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Definition of Pharmacokinetics and Pharmacodynamics

1.  Define the terms 'pharmacokinetics' and 'pharmacodynamics'.

2. What is meant by 'plasma protein binding'? In your answer, explain the effects that plasma protein binding has on the metabolism and elimination of protein bound drugs.

3.  Why should aspirin not normally be administered to a patient who is taking a course of the anticoagulant drug, warfarin?

4.  Explain the 'hepatic first pass effect'. Why is it important to consider this effect when administering drugs orally?

5.  Morphine, a narcotic analgesic, has a half-life of about 2 –3 hours. The half-life of naloxone (Narcan), the “antidote” for narcotic overdose, is approximately 1 hour. What does the term 'half-life' mean, and what implications does this information have for the prescribers of these drugs?

6.  What is meant by 'steady state' concentrations of a drug? Explain how and when a steady state is achieved.

7.  Describe the characteristics and properties of enzymes. What is the difference between competitive and non-competitive enzyme inhibition? Give one example for each.

8.  What happens when a drug acts as an 'antagonist'? Explain how atropine, an anticholinergic, acts as an antagonist at cholinergic receptors. What are the effects of atropine on the human body?

9.  Describe the drug interactions which may occur when the following drugs and/or other substances are administered concurrently:
a.  phenelzine and broad beans or cheddar cheese
b.  tetracyclines and antacids
c.  alcohol and diazepam

Mr FT is a 22-year-old man who has been admitted to your hospital emergency department.He has been working as a labourer at a nearby market garden that specialises in growing flowers.  He was spraying the crops with the organophosphate insecticide Malathion when he collapsed.  He was not wearing the appropriate protective clothing.  You observe that he is conscious and complains of gastrointestinal cramps and nausea.  He vomited a couple of times in the ambulance as he was transported to hospital.  You note the manifestations: profuse sweating, drooling, lacrimation, bradycardia, agitation, muscle twitching and constricted pupils.
Supportive treatment is implemented, which involves respiratory support and the administration of antidotes.His progress is carefully monitored during this critical period.  His recovery is without complications.  He is discharged from hospital several days later.

1.  Underlying this client’s condition is a change in the level of activity of a division of the autonomic nervous system.  Which division is affected and what is the nature of the change? Provide examples of the physiological responses

2.  Which type or types of tissue receptor are involved in this condition?

3.  Explain the mechanism by which the organophosphate insecticides induce this state?

4.  Which clinical drug group do the organophosphate insecticides closely resemble in terms of their action? Why?

5.  Which drug group can be used as an antidote to oppose the effects of the insecticide? Why?

BB, a 5-year-old boy with a history of chronic asthma, has been admitted to hospital suffering a moderately severe asthma attack.  Over a period of time his condition has been well managed using daily inhalation of the corticosteroid beclomethasone, coupled with inhalation of the Beta2 agonist salbutamol when required.  His parents think that this particular attack was brought on by a mild respiratory infection that has been affecting the other members of the family.  
Treatment begins with oxygen therapy and a dose of the Beta2 agonist salbutamol via an inhaler and spacer. A dose of hydrocortisone is administered intramuscularly soon after.  Inhaler treatment is repeated hourly.  After eight hours the acute attack is easing and by 12 hours post admission BB is ready for discharge.

1.  Briefly outline the long-term aims of asthma management, the first-line therapy and the preferred treatment of an acute attach according to the National Asthma Campaign.

2.  Explain why the mild respiratory infection would be considered a trigger for BB’s asthma attack.

3.  What is the rationale for the use of inhaled corticosteroids in the long-term management of BB’s chronic asthma?

4.  a.  What short-term adverse effects would you expect to see with inhaled corticosteroids?

b.  What short-term adverse effects would you expect to see associated with inhaled B2 agonists?)

5.  What problem may be associated with the long-term use of inhaled corticosteroid therapy in young children?

6.  Why has the health team managing BB’s acute attack used an inhaler and spacer to administer the bronchodilator therapy rather than a nebuliser?

7.  How does the systemic administration of the corticosteroid hydrocortisone assist in the recovery after an acute asthma attack?

8.  What aspects of your client’s condition would you monitor during this combined therapy? Why?

Plasma Protein Binding

Pharmacokinetics: Grimsley et al. (2013) presumed that Pharmacokinetics is one kind of disease that described that doing factor of drugs within the body such as movement of drug in body like into, out and through of the body during the time of absorption, metabolism, distribution, excretion, bioavailability, etc. Following table demonstrates the basic parameters of Pharmacokinetics –

Category

Parameter

Formula

Absorption

Bioavailability

Amount of absorption of drug / dose of drug

Distribution

Unbound fraction

Concentration of total plasma / Plasma concentration of unbound drug

Elimination

Metabolic clearance

Concentration of plasma drug / drug metabolism rate

Pharmacodynamics: Unlike Pharmacokinetics, pharmacodynamics not only described the factor of movement of drug into the body but also described the complete factor of drug into the body. In the body, pharmacodynamics involved with several aspects such as receptor sensitivity. Apart from that, pharmacodynamics described the effects of post-receptor as well as the interaction of chemical during absorption. With the help of Pharmacokinetics, pharmacodynamics explains the great relationship between the response and dose such as effect of drug into the body of human being. The response of pharamacologic response depends to its target on the drug binding. At the receptor site, the concentration of drug influences the effects of drug into the body. Due disorders such as aging, mental disorders and other drug, psychological changes can affect the pharmacodynamics of drug.

According to Filipeanu et al. (2015), Plasma Protein Binding (PPB) has potential effects on the efficiency of drug and staying of drug into the body. Dunlop et al. (2011) argued that Plasma Protein binding effects the distribution of drug in several ways such as blood brain barrier, complexity of drug protein that do not permeate the phospholipids bilayers, in the nephrones membranes of glomerular, etc.  In the first pass metabolism, bound drugs are also not available to the enzyms (Bullock & Manias, 2013).

As argued by Bullock et al. (2007), Aspirin offer the alternative to the people that had blood clots in the form of deep veins. It never tolerates the long-term use of thinner blood. On the other hand long term use warfarin is inconvenient (Stahl, 2013). Therefore, use of aspirin in the administered of anticoagulant may effect on the block of effects of the vitamin K. Bennett et al. (2012) stated that blocking of vitamin K prevents the clots of blood that increased the time of making fibrin. If the aspirin used to care about the patient, these medicines does not prevent the blood chemical from working thrombin (Saadatzadeh et al 2011).

 The hepatic first pass effect takes place during the time of metabolism of drug between the site of sampling and administration regarding measurement of drug concentration. When the fraction of dose of drug administered the metabolism escapes in both cases large and small, hepatic first pass effect is very much important. The major site of hepatic first pass effect is usually assumed the liver of a drug administration orally (Maggs et al. 2012). On the other hand, Bullock et al. (2007) suggested that the potential site that affected by the first pass metabolism are blood, lings, arms, gastrointestinal tract, endothelium, vascular, etc. Apart from that, Feuerbach et al. (2010) argued the hepatic first pass effect extent in the liver and it is firmly depends of the large number of psychological factors. The major factors that affected by the hepatic first pass effect on the body are plasma protein, enzyme activity and blood cell binding (Lilley et al. 2014).

Aspirin and Warfarin Interaction

In accordance to Bullock et al. (2007), the term half-life in drugs that means the time of living of drug dose and strength. On the other hand, Feuerbach et al. (2010) cited that half-life in drugs are some metabolized fairly. From the point of view of drug, half-life demonstrated the timeline of strength of the given medication for human body (Peterchev et al. 2012). For instance, patient takes milligram pill. Therefore, the half-life is 13 hours. It means that the 20-milligram pill works in the body system for 13 hours. When the blood level of drug going down or going up, many drug effects occur in the human body primarily. This may affect completely in the human body (Wein et al. 2012). Due to this reason, people faced unwanted side effect that takes place the way of steady state. On the other hand, Greilhuber and Doleal (2009) acknowledged that classify drug effect into 2 groups in terms of changing the stabilized steady state primarily.

From the point of view of drug effect, steady state refers the overall situation fairly in dynamic equilibrium that eliminates the effect of drug in the body (Kacmarek et al. 2013). When the people take half-life drug more than 4 or 5 time, the steady state occurred (Burtis & Bruns, 2014). Therefore, steady state can occur in any condition because it is depend on the substance or introduction regarding removal or destruction of all concentrations, pressures, volumes, etc. However, Feuerbach et al. (2010) argued that steady state obtain in the exercise of moderate muscular during the time of lactic acid removal through production of oxidation, supply of oxygen, muscles, etc (Ruskin et al. 2013).

Bullock et al. (2007) cited that enzymes are the large biomolecules that responsible for the reaction of chemical in human body. It is very much important and necessary for sustaining the life.

competitive and non-competitive enzymes inhibition

(Source: Greilhuber and Doleal, 2009, pp- 392)

On the other hand, , Greilhuber and Doleal (2009) stated that enzyme is the biological catalysts and protein molecule. The rate of reaction in human body can increased due to effect of enzymes. Following table shows the different characteristic and properties of enzymes –

Characteristics

Properties

• Poses great catalysts power

• Demonstrates the varying degree of specificilities

• Detect different optical isomers

• Suggest specific reaction only

• It can be coagulated by the heat, alkaline reagents, concentrated acids, alcohol, etc
• Reduce the activation energy for reaction

• Work best especially in the pH accommodation (optimum pH)

• Have specific shape with particular site such as substrate the reaction speed

• One type of reaction (specific)

Competitive enzyme inhibition: Structure of molecule inhibition is similar like substrate. With the active site of enzymes, inhibitors firmly attached (Crommelin et al. 2013). Compete for enzymes of substrate molecules. Examples are folic acid synthesis. Sulpha drugs given to bacteria, etc (Heinrich et al. 2012).

Non-competitive enzyme inhibition: It very different from competitive enzyme inhibition. The structure is fully different to molecule (Golan et al. 2011). It never competes with the molecule or substrate. Examples are election transport chain, prosthetic group of cytochromo oxidase, etc.

When the drug act as an antagonist it block or dampens the response of agonist mediated instead of provoking a biological response.

When an atropine and anticholinergic act as the antagonist at cholinergic receptors it literally blocks the site of binding for acetycholine as well as prevent the natural muscarinic.

In the human body, atropine affects in several ways such as frequency of adverse effects in the individual intolerance varies firmly, effects at the muscarinic-cholinergic receptors, etc. Apart from that, due to atropine human body faces several side effects such as dehydration, excessive thirst, weakness, hyperpyrexia, feeling clod & hot, chest pain, tongue chewing, etc.

Hepatic First Pass Effect and Its Importance

Phenelzine and broad beans or cheddar cheese: It effects on thinking or reaction in the human body. Apart from that, it increase the blood pressure at high levels that will be very much danger to human body, causing severe and sudden headache, increase the heartbeat rate, continuous vomiting, cold sweat, nausea, stiffness in your neck, etc. 

Tetracyclines and antacids: Interaction of tetracylines have high affinity in the form of chelates that has metallic cations like Al+++, Ca++, Fe++, etc.

On the other hand, interaction of antacids in human body is help in reducing the acidity in stomach and emptied into the duodenum.

Alcohol and diazepam: Feuerbach et al. (2010) argued that alcohol is very much harmful for human body regarding medications over drugs. Alcohol interaction with medications may provide several problems to human body such as dizziness, loss of coordination, headache, abnormal behaviour, fainting, etc.

Major drug interactions from the point of view of diazepam in the human are caused several problems such as aspirin, darvon, clopine, inapsine, orlaam, luvox, etc.

In the human body, automatic nervous system regulates the certain process of body such as breathing rate, blood pressure, circulation of blood etc. Without the conscious of person, this system works automatically. However, , Greilhuber and Doleal (2009) suggested that disorder in the automatic nervous system can affected in ant part of the body. Bullock et al. (2007) depicted that automatic disorders may damage the nerves of human body and occur their own. Therefore, , Greilhuber and Doleal (2009) cited that automatic disorders may progressive or reversible.

Division of the automatic nervous system

(Source: Manvich et al. 2012, pp- 768)

Mr. FT is spraying the crop without any protection. It has been seen that, the patients who admitted into the hospital department is affected by gastrointestinal cramps and nausea. Therefore, it has been analyzed the main division that affected in the body of Mr. FT is autonomic disorder. The changes that identified in the body of Mr. FT were drooling, bradycardia, constricted pupils, lacrimation, profuse sweating, muscle twitching, etc. It has been also examined that rate of heart of Mr. FT was very much high and blood pressure also became high when he is sitting or lying down after stands.

The physiological responses that identified in the body of Mr. FT were increased of urination, increase of defaecetion, increase of muscle tone, increase the rate of respiration, change the heart rate and blood pressure, etc.

There were several types of tissue receptors that involved in the action of Mr. FT such as dilation, perspiration, piloerection, papillary dilation, salivary glands and peripheral tissues, nicotine, muscarinic receptors, beta adrenergic receptors, etc. These are the different types of tissue receptors that identified in the action of Mr. FT.

In this particular action, Mr. FT used chemical in spraying crops into the flower garden. The induced insecticide that includes in spraying of crop were parathion, dichlorvos, diazinon, malathion, etc. The nerve gases in this state were tabrun and soman. Apart from that, the ophthalmic agents were isoflurophate and echothiophate.

Half-Life and Drug Prescriptions

According to Randall et al. (2012), echothiophate is one of the most effective and efficient irreversible that can be used in dilation of pupil especially for the case study of Mr FT. Apart from that, Feuerbach et al. (2010) suggested several clinical group such as endrophonium, neostigmine, demecarium, physostigmine, etc are the most effective clinical group that clos4ely resemble the organophosphate malathion of Mr. FT.

In order to oppose the effects of organophosphate insecticides closely from the body of Mr. FT, need to use the drug group of pralidoxime. It will the specific groups of opposing the current action that described above. Apart from that, need to involve the atropine acts on receptor in terms of protecting the side effect.

Feuerbach et al. (2010) described that that asthma management has several aims in order to protect or reduce the asthma from body of human being. Following are the aims of Asthma Management –

To monitor the patient of asthma and make an adjustment for treating the in own perspective

To motivate the asthma patient in participating in sports and exercise

To prevent the episodes of asthma

To protect the patient from side effect of asthma medicines

To provide less amount of medications to the patient of asthma in order to reduce the disease

To make the patient possibly peak flow rate

For the BB, the hospital department used the combination of high dose therapy with the used of ipratropium bromide (IB). Apart from that, in the hospital the medical department used β2-agonists for improvement of patients in a better way. In order to randomized that asthma of BB, hospital department represented the emergency department (ED) in trems of treating the asthma exacerbation.

In order to treat the asthma of BB, several steps have to be followed by the hospital department such as –

Involvement of long acting bronchodilators in terms of adding the medication to inhaled as an additive therapy such as formoterol, salmeterol, etc.

Need to involve the anti-IgE therapy that will be used for the adolescents with the asthma that comes from allergic asthma.

Provide short acting bronchodilators in terms of quick relief. Moreover, it is also help in exercising regarding induced the symptoms such as ventolin, maxair, etc.

Use of several monoclonal antibodies for the therapy of asthma especially that required for the 5 years aged children.

Need to use anticholinergic agents in terms of decreasing the sputum production such as tiotropium, ipratropium, etc.

Mild respiratory infection considers as the trigger of asthma especially for the case of BB who is the 5 years old age child. This was considered because generally the symptoms of mild respiratory infection resulted several issues such as runny nose, sneezing, painful swallowing, nasal breathing, cough etc. However, it has been identified that the family member of BB admitted the child into hospital due to side effect of nasal problems. Therefore, the symptoms of mild respiratory infection were matched with the found out symptoms of BB. That was the reason of considering mild respiratory infection as a trigger of asthma for BB, the five years old child.

Enzymes and Inhibition

Feuerbach et al. (2010) argued that inhaled corticosteroids is mainly used for them preferred treatment for long-term control of chronic asthma especially for the children. Inhaled Corticosteroids helps in controlling the inflammation and narrowing within the bronchial tubes. The key reason of using inhaled corticosteroids because it allows the medical department in treating the patient on daily basis. For the BB who is an chronic asthma inhaled corticosteroids always allowed in taking care of the patient with beta2-agonists. However, following are the controlling method of inhaled corticosteroids in terms of treating the BB’s chronic asthma –

Treated the children with little different based on age.

Used least amount of medicine for controlling the asthma.

Number of medicine and amount of medicine is increased in a certain stage that control the asthma in a better way.

In order to treat the patient and provide quick relief inhaled corticosteroids treatment is used.

These are the reason of using inhaled corticosteroids for the long-term management of BB’s chronic asthma.

4.A) The short term adverse effect that was identified with the inhaled corticosteroids was osteoporosis and adrenal suppression. Apart from that, several short-term effects are also identified including skin fragility, hirsutism, glaucoma, acne vulgaries, etc (Bonin et al. 2014).

4.B) The expected short terms adverse effect that associated with the medicine of inhaled B2 agonists were –

Muscle Tremors

Irregular heartbeat

Increased heartbeat

Extra pressure on mind

Anxiety

Headache

Nervousness

As opined by Feuerbach et al. (2010), asthma is a critical disease. Therefore, long-term use of inhaled corticosteroids therapy in the human body of young children may be affected by several problems such as –

Impaired growth in childhood

Skin bruising and thinning

Decrease bone mineral density

Cataracts due to high dose

Bronchodilator therapy is an effective health treatment method especially for the asthma treatment because it easily identifies the heath claims of the asthma patient and using short acting beta2-agonist reduces the problem (Fritz, 2013).

The systematic administration of the corticosteroid helps in recovering after an acute asthma attack of the patient via live saving and dramatic benefits. Apart from that, the systematic administrations maximize the therapeutic and achieve several affects through listing the condition of the patient (Ariëns, 2013). Based on the condition of asthma, the systematic administration of the corticosteroid allows the health care specialist in monitoring the patient after acute asthma attack through motivating in participate on sports and exercise.

In response to treatment, the level of control achieved including the adherence success of patient. Apart from that, health care specialist has to develop a treatment plan that will be goal oriented. Moreover, need to take responsibility of taking care of patient about the dedication of treatment. Bullock et al. (2007) suggested that if any difficulties occurred the need to increase the amount as well as number of medications along with frequency. If any problems occur in monitoring as well as controlling the BB’s chronic asthma attack, need to take advice from the asthma specialists for co-management or consultation.

Reference List

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2.  Feuerbach, D., Loetscher, E., Neurdin, S. and Koller, M. (2010). Comparative pharmacology of the human NMDA-receptor subtypes R1-2A, R1-2B, R1-2C and

R1-2D using an inducible expression system. European Journal of Pharmacology, 637(1-3), pp.46-54.

3.  Filipeanu, C., Pullikuth, A. and Guidry, J. (2015). Molecular determinants of the human  2C-adrenergic receptor temperature-sensitive intracellular traffic.

Molecular Pharmacology.


4.  Greilhuber, J. and Doleal, J. (2009). 2C or not 2C: a closer look at cell nuclei and their DNA content. Chromosoma, 118(3), pp.391-400.

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6.  Wein, A., Kavoussi, L., Novick, A., Partin, A., & Peters, C. (2011). Campbell-Walsh Urology Tenth Edition.

7.  Crommelin, D. J., Sindelar, R. D., & Meibohm, B. (2013). Pharmaceutical biotechnology: fundamentals and applications. Springer Science & Business Media.

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Wilkins.

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the benefit of new biodegradable nanoparticles of probiotic extract in murine colitis. Fundamentals of Clinical Pharmacology doi: 10.1111/j. 1472-8206.2011. 00966.

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magnetic stimulation dose: definition, selection, and reporting practices.Brain stimulation, 5(4), 435-453.

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Fundamentals and Artifacts”. Journal of the American Chemical Society, 136(23), 8484-8484.

19. Fritz, S. (2013). Mosby's fundamentals of therapeutic massage. Elsevier Health Sciences.

20. Ariëns, E. J. (Ed.). (2013). Drug Design: Medicinal Chemistry: A Series of Monographs (Vol. 4). Elsevier.

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My Assignment Help. (2016). Pharmacokinetics, Pharmacodynamics, Plasma Protein Binding, Hepatic First-Pass Effect, Half-Life, Enzymes, Atropine, Drug Interactions, Autonomic Nervous System, Tissue Receptors, Organophosphate Insecticides, Asthma Treatment, And Essay.. Retrieved from https://myassignmenthelp.com/free-samples/fundamentals-of-pharmacology.

"Pharmacokinetics, Pharmacodynamics, Plasma Protein Binding, Hepatic First-Pass Effect, Half-Life, Enzymes, Atropine, Drug Interactions, Autonomic Nervous System, Tissue Receptors, Organophosphate Insecticides, Asthma Treatment, And Essay.." My Assignment Help, 2016, https://myassignmenthelp.com/free-samples/fundamentals-of-pharmacology.

My Assignment Help (2016) Pharmacokinetics, Pharmacodynamics, Plasma Protein Binding, Hepatic First-Pass Effect, Half-Life, Enzymes, Atropine, Drug Interactions, Autonomic Nervous System, Tissue Receptors, Organophosphate Insecticides, Asthma Treatment, And Essay. [Online]. Available from: https://myassignmenthelp.com/free-samples/fundamentals-of-pharmacology
[Accessed 13 July 2024].

My Assignment Help. 'Pharmacokinetics, Pharmacodynamics, Plasma Protein Binding, Hepatic First-Pass Effect, Half-Life, Enzymes, Atropine, Drug Interactions, Autonomic Nervous System, Tissue Receptors, Organophosphate Insecticides, Asthma Treatment, And Essay.' (My Assignment Help, 2016) <https://myassignmenthelp.com/free-samples/fundamentals-of-pharmacology> accessed 13 July 2024.

My Assignment Help. Pharmacokinetics, Pharmacodynamics, Plasma Protein Binding, Hepatic First-Pass Effect, Half-Life, Enzymes, Atropine, Drug Interactions, Autonomic Nervous System, Tissue Receptors, Organophosphate Insecticides, Asthma Treatment, And Essay. [Internet]. My Assignment Help. 2016 [cited 13 July 2024]. Available from: https://myassignmenthelp.com/free-samples/fundamentals-of-pharmacology.

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