Adrenergic transmission Flashcards
Adrenergic receptors
-classification
-G protein coupled receptor, catecholamines bind to it
Adrenergic receptors
-types
- Alpha 1
- Alpha 2
- Beta 1
- Beta 2
- Beta 3
- Dopamine
LOOK AT TABLE IN THE SUMMARY
Presynaptic regulation
- alpha 2 receptors
- beta 2 receptors
- Alpha 2 receptors: decrease further release of adrenaline
- Beta 2 receptors: facilitate the release of adrenaline
Main effects of adreno-receptors
LOOK AT TABLE IN THE SUMMARY
Noradrenergic junction (9)
- Tyrosine is transported into the noradrenergic ending by sodium-dependent carrier
- Tyrosine is converted into Dopamine by tyrosine hydroxylase
- Dopamine is transported into the vesicle by VMAT (inhibited by reserpine)
- Dopamine is converted to norepinephrine by dopamine-b- hydroxylase
- Release of transmitter
- Voltage-sensitive Ca2+ channels open
- Increase intracellular calcium
- Vesicle fuses with the membrane (inhibited by bretylium)
- Norepinephrine diffuses out or it is transported into the cytoplasma of the terminal by NET or uptake 2
Which adrenoreceptors does norepinephrine and epinephrine activate?
Norepinephrine –> alpha 1, alpha 2 and beta 1
Epinephrine –> ALL
Noradrenaline transport system (3)
- Vesicular monoamine transporter (VMAT) –> synaptic vesicle membrane, NA=A=ISO
- Uptake 1 (NET) –> neuronal membrane, NA>A>ISO
- Uptake 2 –> non-neuronal cell membrane, A>NA>ISO
Adrenergic drugs - agonists
-classification
Direct acting
- Alpha: nonselective (norepinephrine), alpha 1 selective (pheylephrine), alpha 2 selective (clonidine)
- Beta: nonselective (isoproterenol), beta 1 selective (dobutamine), beta 2 selective (albuterol)
Indirect acting
- Releasers (amphetamine)
- Reuptake inhibitors (cocaine)
Effects of adrenaline (6)
- it is not selective, it has a balanced effect to all adreno receptors
- increases heart rate
- slightly decrease peripheral resistance
- Beta 1 –> causes tachycardia
- Beta 2 –> causes vasodilation
- Systolic pressure would be elevated due to alpha 1 and alpha 2 (leads to vasoconstriction)
Effects of noradrenaline (6)
- high potency to alpha receptors
- increase blood pressure
- increase peripheral resistance
- decreases permeability of blood vessels
- Decreased heart rate –> baroreceptors are activated
- Increases systolic and diastolic blood pressure
Effects of isoproterenol (5)
- tends equally on beta 1 and beta 2
- By action on Beta 2 –> causes vasodilation on muscles
- By action on Beta 1 –> tachycardia
- No effect on systolic
- Slight decrease in diastolic –> because main effect of this drug on blood vessels is on muscle via beta 2
Dopamine (5)
- used in acute heart failure, hypotensive shock
- activates alpha, beta and dopamine receptors in an independent manner
- low doses –> dopamine receptors
- higher doses –> b1 receptors
- even higher doses –> alpha 1 receptors
- Clinical uses of adrenaline (5)
- Unwanted effects
- Contraindications
- cardiac arrest
- anaphylatic shock
- to reduce local bleeding
- to prolong local anaesthetics action
- angina pectoris, cerebral hemorrhages, arrhythmia
- non selective b-adrenoreceptors antagonist users
Alpha 1 adrenoreceptors agonists
- Names
- Clinical use
- Unwanted effects
- Contraindications
- Pseudoephedrine, xylometazoline
- hypotension, nasal decongestion, to cause mydriasis, shock
- hypertension, arrhythmia, headache
- close-angle glaucome, severe hypertension
Alpha 2 adrenoreceptors agonists
- Names
- Clinical use
- Unwanted effects
- Contraindications
- Clonidine, Methyldopa
- in the CNS it inhibit sympathetic nervous system output and lower BP (clonidine), glaucoma, withdrawl in addicts, hypertension (in pregnancy methyldopa)
- sedation, bradycardia, sexual dysfunction
- depression, bradycardia, ischemic heart disease
Beta 1 adrenoreceptors agonists
- Names
- Clinical use
- Unwanted effects
- Contraindications
- Dobutamine
- cardiogenic shock, acute heart failure, after heart surgery
- tachycardia, arrhythmia, increase of myocardial damage
- hypertension, narrowing of aortic heart valve, atrial fibrillation
Beta 2 adrenoreceptors agonists
- Names
- Clinical use
- Unwanted effects
- Contraindications
- Salbutamol
- asthma, chronic obstructive pulmonary disease, premature labor
- tachycardia, arrhythmia, tremor, hypotension
- recent myocardial infarction, coronary heart disease, hypertension
Ephedrine and Pseudoephedrine (4)
- mixed action agonists
- cause activation of adrenergic receptors by direct binding and release of stored NE from pre synaptic terminals
- Ephedrine: vasoconstriction, bronchodilation
- Pseudoephedrine: vasoconstriction, bronchodilation, decrease mucus production
Amphetamine (4)
- treatment of attention-deficit/hyperactivity disorders (ADHD)
- stimulate CNS
- it binds to transporter proteins for amines, enters the neurons and disrupts the storage of monoamines in synaptic vesicles.
- it is able to cause the monoamine transporter proteins to run in reverse, increases the release of monoamines (dopamine and NE) in the synaptic cleft
Adrenoreceptors antagonists t
-classification
- alpha and beta blockers
- can be either selective or non-selective
Alpha
Alpha 1 selective - prazosin
Alpha 2 selective - yohimbine
nonselective - irreversible (phenoxybenzamine) or reversible (phentolamine)
Beta Nonselective (propanolol) Beta 1 selective (atenolol) Beta 2 selective (butoxamine)
Alpha adrenoreceptors antagonists: non selective, a1, a2
- Names
- Clinical use
- Unwanted effects
- Contraindications
- Prazosin (a1 selective), Doxazosin (a1 selective), Tamsulosin (a1 selective), Yohimbine (a2 selective)
- severe hypertension, benign prostatic hypertrophy
- hypotension, tachycardia, nasal congestion, impotence, failure to ejaculate
- intra-operative floppy iris syndrome, painful erection
B- adrenoreceptors antagonists
- Names
- Clinical use
- Unwanted effects
- Timolol, propranolol, metoprolol, labetalol, nebivolol
- glaucoma, anxiety, migrane, angina, heart failure, hypertension
- bronchoconstriction, bradycardia, fatigue, hypoglycemia, cardiac depression
Drugs used in open angle glaucoma (2)
Pilocarpine –> ciliary muscle contraction, opening of trabecular meshwork, increased outflow
Beta blockers - timolol –> decreased aqueous secretion from the ciliary epithelium
Beta blockers (4)
- Propranolol: non selective –> beta 1 and beta 2 antagonism
- Metoprolol: beta 1 selective blockers
- Labetolol: mixed antagonist for beta and alpha 1, non selective for beta 1 and beta 2 antagonism, ISA
- Nebivolol: beta 1 selective blocker
Intrinsic sympathomimetic activity (ISA) (5)
- Both agonism and antagonism at a given b receptor
- Labetalol –> exhibit ISA
- not used after myocardial infarction, may also be less effective in the management of angina and tacharrhythmia
- it depends on the concentration of beta blocker and concentration of the antagonized agent
- Very low amount of noradrenaline –> when the drug binds –> it has agonist activity
- If the amount of norepinephrine increases –> the drug function will change –> it will have antagonist activity
How does the sympathetic system affects…?
- Brain
- Eyes
- Respiratory system
- Heart
- GI
- Bladder
- Immune system
- do not remember anything –> degeneration of cholinergic centers
- pupils dilate in order to see things better
- bronchodilation, stop secretion of respiratory system –> we need more O2
- BP increases
- shut down, sphincter is constricted but the rest is relaxed
- relaxed but sphincters are constricted
- shut down, because it is an energy demanding system
Clonidine
-what is it used for? (6)
- treat high blood pressure
- attention deficit
- hyperactivity disorder,
- drug withdrawal,
- menopausal flushing,
- diarrhea
Adrenergic vs. cholinergic neurons
Cholinergic –> acetlycholine is metabolized by acetylcholinesterase
Adrenergic –> noradrenaline is uptaken, there are NO enzymes to degrade it
What happens in the eye by action of ….?
- alpha 1
- alpha 2
- beta 2
- stimulatory effect –> contraction of iris radial muscle –> dilation of pupils
- decrease aqueous humor formation and increase uveoscleral outflow
- increase aqueous humor formation and decrease uveoscleral outflow
