U22203 (Respiratory, Renal & Cardiovascular Pharmacology): general guide to coursework marking criteria Q1. Answer should include e.g. pharmacological natures of the reagents, sites of action,...

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U22203 (Respiratory, Renal & Cardiovascular Pharmacology): general guide to coursework marking criteria
Q1. Answer should include e.g. pharmacological natures of the reagents, sites of action, relevant receptors occupied and the
involvement of any relevant endothelium derived mediators and any relevant major second messengers in dilator mechanisms
Q2 Answer should include e.g. pharmacological natures of the reagents, sites of action, relevant receptors occupied and the
involvement of any relevant major second messengers in dilator mechanisms
Q3. Answer should include e.g. consideration of relevant phase(s) of relevant cardiac action potential/sites of action, relevant
eceptors occupied and signalling events including the involvement of any relevant second messengers
Q4. Answer should include e.g. consideration of chemical as well as pharmacological natures of these reagents
Q5. Answer should include e.g. consideration of relevant phases of relevant cardiac action potentials/sites/types of action,
elevant receptors occupied and signalling events including the involvement of any relevant second messengers as well as overall
ank potency order for these reagents re raising heart rate and force
Q6. Answer should include e.g. consideration of relevant phases of relevant cardiac action potentials/sites/types of action,
elevant ion channels and relevant mechanisms of excitation-contraction coupling re effects on cardiac force
Q7. Answer should include e.g. consideration of pharmacological nature of ouabain, major site and mechanism of action in vitro
and relevant related cellular chain of events with significance for cardiac force
Q8. Answer should include e.g. consideration of pharmacological nature of verapamil, consideration of relevant phase(s) of
elevant cardiac action potential/site(s) of action and mechanism of action, including effects on relevant ion movement(s)
Q9. Answer should include e.g. consideration of electrical nature of stimulus and relevant mechanisms of action/outcomes for
elevant cardiac ion channels and ion movements and excitability
Q10. Answer should include e.g. consideration of pharmacological nature of propranolol and expected interaction with
autonomic nervous regulation of cardiac function, as e.g. in a whole organism
Q11. Answer should include e.g. consideration of other relevant biological/functional attributes of a whole organism (in vivo)
which could affect pharmacological responses, the influence of which would be avoided by using an in vitro preparation
Q12. The numerical estimate supplied should represent EC50 in µM
NB: references are optional, but not required

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U22203 (Respiratory, Renal & Cardiovascular Pharmacology): coursework

Please submit completed coursework as word document (≤ 1000 words) online by end of Friday, January 10, 2020.
NB: Ensure to enter your student number in both filename of submitted document and in document itself.

Q1. Briefly describe the mechanism of vasodilation to ca
achol and phentolamine in the endothelium-intact, phenylephrine-
preconstricted isolated aorta. (10%)
Q2. Briefly describe the mechanism of relaxation to salbutamol and atropine in the ca
achol-precontracted isolated trachea.
(10%)
Q3. Briefly explain the effects of acetylcholine on heart rate, at a cellular signalling level, in the isolated perfused heart. (15%)
Q4. Comment on why the use of ca
achol in place of acetylcholine is sometimes prefe
ed experimentally. (5%)
Q5. At a cellular signalling level, how do ß-adrenoceptor agonists raise heart rate and force of contraction in the isolated
perfused heart and what is the expected relative order of potency of noradrenaline, adrenaline and isoprenaline with respect to
cardiac effects? (20%)
Q6. Briefly explain the importance of calcium to both heart rate and force of contraction in the isolated perfused heart. (10%)
Q7. Briefly explain the effects of ouabain to raise the force of contraction in the isolated perfused heart. (5%)
Q8. Briefly explain how verapamil is able to reduce the force of contraction in the isolated perfused heart. (5%)
Q9. Briefly explain how high potassium can a
est the heart in diastole in the isolated perfused heart. (5%)
Q10. Describe how the presence of an intact autonomic nervous system might have altered the response to propranolol per se in
the isolated perfused heart. (5%)
Q11. Apart from an intact nervous system, name two more key, physiologically relevant in vivo features that are typically absent
from in vitro preparations. (5%)
Q12. Using data in table 1, estimate the EC50 value for ca
achol in µM, from a plot of the sigmoidal concentration-response
curve. (5%)
Table 1. Contraction in the isolated trachea in response to ca
achol (CCh) (n=1)
Log10 [CCh] (M) in organ bath contraction (g)
-8 0
XXXXXXXXXX
-7 0.3
XXXXXXXXXX
-6 1.2
XXXXXXXXXX
-5 3.25
XXXXXXXXXX
-4 3.5
Answered Same DayJan 07, 2021

Solution

Arundhati answered on Jan 09 2021
52 Votes
6
Respiratory, Renal & Cardiovascular Pharmacology
Student’s Name:
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1. Mechanism of vasodilation
Ca
achol acts on nicotinic as well as muscarinic receptors, and it is administered to decrease intraocular pressure in treating glaucoma[footnoteRef:1]. Phentolamine generates its therapeutic activities through blocking alpha-adrenergic receptors and lead to muscle recreation along with the
oadening of blood containers. The primary action of phentolamine is vasodilation and selecting alpha-blockers can cause relaxation of systematic vasculature that led to hypotension. The mechanism of action of phentolamine is adrenergic alpha antagonist while ca
achol is nicotinic receptors and increase aqueous humor outflow. [1: Ishida H, Saito SY, Horie A, Ishikawa T. Alleviation of mechanical stress-induced allodynia by improving blood flow in chronic constriction injury mice. European journal of pharmacology. 2019 Apr 15;849:67-74.]
2. Mechanism of relaxation
Salbutamol in the mechanism of relaxation increase airflow and provide rapid relief of acute asthma[footnoteRef:2]. The peak of salbutamol is within 30 minutes of administration. It usually acts on beta two adrenergic receptors that are found on smooth muscle airways of lungs. It acts as a functional antagonist for relaxing the airway of spasmogen. Atropine has a relaxation effect at the higher concentration on smooth muscle. It is categorized as an anticholinergic drug and considered as an antimuscarinic agent. It inhibits actions of muscarinic ACH on structures innervated by cholinergic nerves. It is usually used for reducing saliva and other secretions in airways during surgery. [2: Rodríguez‐Ramos F, Andrade‐Moreno MÁ, Alfaro‐Romero A, Balderas‐López JL, Nava
ete A. Gnaphaliin A and gnaphaliin B synergize the relaxant effect of salbutamol but not of ipratropium in guinea pig trachea. Journal of Pharmacy and Pharmacology. 2016 Apr;68(4):533-41.]
3. Effects of acetylcholine on heart rate
It is identified that acetylcholine binds to muscarinic receptors and cause a decrease in the heart rate. In isolated heart muscle, acetylcholine depresses atrial contractions but contain the positive inotropic effect on ventricular muscle under specific conditions[footnoteRef:3]. Moreover, neurons are motivated by the parasympathetic nervous system to issue neurotransmitter acetylcholine at synapses in order to decrease heart rate. When the effect of acetylcholine changes in contractility, isoprenaline produce the heart rate activity in the perfused heart. Increased intracellular level generated by ACH may influence the heart rate at a cellular level. ACH released as neurotransmitter from the cranial nerve that results in reducing cardiac rate. [3: Liu Y, Scherlag BJ, Fan Y, Xia W, Huang H, Po SS. Acetylcholine–Atropine Interactions: Paradoxical Effects on Atrial Fi
illation Inducibility. Journal of cardiovascular pharmacology. 2017 Jun 1;69(6):369-73.]
4. Reason of using ca
achol instead of acetylcholine
Ca
achol is the ca
amate ester and ammonium salt that act as a nicotinic acetylcholine receptor and cardiotonic drug. It is primarily used for treating glaucoma and during ophthalmic surgery. It is considered as a potent cholinergic agent...
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