4. Pharmacologic Adrenergics Flashcards
What are the steps of NE synthesis?
Phenyalanine –> tyrosine –> uptake by nerve–> DOPA –> Dopamine –> taken up into storage granules by active transport –> NE –> release
In renal medulla NE converted to Epi
Enzyme that converts phyalanine into tyrosine?
Phenylalanine hydroxylase
Enzyme that converts Tyrosine to Dopa? What drug inhibits this enzyme?
Tyrosine hydroxylase
Metyrosine
What is the rate limiting step of NE synth?
Tyrosine to Dopa
Tyrosine hydroxylase
Enzyme that converts Dopa to Dopamine? What drug inhibits this enzyme?
Aromatic acid decarboxylase
Alpha methyl dopa
Enzyme that converts Dopamine to NE? What drug inhibits this enzyme?
Dopamine beta hydroxylase
Reserpine
Enzyme that converts NE to Epi?
Phenylethanolamine N methyl transferase
What is the most important way for NE to be removed from the cleft?
Reuptake into presynaptic side (active transport)
How is NE removed from the cleft?
Reuptake into presynaptic side (active transport)
Diffusion into circulation
Uptake by postsynaptic side (active transport)
Metab by COMT & MAO
What enzymes metabolize NE?
Monoamine oxidase (MAO) Catecholomethyltransferase (COMT)
What does MAO do? Where is it located?
Metab catecholamines by deaminating
Pre-synaptic & postsynaptic
What does COMT do? Where is it located?
Metab catecholamines by causing O-methylation
Postsynaptic
Main mechanism of Ach removal from cleft? Main mechanism of NE removal from cleft?
Breakdown
Reuptake
What are Sympathomimetic drugs? What are the 2 main types?
Mimic symp stimulation
Direct (interact with receptor)
Indirect (affect release or reuptake of endogenous)
Combo
What are the direct Sympathomimetic drugs?
NE
Epi
Isopterenol (Iso)
What are the indirect Sympathomimetic drugs?
Amphetamine
Tyramine
Cocaine
Imipramine
Which drug(s) increase NE release?
Amphetamine
Tyramine
Which drug(s) decrease NE reuptake?
Cocaine
Imipramine
How would you test if a drug had direct or indirect Sympathomimetic effects?
Give reserpine to deplete endogenous NE, then give drug. If it works it is direct
Which Sympathomimetic drugs work via a combo of direct & indirect action?
Dopamine
Ephedrine
What are Sympatholytic drugs?
Inhibit NE synth pathway
No longer used very often
What are the Sympatholytic drugs?
Reserpine, Metyrosine, Alpha methyl dopa & Guanathidine
What drug inhibits NE release into the cleft?
Guanathidine
List the non-selective adrenergic receptor agonists in order of potency for alpha & beta:
Alpha = Epi > NE >> Isopterenol Beta = Iso > Epi > NE
What are the non-selective alpha adrenergic antagonists? What are the 2 types?
Phentolamine (reversible)
Phenoxybenzamine (irreversible)
What is the selective alpha 1 agonist?
Phenylepherine
What is the selective alpha 1 antagonist?
Prazosin
What is the selective alpha 2 agonist?
Clonodine
What is the selective alpha 2 antagonist?
Yohimbe
What is the non-selective beta antagonist?
Propranalol
What is the selective beta 1 agonist?
Metoprolol
What is the selective beta 2 agonist?
Metaproterenol, albuterol, ritodrine
What is the location & function of beta 3 receptors?
Stim lypolysis
Fat cells
What are agonists for the Dopamine receptor?
Dopamine»_space; epi
List in order of potency the receptors for NE
Alpha 1 = alpha 2 = beta 1»_space;beta 2
List in order of potency the receptors for Phenylepherine
Only alpha 1
Effects of NE?
Alphas –> increase TPR & BP
Beta 1 –> increased contract
Reflex –> decreased BP
No change in CO due to beta 1 balancing out reflex
Effects of Phenyelepherine?
same as NE
BP is the dependent on what?
TPR x SV x HR
List in order of potency the receptors for low dose Epi
beta 1 = beta 2 > alpha 1 = alpha 2
List in order of potency the receptors for high dose Epi
see NE
Effects of high dose Epi?
see NE
Effects of low dose Epi?
Beta 1 –> increased HR
Beta 2 –> decrease in TPR & decreased diastolic pressure
Alphas –> decreased renal & skin perfusion
Mean arterial pressure only increases slightly (systolic increases but diastolic decreases)
List in order of potency the receptors for high dose Isoproterenol
beta 1 = beta 2
Effects of Isoproterenol?
Same as low dose epi but mean arterial pressure decreases slightly cuz TPR & diastolic pressure a lower more
Effects of Ephedrine?
Mainly indirect but some alpha & beta
Increase contractility
beta 2 –> bronchodilation
low/moderate doses –> increase in HR
high dose –> increased BP with bradycardia
What sympathomemtic drug has a long duration?
ephedrine
Effects of albuterol?
relaxes smooth muscle of airway
Effects of Ritodrine?
relaxes smooth muscle fo uterus –> prevent premature birth
Effects of Dopamine?
Increased blood flow
Moderate dose –> increased HR & contractility
High dose –> increased TPR
Effects of Dobutamine?
Increased contractility, HR & BP
High dose –> increase TPR
Effects of Phentolamine & Phenoxybenzamine?
Decreased TPR
Decreased BP in standing (no change in lying)
Reflex raise in HR & blood volume
Side effects of Phentolamine & Phenoxybenzamine?
Postural hypotension
Tachycardia
Effects of Prazosin?
Same as non-selective but less reflex
Effects of propranalol?
beta 1 –> decreased HR, AV conduction, contractility & CO = decreased BP
Beta 1 –> decrease renin –> decrease ang II
beta 2 –> Acute increase in TPR & increase in airway resistance
Side effects of propranalol?
cardiac depression, lassititude (fatigue) & depression
Effects of metoprolol?
Same as propranalol, but no effect on airway
Where are dopamine receptors located?
CNS & renal
What is the partial beta agonist?
Pindolol
Pindolol is a what? Uses?
Partial beta agonist
HTN
What is the combined alpha beta blocker?
Labetalol
Labetalol is what? Uses?
Alpha & beta blocker
HTN emergency
