Autonomic Nervous System

Question 1

(T/F) While the CNS composes the brain and spinal cord (integrate and coordinate), the PNS composes of the somatic and autonomic nervous system.

Answer 1

True!

*PNS connects CNS to other parts of the body.

Question 2

Somatic nervous system composes of somatic nerves (motor neurons), which are responsible for:

Answer 2

1) Contraction of skeletal muscles
2) Voluntary actions (conscious thought)

*spinal cord connected by motor neurons to muscles

Question 3

Autonomic nervous system is responsible for:

Answer 3

Involuntary actions:

• heart rate and heart muscle contractility
• contraction of smooth muscles (blood vessel, lung airway, GI tract, eyes, urinary bladder)
• gland secretion (lacrimation, salivation, GI tract secretion and sweat gland)

Question 4

What are the two opposing systems autonomic nervous system is divided into?

Answer 4

1) Sympathetic nervous system
2) Parasympathetic nervous system

Question 5

While the sympathetic nervous system arises from the __________, the parasympathetic nervous system arises from ___________ and _________.

Most ganglia of sympathetic nervous system are located in ______________ ____, while ganglia of parasympathetic nervous system are located in/near ______ _______.

Answer 5

Spinal cord T1-12 and L1-3
Brain stem (cranial nerves III, VII, IX, X); Spinal cord (Sacral 2-4)

Paraverterbral chain; target organs

Question 6

(T/F) The sympathetic nervous system has long pre-ganglion fiber and short post-ganglion fiber. The opposite applies for the parasympathetic nervous system.

Answer 6

False!

Sympathetic nervous system: SHORT pre-ganglionic fiber, LONG post-ganglionic fiber

Parasympathetic nervous system: LONG pre-ganglionic fiber, SHORT post-ganglionic fiber

Question 7

Which ANS triggers fight-or-flight responses and is activated in stress/frightening conditions?

Answer 7

The SYMPATHETIC nervous system

*activated in stress (physical/emotional)
*both fight or flight requires body movements (skeletal muscle contractions)

Question 8

Briefly describe what happens to these during sympathetic activation:

1) Eyes
2) Brain
3) Heart
4) Blood vessels
5) Digestive tract
6) Lung airways (trachea, bronchi & bronchioles)
7) Stored energy
8) Sweat glands

Answer 8

1) Eyes: pupil dilates to see better

2) Brain: more alert for quicker reactions

3) Heart: beats harder and faster (more oxygen and nutrients to be circulated to contracting muscles)

4) Blood vessels: IN CONTRACTING MUSCLES dilates - more blood, oxygen and nutrients delivered to the muscles

5) Digestive tract: less active

6) Lung airways (trachea, bronchi and bronchioles): dilate for more oxygen to enter the lungs and the blood

7) Stored energy: in the LIVER, SKELETAL MUSCLES AND FAT tissues (in the form of glycogen n fat) breaks down providing more energy for contracting muscles.

8) Sweat glands: stimulated for heat loss and body temperature regulation.

Question 9

What does the parasympathetic nervous system trigger?

Answer 9

It triggers the rest and digest responses including the three Ds: digestion, defecation and diuresis.

Question 10

Briefly describe what happens to these during sympathetic activation:

1) Eyes
2) Heart
3) Digestive tract
4) Lung airways

What else?

Answer 10

1) Eyes: pupil constricts –> less light –> rest

2) Heart: beats slower –> less oxygen and nutrients need to be circulated

3) Digestive tract –> secretes digestive enzymes and CONTRACTS vigorously; promoting the digestion of food and nutrient absorption + storage

4) Lung airways: constrict –> less oxygen

At certain times, DEFECATION, URINATION or DILATATION of genital arteries occurs

Question 11

What kinds of effects does the sympathetic nervous system have?

What kinds of effects does the para-sympathetic nervous system have?

Answer 11

Sympathetic: DIFFUSE effects (each pre-ganglionic fiber connects with MANY post-ganglionic fibers –> widespread activation)

Para-sympathetic: DISCRETE (localized) effects (each pre-ganglionic fiber connects with only A FEW post-ganglionic fibers)
*it can selectively decrease the heart rate and increase the GI tract activity

Question 12

Parasympathetic activation is associated with energy ________.

Answer 12

Conservation!

*decreased heart rate, bp
*increased GI tract activity + secretions
*permission to empty bladder, open GI sphincter

Question 13

(T/F) During fight-or-flight responses, the blood flow is redirected from skin and visceral regions to skeletal muscles.

Answer 13

True!

There is a VASODILATION of arteries in skeletal muscle.

Question 14

Briefly answer the following questions about the synapse:

1) What is a synapse?

2) What is its function?

3) What is the function of pre-synaptic neuron?

4) What is the function of a post-synaptic neuron?

Answer 14

1) Synapse connects two neurons (in both CNS and PNS): in the PNS, the second neuron can be a target cell.

2) Its function is SIGNAL CONDUCTION. electrical –> chemical (NT) –> electrical

3) Synthesis, storage and release of NTs into cleft.

4) Receptors for NTs

Question 15

(T/F) The somatic nervous system consists of chains of two neurons (nerve fibers) connected by synapses in ganglia.

Answer 15

False!

The AUTONOMIC nervous system consists of chains of two neurons (nerve fibers) connected by synapses in ganglia.

*when the 1st neuron is excited, it releases NTs in the 2nd neuron, exciting it (when the NTs bind the receptors), releasing NTs in the synapse.

Question 16

While the NT of synapses between the pre-ganglionic fiber and the post is acetylcholine in both the sympathetic and parasympathetic nervous system, the NTs of synapses between post-ganglionic fiver and target organs differ.

List them.

Answer 16

Sympathetic system: Norepinephrine (NE) in most tissues, Acetylcholine (ACh) only in SWEAT GLANDS!

Parasympathetic system: Acetylcholine (ACh)

Question 17

(T/F) The somatic nervous system has one neuron that directly connects the target tissue and releases ACh in the synapse.

Answer 17

True!

Question 18

What are the two types of cholinergic receptors?

Answer 18

1) Muscarinic (M) receptors (G-coupled protein receptors)

2) Nicotinic (N) receptors (ligand gated Na+ channels)

Question 18

ACh is the neurotransmitter for?

Answer 18

1) All neurons originated in the CNS
- pre-ganglionic fibers (para/sympa)
- sympathetic fibers for adrenal medulla
- somatic nerve (motor neurons
/neuromuscular junction)

2) Post synaptic nerves for:
- parasympathetic nervous system
- sympathetic nervous system (only sweat
glands)

3) Some neurons in the CNS

Question 19

There are three muscarinic (M) receptors, match them to where they are located:

1) M1
2) M2
3) M3

A) heart
B) smooth muscles and glands
C) some neurons (CNS, autonomic ganglia)

Answer 19

M1: some neurons (CNS, autonomic ganglia)

M2: heart

M3: smooth muscles and glands

Question 20

Where are the nicotinic (N) receptors found in?

Answer 20

Autonomic ganglia, skeletal muscle (neuromuscular junctions) and some CNS neurons

Question 21

What are the agonists and antgaonists of the muscarinic (M) receptors?

Answer 21

Agonists: ACh and muscarine
Antagonist: Atropine

Question 22

For M3 receptors, what does an agonist do in:
1) Smooth muscle
2) Blood vessel
3) Glands

For M2 receptors, what does an agonist do in:
1) Atrial muscle
2) Peacemaker tissue (sinoatrial node)

Answer 22

For M3 receptors: M3 –> Gq –> IP3 (inositol triphosphate) –> Ca2+ release

1) Smooth muscle: stimulates contraction

2) Blood vessel: vasodilation

3) Glands: stimulates secretion

.

For M2 receptors: coupled to Gi –> inhibition of AC (adenylyl cyclase)

1) Atrial muscle: reduced cAMP –> reduced Ca2+ influx via Ca2+ channels —> reduced contractility

2) In peacemaker tissue: With Gβγ subunits, there is an activation of ACh-sensitive K+ channels (hyperpolarizes) and slows heart rate

Question 23

Briefly describe how smooth muscle contraction occurs in 5 steps.

How does relaxation occur?

Answer 23

1) Initiated by Ca2+ release (0.1um –> 10 um)
2) Ca2+ binds to CALMODULIN
3) Ca2+/Calmodulin complex activates MYOSIN LIGHT CHAIN KINASE (MLCK)
4) The MLCK then phosphorylates MYOSIN
5) Myosin binds to ACTIN, triggering contraction

Relaxation: Ca2+ decreases or activation of MLC phosphatase (which counteracts MLCK)

Question 24

How does Nitric Oxide (NO) cause relaxation in vascular smooth muscle resulting in vasodilation?

Answer 24

NO activates guanylyl cyclase (GC) which then activates cGMP. cGMP can: a) inhibit L-type Ca2+ channels b) decrease MLCK c) increase myosin light chain phosphatase these all cause vascular smooth muscle relaxation (vasodilation)!

Question 25

How/where is Nitric Oxide (NO) produced?

Answer 25

In the ENDOTHELIAL CELLS, nitric oxide synthase (NOS) turns L-arginine (L-arg) into NO. Now, there is a generation of basal level of NO. This rapidly diffuses to smooth muscle causing relaxation!

Question 26

(T/F) NO production can be further stimulated by ACh via M3 receptors on endothelial cells. This stimulates NOS to make more NO, resulting in a greater vasodilation of blood vessels.

Answer 26

True!

Question 27

What are nicotinic receptors? What do they do?

Answer 27

Ligand (ACh)-gated Na+ channels (pentamers) When there is a Na+ influx, there is membrane depolarization (excitation), causing: a) excitation of post-ganglionic nerves b) Ca2+ release from Sarcoplasmic Reticulum (SR) --> skeletal muscle contraction c) CNS: excitation of neurons

Question 28

There are two different types of Nicotinic receptors, Nm and Nn. Though they are similar, they have different combinations of subunits. Match them to their definitions: 1) Nm 2) Nn A) found in SKELETAL MUSCLE + neuronmuscular endplates. Agonists: ACh, nicotine. Antagonist: Tubocutarine B) found in POSTGANGLIONIC NEURONS, some presynaptic cholinergic terminals. Agonist: ACh, nicotine. Antagonist: Hexamethonium

Answer 28

Nm: found in SKELETAL MUSCLE + neuronmuscular endplates. Agonists: ACh, nicotine. Antagonist: Tubocutarine Nn: found in POSTGANGLIONIC NEURONS, some presynaptic cholinergic terminals. Agonist: ACh, nicotine. Antagonist: Hexamethonium

Question 29

What are the two types of ADRENERGIC RECEPTORS?

Answer 29

1) α receptors: α1 and α2 2) β receptors: β1 and β2

Question 30

Describe α1 receptors (location + mechanism).

Answer 30

Located in the SMOOTH muscles (blood vessel, urinary bladder, eyes, etc), exocrine glands and CNS. Mechanism: Gq --> PL-C (phospholipase C) --> IP3 (inositol triphosphate) --> SR Ca2+ release ---> CONTRACTION & SECRETION

Question 31

Describe α2 receptors (location + mechanism).

Answer 31

Located in PRE-SYNAPTIC MEMBRANE where it inhibits further NE release (negative feedback "autoreceptor") Gi --> reduced cAMP/PKA --> reduced Ca2+ influx Located in blood platelets Gi --> reduced cAMP --> platelet AGGREGATION *stops any potential bleeding during flight/fight

Question 32

Describe β1 receptors (location + mechanism)

Answer 32

Increases cAMP in HEART and KIDNEY Gs --> cAMP/PKA --> Ca2+ influx - Increased HEART RATE + CONTRACTILITY - RENIN SECRETION (in kidney cells)

Question 33

Describe β2 receptors (location + mechanism)

Answer 33

Location: Smooth muscles (airway, blood vessels in skeletal muscle): Gs --> cAMP --> inhibition of MLCK (myosin light chain kinase) --> relaxation of smooth muscle

Question 34

Pupil size is regulated by the contraction of the iris muscle. What are the two layers of the iris muscle? Which receptors are located in each? What happens when receptors are activated?

Answer 34

1) Circular (sphincter) muscle: M3 receptor: Pupil CONSTRICTS + MIOSIS 2) Radial (dilator muscle): α1 receptor: Pupil DILATES + MYDRIASIS

Question 35

Describe the mechanisms on how the pupil dilates and constricts.

Answer 35

Parasympathetic activation --> ACh --> M3 receptor --> IP3/Ca2+ ---> contraction ---> pupil CONSTRICTS + MIOSIS Sympathetic activation --> NE --> α1 receptor --> IP3/Ca2+ --> muscle contraction --> pupil DILATES & MYDRIASIS

Question 36

What are the 6 steps of general mechanism of synaptic transmission?

Answer 36

1) SYNTHESIS of neurotransmitter from precursor; STORAGE in vesicles 2) EXCITATION (depolarization) of PRESYNAPTIC MEMBRANE: an action potential traveling down the neuron depolarizes the presynaptic nerve terminal 3) ACTIVATION of voltage-gated Ca2+ channels: Ca2+ entry 4) RELEASE of stored NTs: increased Ca2+ --> vesicle fusion with the plasma membrane --> release of NT into the synaptic cleft 5) ACTIVATION of receptors: NTs bind to postsynaptic receptors (ion channels/GPCRs) 6) REMOVAL OF TRANSMITTERS. Transmitter can be degraded by enzymes (6a) in the synaptic cleft or can be recycled into the presynaptic cell (6b) by reuptake transporters.

Question 37

(T/F) Tyrosine turns into DOPA and then into DOPAMINE and then into NOREPINEPHRINE.

Answer 37

True!

Question 38

How is norepinephrine removed from the synaptic cleft?

Answer 38

1) MAO: monoAmine Oxidase (degrades NE) 2) COMT: catechol-O-methyltransferase (degrades NE)

Question 39

NE synthesis is compartmentalized: ________ _______ transporter translocates dopamine into ________ vesicles. In __________ neurons, intravesicular _______ __________ converts dopamine into norepinepherine, stored in vesicles until release. Released NE can also be taken up into presynaptic terminals by the selective ____ transporter (NET akak uptake 1). NE in the cytoplasm of the presynaptic neuron can further be taken up into synaptic vesicles by ________ or degraded by _____ _____ _____ ______.

Answer 39

Vescicular monoamine transporter (VMAT); synaptic Adrenergic; dopamine-b hydrolase NE VMA; mitochondrion-associated monoamine oxidase (MAO).

Question 40

Both norepinephrine and epinephrine are metabolized by _____ and _____ to the same metabolite, __________ acid, which is excreted in the urine.

Answer 40

MAO; COMT; vanillylmandelic acid *by testing the VMA levels in the urine, we can test NE/E levels in the human body.

Question 41

What is phenochromocytoma?

Answer 41

Phenochromocytoma (PCC); a tumor of chromaffin cells (phenochromocytes) in adrenal medulla. Tumors secrete and release large amounts of epinephrine and norepinephrine into the blood. It is a rare cause of hypertension. Primary urinary excretion of VMA is markedly increased; diagnostic test.

Question 42

Match the drugs affecting adrenergic neurotransmission to their definitions: 1) Alpha methyl tyrosine 2) Reserpine 3) Guanethidine 4) Cocaine, tricyclic antidepressants 5) Pargyline A) inhibition of storage B) reuptake inhibitors C) synthesis inhibitors D) MAO inhibitors E) inhibition of release

Answer 42

Alpha methyl tyrosine: synthesis inhibitors Reserpine: inhibition of storage Guanethidine: inhibition of release Cocaine, tricyclic antidepressants: reuptake inhibitors Pargyline: MAO inhibitors

Question 43

The effect of a neurotransmitter is determined by its ________ _______ present on target cells.

Answer 43

Receptor subtype

Question 44

While sympathetic activation (NE/E) in α receptor causes __________, in a β receptor causes _________.

Answer 44

Contraction; relaxation

Question 45

During filling of the bladder, ________ control predominates, causing relaxation of the _________ muscle ( β2) and contraction of the ________ _______ (α1). During micturition, __________ control predominates causing contraction of the _______ muscle , and relaxation of ______ ______ (voluntary control)

Answer 45

Sympathetic; detrusor; internal sphincter Parasympathetic; detrusor; external sphincter

Question 46

A general rule is α1 and β1 ________, while α2 and β2 ________ smooth muscles, glands, and cardiac muscle.

Answer 46

stimulate; inhibit

Question 47

Which one of the following statements is true? 1) Epinephrine has no selectivity for β (β1 = β2), but has high affinity for α1. 2) Norepinephrine has no selectivity for both α and β, so can potently activate all subtypes. 3) Epinephrine leads to vasoconstriction in arteries of skin tissues (α1) and vasodilation in skeletal muscle (β2). 4) Norepinephrine causes all blood vessels to dilate (α1 activation dominates, β2 not active).

Answer 47

3! For 1: Epinephrine has no selectivity for both α and β, so can potently activate all subtypes. For 2: Norepinephrine has no selectivity for α, but a low affinity for β2 (β1 > β2). For 3: Norepinephrine causes all blood vessels to CONSTRICT (α1 activation dominates, β2 not active).

Question 48

What are the four therapeutic uses of epinephrine?

Answer 48

1) Anaphylactic shock (relaxes airway smooth muscle β2+contracts vascular smooth muscle α1) 2) Cardiac arrest - not hear attack (stimulates cardiac contraction β1) 3) Reduce bleeding (vasoconstriction α1) 4) Delay absorption of local anesthetics (vasoconstriction α1)

Question 49

What are the adverse effects of epinephrine?

Answer 49

Arrhythmias (b1) Hypertension (a1) Hyperglycemia (b1 in liver increases glucose)

Question 50

Activation of a1 means smooth muscle contraction (a1 --> ip3 --> ca2+ release), this includes;

Answer 50

1) vascular smooth muscle (esp. blood vessels in extremities) 2) sphincters of digestive tract 3) inner sphincters of lower urinary tract 4) hair erector muscle 5) eye: contraction of radial iris muscle (mydriasis)

Question 51

What is phenylephrine (PE)? What are its clinical uses? What are its adverse effects?

Answer 51

phenylephrine (PE) is an a1 agonist; its action is SMOOTH MUSCLE CONTRACTION (vasoconstriction) Clinical uses: 1) superficial bleeding 2) nasal decongestion 3) hypotensive emergencies 4) mydriasis Adverse effects: hypertension

Question 52

What are prazoSIN and tamsuloSIN? What are their clinical uses? What are their adverse effects?

Answer 52

a1 reversible antagonist; its action is SMOOTH MUSCLE RELAXATION Clinical uses: 1) hypertension (vasodilation) 2) urinary tract obstruction (men w benign prostatic hyperplasia): relaxes smooth muscles in internal sphincter of urethra + prostate gland Adverse effects: 1) orthostatic hypotension + dizziness (excessive vasodilation in veins) 2) reflex heart rate increase (decrease in blood pressure causes sympathetic nervous system to increase heart rate)

Question 53

Match what a2 receptor does in each location when activated: 1) Pre-synaptic neuron 2) Pancreatic islet cells 3) Blood platelets A) promotes aggregation B) inhibits further NE release C) inhibits insulin secretion

Answer 53

1) Pre-synaptic neuron: inhibits further NE release 2) Pancreatic islet cells: inhibits insulin secretion 3) Blood platelets: promotes aggregation *all due to reduced cAMP which reduces Ca2+ influx

Question 54

What is clonidine? What are its clinical uses? What are its adverse effects?

Answer 54

clonidine is an a2 agonist. its action in pre-synaptic neuron is to decrease NE release in both PNS and CNS (causing reduced sympathetic outflow). this leads to VASODILATION in blood vessels as there is less vasoconstriction. Clinical uses: 1) Hypertensive urgencies (Systolic BP > 180) 2) Diagnose phenochromocytoma (PCC) in patients. In health people, there is a reduced serum NE level! Adverse effects: 1) dry mouth 2) sedation (a2-induced inhibition in CNS)

Question 55

What is yohimbine? What are its clinical uses? What are its adverse effects?

Answer 55

it is an ALKALOID from bark of african yohimbe tree; it is an a2 antagonist and its action is to INCREASE PERFUSION OF CERTAIN TISSUES. Clinical use: 1) erectile dysfunction (blockage of these receptors in corpus cavernosum artery; increased Ach release; vasodilation) *mechanism not fully understood Adverse effect: 1) hypoglycemia (increases insulin secretion)

Question 56

Match the non-selective alpha receptor antagonist to their definitions: 1) Phenoxybenzamine 2) Phentolamine A) reversible a1 and a 2 blocker. use to relieve localized vasoconstriction and tissue ischemia. B) irreversible a1 and a2 blocker. can be used orally, long term action (3-4 days). used to control hypertension in patients with PCC until removed.

Answer 56

1) Phenoxybenzamine: irreversible a1 and a2 blocker. can be used orally, long term action (3-4 days). used to control hypertension in patients with PCC until removed. 2) Phentolamine: reversible a1 and a 2 blocker. use to relieve localized vasoconstriction and tissue ischemia.

Question 57

(T/F) Both phenoxybenzamine and phentolamine are used for chronic hypertension.

Answer 57

False! Neither are used for chronic hypertension due to their adverse effects: reflex tachycardia, headache, and dizziness.

Question 58

Both B1 and B2 receptors increase _______ but effects are ______ specific. In heart and kidney, ____ is prevalent. This leads to ______ heart rate and renin secretion. In smooth muscles, ___ is prevalent. This leads to an inhibition of ______, causing smooth muscle _________ (treats asthma and delays preterm labor).

Answer 58

cAMP; tissue b1; increased b2; MLCK (myosin light chain kinase); relaxation

Question 59

What is dobutamine? What are its clinical uses? What are its adverse effects?

Answer 59

Dobutamine is a b1 agonist. It causes powerful increases in heart contractility + rate. Clinical uses: 1) Cardiac arrest + during heart surgery 2) Acute heart failure (short term for cardiac pump failure) Adverse effects: 1) Arrhythmias 2) Increased heart rate (increases O2 consumption --> ischemia/angia)

Question 60

What is salbutamol? What are its clinical uses? What are its adverse effects?

Answer 60

Salbutamol is a b2 agonist. it causes a dilation of airway (bronchodilation). Therapeutic uses: 1) relieve asthma caused by bronchospasm Adverse effects: 1) tremor and anxiety 2) tachycardia (fast heart rate) *selectivity is "relative" to all drugs: salbutamol in high dosages can activate b1 in heart --> tachycardia

Question 61

What is isoproterenol? What are its clinical uses? What are its adverse effects?

Answer 61

Isoproterenol activates both b1 and b2. its action is cardiac stimulation (b1) and bronchodilation (b2). Clinical uses: 1) cardiac disease (arrest, bradycardia, atrioventricular block) 2) no longer used for asthma Adverse effects: 1) arrhythmias (b1) 2) hyperglycemia (b2-mediated glycogenolysis)

Question 62

What are b-blockers? What are their clinical uses? What are their adverse effects?

Answer 62

b blockers are b1 and b2 antagonists. their action is to reduce heart activities (cardioprotection in heart disease) Clinical uses: 1) Heart diseases (angina, myocardial infarction, heart failure, arrhythmias, hypertension) 2) Stage fright + anxiety (CNS effect) Side effects: Come only from B2 blockade! B2 blockers are not clinically useful!

Question 63

What are atenolol and metoprolol?

Answer 63

Selective b1 blockers! In heart it reduces heart rate + contractility and in kidneys it reduces renin secretion (treats hypertension)

Question 64

What are nadolol and propranolol? Why are they not recommended with patients who have asthma and diabetes?

Answer 64

Non selective b-blockers! blocks b1 and b2! Blocking b2 (contraction in smooth muscle) causes bronchoconstriction and prolonged hypoglycemia.

Question 65

What is carvedilol? What does it treat?

Answer 65

It is a mixed acting antagonist. It blocks a1 and b1! It treats CONGESTIVE HEART FAILURE! - reduces heart rate (blocks b1) - reduces blood pressure (blocks a1) - reduces patient mortality

Question 66

What is labetalol? what dpoes it treat?

Answer 66

Non-specific blocker: blocks all subtypes (a1, a2, b1, and b2). It is used to in the treatment of HYPERTENSIVE EMERGENCIES! - decreases heart rate, contractility and peripheral vascular resistance (vasodilation)

Question 67

Match the drugs to their definitions 1) Phenylephrine 2) Clonidine 3) Prazosin 4) Yohimbine 5) Phenoxybenzamine/Phentolamine 6) Dobutamine 7) Salbutamol 8) Isoproteronol 9) Atenolol 10) Butoxamine 11) Propranolol 12) Labetolol A) a1 antagonist B) b2 agonist C) b2 antagonist D) a2 agonist E) b1 antagonist F) a1 agonist G) b1 and b2 antagonist H) a1, a2, b1 and b2 antagonist I) b1 and b2 agonist J) a1 and a2 antagonist K) b1 agonist L) a2 antagonist

Answer 67

1) Phenylephrine: a1 agonist 2) Clonidine: a2 agonist 3) Prazosin: a1 antagonist 4) Yohimbine: a2 antagonist 5) Phenoxybenzamine/Phentolamine: a1 and a2 antagonist 6) Dobutamine: b1 agonist 7) Salbutamol: b2 agonist 8) Isoproteronol: b1 and b2 agonist 9) Atenolol: b1 antagonist 10) Butoxamine: b2 antagonist 11) Propranolol: b1 and b2 antagonist 12) Labetolol: a1, a2, b1 and b2 antagonist

Question 68

What is the difference between direct acting sympathomimetics and indirect acting sympathomimetics of the adrenergic system?

Answer 68

Direct acting sympathomimetics: a and b receptor agonists - directly acts on the receptors Indirect acting sympathomimetics: works by increasing NE level! This can be done by reuptake inhibitors, MAO inhibitors, and displacement drugs.

Question 69

What are the three displacement drugs of the adrenergic system? Briefly describe them.

Answer 69

1) Tyramine 2) Ephedrine 3) Amphetamine and related drugs These bind to uptake 1 (aka NET) and reverse the mode of action, releasing NE stored in vesicles into cytoplasm/cleft! Usually, NET would store the NE in the vesicles from the cleft!

Question 70

Match the following indirect acting sympathomimetics to their definitions: 1) Tyramine 2) Ephedrine 3) Amphetamine + related drugs A) reverse uptake (1) to push out NE (or serotonin) into the cleft and prevent reuptake. net effect is unregulated release of large amounts of NTs into the synapse. B) an alkaloid from plant Ma Huang (chinese med). its derivative, pseudoephedrine and it are mixed acting agonists. they bind to a1 and increase NE release (vasoconstriction). used for treatment of nasal congestion. not available in US cos it can make methamphetamine C) found in foods (cheese, aged meats, soy, yeast, wine, beer + bananas). normally not absorbed significantly (rapid degradation by MAO). used with MAO inhibitors! not available for clinic use.

Answer 70

1) Tyramine: found in foods (cheese, aged meats, soy, yeast, wine, beer + bananas). normally not absorbed significantly (rapid degradation by MAO). used with MAO inhibitors! not available for clinic use. 2) Ephedrine: an alkaloid from plant Ma Huang (chinese med). its derivative, pseudoephedrine and it are mixed acting agonists. they bind to a1 and increase NE release (vasoconstriction). used for treatment of nasal congestion. not available in US cos it can make methamphetamine. 3) Amphetamine: reverse uptake (1) to push out NE (or serotonin) into the cleft and prevent reuptake. net effect is unregulated release of large amounts of NTs into the synapse.

Question 71

How can sympathetic drugs have CNS effects?

Answer 71

Adrenergic neurons (NE) arise in the locus ceruleus and have widespread projections to the cerebellum, hypothalamus, cerebral cortex!

Question 72

Which one of the statements regarding amphetamine is false? 1) It is used to treat attention deficit disorder (improved concentration via CNS stimulation) 2) Its side effects are cardiac simulation, insomnia, tremor, agitation, hallucinations and decreased appetite 3) To treat toxicity, you need to make urine more basic!

Answer 72

3 is false! To treat toxicity, you need to ACIDIFY the urine to maintain the charge on amphetamine (a weak base). This allows it to not be resorbed in kidney tubular cells, enhancing excretion.

Question 73

(T/F) Methamphetamine and methylphenidate are CNS stimulants! Methylphenidate is used to treat ADHD.

Answer 73

True!

Question 74

Choline acetyltransferase _______ ACh, while Acetylcholinesterase (AChE) _______ it.

Answer 74

Synthesizes, Degrades

Question 75

Match the following steps of ACh synthesis and degradation: 1) Step 1 2) Step 2 3) Step 3 4) Step 4 5) Step 5 6) Step 6 A) Newly synthesized ACh is packaged into vesicles for storage. B) ACh in the synaptic cleft is degraded by membrane-bound acetylcholinesterase (AChE) into choline and acetate. C) Choline is transported into the presynaptic nerve terminal by Na+-choline cotransporter. D) Released ACh diffuses in the synaptic cleft and binds to post/pre-synaptic receptors. E) Nerve stimulation --> exocytosis and release F) The cytosolic enzyme choline acetyltransferase catalyzes the formation of ACh from acetyl coenzyme A (AcCoA) and choline.

Answer 75

Step 1: Choline is transported into the presynaptic nerve terminal by Na+-choline cotransporter. Step 2: The cytosolic enzyme choline acetyltransferase catalyzes the formation of ACh from acetyl coenzyme A (AcCoA) and choline. Step 3: Newly synthesized ACh is packaged into vesicles for storage. Step 4: Nerve stimulation --> exocytosis and release Step 5: Released ACh diffuses in the synaptic cleft and binds to post/pre-synaptic receptors. Step 6: ACh in the synaptic cleft is degraded by membrane-bound acetylcholinesterase (AChE) into choline and acetate.

Question 76

Match the following drugs to their mechanisms of action regarding cholinergic neurotransmission: 1) Hemicholinium 2) Vesamicol 3) Botulinum Toxic 4) Nerve gases 5) a-latrotoxin (black widow venom) A) Inhibitors of ACh storage (step 3) B) AChE inhibitors (step 6) C) Stimulates ACh release to cleft. D) Inhibitor of choline uptake (step 1) E) Inhibitors of ACh release (step 4)

Answer 76

Hemicholinium: Inhibitor of choline uptake (step 1) Vesamicol: Inhibitors of ACh storage (step 3) Botulinum Toxic: Inhibitors of ACh release to the cleft (step 4) Nerve gases: AChE inhibitors (step 6) a-latrotoxin (black widow venom): Stimulates ACh release to cleft.

Question 77

Botulinum toxin ______ smooth and skeletal muscle. Hence, it is used to relieve localized ______ spasms and _____ spasms and _____ facial wrinkles. What are its adverse effects?

Answer 77

relaxes skeletal muscle; urinary bladder; reduce Adverse effects: Dry mouth + difficult swallowing.

Question 78

What does a black widow bite lead to?

Answer 78

Black widow bites (esp by female spiders with larger venom glands) causes a-latrotoxin to enter the body and stimulate ACh release to the cleft. This results in excessive activation of ACh receptors and muscle contraction + pain. Analgesic and anti-inflammatory meds can treat it.

Question 79

What are direct-acting cholinomimetics? Give examples.

Answer 79

Direct acting cholinomimetics are cholinergic receptor agonists. They directly bind and activate cholinergic receptors. They include choline esters, plant alkaloids and synthetic drugs (cevimeline).

Question 80

Which one of the statements is true? 1) Choline esters include acetylcholine and its analogs (carbachol + bethanechol). They are rapidly absorbed from the GI tract and distributed to the CNS. 2) Acetylcholine and bethanechol activate both M and N receptors, while carbachol activates M only. 3) All choline esters are hydrolyzed by cholinesterase. 4) Acetylcholine and carbachol induce miosis (decrease pupil size), while bethanechol relives urinary retention and intestinal paralysis.

Answer 80

4! Choline esters include acetylcholine and its analogs (carbachol + bethanechol). They are POORLY absorbed from the GI tract and NOT distributed to the CNS. Acetylcholine and CARBACHOL activate both M and N receptors, while BETHANECHOL activates M only. ONLY ACETYLCHOLINE IS hydrolyzed by cholinesterase (short-acting).

Question 81

Match the plant alkaloids to their definitions: 1) Muscarine 2) Nicotine 3) Pilocarpine A) higher affinity for M receptors, come from pilocarpus. used in glaucoma. B) activate M receptors, come from poisonous mushrooms with no medical use C) activate N receptors, come from tobacco plants. Chewing gum + transdermal patch for smoking cessation.

Answer 81

Muscarine: activate M receptors, come from poisonous mushrooms with no medical use Nicotine: activate N receptors, come from tobacco plants. Chewing gum + transdermal patch for smoking cessation. Pilocarpine: higher affinity for M receptors, come from pilocarpus. used in glaucoma.

Question 82

What is SLUDGE+?

Answer 82

The toxicity of muscarinic receptors when activated summarized. Salivation Lacrimation Urination Defecation Gastrointestinal motility Emesis (vomiting) + Bradycardia *need M receptor antagonists to treat it.

Question 83

Aqueous humor is secreted by _____ processes. It flows through ______ to ______ chamber. It drains through _________ meshwork and _________ canal.

Answer 83

Ciliary Pupil; Anterior Trabecular; Achlemm's

Question 84

Describe glaucoma and list its mechanisms.

Answer 84

Glaucoma is an eye disease associated with ELEVATED INTRAOCULAR PRESSURE. Damage to the eye nerve can lead to loss of vision and blindness. Mechanisms: narrowing of anterior chamber angle - reduced outflow - increased intraocular pressure - optic nerve damage

Question 85

How does pilocarpine and b-blockers like timolol treat glaucoma?

Answer 85

Pilocarpine: stimulates contraction of meridional ciliary muscle (M receptors). opens trabecular meshwork, faster drainage of aqueous humor and reduced pressure. B-blockers: reduces secretion of aqueous humor and pressure.

Question 86

What are neostigmine and endrophonium? What are their mechanisms? What are their clinical uses?

Answer 86

Neostigmine and endrophonium are REVERSIBLE AChE inhibitors. They reversibly inactivate AChE, causing increased levels of ACh. They stimulate N receptors at somatic neuromuscular junctions and M receptors. Clinical uses: - reverses skeletal muscle paralysis - myasthenia gravis

Question 87

What is myathenia gravis (MG)?

Answer 87

An autoimmune neuromuscular disease caused by the blocking/destruction of the ACh receptors by antibodies at neuromuscular junctions. Weakness in skeletal muscle; drooping eyelids; blurry vision; shortness of breath.

Question 88

(T/F) Neostigmine is the longer acting drug for the treatment of MG, while Edrophonium is the short acting (10 min) drug used to diagnose muscle weakness of MG patients using neostigmine.

Answer 88

True! If Neostigmine dose too low: with Edrophonium muscle strength improves.

Question 89

What are irreversible AChE inhibitors? What is their action?

Answer 89

Organophosphate compounds with high lipid solubility. They are extremely toxic! pesticides + nerve gases are examples. Because AChE is inhibited, there is an excessive ACh at the synaptic cleft.

Question 90

What are the three major effects of excessive ACh at the synaptic cleft caused by irreversible AChE inhibitors?

Answer 90

1) Excessive activation of M receptors (gland secretion + smooth muscle spasm) 2) Excessive activation of N receptors (inhibition of neuromuscular transmission --> muscle weakness) 3) CNS effects (seizuer, respiratory depression + coma)

Question 91

What are the treatments of irreversible AChE inhibitors?

Answer 91

1) Decontamination of patients 2) Pralidoxime to reactivate AChE 3) Atropine (M receptor antagonist)

Question 92

What is atropine? What are its clinical uses? What are its adverse effects?

Answer 92

Atropine: alkaloid that blocks M receptors (muscarinic antagonist). Has opposite effects to parasympathetic activation. Clinical uses: 1) Prepare patients for surgery with general anesthesia (reduces salivatory + airway secretions) 2) Relieves urinary bladder spasm and internal spasm (inhibits muscle contraction) 3) Induces mydriasis during an eye exam 4) Treatment of bradycardia 5) Treatment of muscarinic poisoning Adverse effects: 1) Dry eyes, mouth + constipation 2) Urinary secretion 3) Inhibition of sweating (reduced heat loss; hyperthermia) 4) Photophobia

Question 93

Define accommodation of the eyes and the role atropine plays in it.

Answer 93

Accommodation: ability of the eye to change its optical power to maintain a clear image or focus on an object as its distance varies. This is through the contraction of ciliary muscles. Atropine inhibits accommodation by inhibition of ciliary muscle contraction, resulting in blurry vision.

Question 94

What is scopolamine?

Answer 94

Muscarinic antagonist. Also an alkaloid. It has similar action as Atropine. It is used to prevent MOTION SICKNESS.

Question 95

What is scopolamine?

Answer 95

Muscarinic antagonist. Also an alkaloid. It has similar action as Atropine. It is used to prevent MOTION SICKNESS. It blocks ACh neurotransmission from vestibular apparatus to the vomiting center in brainstem; suppression of motion sickness.

Question 96

What is tubocurarine?

Answer 96

Cholinergic (Nicotinic) Antagonist. An alkaloid from curare plants. It is a competitive blocker of N receptors in skeleton muscle (muscle relaxation + paralysis). It was used to induce muscle relaxation during surgeries but newer drugs are available now! Its effects can be reversed by AChE inhibitors.

Question 97

What is succinylcholine? Its action? Its clinical uses?

Answer 97

A DEPOLARIZING antagonist. It is two covalently linked acetylcholine molecules. It causes an excessive activation of N receptors (persistent cell depolarization + prevents subsequent contractions). Its action: initial transient muscle contraction followed by a sustained muscle paralysis. Clinical use: induce muscle relaxation during surgeries; facilitate airway intubation. Its effects CAN NOT be reversed by AChE inhibitors.