adrenergic pharmacology

Question 1

how sensitive are adrenoceptors to adrenaline, noradrenaline and isoprenaline

Answer 1

alpha receptors: adrenaline>noradrenaline»> isoprenaline

beta receptors: isoprenaline> adrenaline»> noradrenaline

Question 2

how do beta receptors differ

Answer 2

beta 1 is excitatory and innervated (synaptic activation)

beta 2 is inhibitory (usually) non innervated (responds to circulating adrenaline)

Question 3

what are main cotransmitters in sympathetic system

Answer 3

ATP, others such as NPY

Question 4

what sympathetic innervation is mediated via Ach

Answer 4

innervation of adrenal medulla via preganglionic neurones, termed a modified ganglion

innervation of sweat glands in skin on muscarinic receptors

Question 5

what is the name of the group that contains adrenalines and dopamine

Answer 5

catecholamines

Question 6

where are beta 1 receptors found and what are the physiological effects of stimulating them

Answer 6

in the heart, juxtaglomerular aparatus and adipose tissue,

heart: increase in rate and contractility

juxtaglomerular apparatus: release of renin

adipose tissue: lipolysis

Question 7

where are beta 2 receptors found and what is effect of stimulating them

Answer 7

bronchial smooth muscle, uterine smooth muscle and skeletal muscle vasculature,

relaxation of smooth muscle

in liver and muscle:

in liver: breakdown of glycogen to glucose via acitvation of protein kinase A

muscle: mediates breakdown of glycogen to lactic acid (may cause hyperlactic academia), also causes increased activation of sodium/potassium ATPase pump, causes blood potassium to drop

Question 8

what type of receptors are adrenoreceptors

Answer 8

all GPCRs

alpha 1 coupled to phospholipase C, so causes increase in IP3 and DAG, Gq

alpha 2 are Go, so inhibit adenylate cyclase

beta receptors activate adenylate cyclase and protein phosphorylation via protein kinase A, both are Gs

Question 9

what effect do alpha 1 receptors have on liver

Answer 9

cause release of potassium from liver to blood

Question 10

where are alpha 2 receptors used post junctionally

Answer 10

(almost always autoreceptors for negative feedback)

post junctionally: cause platelet aggregation

Question 11

what receptors are adrenaline, noradrenaline and isoprenaline selective for

Answer 11

adrenaline: all adrenoreceptors
noradrenaline: all except beta 2
isoprenaline: beta receptors

Question 12

what are clinical uses of adrenaline

Answer 12

treatment of:
anaphylactic shock

glaucoma: acts on alpha 2 receptors, causes vasoconstriction of afferent arterioles, reduces aqueous humour production, so reduces pressure in the eye, also act on veins which drains the canal of schlemm which aids in absorption of the aqeuous humour

cardiac arrest

prolongation of action of local anaesthetics (by vasoconstriction)

Question 13

what action does clonidine have, how is it used therapeutically

Answer 13

alpha 2 agonist

used as antihypertensive drug

Question 14

what are therapeutic effects of alpha 1 agonists

Answer 14

cause vasoconstriction

phenylepherine used as nasal decongestant

used to prolonged local anaesthetic action

Question 15

what is dobutamine

Answer 15

a beta 1 agonist, used for treatment of cardiogenic shock

Question 16

how are beta 2 selective agonists used therapeutically?

what are unwanted effects

Answer 16

salbutamol: used in asthma to produce bronchodilation, in premature labour to relax uterus

unwanted effects: hypokalaemia, tremor, vasodilation leads to fall in blood pressure causing reflex tachycardia

Question 17

what effect do ergot alkaloids have

Answer 17

they are alpha adrenoceptor agonists

derivatives of LSD

are also agonists of 5HT and dopamine receptors

used to treat migraine and postpartum haemorrhage

Question 18

name classic antagonists of adrenoceptors and which ones they work on

Answer 18

phentolamine: alpha 1 and alpha 2 antagonist
prazosin: alpha 1 antagonist (minor alpha 2 antagonism)
propranolol: competitive reversible antagonist for beta receptors
atenolol: beta 1 antagonist (minor beta 2 antagonism)

Question 19

what action does phenoxybenzamine have

Answer 19

irreversible non competitive antagonist for alpha adrenoceptors

acts by forming covalent bond

this type of antagonism shows reduction in slope of log dose response curve and decrease in max response to agonist

Question 20

what are physiological consequences of alpha adrenoceptor blockade

Answer 20

fall in blood pressure, causes sympathetic drive on beta receptors causing reflex tachycardia and sodium and water retention by renin

postural hypotension

nasal congestion

miosis (constriction of pupil)

Question 21

what are therapeutic uses of alpha adrenoceptor blockade

Answer 21

treatment of hypertension and benign prostatic hyperplasia

Question 22

what action does atenolol have

Answer 22

cardio selective beta 1 antagonist

Question 23

what are therapeutic uses of beta antagonists

Answer 23

treatment of angina, hypertension, glaucoma, myocardial infarction, arrhythmias

Question 24

what effect does disulfiram have

Answer 24

is a copper chelating agent;

prevents synthesis of NA by inhibiting dopamine beta hydroxylase, which converts dopamine to noradrenaline

giving L-DOPA increases rate of synthesis

Question 25

what effect does reserpine have?

Answer 25

depletes vesicular storage of NA by preventing passage of catecholamines into storage vesicles

Question 26

what effect does tetrabenazine have, how is it used

Answer 26

short acting noradrenaline and dopamine depletory, used in treatment of hyperkinetic disorders such as huntingtons

Question 27

what effect does clonidine have

Answer 27

alpha 2 agonist, inhibits NA release, is an antihypertensive drug

Question 28

what effect does guanethidine have

Answer 28

enters via uptake and inhibits release of NA, also blocks sodium channels

used as local anaesthetic, has tyramine like actions

Question 29

what are MAO inhibitors used for

Answer 29

treatment of depression

phenelzine is a non selective MAO inhibitor used to treat depression

Question 30

what effect does catechol-O-methyl transferase

Answer 30

only breaks down catechols

found in neuronal and non neuronal tissues

breaks down NA after it is broken down by MAO

Question 31

what are indirect acting sympathomimetics, name one and how does it work

Answer 31

tyramine causes effects of nerve stimulation in absence of nerve stimulation (indirect acting sympathomimetic) by displacement of neuronal NA from cytoplasmic pool

tyramine is taken up by NET (norepinepherine transporter) into terminal

it is then taken into vesicle by vesicular monoamine transporter (VMAT), in exchange for noradrenaline which escapes into cytoplasm

some of this cytoplasmic NA is metabolised by MAO, the rest escapes by retrotransport

this process does not require calcium or exocytosis