Chapter 10: Adrenergics Flashcards
What are the catecholamines?
Norepinephrine, Epinephrine, Dopamine
What is VMAT?
Vesicular MonoAmine Transporter (1 = peripheral, 2 = CNS): a catecholamine/H+ antiporter
Catecholamine pathway of synthesis
Tyrosine --(tyrosine hydrolase)--> L-DOPA --Aromatic L-AA decarboxylase--> Dopamine --(Dopamine beta-hydroxylase)--> NE
2 enzymes of norepinephrine metabolism, and final product
COMT (liver cytosol) and MAO (neuron mitochondria)
***both lead to VMA, a metabolite in urine
Which receptors, alpha1, alpha2, beta1, or beta2, are presynaptic and regulate feedback inhibition of sympathetic transmission?
alpha2
alpha1 receptor: signaling mediatior + overall effects
- Gq (PLC)/Go/Gi,
- contraction of heart(BP), Urogenital, vessels, liver breakdown,
relaxation of GI
alpha2 receptor: signaling mediatior + overall effects
- Gi (decrease cAMP), Go ( dec Ca+2),
- vessel contraction,
“slow stuff down”: platelet aggregation, decreased insulin and NE release
beta1 receptor: signaling mediatior + overall effects
- Gs (increase cAMP),
contraction of heart (BP, HR), increase renin
beta2 receptor: signaling mediatior + overall effects
- Gs (increase cAMP),
relaxation of bronchial and GI smooth muscle,
skeletal muscle and liver breakdown
beta3 receptor: signaling mediatior + overall effects
- Gs (increase cAMP),
lipolysis of adipose tissue
Epinephrine has agonist effects on what receptors?
What does it treat?
beta1 and beta2 at low conc, alpha1 at high conc
beta2 = bronchial, so decreases diastolic BP and treats anaphylaxis
Norepinephrine has agonist effects on what receptors?
What does it treat?
alpha1 and beta1
increases systolic & diastolic BP, TPR, treating shock
Dopamine has agonist effects on what receptors?
What does it treat?
Low doses on D1, high dose on beta1 (heart contractility), highest dose on alpha1 (vasoconstriction)
-trearts shock
What drug is used to treat pheochromocytoma-associated HTN by inhibiting tyrosine hydroxylase?
alpha-methyltyrosine
What treats HTN(but is mostly used experimentally) by irreversibly inhibiting VMAT and can lead to a bad side effect of psychotic depression?
reserpine
What treats HTN by getting transported by NET and concentrating in the transmitter vesicles and displacing norepinephrine, leading to its depletion? This also has a side effect of postural hypotension.
guanethidine, guanadrel
What displaces catecholamines from vesicles, weakly inhibits MAO, and blocks reuptake by NET and DAT, used in ADHD and narcolepsy treatment? It has restlessness and addiction problems
amphetamine (treats both), methylphenidate (only ADHD)
What is found in cold remedies and appetite suppressants, for treatment of rhinitis and nasal congestion?
pseudoephedrine
What is the big contraindication in inhibitors of catecholamine storage? What do they do before decreasing catecholamines (sympatholytic)?
MAOI therapy
- short-term increase of catecholamines (sympathomimetic)
What inhibits NET-reuptake of catecholamines and is used as an anesthetic/vasoconstrictor?
cocaine
phenelzine, iproniazid, tranylcypromine, clorgyline, brofaromine, befloxatone, moclobemide, selegiline:
What are they?
2 main contraindications?
Name the one selective for “A” and for “B”?
- MAO inhibitors (block catecholamine degradation)
- tyramine foods and SSRIs (serotonin syndrome: restlessness, seizures)
- MAO-A selective: clorgyline
- MAO-B selective: selegiline
What increases peripheral vascular resistance by acting on alpha-1 receptors, but limited tratment for shock because of its systemic effects?
methoxamine
What is used in Visine for ophthalmic hyperemia, and acts on alpha-1 receptors?
phenylephrine, oxymetazoline (also alpha-2), tetrahydrozoline
What is used for nasal congestion and acts on alpha-1 receptors, but can give you rebound nasal congestion?
phenylephrine, oxymetazoline(also alpha-2), tetrahydrozoline
What can be used to treat hypotension by acting on alpha-1 receptors to increase vascular resistance?
phenylephrine
What treats hypertension in pregnant women by activating the alpha-2 receptor, but can cause hepatotoxicity and autoimmune hemolytic anemia?
methyldopa
What treats opioid withdrawal and cancer pain by activating the alpha-2 receptor, but can cause postural hypotension, bradycardia, dry mouth, and sedation?
clonidine
What sedates surgical and ICU patients by activating the alpha-2 receptor?
dexmedetomidine
What are guanabenz and guanfacine used for treating, and by what mechanism?
hypertension (via alpha-2 activation, which blocks sympathetic outflow)
What is a nonselective beta1 and beta2 agonist that can be used for bronchoconstriction in asthma, but with its adverse cardiac effects, is preferred to only be used in profound bradycardia in anticipation of putting in a pacemaker?
isoproterenol
isoproterenol, dobutamine, metaproterenol, terbutaline, albuterol, salmeterol
What are these?
beta-agonists, MOSTLY for bronchospasm
What treats pheochromocytoma-associated HTN and sweating by blocking alpha1 and alpha-2 receptors?
phenoxybenzamine(irrev.), phentolamine (rev.)
What treats hypertension and benign prostatic hyperplasia by blocking alpha-1 receptors, but causes orthostatic hypotension?
prazosin (alpha1>alpha2 1000:1) , terazosin, doxazosin
What treats benign prostatic hyperplasia by blocking the alpha-1A receptor, and has a lower incidence of orthostatic hypotension?
tamsulosin
What treats impotence and ED by blocking alpha2 receptors, and causes insulin release?
yohimbine
Nonselective beta blockers that treat glaucoma but cause bronchospasm
timolol, levobunolol, and carteolol
beta-1, beta-2, and alpha-1 blocker for treating HTN that can cause hepatoxicity
labetolol (hepatotoxicity), carvedilol
Beta blocker that treats cirrhotic esophageal varices and has renal excretion
nadolol
Partial agonist and beta-1 and beta-2 receptors for bradycardia or decreased caediacc reserve
pindolol
B1-selective blockers, so have LESS bronchospasm than nonselective beta blockers. However, has impaired recovery from hypoglycemia in diabetics
betaxolol, metoprolol, esmolol, atenolol, nebivolol (B-MEAN by being selective!)
Treats thyroid storms, has very short half life (3-4 minutes)
esmolol
B1-selective blocker that promotes vasodilation via nitric oxide release
nebivolol
