Term
| Go through the process of catecholamine (NE) synthesis, secretion, reuptake, etc.? What are the two points at which it can be degraded and by what? |
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Definition
-Tyrosine-->DOPA (by *tyrosine hydroxylase)
-DOPA-->Dopamine (DOPA decarboxylase)
-Dopamine-->NE (dopamine β hydroxylase)
-NE is then packed into vesicles to await Ca2+ influx from propagated signal after which it ill fuse and exocytose
-It can then bind to **α1 & β1 receptors on the *post synaptic membrane
-NE may also bind **α2 on the *presynaptic membrane, causing *negative feedback
-Can also be reuptaken and put into the *mobile pool (main removal system)
-*COMT metabolizes extracellular NE, and *MAO degrades intracellular free NE (in the mobile pool) |
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Term
| What are the 8 levels at which we can effect NE synthesis, action, and degradation? Give drug names/types? |
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Definition
FOR CNS
1. Methyl-p-tyrosine; blocks tyrosine hydroxylase, the rate limiting enzyme (not used clinically)
2. MAO inhibitors; increases mobile pool
3. Releasers; (for atypical depression)
-*MAO inhibitors and releasers can have a deadly interaction; more mobile NE, and a way to release it
4. Reuptake blockers; (for depression)
FOR CARDIOVASCULAR
5. α2 agonists (less NE) and antagonists (more NE)
6. Reserpine; effects exocytosis
7. Guanethidine; effects exocytosis
PERIPHERAL
**8. Agonists and blockers of α1, and β1 receptors |
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Term
| What can we expect to see from α1 receptors in terms of what tissue they effect and action they have (6)? Side effects? What G-protein do they use? |
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Definition
-They are mostly on smooth muscle and overall cause contraction; Gq-->Ca2+-->contraction
Found in;
-Eye; *mydriasis (radial muscle)
-Arterioles & veins; **vasoconstriction
-Bladder; urinary retention
-Male sex organs; ejaculation (*compliance in blockers)
-Liver; increased glycogenolysis
-Kidney; increased renin (safety valve)
-Note that the arteriole action raises TPR, afterload, and *diastolic pressure, while the vein action raises venous return, preload, and *systolic pressure; net effect is ***raised BP without raised pulse pressure*** |
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Term
| What do we associate increased afterload and increased preload with? |
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Definition
-Afterload, **TPR, and **diastolic pressure are all linked
-Preload, **CO (linked also to venous return), and **systolic pressure are all linked
-More for physio at this point |
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Term
| What can we expect to see from α2 receptors in terms of what tissue they effect and action they have (3)? Side effects? What G-protein do they use? |
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Definition
-They are Gi linked and have an overall inhibitory function
Found in;
-Prejunctional nerve terminal; lower NE release and synth
-Platelets; aggregation (unwanted side effect for those with **hypertension/atherosclerosis)
-Pancreas; lower insulin secretion (bad for **diabetics) |
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Term
| What can we expect to see from β1 receptors in terms of what tissue they effect and action they have (2)? Side effects? What G-protein do they use? |
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Definition
-Both βs and D receptors are Gs linked (increase cAMP)
Found in;
-Heart; it is through the entire conduction system and also exists in the muscle; overall effect is to **increase HR and **force of contraction (*increased O2 consumption is bad news for *angina patients)
-Kidney; increases *renin release
-Remember that CO is a component of BP, so we will be raising HR primarily, but *BP will also rise
-Overall, this is manifested as an **increase in pulse pressure when β1 receptors are stimulated |
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Term
| How is the renin system balanced using adrenergic receptors then? How would increasing amounts of NE effect HR and BP then? |
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Definition
-Overall, the β receptors are more *sensitive to activators and a β response predominates at low doses
-An α response predominates at a higher dose (of NE)
-This means that the α1 receptor acts as a safety valve in the renin system (when there is high NE or Epi levels)
-This will also mean that NE will affect β1 to raise HR and then α1 to raise BP |
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Term
| What can we expect to see from β2 receptors in terms of what tissue they effect and action they have (6)? Side effects? What G-protein do they use? |
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Definition
-They also use Gs and overall relax smooth muscle and increase sugar mobilization and use
-It is the main *fight or flight responder and is **not typically innervated; so responds mostly to **Epi from the adrenal medulla
Found in;
-Blood vessels; **vasodilation
-Uterus; relaxation
-Bronchioles; dilation
-Skeletal muscle; increased glycogenolysis
-Liver; increased glycogenolysis, glycogenisis, & lipolysis
-Pancreas; increased insulin (only slight to stim. uptake)
-Here the *TPR is being lowered, affecting afterload and **diastolic pressure more than systolic
-The net effect is an **lowered BP & increased pulse pressure** |
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Term
| What about for D1 receptors? |
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Definition
-They are also Gs linked and are involved in specific vasodilation actions, increasing perfusion;
-Renal; vasodilatation (increased RBF, GFR, and Na+ secretion)-->important in shock treatment
-Mesentary & coronary vasculature; vasodilation |
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Term
| What is the result of treating shock with increasing amounts of dopamine? |
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Definition
-Like NE, it first acts to stimulate β1 receptors before α1 receptors
In order of effect of increasing dose;
-D1---->increased heart and kidney perfusion
-β1---->increased HR
-α1---->increased BP
-Great crash cart drug for shock! |
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Term
| What is a synthetic D1 agonist and what does it treat? |
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Definition
-**Fenoldopam; used for severe hypertension
-Remember, the first action of dopamine, on D1, is to increase renal and coronary perfusion; both good to treat in hypertension |
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Term
| So, overall, what do the α, β, and D1 receptors do? Which ones effect pulse pressure and why? |
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Definition
-α1; (+)BP (no increase in pulse pressure)
-α2; (-)NE feedback
-β1; (+)HR
-β2; (-)BP & (+)Sugar
-D1; (+) Heart & kidney perfusion
-β1 & β2 are the major ones to increase pulse pressure
-β1; raises CO--> raises systolic
-β2; lowers TPR--> lowers diastolic
-Basically, it is raising the top or lowering the bottom, both of which increase pulse pressure
-α1 raises TPR and venous return (systolic and diastolic); so we get no change in pulse pressure |
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Term
| What are the G proteins for them again? |
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Definition
-α1; Gq
-α2; Gi
-β1, β2, & D1; Gs |
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