Pharmacokinetics: Definition and Processes - Assignment Example

SCH Assignment One Name Institution Date PART A Question 1 Pharmacokinetics is defined as the study of how drugs move through absorption, distribution, metabolism, and excretion. For a drug to effective it must interact with the body; however, the method depends on the drugs properties. Pharmacokinetics influences the route of administration. Absorption refers to the route of entry of the drug into the body. The distribution shows where the drugs go and where it is supposed to go, as well as the implications. Metabolism is the processes that occur and could affect several variables which can be used to help in the activity of the drug. Lastly, excretion refers to how the drug is eliminated from the body. Pharmacodynamics, on the other hand, is the impact of the drug on the body, that is, the results of its concentration and the site of absorption. For instance, the drug half-life, and the intensity of both positive and negative adverse effects. The effect of the drug at the site of action is given by its binding to a receptor. The central nervous system neurons may have receptors that depress pain sensation, cardiac muscle receptors affect the intensity of contraction, and bacteria receptor disrupts bacterial cell wall maintenance. Question 2 Drug efficiency is given by its ability to bind with proteins within blood plasma. Plasma protein binding is the ability of protein blood plasma to form a bond with drugs. A drug may bind to various plasma proteins such globulin (alpha, beta, and gamma), glycoprotein, serum albumin, and lipoprotein. Protein binding is a major determinant of drugs biological half-life, that is, fraction bound or free fraction. Only the free fraction that can interact with drug receptors. The unbound drug component causes pharmacological effect, which is excreted or metabolized. Once the unbound drug is metabolized, the protein-bound drug is released from the body to maintain equilibrium. However, extensive plasma binding increases the component of drug absorbed before unbound drug level is reached. As a result, elimination of protein drug is hindered. When free fraction concentration is low, drug elimination through metabolism is also delayed. Question 3 Anticoagulants drugs such as warfarin are used to treat and prevent blood clotting that occurs in blood vessels. Aspirin can also prevent blood clots; however, they have different effect warfarin is an anticoagulant while aspirin is antiplatelet. The use of both may increase the risk of bleeding, particularly gastrointestinal bleeding (Bullock & Manias, 2013). Aspirin causes gastric erosion and thus increasing the risk of gastrointestinal bleeding in warfarin patients without increasing the INR. The increased risk of bleeding occurs due to several affected pathways. The interaction between warfarin is mainly pharmacodynamics, that is, inhibition of platelet aggregation. It can also be partly, pharmacokinetic due to the displacement of warfarin from the protein binding. Aspirin may interfere with the cytochrome metabolism of warfarin, therefore increasing hypoprothrombinemic response to warfarin. Question 4 The hepatic first-pass effect is when the drug is absorbed and delivered from gastrointestinal tract enters the liver and undergoes biotransformation which reduces its concentration before it reaches the target. This happens when drugs are administered orally, after being absorbed in the gastrointestinal tract, it enters system circulation after passing through portal circulation. When it enters portal circulation, it enters the liver where drug concentration is reduced after undergoing extensive biotransformation. In other words, a portion of the drug is lost during this process. Question 5 A half-life of a drug refers to the amount of time it will take for the drug concentration in the body to reduce to 50 percent. Naloxone is an antidote for morphine overdose, which acts as a competitive antagonist blocking its action. When injected, it is rapidly distributed because it has a half-life of 1 hour. This is shorter than morphine that has approximately 2 to 3 hours, therefore, easing a repeat dosage to stop morphine receptor from triggering for an extended period. In other words, it reverses the effects of morphine agonists. Question 6 Steady State is achieved when both drug input is equal is in equilibrium with the amount of drug eliminated in one dosing interval leading to constant serum drug level. Drugs with a shorter half-life reach a steady state faster compared with drugs with a long half-life. A steady state is achieved after five elimination half-life of the drug. For instance, after the first half-life, a drug will be 50 % steady state. After the second half-life, it will be 75% steady state; third half-life means 87.5% of the steady state. Lastly, fifth half-life, the drug will have reached 97% steady state; therefore, it a drug has a long half-life the longer it will take to reach steady state. Question 7 Enzymes can be denatured by a change in PH, temperature or ionic strength. Enzymes also catalyze specific reactions where substrate binds and react to form products. A cell is responsible for regulating enzymatic reaction. Competitive enzyme inhibition is caused by an inhibitor binding to the enzyme in place of the substrate. Since inhibitor and the substrate are not identical, that is, it does not react when it binds the active site enzyme cannot convert inhibitor into a product. It blocks the active site and prevents the substrate from binding. Alternatively, an inhibitor may not bind to the active site, but another site on the enzyme is causing a change in the three-dimensional shape in the enzyme. This alteration prevents substrate binding. Non-competitive enzyme inhibition occurs when the inhibitor binds to an inhibitory site on the enzyme which is distant from active site preventing the formation of the enzymatic products. In this case, it does not prevent substrate binding, but rather prevent the enzyme from converting substrate into product. Question 8 When drugs act as antagonists means that they bind to the receptor without activating them, therefore, prevent binding of other drugs that bind and activate the receptor, agonists (Bullock & Manias, 2013). Atropine inhibits the muscarinic action of cholinergic receptors on structures innervated by postganglionic cholinergic nerves, and on smooth muscles which respond to endogenous acetylcholine but are not so innervated. Its primary action is competitive antagonism by inhibiting the enzymatic destruction of the cholinergic receptor. Since it binds reversibly and compete for the same binding site, the inhibitory effect can be overcome by increasing concentration of the anticholinergic agent, atropine. The peripheral structures that are inhibited by muscarine are the receptors antagonized by atropine. Atropine eliminates reflex vagal cardiac slowing and prevents the injection of anticholinergic agents. It also reduces the degree of cardiac arrest by stimulating vagus, and heart blockage. Question 9a Broad beans and cheddar cheese have a higher content of tyramine. During phenelzine treatment and two weeks after, patients should not take foods that are high in tyramine. Intake of tyramine during this period can raise the blood pressure to a dangerous level, causing headache, rapid heartbeat, nausea, sensitivity to light and cold sweat. A potentially life-threatening crisis may occur within one hour of ingestion of tyramine products. Monoamine oxidase in the liver and intestine oxidatively deaminates the tyramine in the diet. The monoamine oxidase is thus inhibited; tyramine is absorbed and displaces norepinephrine in the nervous system causing acute severe hypertension. 9b Tetracyclines requires minimum inhibitory concentration of divalent and trivalent metal ions such as Ca, Mg, Al, and Fe in the plasma and antacids can provide more than 90% forming poorly absorbed complexes. Chelation of tetracycline by the metal ions causes complex to be more lipophilic than tetracyclines alone thus preventing its absorption (Bullock & Manias, 2013). The antacid also alters the pH of the environment. The increased PH results in a reduction in dissolution of tetracyclines. As a result, blood levels of antibiotic decreases and reduce absorption of tetracyclines to treat the infection. 9c Using diazepam with alcohol may increase nervous system side effect such drowsiness, dizziness, and so on. It can also intensify the memory-impairing effects of diazepam. PART B Question 1 In this case, the parasympathetic nervous system was primarily affected, since this division is completely composed of cholinergic fibers. Following, the sympathetic nervous system had more stimulation at the receptor, but not adequate to override the parasympathetic nervous system symptoms. Under normal circumstance, the parasympathetic nervous system predominated in the automatic nervous system to regulate body functions. Question 2 In this case, the muscarinic receptors are involved. If the acetylcholinesterase is inhibited by the organophosphate, its concentration will continue to increase. The nicotinic receptors in the preganglionic neurons in sympathetic and parasympathetic nervous system are both stimulated, and also, the postganglionic neurons in the parasympathetic nervous system are stimulated. As a result, the muscarinic receptors will be excessively stimulated. Question 3 Organophosphate inhibits the activity of acetylcholinesterase, an enzyme used to break down acetylcholine chemical that transmits information from the automatic nervous system to other organs of the body (Bullock & Manias, 2013). As a result, this increased the concentration of acetylcholine and continued to influence muscarinic receptors. Stimulation of muscarinic receptor in the myocardium is inhibitory as it leads to a decrease in the heart rate. Muscarinic stimulation of the receptors in the lungs is excitatory as it results in constriction of air passageways. Also, it causes excitatory of muscarinic receptors in the eye, which cause pupil constriction. Organophosphate also causes parasympathetic nervous stimulation of the smooth muscle in the gastrointestinal system causes an increase in contraction of the gastrointestinal motility. Mr. FT profuse sweating may have occurred even though acetylcholine mainly stimulates parasympathetic nervous system; the sympathetic nervous system also has muscarinic receptors in the sweat glands. Therefore, increase concentration of acetylcholine caused by the organophosphate increased the sweating. Since sweating is stimulated by the alpha-adrenergic receptors; the sweat was evident across Mr. FT whole body. Question 4 The Beta-adrenergic receptor antagonist drugs work by blocking the beta receptors thus stopping sympathetic nervous system effect that balances the parasympathetic nervous system homeostasis, and thus causing similar symptoms caused by the organophosphate. Question 5 Atropine is a drug used to block parasympathetic activity caused by the effect of insecticides such as organophosphate poisoning. It is commonly referred as the parasympathetic antagonist that is used to bind to and block the action of muscarinic receptors. Atropine target only the excessively stimulated parasympathetic nervous system receptor until acetylcholinesterase can be used again to hydrolyze acetylcholine. It blocks the action of acetylcholine at the parasympathetic receptors, and thus causing opposite effect we would expect from stimulating the receptor. PART C Question 1 The long-term aims of asthma management are to prevent complications of diseases or treatment by focusing on low-intensity measures with a higher probability to have the greatest influence on the outcome. Therefore, they must focus on producing maximum achievable impacts on all outcome parameters that have been set to ensure that risk of missing long-term aim is minimized. In other words, optimally controlled asthma children will be able to live a normal life. Long term aims of first-line therapy are to ensure that the treatment chosen has been shown to influence the most parameters in order to reduce the risk of under-treatment. ICS is the most preferred treatment for acute attacks according to the National Asthma Campaign. It is considered the most effective agents for gaining and maintaining control of acute asthma attacks. Early treatment of asthma attacks with ICS leads to better lung functions and helps in the prevention of the establishment of an irreversible airflow limitation. Question 2 Respiratory infections are most common causes increase in asthma severity and contribute to asthma development. Respiratory tract infections that are caused by either viruses or bacteria are involved in the asthma pathogenesis (Bullock & Manias, 2013). The respiratory syncytial virus causes bronchiolitis that is associated with childhood asthma. However, with the pathological asthma context, airway bacterial colonization and mycoplasms and chlamydiae infections also play a significant role. They interfere with immunological pathways, thus exacerbating asthma in genetically predisposed people. Its influence on the development of asthma, however, depends on interaction with atopy. This is a stat influence lower airway response infection that may influence the development of allergic sensitization. Question 3 Inhaled corticosteroid (ICS) therapy has been significant in the management of mild-to-moderate persistent asthma. According to the national treatment guidelines, ICS is the most effective and safest method for the long-term management of persistent asthma. Inhaled corticosteroids reduce inflammation in the bronchial tubes and minimize mucus made by these tubes, and this will make BB breathe easily. The ICS therapy treat inflammation and only limited medicine are absorbed into the body. In other words, there are no serious side effects compared to when the corticosteroids are injected or taken as a pill. ICS is the preferred method of the long-term asthma management because it helps control narrowing and inflammation of the airway and is used every day (Bullock & Manias, 2013). Question 4a The common side effect of inhaled corticosteroids is a fungal mouth infection. However, it can be prevented by rinsing the mouth after inhalation. It can also make the users voice to become husky, which are the consequences of oropharyngeal deposition of the steroid and vocal cord muscle weaknesses. But, the can be minimized by application of better inhaler techniques, rinsing with water, or use of nystatin mouthwash. Question 4b The use of inhaled beta-2 agonists is associated with several side effects. This includes faster heart beats, headache, restlessness, and sleeplessness. However, these side effects may improve after a few days. Question 5 Long-term use of inhaled corticosteroid is associated with growth retardation among children. The adverse effect can only understand glucocorticoid and growth suppression in childhood. Glucocorticoid growth suppression occurs as a result of inhibition of GH secretion. It regulates the binding of the GH receptor downward. However, adverse risks of ICS therapy increase when normal exposure exceeds endogenous cortisol production or when normal hormone secretion is disrupted by the pattern of cortisol effect, thus influence effect on growth suppression. Question 6 Asthma management has indicated that children inhalers and spacers have benefits over nebulizers as it results in improved removal of the drug in the lungs than nebulizer and the patient will have fewer side effects. Also, during administration to those undergoing asthma emergencies uses less treatment time than using a nebulizer. If nebulizer is used to treat an acute asthma attack, there is a risk of oxygen desaturation. Question 7 Systematic administration of corticosteroid hydrocortisone reduces the inflammation of the bronchial tubes, making easier for the patient to breathe. However, it travels throughout the body before reaching the bronchial tubes. Systemic corticosteroid hydrocortisone is recommended because it speeds up the resolution of airflow obstruction and reduce the rate of post emergency relapse. It makes the episodes shorter and prevents early reoccurrence of asthma attacks. However, the length of treatment may differ depending on the patient. Question 8 The use of inhaled corticosteroid beclomethasone combined with inhalation of the Beta2 agonist salbutamol is considered an effective method of delivering drugs to the lungs for the control of asthma. This is because inhaled corticosteroid is the most effective anti-inflammatory agents and Beta 2 agonist are a potent bronchodilators. However, it is very difficult to change the level of the inhaled corticosteroid dose, without altering the Beta 2 agonist dose. Consequently, the patient may remain of inadequate or excess of a particular dose. Therefore, the inhaled corticosteroid dose should be monitored and adjusted according to the clients symptom's and best peak expiratory flow. PART D The use thiazide hydrochlorothiazide as an antihypertensive therapy is a good choice unless there is a particular drug contraindication is present. However, Eva still needs to be careful about salt intake; a salt-free diet will be beneficial. Also, Eva must ensure that exercise is part of her lifestyle, salt-free diet, foods high in fibers, a lot of fruits, reduce the food that with saturated fats. Thiazide Hydrochlorothiazide works by eliminating excess fluid and swelling that is associated with heart failure. Thus, Eva should know that she may experience significant weight loss. She should also avoid sun exposure as diuretic increases suns sensitivity. References Bullock, S., & Manias, E. (2013). Fundamentals of Pharmacology (7th ed). Pearson, Australia. Read More