Autonomics

Question 1

3 organs that are only innervated by sympathetics

Answer 1

Peripheral blood vessels
Adrenal medulla
Skin

Everything else gets duel innervation

Question 2

Usually postganglionic sympathetics release what? What are the 3 exceptions?

Answer 2

Usually its NE.

Exceptions are:
Sweat glands (ACh)
Adrenal medulla (modified ganglion, releases epi, NE)
Renal vascular smooth muscle (DA)

Question 3

5 Pharmacologic targets of the cholinergic junction

Answer 3

1. Uptake of choline-Na+/choline transporter (hemicholinium)
2. Storage into vesicles (vesamicol)
3. Release or fusion of vesicles (botulism toxin)
4. Termination (AChE inhibitors like organophosphates)
5. Receptors (agonists and antagonists)

Question 4

Catecholamine biosynthesis

Answer 4

Tyrosine
DOPA (OH added by Tyrosine Hydroxylase)
Dopamine (decarboxylase)
NorEpi (hydroxylase)
Epi (Methylated)

Question 5

2 Catecholamine metabolizing enzymes and where there are expressed

Answer 5

COMT in the kidney, liver, GI and other organs

MAO primarily in neural tissues

Question 6

M2 receptor

Answer 6

Cholinoceptor
Heart (decrease HR)
Gi

Question 7

M3 receptor

Answer 7

Cholinoceptor
Exocrine glands (salivary, lacrimal, stomach secretions, etc…), vessels (release NO to vasodilate), iris circular muscles (constricts the pupil!!!)
Gq

Question 8

Nicotinic (neuronal) receptor

Answer 8

Cholinoceptor
Autonomic ganglia, adrenal medulla
Na+/K+ ion channels

Question 9

Nicotinic (muscular) receptor

Answer 9

Cholinoceptor
Skeletal muscle
Na+/K+ ion channels

Question 10

Alpha1 receptor

Answer 10

Adrenoceptor
VASCULAR SMOOTH MUSCLE, GI, iris radial muscle (dilates the pupil!!!)
Gq

Question 11

Alpha2 receptor

Answer 11

Adrenoceptor
Presynaptic (as AUTORECEPTORS), smooth muscle walls of GI (causes relaxation or dilation)
Gi

Question 12

Beta1 receptor

Answer 12

Adrenoceptor
HEART (SA (Heart rate) and AV (conduction velocity)nodes, and ventricular muscle(contraction strength), juxtaglomerular apparatus of renal tubule
Gs

Question 13

Beta2 receptor

Answer 13

Adrenoceptor
Heart, vascular smooth muscle of skeletal muscle, BRONCHIAL smooth muscle, walls of GI and bladder
Gs

Question 14

Phenoxybenzamine (POB)

Answer 14

Inhibits Alpha 1 and 2 receptors, which also blocks the negative feedback mechanism of alpha 2. Epi and NE build up and act on beta 1 and 2 to increase BP and HR…

Given for symptomatic management of pheochromocytoma- a tumor of the adrenal medulla that results in excess secretion of epi/NE

Question 15

Non-selective beta adrenergic antagonists

Answer 15

Propranolol, nadolol, timolol

Effect is about the some for all beta receptors. This could be bad for peeps with asthma (beta2 in the lungs) or diabetes (beta2 in the liver).

Question 16

Selective beta1 adrenergic antagonists

Answer 16

Metoprolol
Atenolol
Nebivolol- this one is also a vasodilator and is highly beta1 selective

Question 17

Alpha1 antagonists

Answer 17

Prazosin - dilates arteries and veins

These do a great job managing hypertension, and they also decrease the urethral tone and help to alleviate bladder outlet obstruction in BPH.

Question 18

Alpha2 agonists

Answer 18

Clonidine and guanabenz

Centrally acting, and decrease central sympathetic outflow. Remember that alpha2 is an AUTORECEPTOR and is inhibitory.

Question 19

Mixed alpha/beta antagonists

Answer 19

Carvedilol

More effective at beta than alpha1, and works well for CHF with decreased systolic function.

Question 20

How does structural modification alter the pharmacokinetics of choline esters?

Answer 20

Methylation increases selectivity for muscarinic receptors

Carbomol increases AChE resistance

Question 21

Effects of direct acting muscarinic agonist in the EYE

Answer 21

M3 receptor
Miosis
Aqueous humor outflow and relief of intra-ocular pressure and glaucoma

Question 22

Effects of direct acting muscarinic agonist in the CARDIOVASCULAR SYSTEM

Answer 22

Heart: M2 receptor
Decreased HR and hyperpolarization

Vessels: M3 receptor
low dose- endothelial release of NO leading to vasodilation of vascular smooth muscle
high dose- IP3 production in vascular smooth muscle leading to vasoconstriction

Question 23

Effects of direct acting muscarinic agonist in the LUNGS

Answer 23

M3 receptor

Bronchoconstriction and increased secretions

Question 24

Effects of direct acting muscarinic agonist in the GI

Answer 24

M3 receptor

Increased motility, and secretions and relaxation of sphincters

Question 25

Effects of direct acting muscarinic agonist in the GLANDS

Answer 25

M3 receptor | Increased secretions

Question 26

Effects of direct acting muscarinic agonist in the BLADDER

Answer 26

M3 receptor | Detrusor contraction and sphincter relaxation

Question 27

Effects of direct acting muscarinic agonist in the CNS

Answer 27

M2 receptor mediated tremor, hypothermia, anti-niciception M3 receptor in hypothalamus reduction in apetite, diminished body fat mass

Question 28

Side effects of muscarinic agonists

Answer 28

DUMBBELSS ``` Diarrhea Urination Miosis Bronchoconstriction Bradycardia Excitation (CNS/Skeletal) Lacrimation Salivation Sweating ```

Question 29

Side effects of Atropine

Answer 29

``` Hot as a hare- increase body temp/HR Dry as a bone- no lacrimation, salivation, sweating Red as a beet- flushed skin Blind as a bat- mydriasis, cycloplegia Mad as a hatter- disoriented ```

Question 30

Effect of autonomic ganglion blocking agents in the EYE

Answer 30

Parasympathetics usually predominate, so ganglion blockage would cause mydriasis and cycloplegia

Question 31

Effect of autonomic ganglion blocking agents in the CNS

Answer 31

Sedation, tremor, choreiform movements, mental aberrations

Question 32

Effect of autonomic ganglion blocking agents in the CARDIOVASCULAR

Answer 32

Heart- Parasympathetics usually predominate, so moderate tachycardia would be observed Vessels- only sympathetics, so loss of vascular tone would be noted

Question 33

Effect of autonomic ganglion blocking agents in the GI

Answer 33

Parasympathetics usually predominate, so loss of peristalsis, decreased secretions and contracted sphincters would be observed

Question 34

Effect of autonomic ganglion blocking agents in the GU

Answer 34

Urinary retention, and no point or shoot