pharmacology assignment

pharmacology assignment

All textbooks in pharmacology present tables and figures that illustrate the complex array of physiological
effects produced by activation of the sympathetic and parasympathetic nervous systems. Referring to
Figure 11-2 on page 193 and Table 11-1 on page 194 of Bryant and Knights, Pharmacology for Health
Professionals, 3rd Edition, 2011, recreate and complete the following table in your workbook;
?? For each body system list the effect of activating the parasympathetic and sympathetic nervous
systems in the first two columns, then in the third column, describe a clinical symptom or condition
that may be observed in someone with a highly activated parasympathetic nervous system. (Total of
7.5 marks for Question 1)
Body System Parasympathetic Sympathetic Clinical Symptom /
Condition
e.g. Heart – Rate Decrease Increase Bradycardia
Heart – Force of
Contraction Decreases(Atria) ?? Increases?? Shock and
Faintinghypotension/heart failure
Pupil Dilationconstriction Dilation Mydriasismiosis
Lung Bronchiolar smooth muscle
contraction??
Bronchiolar smooth muscle
relaxes?? Asthma (bronchoconstriction) ??
Stomach
Increases gastric secretion
increased motility
Smooth muscle wall contraction
Sphincter relaxation??
Smooth muscle wall relaxation
decreased motility
Sphincter contraction??
DiarrheaDiarrhoea??
Male Sex Organs Erection?? Ejaculation?? Shock and fainting priapism
(2.5 Marks) (2.5 Marks) (2.5 Marks)
?? 4
Workbook Learning Activity 2
Recreate and complete the following table in your workbook;
?? For each drug; in the first column, identify ONE paramedic indication, then in the subsequent
columns, list the molecular target involved in the identified interaction, the type of interaction (i.e.
agonist / antagonist / allosteric modulator / inhibitor), and briefly explain how this interaction of the
drug with the molecular target accounts for the observed therapeutic effect for that indication. (Total
of 25 marks for Question 2)
Drug Paramedic
Indication
Drug
Target
Type of
Interaction Therapeutic Effect
e.g.
Salbutamol Acute Asthma ??2-
adrenoceptor Agonist
Activation of ??2-
adrenoceptors in the lung
causes relaxation of the
bronchiole smooth muscle,
bronchodilation and
increased airflow.
Adrenaline Asthma?? ??2-
adrenoceptor?? Agonist??
??2-adrenoceptors activation in the
respiratory system stimulate the
activation of adenylyl cyclase
therefore increasing cAMP
concentration which stimulate
relaxation of bronchiolar smooth
muscles and bronchodilation,
increasing air passage… ??
Fentanyl
Severe pain
Adjunct in
anaesthesia??
?? receptor??
Variable affinity
to ?? and ??
Agonist??
Close voltage gated calcium and
potassium channels via ??, ?? and ??
receptors therefore reducing nerve
transmitter release, hyperpolarization
and postsynaptic neuron inhibition??
Ondansetron
Surgical and
chemotherapy
induced nausea and
vomiting??
5-HT32??
(serotonin)
receptor
Antagonist??
Block serotonin receptors in the
vomiting centre, chemoreceptor
trigger zone and peripheral extrinsic
intestinal vagal and spinal afferent
nerves ??
Midazolam
Panic attacks
Acute anxiety attacks
Relaxation of skeletal
muscles
Insomnia and sleep
disorders
Epileptic/seizures
GABAA
receptor??
Agonist allosteric
modulator
Bind to GABAA and facilitate GABAmediated
chloride ion channel
opening and enhancing membrane
hyperpolarisation??
Ipratropium
Acute
Bronchospasms
(Asthma) ??
M (muscarinic)
receptor?? Antagonist??
Muscarinic antagonist competitively
inhibit acetylcholine effects at
muscarinic receptors blocking airway
?? 5
smooth muscle contraction and mucus
secretion Bronchodilation
Atropine
Organophosphates,
carbamates and
anticholinesterase
inhibitors
Retinal examination
(fundoscopy)
bradycardia
M (muscarinic)
receptor?? antagonist??
Competitive antagonist at all M
receptors causing mydriasis and
inhibiting muscarinic excess caused
by poisoning increased heart rate
Adenosine
Paroxysmal
supraventricular
tachycardia??
Ca2+????and??K+
A1/A2
Blocks Ca2+ and
activated K+
agonist
Activates inward potassium rectifier
channels and inhibits calcium
channels causing hyperpolarisation
and Ca2+ action potentialSlows AV
node conduction/vasodilation
Ketamine
Anaesthesis and
analgesic(Pain
reliever) ??
NMDA Receptor
??
Blockade(Antagonist)
??
Blocks NMDA therefore inhibiting
central stimulation of pain at
supraspinal and spinal levels analgesia
??
Naloxone Opioid overdose and
addiction??
??,?? and ?? opioid
receptor?? Antagonist ??
Rapid antagonist at all of opioid
receptors therefore reducing all opioid
effects (e.g. respiratory depression) ??
Aspirin
Unstable angina
Myocardial infarction
Mild-moderate pain
Transient ischemic
attacks
Coronary artery
thrombosis??
COX 1
(Cyclooxygenase)
??
Antagonist(Inhibitor)
??
Irreversibly inhibits cyclo-oxygenase
enzyme reducing inflammation and
platelet(clotting) effects??
(5 Marks) (5 Marks) (5 Marks) (10 Marks)
Workbook Learning Activity 3
In pharmacodynamics, a drug can be thought of as ‘selective’ when it shows a significant preference for
interaction with one molecular target, even though it may be faced with many molecular targets to choose
from. Indeed, salbutamol can act as an agonist at all ?? adrenergic receptors, but at therapeutic doses it
‘selects’ the ??2 adrenergic receptor subtype in preference to others.
In this workbook learning activity you will need to recreate and complete the following table in your
workbook, considering the drugs used in your clinical practice as a paramedic:
?? In the first column, list FIVE receptors from different classes, then list their endogenous
agonist(s) in the second column.
Receptor Endogenous Substrate Selective agonist or antagonist
used in paramedic practice
?? 6
?? In the third column give an example of ONE drug that is a clinically
relevant SELECTIVE agonist OR antagonist for each of the receptors. (Total of 10 marks for
Question 3)
Workbook Learning Activity 4
Antagonists at receptors for neurotransmitters or hormones are often used clinically.
1. Consider drugs that are antagonists of ?? adrenergic receptors and briefly explain how they
produce clinically useful effects.(2.5 marks)
?? blockers occupy beta receptors and competitively reduce receptor occupancy of
catecholamines and other beta agonists. A few bind irreversibly to beta receptors.
They therefore inhibit activity of beta adrenergic stimulation in sites with the receptor,
for example in the heart and blood vessels in treatment of hypertention.(Potentiation
of adrenergic innervations)(1.5)
2. Considering the actions of ??-adrenoceptors in the body identified in part (1), would it be
the most appropriate treat unc
omplicated hypertension in 68 year old patient with
moderate asthma and renal impairment with atenolol, metoprolol or propranolol? Briefly
explain the reasons for your decision. (5 Marks; Total of 7.5 marks for Question 4)
Metoprolol ??
Hypertention is treated by blockade of beta 1 receptors(dominant adrenergic receptor
in the heart) to reduce contractility and heart rate. Beta adrenoceptor blockade also
has a positive role in renal impairment where they reduce Renin secretion which
reduces the vascular tone and renal blood flow and therefore reducing the renal
workload. Asthma is aggravated by stimulation of beta 2 receptors due to the
bronchoconstriction it exhibits. Propranolol is a non-selective beta adrenergic blocker.
Despite having beta 1 blockade which is beneficial, it also causes beta 2 blockade
which may worsen the patient’s asthmatic condition. Metoprolol and atenolol are the
best to use in the patient’s condition since they reduce myocardial contractility and
renin production via their beta 1 blockade. Metoprolol is however more effective than
atenolol in reducing hypertension complications and heart failure.(4) Atenolol is
eliminated by the kidneys which is not ideal in this situation.
??1 adrenoceptor ?? Epinephrine adrenaline Atenolol (antagonist)??
??2 adrenoceptor Epinephrine Isoproterenol(Agonist)
??1 adrenoceptor Norepinephrine Prazosin(antagonist)
??2 adrenoceptor Norepinephrine Clonidine(agonist)
5-HT1A?? Serotonin?? Buspirone (agonist)??
5-HT2 Serotonin Cimetidine(antagonist)
Workbook Learning Activities for Module 2

Workbook Learning Activity 1

All textbooks in pharmacology present tables and figures that illustrate the complex array of physiological effects produced by activation of the sympathetic and parasympathetic nervous systems. Referring to Figure 11-2 on page 193 and Table 11-1 on page 194 of Bryant and Knights, Pharmacology for Health Professionals, 3rd Edition, 2011, recreate and complete the following table in your workbook;
• For each body system list the effect of activating the parasympathetic and sympathetic nervous systems in the first two columns, then in the third column, describe a clinical symptom or condition that may be observed in someone with a highly activated parasympathetic nervous system.
Body System Parasympathetic Sympathetic Clinical Symptom/Condition
Heart-Force of Contractility Decrease(A)
Increase (A) Low stroke volume (B)
Pupil Miosis (A) Mydriasis(A) Opioid intoxication such as morphine and heroin and intoxication of organophosphate pesticide(B)

Lung Bronchoconstriction and hypersecretion(A)
Bronchodilation (A) Asthma (B)
Stomach Increase motility and sphincter relaxation(A) Decrease motility and sphincter contraction(A) Diarrhea(B)
Male sex organ Erection(A) Ejaculation(A) Priapism due to block of sympathetic nerve (C)

(A) = (Bryant & Knights 2011)
(B) = (Rang et al. 2012)
(C) = (Sniderman et al. 2011)

Workbook Learning Activity 2

Recreate and complete the following table in your workbook;
• For each drug; in the first column, identify ONE paramedic indication, then in the subsequent columns, list the molecular target involved in the identified interaction, the type of interaction (i.e. agonist / antagonist / allosteric modulator / inhibitor), and briefly explain how this interaction of the drug with the molecular target accounts for the observed therapeutic effect for that indication.

Drug Paramedic Indication Drug Target Type of Interaction Therapeutic Effect
Adrenaline Cardiac arrest a1ß1 and ß2 adrenergic receptors Agonist Stimulation of a1ß1 adrenergic receptors of smooth muscles in the cardiovascular system increases ventricular contraction, heart rate and arteriole constriction in peripheral blood circulation.
Fentanyl Acute pain µ Opioid receptors Agonist Interacts with µ Opioid receptor decreasing
pain impulse transmission at the spinal cord levels and higher in the
central nervous system
Ondansetron Nausea and Vomiting Serotonin receptors Antagonist Ondansetron binds to 5-HT3 receptors in the chemoreceptor trigger zone in the medulla which is sensitive to any chemical stimuli. Therefore, Antagonist-receptor complexes will prevent the vomiting reflex.
Midazolam Seizures Benzodiazepine and gamma-aminobutyric acid (GABA) receptors Agonist Neural inhibition is mediated by interaction midazolam and GABAA receptors which lead to opening chloride channels. Consequently, the effects of midazolam are felt i.e. anti-convulsant effect.
Ipratropium Asthma Cholinergic (muscarinic) receptors Antagonist Ipratropium causes relaxation of smooth muscles of the airways. The secretions of the airways are also dried up. This occurs through inhibition of parasympathetic activity by blocking acetycholine release.

Atropine Sinus bradycardya Cholinergic (muscarinic) receptors Antagonist It acts antagonistically to acetycholine on the muscarinic receptors. When the vagal effects on the SA node are blocked, tachycardia ensues. The heart rate is increased by the hyperpolarization of the SA node by the acetycholine.

Adenosine Supraventricular tachycardia Adenosine receptors Agonist The drug causes short-lived blockage of the heart at the AV node. This is through increased efflux of the K+ due to hyperpolarization of the cells. The hyperpolarization is often due to reduction in cAMP since the adenylyl cyclase is inhibited by the action of adenosine on A1 receptor.

Ketamine Multiple fractures N-methyl-D-aspartate (NMDA) receptors Non Competitive Antagonist Analgesia results due to inhibition of calcium influx. This is through PCP binding of ketamine within the NMDA channel. In the dorsal horn neurons, sensitization is prevented as a result of antagonism of the NMDA receptor. By inhibiting NO synthesis, ketamine ends up inhibiting the enzyme nitric oxide synthase, thus pain perception is greatly reduced.

Naloxone Opioid intoxication µ(Mu), d

( Delta) and ?

( kappa) Opioid receptors Antagonist Naloxone competitively binds to opioid receptors against the effects of opioid agonists like morphine and heroin which causes depress the respiratory and the nervous systems.
Aspirin Acute myocardial infarction Cyclooxygenase Antagonist Aspirin inhibits synthesis of thromboxane factor A2 through occupation of the active site of cyclo-oxygenase, which ultimately prevents platelet aggregation.
Adapted and modified from (Rang et al. 2012)
Workbook Learning Activity 3

In pharmacodynamics, a drug can be thought of as ‘selective’ when it shows a significant preference for interaction with one molecular target, even though it may be faced with many molecular targets to choose from. Indeed, salbutamol can act as an agonist at all ß adrenergic receptors, but at therapeutic doses it ‘selects’ the ß2 adrenergic receptor subtype in preference to others.
In this workbook learning activity you will need to recreate and complete the following table in your workbook, considering the drugs used in your clinical practice or that you may encounter as a paramedic:
• In the first column, list FIVE receptors from different classes, then list their endogenous agonist(s) in the second column.
• In the third column give an example of ONE drug that is a clinically relevant SELECTIVE agonist OR antagonist for each of the receptors at therapeutic concentrations.
Receptor Endogenous Substrate Selective agonist or antagonist used in paramedic practice
Muscarinic receptors (G protein coupled receptors) Acetylcholine Atropine sulfate (selective antagonist)
Glucocorticoid receptors (nuclear receptors) Cortisol Dexamethasone (synthetic glucocorticoid and selective agonist)
Histamine receptors (G protein coupled receptors) Histamine Promethazine (selective antagonist of histamine1 receptors)
Opioid receptors (G protein coupled receptors) Enkephalins, ß-endorphin and dynorphin A
Fentanyl (selective agonist for µ opioid receptor)
Adrenergic receptors (G protein coupled receptors) Epinephrine and nor epinephrine Adrenaline (selective agonist for a1ß1 and 2- adrenergic receptors)

Adapted and modified from (Rang et al. 2012)

4. Antagonists at receptors for neurotransmitters or hormones are often used clinically.

1. Briefly explain how drugs that are antagonists of ß-adrenoceptors produce clinically useful effects
ß blokers Selective ß1 adrenergic receptor (cardioselective) Selective a1 adrenergic receptor (vasodilation)
Acebutolol + –
Alprenolol – –
Atenolol + –
Betaxolol + –
Bisoprolol + –
Carteolol – –
Carvedilol – +
Esmolol + –
Labetalol – +
Metoprolol + –
Nadolol – –
Nebivolol + +
Oxprenolol – –
Penbutolol – –
Pindolol – –
Propanolol – –
Timolol – –

(+) = selective and (-) = not selective. Adapted and modified from (Prisant 2008).

Beta-blockers interact with ß1and ß 2 adrenergic receptors that are able inhibit sympathetic activities in the heart, smooth muscles of blood vessels, bronchi and gastrointestinal tract, skeletal muscles and the liver. By acting selectively to ß1, ß2 or a1 adrenergic receptors, those drugs show therapeutic effects mediated by their cognate receptors in body organs. For example, ß1 adrenergic receptor is expressed in the heart and administration of ß1 antagonists such as atenolol and metoprolol (as described in above table) will inhibit sympathetic activity only in the heart which decreases heart rate, contractility and automaticity and little effects are observed in other tissues with ß2 and a1 adrenergic receptors. Meanwhile, non-selective ß antagonists like propanolol will exert their effects in all body organs which express ß1, ß2 and a1 adrenergic receptors (Rang, et al. 2012).

2. Considering the actions of ß-adrenoceptors throughout the body, would it be most appropriate to treat uncomplicated hypertension in 68 year old patient with moderate asthma and clinical renal impairment (GFR 60mL/min) with atenolol, metoprolol or propranolol? Explain the reasons for your decision.

To treat a hypertensive patient with lung and renal disorders, I prefer to give her/him metoprolol. Basically, atenolol and metoprolol are similar as selective ß1 antagonists which are administered to patients with hypertension, angina pectoris, dysrhythmias, chronic heart failure and myocardial infarction (Wander, et al. 2009; Rang, et al. 2012). However, they have differences regarding with absorption, metabolism and elimination (AFT Pharmaceuticals Ltd, 2009; Wander et al. 2009). Atenolol is partially absorbed, reaches peak levels in plasma after 2 hour administration, not metabolised by the liver, eliminated unchanged in the kidney wi
th half-life 6-7 hours and accumulated in patients with renal failure (Wander et al. 2009). On the other hand, oral administration of metoprolol is completely absorbed, metabolised by CYP2D6 isoenzymes in the liver, eliminated in the kidney with half-life approximately 3.5 hours. The clearance rate does not change in patients who have normal and abnormal renal functions (AFT Pharmaceuticals Ltd, 2009; Wander et al. 2009).