Sympathomimetics Flashcards
Drugs with sympathomimetic activity will be
interacting with GPCrs metaboprotpic
All adrenergic receptors are
GPCRs (alpha and beta) (metaboptropic)
Two main types of
alpha
three main types of
beta
Alpha 1 is associated with
Gq which activates phospholipase C and cleaves DAG and IP3 which both function as secondary messengers.
All beta receptors are associated with
Gs G proteins
Gs proteins are associated with
Adenyl cyclase the increased cAMP, then further activation into the cell.
Alpha 2 is associated with
Gi- which are associated with Adenyl Cylase, but they actually block Adenyl cyclase.
So, a lot of alpha 2 receptors will be expressed presynaptically and activation of these recptors will be inhibitory and block a lot of things.
Alpha 2 is less common in
periphery , but can be found in the CNS.
Phenylephrine and methoxamine
(alpha agonist ) a1>a2»»»»»B (almost none to beta)
Norepinephrine
(mixed) a1=a2; B1»B2
Epinephrine
(mixed)a1=a2; B1=B2 this activates all alphas and all betas and is why can be a lifesaving drug. Released from adrenal medulla so it gets distributed in the entire system and effects all its receptors.
Dobutamide
B1>B2»»>a this is a beta agonist
Isoproterenol
B1=B2»»>a (beta agonist )
Albuterol, terbutaline, metaproterenol
B2»»B1»»>a (beta agonist) mostly beta 2
Dopamine
D1=D2»B»a (dopamine agonist )
Fenoldopam
D1»D2 (dopamine agonist)
If treating a condition that is specific to beta , you want to be more
selective
Catchcholamines with two hydroxyl groups on the molecule
norepinephrine
epinephrine
isoproterenol
dopamine
“DINE”
won’t have CNS effects because they are polar
Noncatecholamines sympathomimetics
phenylephrine
ephedrine
amphetamine
metamphetamine
these do have CNS effects
“MEAP”
What effects do noncatecholamines sympathomimetics have on the periphery?
increase BP
increase heart contractions
increase risk of MI
does this because it affects receptors on the periphery.
Alpha 1 effects which organs
Most vascular smooth muscle (innervated)
Pupillary dilator muscle (contraction dilated pupils)
Pilomotor smooth muscle (hair)
Prostate (contraction)
Heart (increase force of contraction)
Beta 1 effects
heart, juxtaglomerular cells (increases force and rate of contraction; increases renin release)
Beta 2 effects
Respiratory, uterine, and vascular smooth muscle (promotes smooth muscle relaxation)
Skeletal muscle (promotes potassium uptake)
Human liver (activates glycogenolysis)
Beta 3 effects
bladder ( relaxes detrusor muscle)
fat cells (activates lipolysis)
D1 effects
smooth muscle (dilates renal blood vessels)
D2 effects
nerve endings (modulates transmitter release)
These receptors are extremely highly expressed in the heart
Beta 1
So, if epi /ephidrine is used, it will activate all receptors and cause contraction
this is desired with anaphylaxis
Nasal spray contains
alpha 1 agonist which causes vasoconstriction
same principle is used to stop eye watering
Alpha one agonist can
raise BP
Nasal sprays are contraindicated in patients with
high blood pressure because they contain alpha 1 agonist which can raise blood pressure even more
Alpha 1 decongestants are prohibited with prostate hyperplasia, why?
Because they cause contraction of the prostate gland which can squeeze the urethra and cause problems.
Activation of Beta 1 ?
causes increase force and rate of contraction.
If force and rate increases then it requires more oxygen which could lead to MI in patients with atherosclerosis
Isoproterenol activates ?
B1=B2 and is used to induce MI in model organisms because it increases the force of contraction requiring the heart to need more oxygen which leads to MI, so B1 agonist is not used very often.
Beta 2 receptors are very common in
respiratory tract, uterus, and vascular and smooth muscles
Drugs that activate B2 promote smooth muscle relaxation which is desired in the respiratory tract.
B2 agonist are used to treat
Asthma because they instantly open up the airway by activating B2 receptors. Also sometimes used to stop premature labor.
When treating asthma, you want to be sure that the drug is very
selective for B2 because you do not want to activate B1, otherwise you would increase BP and increase cardiac demand.
It is almost not possible to be this selective, so B2 agonist are contraindicated in patients with HTN or remarkable cardiac history such as (MI)
So, how do we treat these patients with asthma?
We go on the fact that apart from adrenergic receptors, we also have muscarinic receptors in our airways, so instead of a B2 agonist, we could use cholinolytics because these will cause bronchodilation whereas cholinomimetics will induce bronchoconstriction.
