Drugs that Affect Sympathetic Activity Flashcards
Explain 2 types of cholinergic receptors- similarities and differences
Nicotinic receptors- binding of Ach causes opening of Na channels
Muscarinic receptors- binding of Ach causes secondary messenger system
- Both integral membrane proteins activated through the binding of Acetylcholine
However both have different mechanisms of action
In the autonomic NS what tissues are innervated
Innervation of many internal organs- heart, lungs, eyes, pancreas, bladder, intestine, adrenal medulla, sweat glands
Typically both innervate same organs with antagonistic effects
However, smooth muscle of blood vessels and heart only innervated by sympathic system
Explain types of neurotransmitters and receptors in sympathic NS
Mainly noradrenaline released from post ganglionic neurons and acetylcholine from preganglionic neurons
1) pre-ganglionic neuron- nicotinic receptor - post ganglionic neuron- noradrenaline- blood vessels and others
2) pre-ganglionic- nicotinic synapse- post ganglionic neuron- muscarinic receptor - sweat glands
3) 1 neuron going to the adrenal medullar with nicotinic receptor
What neurotransmitters are found in the parasympathic NS
1) preganglionic neuron- nicotinic receptor (Acetlycholine)- post synaptic neuron- muscarinic receptor
Where is the neurotransmitter released and what affect does this have?
- At Post- ganglionic nerve
- into varicosity
- Innervates organ
- Releases transmitter
- Activates receptor
What are adrenoceptors
Receptors activated by adrenaline or noradrenaline
Difference between a and B adrenoceptors- explain location, effect and endogenous ligand for A1,2 and B1 and 2 receptors
a1- in smooth muscle of arteries and veins, anus, spincter and bladder
Causes contraction- controlling movement of fluids- due to the release of noradrenaline
a2- sympathic nerve endings/ varicosities and in CNS- inhibiting noradrenaline release from psstganglionic sympathetic nerves/ central nerves
B1- heart- increased heart rate, conduction velocity and contractility due to noradrenaline from postganglionic sympathetic nerves
B2- smooth muscle in arteries/ veins and bronchial smooth muscle- relaxation- caused by adrenaline from adrenal medulla
Are there drugs that can block/ activate adrenoceptors- give one example of a B2 agonist and its use
Different drigs selectively activating and blocking just the a adrenoceptors or just a1/a2 or some drugs have no selectivity (hence side effects)
salbutamol- this is a selective B2 agonist used in asthma to relax smooth muscle
What is sympathomimetics
That which is able to mimic the actions endogenous agonists in the sympathetic NS
- Hence activating receptors
Acting through several mechanisms
- Directly activating post synaptic receptors
- Blocking breakdown and reuptake of certain neurotransmitters
Stimulating the release of neurotransmitters
Difference between directly and indirectly acting sympathomimetics?
Directly acting sympathomimetics- directly bind to and activate the post synaptic receptors
Indirectly acting sympathomimetics- Blocking breakdown and reuptake of certain neurotransmitters or
stimulating the release of neurotransmitters
Clinical uses of directly acting sympathomimetics e.g. adrenaline
- Cardiac arrest-can start, or increase heart rate and cardiac output through stimulation of B1
- Adrenaline can be administered intravenously or intra-cardiac
- Treat symptoms of sepsis and septic shock- immune system causes overreaction to an infection- can lead to dangerously low blood pressure
- Anaphlactic shock- hypersensitive immune response- symptoms due to degranulation of mase cells causing release of histamine causing bronchospasm (constriction of airways due to histamine release) and causing respiratory distress
Treated with EpiPen (containing adrenaline)
Non-specific so causes - Bronchodilation through interaction with B2 receptors
- Increases blood pressure through interaction with cardiac B1 receptors
- Peripheral vasodilation through binding with a2 receptors in arms/ legs (leading to hypotension, fainting and unconsciousness)
- Bronchial asthma- inflammation of airways so airflow to lungs reduced
Hence inhalation of B2 adrenoceptor agonist salbutamol used to mimic sympatric dilation
Explain process of salbutamol in asthma
- Salbutamol binds to B2 adrenoceptor
- Couples with a G protein
- Sets of a cascade of secondary messenger events
Also produces cAMP
- Prevents the myosin light chain kinase being formed
- Hence cant bind to Ca-calmodulin conplex and promote contraction of smooth muscle
Clinical uses of indirectly acting sympathomimetics
Tricyclic antidepressant (TCA) used to treat depression and affective (mood) disorders
- Enhances action of function of NA and 5-HT (serotonin) in the brain
- Block reuptake of NA by varicosity
- Heightened sympathetic excitation
- tachycardia (B1), vasoconstriction (a1)–> hypertension
Action of TCA
- NA normally binds to a or b receptors
- TCA will block the reuptake mechanism of NA hence more is present in the synapse
What does an antagonist do
An antagonist bocks agonist receptors
What drugs act as antagonists for a and b receptors after noradrenaline release
- Propranolol- B receptors
- Prazosin- a receptors
- Hence preventing vasoconstriction, hyper tension, tachycardia
Explain use of adrenoceptor B1 antagonists
- Ischaemic heart disease
- atherosclerosis of coronary blood vessels- angina and could lead to heart attack
- Propranolol- stops heart working too heart by blocking sympathetic tone (impulses to heart) which would normally be activated when doing work
Reduce/ limit symptoms of pain/ angina - Blocks both B1 (heart) and B2 receptors (lungs) causing bronchospasm hence salbutamol also needs to be taken
- OR use atenolol (selective antagonist for B1 only)
Explain action of cocaine and amphetamine
- cocaine
- Blocks reuptake of NA in periphery causing tachycardia, vasoconstriction and hypertension due to heightened sympathic excitation
- Blocks reuptake of dopamine in the brain
Amphetamine- taken up in neuronal uptake and causes exocytosis of NA into varicosities at the periphery
- causes release of dopamine in brain
Explain use of a1- adrenoceptor antagonist for hypertension and problems
- Hypertension- increased peripheral vascular resistance due to increase in sympathetic activation of a receptors on blood vessels
- Doxazosin and prazosin- These agonists decrease peripheral vascular resistance- promoting vasodilation and decreasing blood pressure
However cause postural hypotension- decrease in reflex vasoconstriction occurring upon standing up causing faint and dizziness (as blood rushes from brain to legs)
Explain use of a1- adrenoceptor antagonist for benign prostatic hypertrophy and problems
Enlargement (hypertrophy) of the prostate= occurs in men, typically over 40, where the prostate extends typically into bladder obstructing flow of urine
Disorder of bladder function
- Frequent need to urinate (esp night nocturia)
- Weak urine stream - difficult to start urination
Dribbling at end urination as unable to completely empty bladder
- Inhibit a adrenoceptors improves bladder opening as stops contraction caused by a1 agonists
- Tamsulosin- selectivity to bladder yet causes postural hypotension
