Tutorials_adrenergics

  1. The adrenergic receptor activation lead to wider spectrum of effect on the cell in a manner similar to muscarinic receptor but not nicotinic receptor. Why?
  2. Which of the adrenergic receptor subtypes reduce the cellular level of cAMP upon activation?
  3. Which of the following muscles are not affected by adrenaline and why? (cardiac muscles, skeletal muscles, smooth muscles). Of course it is skeletal muscle, but why?
  4. Draw the structure of adrenaline
  5. Mention names of two switches and two non-switches targets used to control the adrenergic activity of adrenergic neurons
  6. Mention names of one switches and one non-switch targets used to control the adrenergic activity of cholinergic neurons
  7. The compounds which activate adrenergic neurons can be classified into catechols and non-catechols. Which of the two is not bind to switch receptor (i.e. GPCR)?
  8. Mention three important enzymes involved in noradrenaline synthesis? and which one mainly controls the rate of synthesis?
  9. Mention two enzymes responsible for noradrenaline metabolism, one of them responsible for deactivating noradrenaline within the neuron and the other deactivate noradrenaline outside the neuron.
  10. Which of the following enzymes metabolizes noradrenaline into adrenaline within the adrenal medulla

A)Tyrosine hydroxylase

B)Dopa decarboxylase

C)Dopamine beta-hydroxylase

D)N-methyl transferase

  1. Why salbutamol is a catecholamine, however it is selective for beta2-receptors. Why?
  2. Why salbutamol is a catecholamine, however it has longer half-life in the body. Why?
  3. How you can switch the selectivity of adrenaline analogues toward beta2-receptors?
  4. How you can identify the compounds which produce their adrenergic effect without binding to adrenergic switch? Is it through the presence or absence of catechol group?
  5. Does each selective analogue have higher affinity to receptor?
  6. Why pseudoephedrine has lower CNS side effects even though it is lipophilic (LogP= 1.3)?
  7. What is the pharmacological application of switching ON each of α1, α2, β1, and β2 adrenoceptors?
  8. Changes in structure not only affects receptor subtype selectivity, but also affect absorption, oral activity, metabolism, degradation, and thus duration of action. How?
  9. What are the consequences of changing catechol group (phenolic alcohols) on metabolism, penetration of BBB, selectivity to adrenergic receptor subtypes?
  10. Salmefamol is a selective beta2 agonist even though N-alkyl substitution is of similar bulkiness to that of labetalol (the beta2-antagonist)?
  11. It usually common that increasing selectivity is associated with reduced affinity to receptor. Can you explain why?
  12. Discuss the benefits of Cα-alkyl substitutions on metabolism (half-life), penetration of BBB, resistance to MAO, affinity to adrenergic receptors.
  1. How you can differentiate adrenaline analogues which are resistant to COMT metabolism?
  1. How you can switch selectivity of arylimidazolines from non-selective alpha agonists into selective alpha1-agonist by modifying he aromatic substitutions?
  2. To which group of compounds does clonidine belong? (phenylethylamines or arylimidazolines?)
  3. How the ortho-substitutions on aromatic ring of arylimidazolines can affects the selectivity toward alph-adrenoceptors?
  4. Tyrosine hydroxylase can bind tyrosine as substrate. Metyrosine differs from tyrosine by single substitution thus can compete tyrosine on the enzyme. What is the medicinal use of metyrosine?
  5. Dopadecarboxylasee can bind L-dopa as substrate. Carbidoba differs from L-dopa by by single substitution thus can compete L-dopa on the enzyme. What is the medicinal use of carbidopa?
  6. Why levodopa is usually given in combination with carbidopa?