Case studies and short answer question relating to the peripheral nervous system PDF

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Tutorial case studies with comprehensive answers
Course Co-ordinator Sheila A Doggrell...

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LSB384 Pharmacology for Health Professionals Tutorial: Case studies and short answer question relating to the peripheral nervous system

Case studies Paul A suffers from peanut allergy. On Monday morning, Mrs A dropped her son Paul off at the Kindergarten, on her way to work, as usual. Later that day, the head of Kindy phoned, to say that there was a major problem, as Paul had been given a peanut sandwich at morning break by one of the other children, and had developed a serious hypersensitivity reaction. Fortunately, one of the staff was a trained nurse, and used the EpiPen, and Paul was now recovering.

Which drug does an EpiPen contain? Adrenaline How does this drug overcome a serious hypersensitivity reaction? In anaphylaxis there is vasodilation and bronchoconstriction. Adrenaline is both an -adrenoceptor agonist. As an -adrenoceptor agonist it promotes peripheral vasoconstriction and increases venous return and as a -adrenoceptor agonist it dilates the bronchial and gastrointestinal smooth muscle, increases the force of the heart contractions and decreases the inflammatory mediator release, hence counteracting the anaphylaxis.

Are there any unwanted effects of this drug when used in hypersensitivity reactions?

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Tachycardia – from stimulation of -adrenoceptor which increases myocardial contraction and therefore increase in heart rate Hypertension – from stimulation of -adrenoceptor causing an increase in peripheral vascular resistance and therefore an increase in blood pressure. Raised blood glucose levels – from stimulation of -adrenoceptor which decreases insulin release and the uptake of glucose by peripheral tissues, raising BGL.

On Wednesday, Mrs A took her father, Arthur, who has chronic obstructive pulmonary disease (COPD) to the doctor, as his COPD was not well managed with salbutamol.

What other bronchodilator that affects the parasympathetic nervous system could Arthur have been prescribed? Ipratropium – inhibits interaction of Ach at receptor sites on the bronchial smooth muscle resulting in bronchodilation. Explain how both drugs interact with the autonomic nervous system. Autonomic nervous system is made up of the sympathetic (SNS) (fight or flight response) and parasympathetic (PNS) (conserves energy and body resources) nervous systems. Salbutamol – 

mimics some of the effects of SNS stimulation ( heart rate,

 vasoconstriction,  bronchodilation) = sympathomimetic 

-adrenoceptor agonist



causes bronchodilation by action on the -adrenoceptors , causing increased levels of cAMP which relaxes smooth muscles. It acts as a functional antagonist of airway smooth muscle contraction.

Ipratropium

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

blocks some of the effects of the PNS like  heart rate & bronchoconstriction = parasympatholytic



Anticholinergic bronchodilator / antimuscarinic agent.



In the PNS, Acetylcholine (Ach) muscarinic receptors (M2 & M3) that are present on bronchial smooth muscle cells and glands, mediate the contraction of smooth muscle (bronchoconstriction) and stimulation of bronchial secretions. Ipratropium binds to muscarinic receptors mimicking the action of Ach on the PNS, reversing the Ach –mediated bronchoconstriction

Salbutamol + ipratropium combined 

combined  adrenoceptor agonist plus antimuscarinic (SNS + PNS effects) may give a better bronchodilation in COPD.

On Friday, Mrs A went to the hospital to pick up her neighbour Mrs B, who had had elective surgery. The nurse approached Mrs A, and told her that unfortunately the effects of the drug given to Mrs B to relax her muscles, which was supposed to wear off quickly, hadn’t. Apparently, Mrs B was the 1 in 3000, who did not recover from this drug quickly. The nurse suggested Mrs A come back the next day to pick up Mrs B. Which drug was Mrs B given as a muscle relaxant? Succinylcholine (also known as suxamethonium) It inhibits nerve impulses by acting as an agonist at the nicotinic receptors. Binding with these receptors results in persistent stimulation and depolarisation, antagonising the action of Ach causing paralysis of the skeletal muscle. Why was she slow to recover from it? Succinylcholine is rapidly metabolised by psuedocholinesterase so effects normally only lasts 5 minutes. 1/3000 people do not have pseudocholinesterase so cannot metabolise succinylcholine quickly, with effects lasting 20h. Could Mrs B’s prolonged paralysis have been reversed with an anticholinesterase? 3

No, as it will not reverse depolarising neuromuscular blockers like succinylcholine. In the case of non-depolarising drugs it can be reversed by anticholinesterase as it will compete for the nicotinic receptors, hence more Ach will decrease the effect of the antagonist. However, in the case of depolarising drugs, being agonists rather than reversible antagonists, they maintain the depolarised state and use of an anticholinesterase agent will actually prolong the depolarisation blockade.

Which group of drugs should Mrs B be given in the future for muscle relaxation during anaesthesia? Non-depolarising drugs such as Mivacurium, Vecuronium, and Rocuronium. They can be reversed by anticholinesterases, by the increased Ach competing with the non-depolarising agent and will replace it.

How do the muscle relaxants work? Normally the stimulation of the the nicotinic receptors (N M –receptors responsible for skeletal muscle action) by Ach triggers muscle action potential and inturn muscle contraction. For the neuron to receive another impulse, Ach is broken down. Acetylcholinesterase breaks down the Ach preventing accumulation of Ach and constant stimulus and continuous muscle contraction. Neuromuscular blockers inhibit this process. 2 types: 1. Non-depolarising: competitively block the action of Ach on NM –receptors, blocking the normal feedback loop that increases Ach release. 2. Depolarising: bind to the NM-receptors, causing persistent depolarisation and loss of excitability as Na+ channel remains open and can no longer respond to electrical stimulus hence paralysis.

SAQ

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Discuss with named examples, the clinical uses and adverse effects of drugs that antagonise the effects of noradrenaline and/or adrenaline at β-adrenoceptors. Effects of noradrenaline and adrenaline at β-adrenoceptors Activation of SNS leads to release of Noradrenaline  

stimulates -adrenoceptor of the heart to  heart rate and force 

cardiac output. 

stimulates -adrenoceptor in the blood vessels resulting in vasoconstriction. The combination of the cardiac output & vasoconstriction results in  BP.



stimulates -adrenoceptor of the kidney   renin secretion  angiotensin II system  vasoconstriction & aldosterone release  salt and water retention  BP.

The release of adrenaline by SNS activation 

stimulates -adrenoceptor in the blood vessels resulting in vasoconstriction



stimulates -adrenoceptor on blood vessels in skeletal & bronchial smooth muscle  vasodilation and bronchodilation.

Combination of vasoconstriction + vasodilation  little effect on the heart or BP. 

In fight or flight response and higher concentrations of adrenaline stimulates -adrenoceptor of the heart to  heart rate



stimulates -adrenoceptors of the liver tp promote conversion of glycogen to glucose and amino acids to glucose, overcoming hypoglycaemia.



Stimulates -adrenoceptors in the eye to promote aqueous humour formation   pressure in the eye.

Drugs that antagonise the effects of noradrenaline and/or adrenaline at β-adrenoceptors.

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-Blockers  eg. Propanol 

non–selective β-adrenoceptor antagonists



Prevent NA stimulating -adrenoceptor of the heart   heart rate & force



Prevent NA stimulating -adrenoceptor of the kidney  activity of renin-angiotensin system   BP.



Inhibits vasodilation by adrenaline

Clinical use = Treatment of hypertension. Adverse effects = 

decreased exercise capacity due to the  NA release. NA allows an increased exercise tolerance due to  Heart rate & force.



 vasodilation  less heat delivered to extremities  cold fingers & toes.



Bronchoconstriction by preventing stimulation -adrenoceptor on bronchial smooth muscle by adrenaline  may precipitate asthma attack in asthmatics.



Hypoglyceamia due to its inhibition of adrenaline to promote production of glucose by its stimulation of -adrenoceptors of the liver  may be a problem in diabetics.

eg. Atenolol 

Selective (but not specific) -adrenoceptor antagonist



Prevent NA stimulating -adrenoceptor of the heart   heart rate & force

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

Prevent NA stimulating -adrenoceptor of the kidney  activity of renin-angiotensin system   BP.



Inhibits vasodilation by adrenaline

Clinical use = Treatment of hypertension. Adverse effects = 

Less adverse effects than propranolol – less ability to get into CNS.



Contraindicated in asthmatics as can have some -adrenoceptor effects as its not specific for -adrenoceptor



Can be used with caution in diabetics as more selective than Propranolol.

Eg. Esmolol 

Short acting non–selective β-adrenoceptor antagonist

Clinical use = Used in hypertensive emergency to reduce BP quickly. Eg. Timolol

-adrenoceptor antagonist  blocks the stimulation of  -adrenoceptors in the eye by adrenaline



which  aqueous humour formation   pressure in the eye.

Clinical use = Used in drops for glaucoma Adverse effects = 

needs to be local use only as has potential to block all -adrenoceptors in the body.

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