Adrenergic Pharmacology Flashcards
Guanethidine
is a false transmitter for NA- and reduces its release
NA has a higher selectivity for
alpha, less for beta 1 and even less for beta 2, NA has a higher potency hat beta 2 than adrenaline
Adrenaline has a higher selectivity for
beta, and has a higher potency at alpha and beta1 than NA
Isoprenaline has no potency at
Alpha
Vesicular Transporter
Substrates: Tyramine, Amphetamine, MDMA
Blockers are reserpine and tetrabenazine
NA is stored in small (200nM) and large (400nM) vesicles
Neuronal transporter
Substrates: competitive, transported: Amphetamine and Tyramine, MDMA stays in the syntaptic cleft
Inhibitors (are not transported): Cocaine, Methylphenidate(ritalin) and some antidepressants
MAO
(MAO) monoamine oxidase – oxidative deamination; inhibited by Phenylenzine- irreversible - increases NA, A, dopamine, 5HT conc in synapse by preventing breakdown
Phenylenzine is used as a antidepressant and anxiolitic
- phenelzine is effective in treating dysthymia,[3] bipolar depression (BD),[4] panic disorder (PD),[5] social anxiety disorder (SAD),[6] bulimia,[7] and post-traumatic stress disorder (PTSD).
COMT
Catechol-O-Transferase- tansfers OH group- inhibited by Tolcapone
Tolcapone is selective and reversible.
It is used in the treatment of Parkinson’s, as it reduces the breakdown of L-Dopa by COMT in the periphery and of dopamine in the brain
Potency
is a measure of drug activity expressed in terms of the amount of drug required to produce an effect of given intensity- E efficacy
Selectivity
refers to the differing affinities with which ligands bind to their binding sites - Ka
Selective Alpha1 Agonist
Phenylephrine- used for nasal decongestion (or pupil dilation or increase in bp, through baroceptor reflex can also cause bradycardia)
Selective Alpha2 agonist
Clonidine- used to treat high blood pressure, attention deficit hyperactivity disorder, anxiety disorders, withdrawal (from either alcohol, opioids, or smoking), migraine, menopausal flushing, diarrhea, and certain pain conditions. It is classified as a centrally acting α2 adrenergic agonist and imidazoline receptor agonist that has been in clinical use for over 40 years.
Alpha methyl noradrenaline is also alpha 2 selective
Salbutamol
Beta 2 agonist - short acting, asthma, and chronic obstructive lung disease
Phenoxybenzamine
Non-selective, irreversible, Alpha antagonist -used in the treatment of hypertension, and specifically that caused by pheochromocytoma. It has a slower onset and a longer lasting effect compared with other alpha blockers.
Selective Alpha 1 antagonist
Prazosin- to treat high blood pressure and anxiety, PTSD, and panic disorder.
alpha 1 receptors are found,
Propranolol
Non-selective Beta antagonist- to treat high blood pressure, a number of heart dysrhythmias, those with thyrotoxicosis, and essential tremors.[1] It is used to prevent migraine headaches, and further heart problems in those with angina or previous myocardial infarction; class 2 antiarrythmic drug
Atenolol
Beta 1 antagonist- is developed as a replacement for propranolol in the treatment of hypertension. It works by slowing down the heart and reducing its workload. Unlike propranolol, atenolol does not pass through the blood–brain barrier thus avoiding various central nervous system side effects.
Beta 1 receptors are only in the heart and mediate increase in heart rate and force
used in: Antihypertensive, Cardiac dysrhythmia, Angina, Glaucoma
Baroceptor reflex- NA
Noradrenaline activates alpha1 receptors in vasculature, causes vasoconstriction and rise in bp
- vasoconstriction i sensed by baroceptors- baroreflex- vagus nerve - stimulation of musc receptors, decrease in heart rate
NA also directly increases heart rate and force via beta2 rs, but the overall effect is a decrease in heart rate
Adrenaline acts like NA at high conc, bc it preferentially activates alpha receptors then due to a higher potency there
Baroceptor Reflex- Isoprenaline
Isoprenaline causes an increase in heart rate and force (CO) due to activation of beta1 receptors in the heart. It also causes a reflex tachycardia via the stimulation of beta2 receptors in the blood vessels which causes vasodilation.
Therefore baroceptor and heart effects are synergistic
Adrenaline acts like isoprenaline at low doses, bc it binds preferentially at beta due to higher selectivity.
Anaphylactic shock, Hypotensive crisis
Adrenaline is used which activates beta2 - dilation of bronchi and alpha1 activation which causes vasoconstriction and Beta 1 activation- increase in heart force and rate - baroceptor reflex?
