Autonomic Pharmacology Flashcards
How does the nervous system exert its effects. By;
- the rapid transmission of electrical impulses over nerve fibers that terminate at effector cells,
- which specifically respond to the release of neuromediator substances.
The nervous system is divided into two name em
Central nervous system and peripheral nervous system
The peripheral system is divided into two name em and explain em
Efferent division and afferent division
(Motor)Efferent- sends impulses away from the CNS to other parts of the body
(Sensory )Afferent- sends impulses to the CNS
Division of the efferent with examples of each
Autonomic and somatic nervous system
Example of autonomic motor nerves- nerves attached to these smooth and cardiac muscle , glands
Example of somatic motor nerves- nerves attached to the skeletal muscles
Division of the Autonomic nervous system
Enteric , parasympathetic and sympathetic
Which areas in the brain are extremely important in the control of the Autonomic nervous system or ANS
Medulla oblongata- Involved in the integration of cardiovascular reflexes and blood pressure control
•Hypothalamus - is the principal integrative Centre for the entire ANS
Receptors detect changes in the body or the body’s environments then send the changes thru afferent arc to the sensory nervous system to the Central nervous system then the brain issues instructions through the efferent arc to the motor nervous system and to the effector organs . True or false
True
Explain the sympathetic nervous system
mobilizes the body during extreme situations
•the “fight-or-flight” system
•Involves E activities – exercise, excitement, emergency, and embarrassment
•Heart rate increases, and breathing is rapid and deep
•The skin is cold and sweaty, and the pupils dilate
When the pupils dilate in the sympathetic nervous system, what occurs
It causes the eye to see far and not near objects
Which part of the nervous system performs maintenance activities and conserves the body’s energy
Parasympathetic
Which part of the nervous system involves the D activities, exampleA defecation, digestion, diuresis
Parasympathetic
In which nervous system type are Blood pressure, heart rate, and respiratory rates low
,Gastrointestinal tract activity is high
And The skin is warm and the pupils are constricted
Parasympathetic
Both the para and sympa are two opposing systems which counterbalance each other’s activity. True or false
True
Name one example of how para and sympa oppose each other
When you’re angry, sympa is working so you don’t even feel hungry but when you’re not angry anymore you start to feel very hungry if you’ve not eaten this occurs due to the para
Which nervous system uses both para and sympa and functions independently of the CNS
Enteric nervous system
List four functions of the enteric system
collection of nerve fibers that innervate the
•gastrointestinal (GI) tract,
•pancreas,
•gallbladder, and
•it constitutes the “brain of the gut.”
•It controls motility, exocrine and endocrine secretions, and microcirculation of the GI tract.
Neurotransmitters are secreted and act on the effector organs or on another close neuron . True or false
True
Neurons with Myelin sheaths have their impulses transmitted faster than neurons without myelin sheaths. True or false
True
Somatic nervous system secreted which neurotransmitter to act on skeletal muscles
Acetylcholine
Somatic nervous system neurons have no ganglion or post ganglionic neuron. True or false
True
What is a ganglion
A place where neurons synapse or meet
The preganglionic neurons is closer to the spinal cord and closer to the ganglion true or false
True
In the sympathetic nervous system, the preganglion is shorter than the post ganglion true or false
True
For the para, the pre is very long and the post ganglion is short. True or false
True
Instead of a ganglion, there is adrenal medulla. Acetylcholine is produced by the first neuron and it sends impulses to the adrenal medulla to produce epinephrine and norepinephrine. True or false
True
What are the two ways sympathetic nervous system sends impulses to its effector organs
- Preganglionic neurons releases or secretes acetylcholine and this sends signal to the post ganglion to produce norepinephrine to work on effector organs(smooth muscles example what happens in a blood vessel)
- Neuron releases acetylcholine which makes the adrenal medulla to produce epinephrine and norepinephrine to be sent through blood vessels to the glands
In the parasympathetic- both post and pre secrete acetylcholine while in the sympa, pre secreted Acetylcholine ad post secretes epinephrine and norepinephrine. True or false
True
In the somatic nervous system- there are no ganglion whether pre or post true or false
True
Name four differences between para and sympa
Sympathetic
Origin of fibers is in the Thoracolumbar region of the spinal cord
Short preganglionic and long postganglionic
Ganglia are Close to the spinal cord
Neurotransmitter is acetylcholine and epinephrine and norepinephrine
Parasympathetic
Origin of fibers is in the Brain and sacral spinal cord
Long preganglionic and short postganglionic
Ganglia are In the visceral effector organs
Neurotransmitter is Acetylcholine
In sympa Preganglionic neurons synapse with many postganglionic neurons but in para
Preganglionic neurons synapse with few post- ganglionic neurons
Why
Cuz sympa, the pre neurons is shorter than the post neurons so there are more post. This is also why when receptors pick up changes in the sympa, more than one action can occur at the same time. You heart will beat faster at the same time you’ll be running very fast at the same time your eyes will be dilated.
The post is more so
More of the neurotransmitter is released to work on effector organs
But in para, actions occur one at a time because the post is lesser than the pre.
Heart has sympa and para innervation true or false
True
Alpha and beta recptors on the heart are for the sympa
And muscarinic receptor on the heart for the para
True or false
True
Beta one receptor increases the rate and force on contraction of the heart when what happens
When the beta 1 receptor is Activated by norepinephrine .
This increases cardiac output
Blood vessels have which receptors on them
Alpha 1 and beta 2 receptors from the sympathetic
When alpha is stimulated- there is vasoconstriction
When beta is inhibited- there is vasodilation
Radial muscle of the iris has a sympa innervation which causes what to the pupil
Dilation of the pupil
Sphincter muscle is innervated by the para muscarinic receptors which cause what to the pupil
Constriction
Vasoconstriction increases total peripheral resistance true or false
True
What two things cause an increase in bp
Cardiac output and total peripheral resistance
In sympa, saliva is thick and scanty while in para, saliva is watery and profuse true or false
True
Which system causes the relaxation and constriction of the bronchioles
Relaxation- sympathetic causes by beta 2 receptors
Constriction- para
In para, you get an erection due to the excitation of the muscarinic receptors
In sympa you get an ejaculation due to the alpha receptors excitation. True or false
True
Name some ways organs are innervated
Organs which receive both innervation from the para and sympa, the effects of the 2 divisions are usually opposed or antagonistic
Example the heart, bronchioles, GI tract and bladder
Even tho some organs have innervation from both organs, some organs are dominated by the sympa while others are dominated by the para.
Example- GI is innervated by both para and sympa but para dominates
Urinary bladder and salivary gland( para dominated)
Veins and sweat glands( sympa dominates)
Some organs receive two innervation from the sympa and para but the effects are complimentary
Example- salivary glands
Sympa makes saliva thick and not much but para makes saliva watery and more
So when you’re hungry the para works but when you’re anxious your saliva becomes thick even tho both make you produce saliva
Some organs have only one innervation- so they are regulated by increasing or decreasing activity of the nerves that innervated them. Example- 1.sweat glands ( it is under the sympa but is not norepinephrine that causes the sweat glands . It is the acetylcholine that is released . 2. Blood vessels
In some organs the control of function is regulated by opposing branches of the ANS but each branch exerts its activity on different cells.
•pupil
When one is under the para- the circular muscle constricts thereby pulling the radial muscle causing the pupil to be constricted true or false
But sympa- radial contracts and pulls circular muscle making pupil dilate for organ true or falseinnervation where there are opposing effects but each branch affects its own activity
True true
Name three interactions of the autonomic system
Interactions of the Autonomic Divisions
•Most visceral organs are innervated by both sympathetic and parasympathetic fibers
- This results in dynamic antagonisms that precisely control visceral activity
- Sympathetic fibers increase heart and respiratory rates, and inhibit digestion and elimination
- Parasympathetic fibers decrease heart and respiratory rates, and allow for digestion and the discarding of wastes
Which division of the nervous controls controls blood pressure and keeps the blood vessels in a continual state of partial constriction
Sympa
Which drugs are used to treat hypertension
•Alpha-blocker drugs interfere with vasomotor fibers and are used to treat hypertension
Importance of sympa tone or vasomotor tone
Constricts blood vessels and causes blood pressure to rise as needed
•Prompts vessels to dilate if blood pressure is to be decreased
Drugs that block para responses do what
ncrease heart rate and cause fecal and urinary retention
Sympa division overrides para during stress and fight or flight and para overrides sympa during relaxation true or false
True
Which division of the nervous system controls the activity of the adrenal medulla, sweat glands, arrector pili muscles, kidneys, and most blood vessels and
•Thermoregulatory responses to heat
•Release of renin from the kidneys
•Metabolic effects
Sympa
Mixture of semen and sperm triggers sympa tone to trigger man to ejaculate. True or false
True
Name the four events that are involved in neurochemical transmission
axonal conduction
- synthesis and release of neurotransmitter
- receptor events
- catabolism of the neurotransmitter
Explain axonal conduction and depolarization
When a neuron is there it is at a resting stage and is stable. As soon as there is an impulse and it exceeds the threshold there is an opening of a sodium channel or gate and it enters into the neuron and becomes positively charged and depolarization occurs. Depolarization means action potential is enough to activate a neuron.
There is axonal conduction due to action potentials
When neurochemicals are produced and they are in the vesicles and are at the terminal end of the neuron and is waiting to be released, what happens
It needs action potential before anything can occur. Depolarization causes the extra cellular part of the nerve to be negative and the intracellular part to be positive due to the movement of Na+ into the neuron this causes the influx of calcium. Calcium ion Ca2+destabilizes the vesicles . Vesicles moves and fuses with the nerve terminal membrane leading to exocytosis and the neurotransmitter is released and move to the effector tissue by diffusion.
Neurons communicate to each other through neurotransmitter and communicate within themselves through action potentials, depolarization . True or false
True
present at rest and is the result of permeability changes that occur at the axonal surface as an impulse is propagated along a nerve fiber
- A suprathreshold stimulus will increase the permeability of the fiber to Na in relation to K inwardly. True or false
- This positively charged Na increases the membrane potential from -85mV toward zero true or false
•Repolarization does not occurs rapidly as the axon becomes relatively impermeable to Na and relatively more permeable to K true or false
•This reestablishes the negativity of the interior of the cell
True or false
True true
False( it does )
True
Explain neurotransmitter release
This is triggered by the arrival of the axonal action potential at the nerve terminal
Action potential initiates an inward movement of Ca+ into the nerve terminal
This triggers exocytotic discharge of neurotransmitter from vesicles
Potassium coming out is called repolarization true or false
True
What happens when the neurotransmitter binds to the receptors
excitatory transmitter substances, there is an increase in permeability to a number of ions with depolarization of the post junctional neuron
- If inhibitory, the combination of transmitter and receptor may result in selective increases in the permeability to either K or Cl
- This produces an increase in resting potential (hyperpolarization), stabilization of the membrane and reduction in the excitability of the neuron
Explain catabolism of the neurotransmitter
Termination of action of transmitter by diffusion from synaptic region. Eg. NA
•Destruction of transmitter by enzymatic mechanism Eg. Ach(acetylcholinesterase) against acetylcholine
•Destruction of transmitter by reuptake Eg. NA
Epinephrine or norepinephrine is. Catabolised by COMT and MOA- mono amine oxidase and
Example of neurotransmitters which are not acetylcholine or norepinephrine or epinephrine are called
Nonadrenergic - Noncholinergic Transmission (NANC)
•NANC since these neurons release neither norepinephrine nor Ach
Example nitric oxide, capsaicin ,
ATP, which is found e.g. in postganglionic sympathetic neurons of blood vessels and may contribute to the fast contraction of smooth muscle cells, γ ‐aminobutyric acid (GABA) and serotonin which are found in enteric neurons and are involved in peristaltic reflexes, dopamine, found in some sympathetic neurons (e.g. kidney) and involved in vasodilatation and NO which is released from pelvic or gastric nerves and plays a role in penile erection or gastric emptying. A variety of peptides have also been described to function as NANC transmitters, e.g. neuropeptide Y (postganglionic sympathetic neurons), vasoactive intestinal peptide…
Explain how epinephrine is produced in the neuron
Tyrosine from the extra cellular fluid enters the nerve via a sodium dependent transporter and is acted on by tyrosinehydroxylase and becomes dopa . Dopa is acted on by dopa decarboxylase and becomes dopamine.(DA)
This enters the vesicles and is converted to norepinephrine by dopamine beta-hydroxylase.
This is reversible
When norepinephrine is not in the vesicles or is released what happens to it
It is acted on by mono amine oxidase
If there is no neurotransmitter produced in the neuron but the vesicles is close to the terminal end of the axon what happens
There will be nothing released so there will be no activation of the receptor
True or false
Impulse from the brains travels through the pre and is transported to the other neurons and action potential transports this information. When it finally gets to the end of the neuron then the whole calcium thing will happen for the release.
True
What is molecular pharmacology
They study how drugs interact with the cells of the body and their effects on bodily processes
NANC‐transmitters often function as co‐transmitters, which are released together with acetylcholine or noradrenaline true or false
True
What are adrenergic receptors
adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine and epinephrine produced by the body,
Arteries have which type of sympa receptors on em
Alpha receptors
What are cholinergic receptors
Cholinergic receptors are receptors on the surface of cells that get activated when they bind a type of neurotransmitter called acetylcholine. There are two types of cholinergic receptors, called nicotinic and muscarinic receptors - named after the drugs that work on them.
Name three other neurotransmitters apart from acetylcholine , norepinephrine and epinephrine
acetylcholine, dopamine, gamma-aminobutyric acid (GABA), glutamate, histamine, norepinephrine, and serotonin)
At the junction between two neurons (synapse), an action potential causes neuron A to release a chemical neurotransmitter. True or false
True
Differencebetween ganglion and synapse
bodies that house millions of synapses. … Synapse is located in the ganglion. The key difference between ganglion and synapse is ganglion houses millions of synapses while synapse is a small junction where two neurons come closer during the signal transmission
The enzyme mono amine oxidase is more in which receptors
Adrenergic
The enzyme COMT (catechol-O-methyltransferase)is found more in where
Tissues specifically the liver
Where did dopamine originate from and what does it innervated
Thoracic side and innervated the Renal vessels
Which enzyme converts phenyl alanine to tyrosine
Phenylethanolamine-N-methyltransferase (PNMT)
Which step in the synthesis of norepinephrine is known as the rate determining step
Conversion of tyrosine to dopa
Full meaning of dopa
Dihydroxyphenylalanine
Or 1,3,4-dihydroxyphenylalanine
People with lots of phenylalanine which is an essential amino acid have lots of catecholamines in their body . True or false
True
What is the name given to drugs that act anywhere along the neuron and drugs that interact with receptors on the tissue
Pre synaptic drugs and post synaptic drugs
Norepinephrine and epinephrine are both released by the adrenal medulla straight into the blood. Which of the two is released more?
Epinephrine
The adrenal
Medulla is said to be a modified post ganglionic neuron true or false
True
Which receptor dominates on neurons
Nicotinic receptor
Activation of nicotinic receptors causes depolarization true or false
True
Which neurotransmitter facilitates transmission of info from the pre to post
Acetylcholine
What are the two ways by which norepinephrine action is terminated
1.a . Uptake1(neuronal uptake )-70percent of NE goes back into the neuron from the synapse
b. Uptake2(extraneuronal uptake) Ne is diffused into the receptor
C. Uptake3(intraneuronal uptake)- movement of NE into the vesicles from the cytoplasm
2. Enzyme degradation by COMT and MOA
3. Alpha 2 receptor located on the nerve terminal end is stimulated and inhibits the further release of NE
How is Ne conserved
When it enters the vesicles
What is called a false neurotransmitter
Methyl noradrenaline
Which drug stops the synthesis of the neurotransmitters by inhibiting the rate limiting enzyme
Metyrosine or alphamethyltyrosine.
This inhibit tyrosine hydroxylase preventing catecholamines from being produced
When is metyrosine used
In controlling cardiovascular diseases as a complication to a lore complex disease such as phaeochromocytoma which is tumor of th adrenal gland. This tumor causes adrenal medulla to produce lots of NE and E leading to high bp so metyrosine controls the bp by stopping the synthesis of NE
Once it is c trolled then surgery is done to remove the tumor
When is methyldopa used , which people are best suited to use methyldopa and when is carbidopa used
It inhibits dopa carboxylase thereby preventing dopamine from being formed. And is very suited for pregnant women with hypertension
Parkinson’s disease there is a dopamine deficiency. Dopamine cannot be given cuz even tho it is given it will not go to the effector organ which is in the brain.so carbidopa causes the production of dopa which ends up causing the production of dopamine later while making sure not too much of the dopamine is produced. It is a combo of dopa and dopa decarboxylase.
What is the mechanism of action for
Methyldopa
Methyldopa in itself is not strong enought to prevent NE from being produced directly because the enzyme will see it as a substrate to be acted upon.
So methyldopa goes thru the same process as norepinephrine and becomes methyldopamine and then methylnorepinephrine . Once it is released into the synapse it stimulates alpha 2 receptors on the nerve terminal ending which inhibits further release of norepinephrine
Which drug blocks uptake three pathway and inhibits the storage of NE
Reserpine
It also stops dopamine from entering the vesicles and becoming NE
Herbal drug, used to treat hypertension and insanity
•Disrupts the transport process of NA->vesicles
•Nerve impulse releases “empty” vesicles
•Get a profound fall in blood pressure
•Major side-effect is depression; suicide common ( NA in the brain)
There is no cholinergic drug that stops the storage of neurotransmitters
Which adrenergic drugs and cholinergic inhibit the release of neurotransmitters
guanethidine, clonidine
Choli-botulinum toxin
Which adrenergic and cholinergic drugs stop the neurotransmitter from interacting w the receptors
prazosin (a-receptors)
propranolol (b-receptors)
Cholinergic
atropine (muscarinic) ,hexamethonium (N1)
d-tubocurarine (N2)
Which adrenergic and cholinergic drugs prevent the destruction of the neurotransmitters in the synapse
pyrogallol (COMT-inhibitor)
pargyline (MAO-inhibitor)
cocaine (uptake blocker)
physostigmine (cholinesterase inhibitor)
How does cocaine work
It is an uptake 1 pathway blocker which increases amount of NE thereby increasing bp
Which cholinergic drug stops the recovery of the post junctional membrane
succinylcholine
Which drugs are uptake 2 blockers
Corticosteroids
Phenoxybenzamine
Reserpine
Epinephrine is a major hormone of the adrenal medulla true or false
True
Catecholamines are - dopamine, NE and E
Name two drugs that are sympathomimetic and one neurons blocker drug
Cocaine and tyramine
Guanethidine
What happens in the cheese reaction
A hypertensive patient takes in lots of food containing lots of tyramine (uptake 1 blocker) such as cheese and red wine while taking anti hypertensive drugPARAGYLINE which is an MAO INHIBITOR . The tyramine displaces NE from the vesicles . AND THE mAO inhibitor stops mao from causing the termination of NE leading to too much NE in the system thereby causing acute high bp and a severe throbbing headache leading to death due to inracranial haemorrhage
It can also occur in people who aren’t hypertensive if they take in tyramine food substances while also taking MAO inhibitors.
Normally Tyramine foods are metabolized by MaO
Name one trycyclic antidepressant
Imipramine
Mechanism of action of amphetamine
Substrate for Uptake 1.
2. Enters nerve terminals and
displaces NA from vesicles.
3. The NA not destroyed by MAO,
can be counter transported out of
the terminal via Uptake 1.
4. Amphetamine can also inhibit
MAO - further augmentation
of NA actionsCNs actions of amphetamine
CNS actions of amphetamine CNS stimulation Locomotor stimulation Euphoria Loss of appetite (leading to anorexia).
Effects of amphetamine substance abuse
Tolerance -higher concentrations and more frequent administration are required to gain the same “high”.
Development of psychosis
Addicts suffer from: auditory and visual hallucinations, paranoia and aggression.
Therapeutic effect of amphetamine
Treat narcolepsy,
Postpone fatigue/sleep (in emergency situations)
Treat obesity
Name two releasing agents of NE which are indirect adrenergic agonists
Amphetamine
Tyramine
Cocaine
What are the receptors on the receptor organ that NE acts on
Beta and alpha 1 receptors
What are alpha blockers mainly used for
Managing hypertension
Drugs that selectively block only alpha 1 receptors are better than those that block either alpha 1 or alpha 2 receptors
Why
Cuz if you use a drug that blocks both receptors, too much NE will be produced and the beta receptor will be acted on since both alpha receptors are being blocked and the drug will have no other choice but to bind on the beta receptor so when the beta receptor is activated it causes tachycardia and palpitations due to the increased amount of NE
Uptake 1 has the largest capacity for which neurotransmitter and uptake 2 has the Largest capacity for which neurotransmitter
NE and E
Name one example of uptake 2 blockers
Corticosteroids specifically cortisol
These are actually mainly used as anti inflammatory drugs in asthma
Name one selective alpha 1 blocker
Prazosin
Name two alpha 1 and 2 non selective blockers
Phentolamine(reversible antagonism)
Phenoxybenzamine (irreversible antagonism cuz it binds covalently to the alpha 1receptor so the bond can’t be broken easily)
E is not a neurotransmitter in the peripheral nervous system and is a bronchodilator. True or false
True
Synthesis of NE is blocked by
Reserpine
Catecholamines are called so because
Presence of catechol rings
Biotransformation of catecholamines
They are converted to biologically inactive substances
NE is converted to Normetanephrine by COMT and can be converted by MAT to 3-methoxy4-hydroxymandelic acid
NE can also be converted to dihydroxymandelic acid by MAO and converted to 3-methoxy-4-hydroxy mandelic acid by COMT
E can be converted to Metanephrine by COMT and to 3-methoxy-4hydroxy mandelic acid by MAO
E can also be converted to dihydroxymandelic acid by MAO to 3-methoxy-4-hydroxymandelic acid
What shows a person has phaeochromocytoma
Person has lots of 3-methoxy4-hydroxymandelic acid in the pee
Name one alpha 1 agonist
Phenyephrine
Name two MAO inhibitors and one COMT inhibitor . MAO inhibition causes increase in sympa activity
Phenelzine Selegiline ( selectively degrades dopamine ) it’s used in Parkinson’s disease
COMt inhibitors- Tolcapone
Beta 1 receptors are dominant where
In the heart
Cocaine can get into the brains true or false
True
Catecholamines can’t get into the brain because they can’t cross bloodbrain barrier
True or false
True
One organ can have two different receptors on them. Give an example
In the eye, alpha 1 receptors are on the radial smooth muscle and beta 2 receptors are on the cilliary epithelium and they cause sympa innervation
Name the types of muscarinic and nicotinic receptor and where they’re found most
Muscarinic- M1,M2,M3
Nicotinic- NN and NM subscript n and m tho ( NM is in the muscles and Nn is in the ganglion and adrenal gland)
Half-life of ACH is very long. True or false
False
How is acetylcholine produced, released and biotransformed
Choline is transported from the extra cellular fluid thru a sodium dependent transporter into cytoplasm and into the cholinergic nerve terminal. It interacts w Acetyl coA from the mitochondria. An enzyme ChAT produces Ach from the combination of acetyl co A and choline.
Release:
When Ach is formed , it is transported into the storage vesicles which contain ATP and peptide. Calcium ions causes release of Ach and it diffuses. It interacts w either muscarinic receptors or nicotinic receptors. If it interacts w N, it produces sympa causing the adrenal medulla to produce NE or E while if it interacts w muscarinic it’s parasympathetic.
Biotransformation- at the neuroeffectkr junction , cholinesterase enzyme is responsible for the termination of action of Ach. It rapidly hydrolyzes Ach and converts it into choline and acetate. Acetate is biotransformed by the liver and choline is recycle and taken back into the neuron to start the whole cycle again.
Name the types of cholinesterase
Acetyl cholinesterase (true cholinesterase) - main enzyme which breaks down Ach and is usually at the neuroeffector junction
Plasma cholinesterase(pseudo or false cholinesterase or ChE)- it has greater affinity for butyrycholine
What inhibits choline uptake
Hemicholiniums specifically Hemicholine
What prevents Ach transport into the vesicle
Vesamicol
What blocks the exocytotic release of Ach by preventing fusion of VAMPS AND SNAPS
Botulinum toxin
Name one cholinesterase inhibitor
Physostigmine
Tamoxifen is an oestrogen receptor , morphine for opioid,aspirin and tantidine for histamine
True
amount in body is divided by plasma conc times is volume of distribution and half life is 0.693 times VD divided by clearance
True
Glycine is calcium voltage gated.Veratridine is sodium channels,benzodiazepine is GABAA,dihydropiridine is calcium,
True
Glycine is calcium voltage gated.Veratridine is sodium channels,benzodiazepine is GABAA,dihydropiridine is calcium,
True
