Download Lecture 19

Lecture 19:
Catecholamines:
-They work at two receptors (α,β)
-α receptor are excitatory (constriction effect)
-β receptor inhibitory on smooth muscle
-β1 found in the heart
-β2 found in the lung
this not from the lecture it can help you to understand the receptors :
-α1 : mainly effect is constriction
-α2: mainly has feedback inhibition for neurotransmitter
-β1: Found in the heart (1 heart)
-β2: founf in the lung (2 lungs)
-Most of the addict persons after stop using the drug they are easily can back to it.
-L-Dopa most important Drug f or Parkinson's disease (can cross BBB unlike dopamine)
-usually dopa derivatives must be given with carbidopa to inhibit the decarboxylase from
degrade L-Dopa in the bloodstream.
-dobutamine it reach the heart but not the brain.
-carbidopa inhibit the decarboxylation duo to caboxylase enzyme
-dobutamine effect β2 receptors
-dopexamine: effect β1 so it uses for cardiac arrhythmia.
-phenylephrine it the same as adrenaline.
-methyldopa: most widely uses drug
**Noradrenalin(norepinephrine)
- orally inactive drug (injection is used)
-act at α adrenergic receptors so it will constrict vascular muscle(vessels) so resistance will
increase and as a result blood pressure will increase.
-ephedrine: Phenylethelamine(mimic the effect of adrenaline) .
-unfortunately, many of the weight loss products can contain ephedra and it come from
china called ma huang (effect of ephedra is increase blood pressure so if the patient had
hidden hypertention this will lead to severe problems)
-Radactine (Phenylethelamine)( sudden increase in blood pressure this will lead to death).
-Coffee
Cafaine increase CAPM
increase the production of phynelethylamine
so this will lead to stimulation
-All stimulat of CNS is appetite suppressant.
-Methyldopa it compete with noradrenalin but doesn't compete with dopamine , work at
α receptor so excitation of blood pressure, uses for anaphylactic shock.
-how they modify the drug?! And how to make them more selective for receptors?!
the first drug have been discovered is propranolol (inderal): the structure have two
benzyl ring(naphthaline ether) so become heavier and more lipophilic and it has an
additional ether group, also, bulky group.
Note: the discovery of any new drugs is by changing in the structure by adding or deleting
any groups in the compound such in case of propanolol and atenolol( comparison between
them from the slide)
-atenolol:it have amyl group / they change the naphthaline group.
-bambuterol: didn't successes in the market.
β2 selective drug:
-Salbutamol(albuterol): they add bulky group and methanol .
Treatment of intraocular (glaucoma): betaxolol timelol …. Etc
Sometime propranolol given for treatment of migraine in small doses(why? Because
migraine is dilation of cranial vessels in the brain so we need to constrict it by this
mechanism of action)
-we don't have pure agonist or pure antagonist***
-if we think that we can use these drug for hemorrhoid it can be possible choice.
Inactivation of catecholamine:
-Dopamine is inactivated by Catechol –o- methyltranferase (CoM) or by monoamine
oxidase (Mao).
-patient have hyperpressure and I make activation for the enzyme which degraded the
catecholamine ! (this will decrease blood pressure) but the first side effect is depression.
-tranquillizer have the same mechanism of action.
-the first step of their degradation is methylation .
-ephedrine can be degraded by these enzyme also
-when we use adrenaline and ephedra( we notice that adrenaline more potent because it
have already made additional step in it's metabolism which is methylation)
-when you get angry the relax these two enzymes will start working at adrenaline.
-Depressed person has low adrenaline level so we use MAo inhibitor in order to increase
the level of adrenaline (can make cause increase blood pressure as side effect)
-if I eat cheese and any food containing amines it will increase the precursors of
catecholamine.
-if you take Mao inhibitor and eat cheese that will lead to toxication( contraindication )
-Entacapone: become more bulky
Maybe it can use: Antidepressant/ migraine / or used t o increase hypertention
Search about this drug!