TOPIC C: ANS Flashcards
What form of communication does noradrenaline rely on
Synaptic communication
What form of communication does adrenaline rely on
Endocrine communication
Outline the synthesis of noradrenaline
Occurs in adrenal medulla and neurons
Tyrosine transported into cell and converted to DOPA by tyrosine hydroxylase
DOPA converted to dopamine by DOPA decarboxylase
Dopamine put in storage vesicles by VMAT protein and then converted to NA by beta hydroxylase in vesicle
Explain termination of NA by reuptake
Reuptake of NA into neurons is most important and immediate effect
Reuptaker protein
NA that doesn’t go back into storage is metabolised by monoamine oxidase (MAO)
Outline the synthesis of adrenaline
Occurs in adrenal medulla
Adrenaline is synthesised from noradrenaline by PNMT enzyme
What is a beta 1 receptor usually involved in
force and rate of contraction
What is a beta 2 receptor usually involved in
relaxation
Where are beta 1 receptors found
heart
liver
skeletal muscle
Where are beta 2 receptors found
lungs (bronchial smooth muscle)
blood vessel beds in skeletal musclw
Where are beta 3 receptors found
White and Brown adipose tissue
Skeletal muscle
What beta receptors are involved in sympathetic energy metabolism. And what do they do
1: Glycogenolysis in liver and muscle by activating glycogen phosphorylase and inhibiting glycogen synthase by cAMP pathway. Uptake of glucose into muscle
3: Lipolysis in WAT. Thermogenesis in BAT. By cAMP pathway
How does BAT thermogenesis by the beta 3 receptor work
Uncoupling protein 1 (UCP-1) generates heat instead of ATP in mitochondria.
cAMP pathway encourages lipolysis and fatty acids are used to produce heat
What beta receptor is involved in cardiovascular function. And what does it do
beta 1 increases:
force of contraction, HR, AV conduction, CO SV
What would a beta 1 antagonist do with respect to exercise
decrease exercise tolerance due to beta 1 involvement
What beta receptor is involved in bronchiolar function. And what does it do
beta 2
Circulating catecholamines like adrenaline cause bronchodilation
What is a side effect of beta 2 agonists used for bronchodilation
muscle tremor due to beta 2 receptors also being in skeletal muscle
What is a side effect of beta 2 antagonists used for bronchodilation
bronchospasm
worsening of asthma in asthmatics
What beta receptor is involved in sympathetic skeletal muscle function. And what does it do
beta 2
vasodilation
what are examples of a non selective agonist and antagonist of beta receptors
agonist: isoprenaline
antagonist: propranolol
what are examples of selective agonists and antagonists of beta 1 and 2 receptors
1 agonist: dobutamine
1 antagonist: metoprolol
2 agonist: salbutamol, clenbuterol
2 antagonist: —
Expected effects of beta receptor agonists
increased HR and force
Increased blood flow to skeletal muscle
Widening of bronchi
Enhanced muscle tremor
Expected effects of beta receptor antagonists
Fatigue
Cold extremities
Narrowing of bronchi
Steadiness of skeletal muscle
What the main effects on the body due to sympathetic nerve stimulation
Mydriasis (eye dilation)
Bronchodilation
Tachycardia
Decreased GI motility
Define pharmacokinetics
How the body interacts with the drug
Define pharmacodynamics
How drugs act to alter body function
What are the roles of the liver
distribution of nutrients
metabolism
excretion
destruction of toxic substances
storage of iron, vitamins
What are active and pro drugs
Active drugs are drugs which can act straight away on the body.
Pro drugs need to be metabolised first to a different product which is active.
What are the 4 steps of the pharmacokinetic phase
absorption
distribution
metabolism
excretion
Why do drugs need to have components of both lipid and water solubility
cross lipid membranes to get into cells
cross water filled spaces to be distributed
What are 4 ways of administering a drug
inhalation
intranasal
topical (skin, eye, ear)
Intravenous
Explain the thiopentone example
intravenous drug used as an induction anaesthetic.
anaesthesia reached within 20 seconds due to intravenous meaning reaches brain quicker
lasts only for 5-10 minutes not by being metabolised but by being redistributed into other tissues
What does the liver do in metabolism of drugs
converts lipid soluble to water soluble to be excreted in urine (called bio-transformation)
Explain phase 1 of drug metabolism in the liver
makes drug more polar by adding reactive group and permitting conjugation
cytochrome P450 family of enzymes
Explain phase 2 of drug metabolism in the liver
Conjugates drug and adds endogenous compound to increase polarity
UDP glucuronosyl transferase
Outline cytochrome P450 family of enzymes
drug metabolising enzymes in liver and small intestines
also involved in biosynthesis and degradation of endogenous substances
CYP3A4 common enzyme
Factors affecting drug metabolism
Genetic variability Race and ethnicity Age Gender Diet Disease Drug interactions
Toxicity of paracetamol example
Normally metabolised by glucuronide sulfates, small percentage converted to NAPQI (toxic)
NAPQI detoxified by glutathione
when glutathione is depleted, NAPQI reacts with thiol groups on liver cell membranes
Body needs a lot of glucuronide sulfates and glutathione to process paracetamol safely.
