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Pharmacodynamics And Potential Adverse Effects

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Question:

Describe about the Pharmacodynamics and Potential Adverse Effects?
 
 

Answer:

A: Pharmacokinetics- This concept refers to the manner a body usually reacts to various drugs. This explains largely about physiological matter which occurs once the drug enters into a body. However, the concept of pharmacokinetics includes absorption, breakdown, distribution and clearance of drugs from a human body.

B: Pharmacodynamics: This concept relates to the biochemical as well as physiological processes underpinning actions of drugs, that is mechanism of actions of drugs, reflecting how drugs impact upon body. It involves physical action as well as chemical actions , also through actions of receptor/enzymes.

Plasma protein binding:

This concept means abilities of drugs to bind proteins along with blood plasma. Considerable level of influences of plasma protein bond upon metabolism of drugs and removal of protein included drugs refers to the increment within the drug’s half-life. In addition, the extent to which drug may be added to plasma proteins impacts upon its distribution in multiple ways. Binding of Plasma protein tends to lessen the drug availability for act of diffusion or transporting to the target organ of drug since generally, only the unbound drug form can capably diffusing across membranes (YOKOMASU et al., 2008). Plasma protein binding can also lessen the transportation of drugs towards nonvascular compartments like adipose tissue. On account that a highly protein-included drug intends to stay in the systemic circulation, the drug bears a relatively less volume of distribution. Co-administration of several drugs, each being is highly bound towards plasma protein may lead to a greater than expected concentration of plasma of free form including one or more drugs. This may even occur due to the competence of co-administered drugs for similar binding place upon plasma protein. Increasing concentration of free drug may have have the potential to result in enhanced therapeutic or toxic impacts of drug.

3: A patient involved in consuming anticoagulant drug warfarin must not be recommended with salicylate drug aspirin simultaneously unless these people undergo vascular surgery. It is because both of the mentioned drugs include protein bound, also that aspirin possess much stronger affinity for proteins than that of warfarin; therefore aspirin (strong binder) dislocates warfarin (weak binder). Minute amounts of drug warfarin joins to protein places and so highly active warfarin (free drug) exists within the blood, quite like administering dos enhanced age of warfarin. It may poison the patient as well as result in heavy bleeding, and sometimes even prove more fatal, as warfarin is considered as a highly toxic drug as well as aspirin is said to intensify actions as well as effects of the drugs.

Aspirin is said to offer alternatives to individuals that possessed blood clots within the deep veins. It usually never bears the prolonged utilization thinner blood. On the other side, prolonged utilization of warfarin is not appropriate at all and rather inconvenient (Yang and Rodrigues, 2010). Thus, using aspirin within the administered anticoagulant can impact upon the block of vitamin K. Block of vitamin K restricts clotting of blood which gets increased at the time of preparing fibrin. The aspirin when utilized to care for the patients, these drugs do not restrict the blood chemical from working thrombin.

4: Hepatic first pass effect means the process in which drugs pass to the bloodstream or even the lymph directly from the intestine, and from there towards the liver to get metabolised as well as largely destroyed. The importance of emphasizing upon hepatic first pass impact while administering oral drugs refers to the fact that majority of drugs are usually metabolized by liver. Here, only a small amount of any active drug moves from liver to any other circulatory systems. But, availability of the drug may be referred as considerably lessened by the first pass technique. Other means of drug administration like intravenous, sublingual, intramuscular and suppository may in fact evade such first pass effect since they allow drug absorption into systemic circulation (Wright, 2000). Main four primary systems which impact first pass effect of drugs are the enzymes of the gastrointestinal lumen, bacterial enzymes, gut wall enzymes, and hepatic enzymes. The drug absorption is specifically determined by the bioavailability of drugs like a drug which bears poor absorption when these are administered orally may be induced using different routes like intravenously or inhalation for example.

5: Half life: This concept refers to required time in the process of concentration of serum plasma within the human body for decreasing to half (50%); at least four or five half-lives to steady state. Prescribers often face several potential issues related to drugs administration; nevertheless quite imperative for these prescribers to accept factors which impact half life of drug like that of structure of drug, individual ability of drug metabolising, age, weight, lipophilic nature of the drug, stomach acidity (pH) and that of intestines  (Bae et al., 2009).

6: The concept of ‘Steady state’ concentration of drug means concentration achieved on administering drug equally to the quantity of drug removed within single dosing interval leading to a constant level of serum drug. As repeated drug doses are administered, the plasma concentration develops that reaches a level of steady state. It is when the level of drug within the plasma has developed a concentration extent which is therapeutically effective. As long as regular doses would be administered for balancing the level of drug that is cleared the drug would remain active (Banker and Clark, 2008). The normal time that is taken for reaching the steady state is around four or five times the half life of such a drug.

7: Characteristics of enzymes: In a chemical manner, normally enzymes are globular proteins (for instance, molecules of RNA and ribosome) that are basically found within nuclear cellular areas. These enzymes are basic reactants which usually break down highly complex chemical compounds. These permit occurrence of chemical reaction which has a fast property suitable for supporting life. These enzymes are not changed at the time of chemical reaction, remain available only in small amounts within cells; however, these are quite specific for their own substrate.

 

The distinction between competitive as well as non-competitive inhibition refers to the fact that during competitive inhibition process, drug normally resembles that of an enzyme substrate or natural receptor, and so said to compete with specific natural substrate to bind into the site of binding upon the enzyme (Caldwell, 2005). For instance, specific antimicrobials like sulphonamides as well as bactrim possess same structure of para-4-aminobenzoic acid (PABA). The sulphonamides is said to compete to bind to any enzyme which prepares folic acid from PABA; so this inhibits chemical reaction. During the process of non-competitive inhibition, normally drug does not reflect natural substrate, yet binds to another alternative place upon the enzyme, and then changes the entire structure of the receptor or enzyme so that no longer it may bind with any natural substrate. For instance, heavier metals such as mercury, arsenic, carbon monoxide usually bind irreversibly with haemoglobin at place apart from oxygen.

8: Agonist usually refers to a drug that changes the physiology of any cell by means of bind with a plasma membrane or even intracellular receptors like nor-adrenaline or nor-epinephrine. Antagonist means a drug which blocks the receptor to prevent endogenous neurotransmitters from binding. Any drug which acts as an antagonist actually blocks responses initiated by agonists. Here, Atropine is said to work by binding with any acetylcholine receptors at nerve synapse, thereby allowing no messages to transmit (Chengliang, 2012).

Main impacts of atropine include an increase of heart rate along with sometimes a tachycardia and inhibition of secretions (that causes a dry mouth) as well as ‘relaxation of smooth muscle within the gut, biliary tree or urinary tract. As atropine passes the barrier of blood brain, central nervous system impacts may be experienced like during amnesia, confusion or excitation. Dilation of pupil as well as paralysis of accommodation takes place, along with an enhancement of intraocular pressure particularly within patients suffering from glaucoma (Doern, 2001). Other advantageous impacts of such atropine are its ability for decreasing gastrointestinal secretions, gastric juice, and motility specifically for patients having peptic ulcers.

9: Phenelzine as well as broad beans: both these drugs have impacts upon serotonin which is a chemical existent in brain. If these substances get combined, possibility of danger may arise that may cause severe effects with excessive accumulation of chemical serotonin within the brain.
 
Tetracyclines as well as antacids: at some phase antacids include aluminium that may combine along with tetracycline including the amount of it absorbed within the body and this may be reduced drastically (EL-LAKKANY and NOSSEIR, 2007). Therefore, lesser effective tetracycline would be available within the body for utilizing. Therefore, it may fail to prove effective in targeting or even fighting infections.

 

 
Alcohol as well as diazepam: Alcohol as well as diazepam form central nervous system depressants which mean that they may reduce activity of brain. Consequently, consumption of alcohol during ongoing treatment with this diazepam can cause serious negative reactions resulting in impaired judgment. For daily consumption of alcohol, often liver enzymes get stimulated constantly that induces tolerance towards the drug and thereby reducing the impacts (Tominaga, 2002).
 
Part of the autonomic nervous system of Mr.FT which is affected by Malathion constitutes parasympathetic nervous system. Like all organophosphate insecticides, Malathion inhibits the acetylcholinesterase as well as alters transmission of cholinergic synaptic. Hence, when parasympathetic division gets activated, it would lead to production of some major effects such as pupil constriction, secretion from digestive glands like that of salivation, duodenal glands, gastric glands, pancreas, intestinal glands, and the liver, also vomiting as well as diarrhoea, enhanced activity of smooth muscle with gastrointestinal tract, decreased heart rate, constriction of bronchi and also negative inotropic impacts, contracting of urinary bladder during urination, and relaxation of  rectum at the time of defecation (Hee Lee, 2000).
 
Various sorts of tissue receptor which are likely to get affected are that of muscarinic (located at junction of cholinergic neuromuscular within division of parasympathetic, also some within sympathetic division) as well as nicotinic (located upon surfaces of ganglionic cells of parasympathetic as well as sympathetic divisions located at the junction of neuromuscular belonging to somatic nervous system) receptors  (Savarese, 2005).

Mechanism of Organophosphate insecticides in toxicity refers to the acetylcholinesterase inhibition, causing an accumulation of neurotransmitter acetylcholine as well as continuous stimulation of receptors of acetylcholine. The Organophosphate insecticides is said to induce the parasympathetic nervous system with an enzyme named phosphorylating acetylcholinesterase (that binds irreversibly along with that of acetylcholinesterase) at every nerve ending. The enzyme Acetylcholinesterase is breaks down acetylcholine within the junction of neuromuscular. It causes a loss of acetylcholinesterase in order that effecter organ gets overstimulated with immense of acetylcholine at nerve ending  (Hui, 2012). The mechanism is said to impact both muscarinic as well as nicotinic receptors within parasympathetic as well as sympathetic systems along with that of neuromuscular junctions.

Organophosphate insecticides usually resemble that of clinical drugs named anticholinesterase in context to its action. Thus, the clinical drug groups are quite similar in context to their actions- physostigmine, neostigmine; but these drugs often have reversible impacts (Jusko, 2012). It shows that these drugs may possess capability to displace the insecticides from those enzymes, thereby reactivating the activity of cholinesterase. Further, drug like echothiophate iodide also an irreversible organophosphate anticholinesterase used clinically.

The standard process of treatment for Mr FT would include reactivation of inhibited acetylcholinesterase along with an antidote named oxime and that of pralidoxime as well as reversing of biochemical impacts of acetylcholine along with atropine.

 

Pralidoxime Iodide: Pralidoxime is said to reverse depression of cholinesterase and so relieves both muscarinic as well as nicotinic impacts of poisoning. It is said to work with reactivating of cholinesterase including that of slowing the process of ageing of phosphorylated cholinesterase towards a non-reactivatable form (Lemley et al., 2010).

Atropine Sulphate: The purpose of atropine antidotal therapy in case of organophosphate poisoning includes antagonising the impacts of increased concentrations of acetylcholine in organs with muscarinic receptors. This serves as strong blocking agent for acetylcholine but ineffective to reverse the process of inhibition of cholinesterase. 

The chronic disease that has been affecting people from all the age group is asthma. There is obstruction in the flow of air. It shows problems in the respiration of the individual. The National Health campaign aims at management of the Asthma of the individuals. This will improve the well being of the individuals and the severances of the symptoms of the disease will be reduced.

a.) Management of Asthma – long term mission

The chronic symptoms causing discomfort such as breathlessness, coughing should be averted.

The normal function of the pulmonary has to be preserved.

Exercise has to be done to preserve the normal activity (LeWitt, 2014).

The need for the visit to the emergency departments at hospitals has to be avoided.

Medication with little side effects has to be taken.

The management technique of families for asthma has to be followed.

b.) Treatment of acute Asthma – First line therapy

The inflammation of the lungs is stabilized by this technique. This is done by the passage ways of the lungs are prevented from getting inflated. This is achieved by the inhalation of corticosteroids or the prophylactic agents for the attacks of asthma. An inhaled β2 agonist has to be used if the propensity to exposure increases. The bronchodilators can be combined with the nebulizer to for a patient suffering from severe attack of asthma. Oral administration of corticosteroids during the asthmatic attack can be helpful (Rañó, 2014). This has helped to stop the saturation by 93%. Rectification of the hypoxic condition of a child is important to prevent the child from asthmatic attack. The treatment to the child can be provided by treating with β2 agonists. The oral way of treatment via the corticosteroids is also useful. The metered dose salbutamol inhaler is very effective in getting positive results.

The inflammation of the passage of the airway characterizes Asthma. This concludes in attack by asthma creating an obstruction with the airflow through the air ways. The bulge of the mucous membrane causes the obstruction. The fluid inside the airways which is inflammatory and the muscle contraction also causes obstruction. Children Can have severe obstruction in the flow of air for having a small way for passage of air. If not avoided then smoking, respiratory infection, air pollution, fumes, airborne allergen, certain type of foods and dusts contributes to the attack in BB’s in asthma.

The inhale corticosteroids are very effectual (anti-inflammatory potential) manager for the control in long-term and are widely chosen by patients who grow to unrelenting asthma syndrome. Nevertheless, the use of inhaled corticosteroids therapy for control in long term concentrated on treatment of inflammatory system and has the ability to prevent the inflammation occurrence and reduce the inflammatory airway, while preventing serious symptoms of asthma and preserving control over them (Seyberth, Rane and Schwab, 2011).

 

a) According to the encountered short-term effects after using corticosteroids inhale, the range of likely negative effects is expected to develop infections which are opportunistic in nature like the Candida albicans pharyngeal and the croaky voice concluding the immune function being suppressed of pharyngeal mucosa after utilizing the corticosteroids (Scully, 2008). It should be kept in mind as in case of the children these agents stifle the hypothalamic-pituitary region particularly when they are directed for a long time period at a very high dose. Children who suffer from mild asthma were observed with growth disturbance in short term which is a side effect of inhaling corticosteroids (Johnson, 2010). According to some data there is a propensity for affecting bone mineralization after using corticosteroids. It can also increase in the suppression of adrenal and syndrome of drug-induced Cushing’s as a termination (Walsh, Czervinske and DiBlasi, 2010).

b) In accordance to Short term consequences which are connected with the β2 agonists, certain effects of short term were scrutinized like Tachyphylaxis that is the reduced responsiveness to the medication because of desensitization and down-regulation of the β receptors in the tangential lymphocytes and the receptors present in the lungs. There are also some other negative effects considered to be minor such as, metabolic effects, headache, tremor and palpitations which are encountered relating to the quantity of the doe used (Walsh, n.d.).

The ICS are the most chosen regimen for therapeutic conditions in case of children chronic asthma and as the provider of the most accessible anti-inflammatory treatment. The use of long term medication of inhaled corticosteroids ascertains potential negative effects especially on the adrenal function, the velocity of growth and the obstruction of linear growth, ocular disorders and osteoporosis. According to various proofs demonstrated that the agent of potent anti-inflammatory suppress the region of hypothalamic-pituitary which is not a sustained effect for a long term as the child reaches the height of normal as in mentioned in the 4a question.

Due to the delivery of medicine being quicker after using inhaler than a nebulizer, it is preferred by many. Moreover it is a small device that can be easily carried during emergency and other necessary requirement moment. A device used with metered-dose inhalation in combination for satisfactory inhalation is known as spacer. It is a satisfactory inhalation for individuals who are not comfortable with coordination of hand-breath. However the BB’s acute incident managing health team applied both spacer and inhaler ( for administering the B2 inhaled agonist by MDI) only for the reason that they permitted for better medication deliverance by increased inhalation and actuation coordination, infectious haze as it releases inhalation of meter dozed and allows having drugs with no enduring, remain in the mouth. The team of managing dis not utilizes the nebulizer because obvious benefits were not ascertained in comparison to spacer and inhaler. As moisture and warmth is combined with the use of nebulizer, it is often remarked for carrying danger of microbial contamination. In case of asthma that causes threat to life nebulizer becomes valuable when through oxygen the b2 agonist high doses are necessarily controlled. In case of Pediatric urgency, Nebulization becomes less efficient. It becomes hard to control and another disadvantage is that it is expensive cannot be transferred or carried like spacer or meter-dose inhaler and similar devices. The corticosteroid hydrocortisones strategic control helps in recovering during or after and attack of acute asthma with the duration and sternness of the acute attack and it helps to prevent relapse. The Hydrocortisone attains prompts condition of allergy and swelling in the body. In response to an allergen or irritant this hormone is discharged in the body. With the reason of providing corticosteroid to the asthmatics is to make the lining of airways calm which has been influenced by atmospheric change or irritant.

When the patient is under the combined treatment for recovery form an attack of acute asthma, it is crucial to control the corticosteroids level in the body since a sudden treatment halt may conclude in shock, vomiting nausea and can eventually conclude in disturbance in the functions of adrenal. The controlling of dosage would reduce the negative effects like adrenal axis of hypothalamic-pituitary, fractures and osteoporosis because of mineralization of bone in low density and developmental disturbance.

The subsequent required to be monitored:

The rhythm and rate of the cardiac

The blood pressure

The levels of oxygen concentration and

The sounds of chest

It is so because they are crucial signs that will alter in retort to the treatment that allows medical practitioner for continuation and adjustments for necessary treatments.

 

 

References

Bae, S., Yang, K., Aryal, D., Kim, Y. and Lee, M. (2009). Pharmacokinetics of amitriptyline and one of its metabolites, nortriptyline, in rats: Little contribution of considerable hepatic first-pass effect to low bioavailability of amitriptyline due to great intestinal first-pass effect. Journal of Pharmaceutical Sciences, 98(4), pp.1587-1601.

Banker, M. and Clark, T. (2008). Plasma / Serum Protein Binding Determinations. Current Drug Metabolism, 9(9), pp.854-859.

Caldwell, J. (2005). GW280430A: Pharmacodynamics and Potential Adverse Effects. Anesthesiology, 102(4), pp.862-863.

Chengliang, T. (2012). Determination of plasma protein binding rate of vitexin. China Journal of Chinese Materia Medica.

Doern, G. (2001). Fluoroquinolone Pharmacodynamics and Efficacy. Chest, 120(1), pp.319-320.

EL-LAKKANY, N. and NOSSEIR, M. (2007). Pharmacodynamics of pentoxifylline and/or praziquantel in murine schistosomiasis mansoni. APMIS, 115(3), pp.184-194.

Hee Lee, Y. (2000). Regional oral absorption, hepatic first-pass effect, and non-linear disposition of salmon calcitonin in beagle dogs. European Journal of Pharmaceutics and Biopharmaceutics, 50(2), pp.205-211.

Hui, K. (2012). Determination of plasma protein binding rate of isopropylidene-shikimic acid. China Journal of Chinese Materia Medica.

Jusko, W. (2012). Changes to journal of pharmacokinetics and pharmacodynamics. Journal of Pharmacokinetics and Pharmacodynamics, 39(1), pp.1-1.

Lemley, C., Wilmoth, T., Tager, L., Krause, K. and Wilson, M. (2010). Effect of a high cornstarch diet on hepatic cytochrome P450 2C and 3A activity and progesterone half-life in dairy cows. Journal of Dairy Science, 93(3), pp.1012-1021.

LeWitt, P. (2014). Levodopa therapy for Parkinson's disease: Pharmacokinetics and pharmacodynamics. Movement Disorders, 30(1), pp.64-72.

Rañó, I. (2014). Results on the Convergence of Braitenberg Vehicle 3a. Artificial Life, 20(2), pp.223-235.

Savarese, J. (2005). GW280430A: Pharmacodynamics and Potential Adverse Effects. Anesthesiology, 102(4), pp.863-865.

Tominaga, M. (2002). Effect of portal vein embolization on function of the nonembolized lobes of the liver: Evaluation by first-pass hepatic lidocaine extraction in dogs. Surgery, 132(3), pp.424-430.

Wright, D. (2000). Application of fluoroquinolone pharmacodynamics. Journal of Antimicrobial Chemotherapy, 46(5), pp.669-683.

Yang, Z. and Rodrigues, A. (2010). Does the Long Plasma Half-Life of 4β-Hydroxycholesterol Impact Its Utility as a Cytochrome P450 3A (CYP3A) Metric?. The Journal of Clinical Pharmacology, 50(11), pp.1330-1338.

YOKOMASU, A., YANO, I., SATO, E., MASUDA, S., KATSURA, T. and INUI, K. (2008). Effect of Intestinal and Hepatic First-pass Extraction on the Pharmacokinetics of Everolimus in Rats. Drug Metabolism and Pharmacokinetics, 23(6), pp.469-475.

Scully, C. (2008). Oral and Maxillofacial Medicine: The Basis of Diagnosis and Treatment. 2nd ed. Churchill Livingstone, p.408.

Seyberth, H., Rane, A. and Schwab, M. (2011). Pediatric Clinical Pharmacology. Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg.

Walsh, B., Czervinske, M. and DiBlasi, R. (2010). Perinatal and pediatric respiratory care. St. Louis, Mo.: Saunders/Elsevier.

Walsh, B. (n.d.). Neonatal and pediatric respiratory care.

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