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
