action
Ephedrine may cause this adverse action______ if taken with ________.
HTN crisis
moa inhibitors
Isoproterenol and epinephrine are
equally effective in stimulating
release of free fatty acids and in
energy production
The duration of action of isoproterenol is somewhat longer than
epi
Inotropic
force of contraction
Chronotropic
rate
Dromotropic
conduction speed
Metaproterenol is a?
bronchodilator
selective B2 agonist
resistant to methylation by COMT
Terbutaline is a
Terbutaline is a bronchodilator selective B2 agonist can be give subq 0.25mg can repeat Q15 rapid onset
Albuterol is
bronchodilator
selective B2 agonist
works in 15 min
Levalbuterol is
bronchodilator
selective B2 agonist
R-enantiomer= less SE
Ritodrine is
Tocolytic
selective B2 agonist
Phenylephrine is epinephrine minus
hydroxyl group at pos 4
Phenylephrine is an A1 selective agonist but acts on ________at high doses.
B1
Baroceptor response often stay intact if using
clonidine or dexmedetomidine
Fenoldopam is
D1 receptor agonist
vasodilator for acute treatment of severe HTN
Amphetamine and dextroamphetamine
Acts indirectly by releasing biogenic amines
from storage sites in nerve terminals
– Activates RAS
– Can cause psychosis (5-HT mediated)
– Anorectic, locomotor stimulant (DA mediated
Phenoxybenzamine 6 things what is it? where does it bind? causes? enhanced by what? Useful in two things?
-Phenoxybenzamine-vasodilator
-Blocks A1 & A2 irreversibly/Antagonists
-Causes decrease in SVR and increase in CO
(reflex)
– Hypotension enhanced with b2 agonists
– Useful in pheochromocytoma and in
-autonomic hyperreflexia, SC injury
Phentolamine 5 what is it use duration S/E contra in who
Phentolamine Blocks A1 &A2 receptors COMPETITIVELY – Mainly used in preoperative management of pheochromocytoma • Same as phenoxybenzamine, but short-lived (~15 min following IV bolus) – Causes release of histamine • Contraindicated in CAD
Prazosin
Prazosin/CHF
Potent A1 receptor antagonist/no A2 blockade (no increase in NE release)
• Blocks A1 receptors in arterioles
• Decreases SVR & venous return to heart
– Does not usually cause increase in HR or SV
• half-life 2-3 hours
• Terazosin (Hytrin®) is structural analog of
prazosin
– Also has high specificity for A1 receptors
A1-Adrenergic Antagonists
Therapeutic uses
2
A1-Adrenergic Antagonists
Therapeutic uses
-CHF/A1 receptor blockade dilates arteries
• Decrease afterload and preload
-BPH
• A1 receptor antagonists reduce resistance in some
patients
• A1 receptors in bladder trigone and urethra contribute to
blockage
• Essential hypertension & prostatic hypertrophy
(prazosin, doxazosin, terazosin)
Yohimbine
inhibits what
Erectile dysfunction (Yohimbine) • Blockade with selective antagonists (yohimbine) can increase sympathetic outflow A2 receptor antagonist • Increase SNS activity • Inhibits the function of monoamine oxidase enzymes
Therapeutic Uses of A Blockers
(Antagonists)
5
- Hypertension
- Pheochromocytoma
- Benign prostatic hyperplasia
- Peripheral vascular disease
- Erectile dysfunction (Yohimbine)
Beta Antagonists (B-Blockers) used to treat 4 cardiac issues
Used to Tx: CAD, HTN, HF, tachydysrhythmias
Cardiac selective (β1 receptor) drugs
Atenolol, metoprolol, esmolol
-Relative selectivity; much less vascular, bronchial smooth
muscle, and metabolic effects
Beta blockers Intrinsic sympathomimetic activity (ISA) (partial
agonist activity) drugs
Pindolol, acebutolol
Less slowing of HR at rest; exercise induced ↑ HR still blunted
like non-ISA β-blockers
Beta blocker Membrane stabilizing activity (MSA)
Acebutolol, labetalol, metoprolol, pindolol, and
propranolol
Beta blocker that vasodilates
Nebivolol vasodilates via endothelial dependent
NO pathway
B antagonists block
renin release caused by
SNS stimulation
Reduction in plasma renin activity causes anti-HTN
Beta blockers cause these negative effects on the heart
decreased sinus rate, spontaneous &
depolarization of ectopic foci
Propranolol is life threating to what patient population? Why
COPD & asthma
blocks B2 receptor
Beta blockers cause hypoglycemia. Why ?
4
Beta blockers cause hypoglycemia. Why ?
Metabolic effects
– Catecholamines promote glycogenolysis and mobilize glucose in response to hypoglycemia
-B adrenergic antagonists may block this response
-B2 receptor blockade may inhibit hepatic
response to insulin-induced hypoglycemia
-B3 adrenergic antagonists attenuate the
release of free fatty acids from adipose tissue
Propranolol
non selective beta
Interacts with B1& B2 receptors with equal
affinity
Highly lipophilic with large VD
• Crosses BBB
– Lacks intrinsic sympathomimetic activity
– Extensively metabolized
– Propranolol may be administered IV for
management of life-threatening dysrhythmias
or to patients under anesthesia
• 1-3 mg administered slowly
• If bradycardia is profound - atropine may be used
Metoprolol
Metoprolol – β1/β2-receptor affinity (30:1); membrane stabilizing activity (MSA); no ISA – Primarily liver metabolism – ½ as potent as propranolol – Short elimination half-life 3.5 hrs
Atenolol
β1/β2-receptor affinity (30:1); no MSA or ISA
activity
– Primarily excreted via kidneys; no first-pass
metabolism
– Elimination half-life 6.5 hrs, so once daily dosing
Pindolol
Nonselective β–blocker that has MSA and
ISA
Acebutolol
β1-selective with ISA
Esmolol
β1-selective; IV rapid onset and offset
(<10 min.)
– Rapid hydrolysis by non-specific esterases
Esmolol
Esmolol
• B1 selective adrenergic antagonist with very
short duration of action t1/2B 8-9 minutes
• Esmolol has an ester linkage (nonspecific
esterases – red blood cells)
• Rapidly hydrolyzed
• Onset (2 minutes) and cessation of B
adrenergic blockade are rapid
• Peak hemodynamic effect in 10 minutes
• Esmolol has little, if any, ISA
• Anesthesia uses:
– Rapid, brief control of ↑ HR (i.e.: to prevent tachycardia
from intubation stimulation)
– Infusions can be quickly terminated if needed
POISE
Dont hold beta blockers, control rate <80
beta blocker time out
Labetalol
Competitive antagonists at A1 and B receptors – Selective a and nonselective b blocker – Racemic mixture with 4 stereoisomers a1 blockade leads to arteriolar dilation b1 blockade leads to decrease in BP by blocking reflex sympathetic stimulation • 5x-10x more potent b blocker than a blocker (7:1) • Extensively metabolized in liver • Elimination half life of 5 hrs • Onset 2-5 minutes, peak 5-15 minutes, and DOA 2-4 hrs • 5-10 mg TTE every 10 minutes
Adverse Effects of Beta Blockers
8
• Bronchoconstriction • Bradycardia, A-V block, cardiac arrest • Decreased cardiac output • Sudden withdrawal problems • Hypoglycemia problems • Diminished exercise performance • Possible changes in blood lipids • Potential CNS effects
use__________for bronchial asthma
drug
albuterol
use__________for cardiogenic shock
drug
dopamine/dobutamine
use__________for rhinitis
drug
phenylephrine
use__________for HTN
drug
prazosin
use__________for angina pectoris
drug
propranolol
use__________for supraventricular arrhythmias
drug
atenolol
use__________for BPH
drug
terazosin or prazosin
Therapeutic Uses of Beta
Blockers
8
- Hypertension
- Ischemic heart disease
- Cardiac arrhythmias
- Obstructive cardiomyopathy
- Congestive heart failure
- Open-angle glaucoma B1
- Migraine headache
- Muscle tremor, performance anxiety propranolol
Indirect acting irreversible muscarinic?
echothiopate
indirect acting reversible muscarinic?
3
edrophonium, neostigmine, physostigmine
Bethanechol
M3 muscarinic agonist
Used post-op to treat urinary retention and
abdominal distention
– Treat neurogenic G.I. atony and megacolon
(increase intestinal motility)
Pilocarpine
m3 muscarinic
Pilocarpine - topical miotic, glaucoma (decrease
intraocular pressure
Muscarinic Agonists
Clinical Uses
Reduces IOP by causing contraction of ciliary body • facilitates aqueous humor outflow • can be treated with cholinergic agonists or cholinesterase inhibitors
Atropine
CNS effects occur with high doses of
atropine
– effects from restlessness to somnolence
– toxic doses cause more prominent symptoms
• disorientation, hallucinations, and delirium
– larger (toxic) doses cause depression,
circulatory collapse
scopolamine
less likely to change heart depresses RAS – may cause delayed awakening from anesthesia – used for motion-sickness • blocks medullary impulses arising from vestibular overstimulation • transdermal (postauricular) provides sustained blood levels Scopolamine in therapeutic doses may be used for sedation – can be combined with an opioid – drowsiness, amnesia, and fatigue – Intravenous dosing (0.3-0.6 mg
Glycopyrrolate
chem structure
doesn’t do what
why
Glycopyrrolate is a quaternary amine
– devoid of sedative effects
– does not cross BBB
Muscarinic relatively contraindicated
in narrowangle
glaucoma
• causes flow obstruction
• interferes with flow of aqueous humor
Scopolamine produces sedation
Scopolamine produces sedation by decreasing activity of the RAS (100x more than atropine) – Also effects other areas of brain resulting in amnesia • May have delayed awakening • Physostigmine is effective in reversing restlessness or somnolence from CNS effects of tertiary amine antimuscarinics
Scopolamine produces sedation by
Scopolamine produces sedation by decreasing activity of the RAS (100x more than atropine) – Also effects other areas of brain resulting in amnesia • May have delayed awakening • Physostigmine is effective in reversing restlessness or somnolence from CNS effects of tertiary amine antimuscarinics
Tiotropium - DOA
> 24 hrs
Most potent antisialagogue in order order of potency
scopolamine
glycopyrrolate
atropine
Horner Syndrome
Stellate ganglion – Superior, middle, and cervicothoracic ganglia – Spinal segments T1-4/5 synapse here – Provide SNS innervation of ↑ ext., head, neck – So? – Horner syndrome • Ptosis • Miosis • Anhidrosis • Enophthalmos • Redness of face and conjunctiva
Dopamine
Precursor of NE
• Effects are mediated through D1 receptors
• Low doses primarily activate D1 receptors
– Vascular postjunctional D1 receptors in renal
and mesenteric blood vessels
– 0.5-3.0 mcg/kg/min
• Moderate DA dosages act on B1 receptors
– 3.0 - 10 mcg/kg/min
Higher dosages 10 - 20 mcg/kg/min primarily act
at a1 receptors
– Leads to vascular vasoconstriction
– Low dose increased renal blood flow and GFR
– Moderate dose increases myocardial contractility and
increase in CO
– High dosages vasoconstriction
• Benefit to renal perfusion may be lost
– Dopamine is an important central neurotransmitter
• Peripherally administered dopamine has no central side
effects
• Substrate for MAO & COMT
– Half-life of about a minute
Ipatropium/tiotropium
quaternary compounds used to treat reactive
airway disease
– used as an inhalant
– does not impair mucociliary elevator
– toxicity not usually a problem since this
compound is poorly absorbed from lungs into
circulation
Echothipoate
irreversible indirect
glaucoma
Carvedilol is similar to ___________and good for
labetalol, chf
