Pharmacology - Watson Flashcards
What is the primary transmitter in nicotinic receptors?
Acetylcholine
Explain what M1 and M2 receptors cause when Ach binds
Also what is the effect of neuropeptides?
M1 –> Causes K+ channels to close, causing a slow EPSP
M2 –> Causes an increase in K+ conducatance, causing hyperpolarisation (slow IPSP)
Neuropeptides act as co-transmitters –> causing late/slow EPSPs
Why are local anasthetics co-administered with a vasoconstrictor?
To prevent the anasthetic going elsewhere in the body (to keep it local to the ganglion that its injected into)
What are the different drugs that can be used to block different parts of the synthesis pathway of noradrenaline/adrenaline?
(a)-methyl-p-tyrosine –> Inhibits the Tyrosine Hyroxylase
Carbidopa –> Inhibits DOPA Decarboxylase
Often taken with Levodopa to reduces levodopas peripheral effects
How is the release of NA regulated?
Normally the depolarisation of a nerve terminal causes Ca2+ channels to open, which cause NA to be released from vesicles
The NA then binds to presynaptic receptors (a2-adrenoceptors) when there is too much
This causes the inhibition of adenylyl cyclase, which limits the amount of cAMP thats produced….so less calcium channels are opened
Explain how NA transmission can be terminated?
Neuronal Epinephrine Transporters (NET) are located on the presynaptic membrane, and reuptake NA into the presynaptic nerve terminals
Vesicular Monoamine Transporter (VMAT) uptakes NA back into vesicles, with ATP. This is because they have oppostie charges, so vesicle leakage doesn’t occur.
Extraneuronal Monoamine Transporter (EMT) actively transports NA into the post synaptic cell, where is it metabolised by catechol o-methyl Transferase (COMT)
How do the following drugs work to prevent NA transmission?
Methydopa
Guanethidine
Reserpine
Methyldopa –> An a2 agonist, so promotes the inhibition of adenylyl cyclase
Also inhibits DOPA decarboylase (like carbidopa)
Guanethidine –> A substrate for NET and VMAT (so accumulates in vesicles), preventing depolarisation
Reserpine –> Inhibits VMAT, so NA floats around outside before being matabolised by MAO
There are 3 types of B, and 2 types of A adrenoreceptors…. but which GPCRs do they bind to?
A1 –> Gq Which activates Phospholipase C
B1/2/3 –> Gs Which activates Adenylyl cyclase
A2 –> Gi Which inhibits Adenylyl cyclase
What are some of the uses/effects of direct sympathomimetics?
(A)1 Selective –> Vasoconstrictors (eg, phenylephrine)
(A)2 Selective –> Prevent NA release, so reduce BP (eg, clonidine) with their main action in the medulla
B Agonists –> Increase cardiac contractility (eg, adrenaline in anaphalactic shock)
Give some example of indirect acting sympathomimetics
And how do they work?
Amphetamines –> Substrates of NET/VMAT and inhibit MAO…..so there is a greater conc of NA in the synapse
Cocaine –> Inhibits NET, so there is more NA in the synapse
Name some examples of non-selective (a)-adrenoceptor antagonists
Labetalol/Carvedilol
Phenoxybenzamide –> long lasting due to convalent bonding
Also blocks Ach, 5HT and histamine
Phentolamine –> Short acting, and more selective
What are selective A1 antagonists?
-azosin drugs –> eg, Prazosin and Doxazosin
Directly block the action of NA/A on smooth muscle –> Causing vasodialation….and so a fall in BP
Causes less tachycardia than non-selective antagonists, but still causes postual hypotension
Name an a2 selective antagonist
Yohimbine
What are some of the unwanted effects of B-Blockers?
Bronchoconstriction –> Via B2 receptors
Bradycardia
Hypoglycaemia –> due to glucagon release normally occuring due to adreanline binding to B2 receptors. B-Blockers also blocks hypoglycaemia symptoms such as tremors –> causing ‘hypoglycaemic unawareness’
Fatigue
Cold Extremities –> Due to loss of B2 mediated vasodialation
Lucid Dreams
Atenolol and Timolol are example of what?
B1 selective B antagonists (blockers)
What are the key characteristics of Metabolic Syndrome?
Abnormal carbohydrate and lipid metabolism
Insulin resistance
Elevated fasting blood glucose
Hypertension
Dyslipidaemia
What are the risk factors for Metabolic Syndrome?
Visceral obesity
Age and Weight
Race –> More prevelant in afro-carribean/asian population
Having Non-alcoholic liver disease
A history of gestational diabetes (pregnancy)
Smoking –> due to increasing cortisol levels via the sympathetic nervous system
Having metabolic syndrome is a key risk factor for what 2 other diseases?
T2DM –> 5 fold risk
CVD –> 2 fold risk
What are adipocytes?
Three types –> White/Brown/Brite
Brown –> Used in thermogeneosis… has high levels in neonates, but falls drastically with age
Brite –> Used in the storage and expenditure of fats
These secrete adipokines….such as Leptin and Adiponectin
Explain what the 2 adipokines are
Leptin –> Suppresses hunger (stimulates satiety)
Its levels increase in obesity….but you can become resistant to it…especially in a high fructose diet!!
Adiponectin –> Increases insulin sensitivity and fatty acid catabolism (decreasing triglycerides). Also decreases hepatic glucose production
Levels drop in obesity
Levels can be increased by glitzone drugs (thiazolidinediones)
Why is an increased conc of Urea an indicator for metabolic syndrome?
As arginase is increased in MS, causing more of L-arginine to be converted to urea…. instead of being converted to NO (a vasodialator)
What is peroxynitrite?
The end product of ROS reacting with NO……preventing NO from acting as a vasodilator
Why could a faecal transplant be useful for those suffering from Metabolic Syndrome?
As during MS, acetate-producing bacterial populations are selected in the gut due to the high fat/sugar diet
This stimulates insulin and grehlin (hunger hormone) production
Therefore this leads to obesity
However a faecal transplant can add healthy/normal bacteria back to the gut
