block 3-adrenorecptors

Question 1

adrenoreceptors(adrenergic receptors)

Answer 1

mediates the actions of adrenaline and noradrenaline

Question 2

adrenaline

Answer 2

hormone= released by chromaffin cells in the adrenal medulla

Question 3

noradrenaline

Answer 3

a neurotransmitter. released by noradrenergic neurons in the central and autonomic nervous system

Question 4

noradrenaline in the CNS

Answer 4

-participate in modualling attention, perception,learning/memory and (sexual) arousal
-noradrenergic projections mainly originate from the noradrenergic nuclei. the largest noradrenergic locus oeruleus which sens projections that innervate the cortex, amygdala, hippocampus etc…

Question 5

ganglion

Answer 5

A ganglion is a cluster of nerve cell bodies located outside the central nervous system that serves as a relay and processing centre for nerve signals, especially in the peripheral and autonomic nervous systems.
-the gap between cells

Question 6

pre -ganglion neurotrasmitter on the parasympathetic neurone

Answer 6

-ACh acting on nicotinic acetylcholine receptors

Question 7

pre-ganglion neurotransmitters at the in the sympathetic system

Answer 7

ACTh acting on the nicotinic acetylcholine receptors

Question 8

post ganglion neurotransmitter in the parasympathetic system

Answer 8

-ACh acting on the muscarinic receptors

Question 9

post ganglionic neurotransmitters in sympathetic system

Answer 9

-noradrenaline acting on adrenoreceptors

Question 10

varocosities

Answer 10

-sympathetic innervation at the noradrenergic neuro-effector junction=the sympathetic nervous system is sending signals to a target tissue via nerve fibers that release noradrenaline, allowing the sympathetic nervous system to control or modulate the function of that tissue.
-here neurotransmitters are stored and released

Question 11

adrenergic transmission step 1: synthesis

Answer 11

• noradrenaline is syntheised from the amino acid tyrosine which we absorb in our diets within the nerve terminal
  -the rate-limiting enzyme for noradrenaline synethisis= tyrosine hydroxylase
  -tyrosine is converted to DOPA= dopamine via DOPA decarboxylase
  -dopamine is taken up by vesicles= noradrenaline via dopamine B-hydroxlase
  -chromaffin cells on the adrenal medulla converts noradrenaline to adrenaline

Question 12

adrenergic transmission step 2 storage/compartmentation

Answer 12

-Noradrenergic terminal vesicles possess a dopamine/noradrenaline
transporter that allows accumulation of noradrenaline at high concentrations (0.5 - 1 M) inside vesicles

Question 13

adrenergic transmission step 3:release

Answer 13

-Noradrenaline release is triggered by depolarization of the nerve terminal
Ca2+ influx and vesicle fusion with the pre-synaptic plasma membrane.

Question 14

adrenergic transmission step 4: signal transmission

Answer 14

Released noradrenaline can bind adrenoceptors located either pre- or post-
synaptically

Question 15

adrenergic transmission step 5:siginal termination

Answer 15

Noradrenaline is rapidly removed from the synaptic cleft by a high-affinity
uptake mechanism (“Uptake-1” = noradrenaline transporter (NET)). Any
noradrenaline evading this mechanism is cleared by “Uptake-2”.

Question 16

adrenal transmission step 6:metabolism

Answer 16

within the terminal noradrenaline can be metabolized into different end products

Question 17

pharmacological manipulation of adrenergic transmission

Answer 17

-a-methyltyrosine= competitively inhibits tryosine hydroxlase, blocking noradrenaline synthesis
-a-methylDOPA=converts to a-methylnoradrenaline its differs to noradrenaline
-its not metabolised so accumulates in the vesicles
-it is a selective agonist at some adrenoceptors e.g. a2 -adrenoceptors
-Therefore, administering α-methylDOPA causes the accumulation of a
“false transmitter” that out-competes noradrenaline and results in
decreased transmission at sympathetic neuro-effector junctions

Question 18

what’s the role of presynaptic receptors at a2-adrenoreceptor

Answer 18

• Presynaptic receptors often respond to the transmitter released by the
  terminal (“autoreceptors”). This can result in an increased or decreased
  likelihood of further transmitter
• Presynaptic α2-adrenoceptors act as inhibitory autoreceptors decreasing
  noradrenaline release from the terminal.
• α2-adrenoceptors are Gi/o-coupled GPCRs that can decrease adenylyl cyclase
  activity and decrease N/P/Q-type voltage-gated Ca2+ channel opening.

Question 19

factors affecting drug absorption

Answer 19

• Site/method of administration
  (ii) Molecular weight – main determinant of rate of diffusion
  (iii) Lipid solubility – ability to cross lipid membrane by diffusion
  (iv) pH and ionization
  -At low pH weak acids will be mainly in un-ionized form
  Only uncharged species can diffuse across lipid bilayer
  Stomach (pH 3) - weak acids e.g. aspirin uncharged & absorbed
  (v) Carrier mediated transport – active or facilitated
  for polar molecules e.g. amino acids and metal ions
  used by drugs similar to natural substances
  DiffCoeff. α 1/√MWt

Question 20

drug distrubution

Answer 20

Distribution of a drug based on permeability and lipid solubility of the different body compartments

Question 21

blood brain barrier

Answer 21

-based if Paul Ehrlich injection experiment. found that if you inject dye into the brain it stays in the brain and doesn’t go to the rest of the body. same vice versa
-this is because Endothelial cells of blood vessels supplying the brain form tight junctions a barrier to systemically acting drugs
-Only small, fat-soluble drugs can usually cross, which is important to consider for designing medications that target brain conditions
-In cases of inflammation, these tight junctions may weaken or “leak,” allowing more substances to enter the brain. This can impact drug delivery and also make the brain more vulnerable to certain substances that normally wouldn’t get in.

Question 22

drug metabolism

Answer 22

-enzyme modification prior to excretion occurs
-Normally abolishes pharmacological activity (are
exceptions eg. thienopyridines: prodrugs: P2Y12 inhibition)
-

Question 23

drug metabolism phase 1

Answer 23

-usually oxidation, reduction or hydrolysis by
Cytochrome P450 (CYP) monooxygenase system (SmoothER)
CYP enzymes (family of enzymes) involved in drug
metabolism in the liver (93% of known drug metab)
e.g. CYP1A2 acts on caffeine, paracetamol

Question 24

phase 2 of drug metabolism

Answer 24

conjugation – addition of substituent group
(eg.methyl, sulphate, acetyl) – normally inactivates the drug whereas phase 1 might not
(Both phases ↓ lipid solubility: thereby increase kidney clearance)

Question 25

drug excretion

Answer 25

• via the kidney
  -Glomerular filtration: ~20% of glomerular blood flow: cut-off ≈20kDa
  (99% water reabsorbed: passive diffusion of lipid-soluble substances follows
  -Active tubular secretion: many drugs, esp. weak acids,
  important for plasma protein bound drugs
  Renal disease can affect drug clearance - toxicity
• penicillin rapidly cleared from the blood due to filtration
  and active secretion vs diazepam cleared v. slowly
• urine pH influences excretion of weak acids & bases

Question 26

basic renal process

Answer 26

Glomerular filtration: non-discriminant
filtration of a protein-plasma free plasma
from the glomerulus into Bowman’s capsule
- Tubular reabsorption: selective
movement of filtered substances from the
tubular lumen into the peritubular
capillaries
-Tubular secretion: selective movement
of non-filtered substances from the
peritubular capillaries into tubular lumen
- Urine excretion: creation of the medulla
vertical osmotic gradient

Question 27

what affects drug excretion ?

Answer 27

Renal disease can affect drug clearance - toxicity

Question 28

half life (T)

Answer 28

-time for [drug] to decrease by 50%

Question 29

drug absorption

Answer 29

-in most cases to circulate to tissue via the plasma
-Oral & swallowed (most small molecule drugs
-Sublingual (absorption from oral cavity: RAPID
-epithelial surfaces e.g. skin
-inhalation
-injection-= the most direct route
-via the rectum =usually when a patient can’t absorb drugs orally because of vomiting etc..