PHARMACOLOGY III Essay Example

Pharmacology Assignment 3

Pharmacology Assignment 3

Question 1

Pharmacokinetics is a common term that generally means ‘what the body does to the drug. In details, it entails the motion of drug constituents in the body from the time they are introduced into the body until they are released after use. These are physiological processes that are detailed and are targeted to the achievement of the drug requirements in the body. Pharmacokinetics consists of four principle processes namely absorption, distribution, metabolism and excretion (ADME). This shows that the process is actually a chronology of events.

Absorption

This enables the drug gain access to the compartments of the body especially blood. This will determine the amount of drug circulating in the blood commonly referred to as bioavailability. To gain access to these compartments, it is necessary that the drug crosses membranes. For example, in oral administration, the drug has to cross the membranes of the epithelial lining of the gastrointestinal system in order to access the portal circulation (Bullock & Manias, 2016).

Distribution

This is whereby the drug, after gaining access to blood, is transported to its site of action. Distribution majorly lies on the drug’s solubility in plasma. Distribution also evaluates the ability of drug molecules to cross the common physiological barriers such as placenta and the blood brain barrier. In this case, drug ionization is also key (Bullock & Manias, 2016).

Metabolism

This is a process whereby the lipophilic absorbed molecules of the drug are made less lipophilic or more hydrophilic to prevent their reabsorption during the excretory process. This process also detoxifies the molecules so that they become less harmful to the body. Metabolism, in some instances also activates the drugs to their active form. Major site for metabolism is the liver by microsomal enzymes in hepatocytes (Bullock & Manias, 2016).

Excretion

Principally occurs in the gastrointestinal tract and the renal system. Drugs can either be excreted as metabolites or in the unchanged state in either urine or bile (Bullock & Manias, 2016).

Drugs can mediate their effects in a number of mechanisms. These mechanisms are targeted towards the reversal of physiological processes from the disease state to the normal state.

  1. Dugs work by simple chemical action by using their inorganic compounds or non-complex organic compounds to act on the simple chemical systems and processes. An example is the use of Magnesium Hydroxide to treat hyperacidity in the stomach.

  2. The body comprises of a few physical activities and some drugs act on these. Osmosis is one of the physical activities and solely relies on concentrations of fluids. This is the mechanism used by activated charcoal to relieve a patient from flatulence.

  3. Drugs that act on enzymatic activities act by either competitive inhibition whereby the molecule competes with actual enzymes for binding site without eliciting actions or non-competitive type whereby the molecule has similar actions as the previous but has a binding site that is different from that of the enzyme. In these categories, we have warfarin and aspirin respectively.

  4. Some drugs act on receptors by stimulating them to produce conformational changes that initiate some of the biochemical processes. The classical receptors here may be linked to ion channels, G-proteins, tyrosine kinases or DNA interactions (Bullock & Manias, 2016).

Question 2

The desirable effect of treatment of type 2 diabetes is a hypoglycemic therapy to reduce the levels of blood glucose in circulation. Insulin is only indicated when oral hypoglycemic agents and other modification of lifestyle fail in the glycemic control. Unless this scenario occurs and the patient responds positively to other hypoglycemic therapy, insulin should not be indicated (Bullock & Manias, 2016).

Checking Blood Glucose Levels

Hyperglycemia is a condition whereby there is an elevation in blood glucose levels. Symptoms become severe when levels rise above 15 mmol/L, fasting blood glucose of above 6 mmol/L and glycosylated hemoglobin above 53 mmol/mol. However, age should be always put into consideration. In control of the condition, blood glucose tests should be done routinely (Bullock & Manias, 2016).

Administration Technique

Since insulin can be destroyed by gut enzymes when administered orally, it is administered by either subcutaneous or intravenous routes. Abdomen, thigh and upper arm are the common sites for subcutaneous injection. Skin is pinched up to prevent injection into blood vessel and needle inserted at a 45° angle (Bullock & Manias, 2016).

Hypoglycemia and Hyperglycemia

Hypoglycemia is characterized by rapid pulse, sweating, weakness, headache and blurred vision; however, symptoms often vary from one person to another. Common signs of hyperglycemia are thirst, frequent urination, fatigue and a dry and itchy skin. The blood sugar levels should also be monitored occasionally using a glucometer (Bullock & Manias, 2016).

Strategies in illness and exercise

Diabetes is associated with increased risk of infections and poor healing. In suspicion of illnesses, medical attention should be sought. Participation in mild exercise is also advised. Highly vigorous activities can potentiate hypoglycemia that is deemed worse than hyperglycemia (Bullock & Manias, 2016).

Question 3

There are different agents that are used in the treatment of asthma ranging from bronchodilators to anti-allergic drugs.

Salbutamol is a β adrenergic receptor agonist that acts by binding to the β receptors of the bronchial muscles to induce bronchodilation. The inhaled form is capable of achieving faster onset and adequate concentrations locally in the respiratory tract. The drug also has mild anti-inflammatory effects and hyperpolarizes the airway smooth muscles.

Sodium cromoglycate is an agent used in asthma prophylaxis and falls under the class of mast cell stabilizers. Their efficacy is high in children hence their recommendation in these ages. In acute asthma, these drugs are not effective. These drugs prevent influx of calcium ions into mast cells that would otherwise modulate degranulation and release of autacoids and chemical mediators of allergic responses.

Oral prednisolone is a systemic corticosteroid. They prevent relapse of acute asthma and reduces the duration and severity of an asthma attack. They prevent broadly the efficacy of anti-inflammation by preventing the synthesis of arachidonic acid by phospholipase A2 and reduces the hyper-responsive nature of the bronchial airway (Bullock & Manias, 2016).

The three groups of drugs can be used in combination especially for the management of severe asthma and stabilizing an asthmatic patient after status asthmaticus. Independently, some drugs may not achieve desired relief to the patient. For instance, sodium cromoglycate is not as effective in adults as in children (Limbird et al., 1996)

Question 4

TCAs and SSRIs

Tricyclic antidepressants are drugs that block both the serotonin and norepinephrine reuptake in the cells of the nervous system and may relieve some pains of neuropathic nature such as diabetes peripheral neuropathy. SSRIs on the other hand principally act by inhibiting the reuptake of serotonin. SSRIs pose less of the sedation problems and the adverse effects are milder compared to that of the TCAs that presents also with anticholinergic adverse effects as complications during administration (Bullock & Manias, 2016).

Non-selective MAOIs and the RIMAs

Non-selective MAOIs act on the synaptic regions to prevent the level of degradation of excess transmitter after it has been released. They irreversibly inhibit monoamine oxidase enzyme and the drug action persists for around two weeks. Examples are phenelzine and tranylcypromine. As opposed to non-selective MAOIs, RIMAs such as Moclobemide increase dopamine concentrations within the synapse and their effects are reversible. Some RIMAs specific to MAO-B can also be used as anti-Parkinsonian agent. MAOIs require low tyramine diet which is not the case in RIMAs (Bullock & Manias, 2016).

TCAs and tetracyclic antidepressants

Tetracyclic antidepressants are commonly known as second generation antidepressants and are used as first line treatment of depression whereas TCAs are not always preferred due to the patient characteristics that accompany their administration. The tetracyclic antidepressants block presynaptic α receptors and noradrenaline reuptake; Tricyclic Antidepressants block the reuptake of amine at the presynaptic terminals (Bullock & Manias, 2016).

TCAs and Non-Selective MAOIs

TCAs are not always the drug of choice due to their personal effects whereas non-selective MAOIs have limited personal effects. TCAs exhibit anticholinergic effects as the adverse effects which is not the case in Non-Selective MAOIs. Non-selective MAIs have less extramydal effects compared to the TCASs (Bullock & Manias, 2016).

SSRIs and SNRIs

SSRIs are precise to the uptake of serotonin in the synapse exclusively whereas SNRIs are of wide use since they inhibit reuptake of both Norepinephrine and Serotonin. SSRI therapy does not respond in any way to the progressive increase in dosage whereas SNRIs do (Bullock & Manias, 2016).

Question 5

Adrenergic Receptors

α1 receptors are situated in blood vessels and they regulate tissue perfusion and blood pressure. They are also located on the iris radial muscle, GIT smooth muscles and sphincters and respiratory tract smooth muscles. Oxylmetazoline stimulates the activities of these receptors leading to vasoconstriction hence their use in emergent treatment of hypotension.

β1 receptors are mainly located in the myocardial layer of the heart and has an association with the GIT smooth muscles and sphincter and adipocytes. Dobutamine is a selective agonist of this receptor that is able to increase myocardial contractility and rate as well as induction of lipolysis in adipose tissues. They are majorly used in cardiac arrest.

β2 receptors have a distribution majorly on airway bronchial muscles. It may also be located on other sites such as the skeletal muscle. On stimulation, these receptors produce bronchodilation. A drug capable of producing these effects is Salbutamol hence their use in management of bronchial asthma.

α2 have a presynaptic dominance and are found on all adrenergic nerve terminals. Its activation has a negative effect on the release of transmitters hence their synaptic build-up. Clonidine, one of the agonists of these receptors, has been used in the treatment of hypertension (Bullock and Manias, 2016).

Cholinergic Receptors

Muscarinic receptors are located peripherally and centrally. They are found in the iris, lacrimal glands, digestive glands, GIT, bronchioles and urinary tract. Subtypes include M1, M2, M3, M4 and M5. Their stimulation causes vasoconstriction of vessels to the skin and external genitalia or vasodilation of those to the skeletal muscles. Pilocarpine has been used to manage glaucoma (Bullock & Manias, 2016).

Question 6

Glyceryl trinitrate (also known as Nitroglycerin) are moderately volatile organic nitrates that are used in the treatment of angina pectoris. They are, in the intracellular environment, converted to nitrite ions and later nitric oxide. This increases the cGMP leading to dephosphorylation of myosin light chains hence the relaxation of smooth muscles of the blood vessels. Vasodilation causes pooling of blood in veins which diminishes preload and dilates coronary blood vessels to increase perfusion. This reduced the incidences of Myocardial Infarction. The major adverse effect associated with this drug is headache. Tolerance also develops rapidly (Bullock & Manias, 2016).

Diltiazem

This is a Calcium Channel Blocker that has intermediate actions and is used to manage variant angina caused by abrupt coronary spasm. It has a unique role in this class due to its ability to relieve coronary artery spasm. Administration of Diltiazem exposes one to constipation and reflex tachycardia which all present as toxicities of its administration (Bullock & Manias, 2016).

Frusemide

Unlike other diuretics, Frusemide is associated with elimination of Calcium ions hence mimicking the role of Calcium ion blockers by getting rid of most of the calcium. This enhances vasodilation of coronary vasculature. The common adverse effects include Ototoxicity, Hypomagnesemia, Hyperuricemia and acute hypovolemia (Bullock & Manias, 2016).

Potassium Chloride and Potassium Rich diet

These are majorly aimed at balance of potassium ions associated with loss due to therapeutic agents (Bullock & Manias, 2016).

In coronary vasculature occlusion associated with platelet aggregation, aspirin has proved to be much effective. This is by reducing the risks of ischemic attacks and stroke, reducing the occurrence of myocardial infarction, reducing the recurrence of myocardial infarction as well as reducing other cardiovascular events associated with the platelet aggregation events. It can easily lead to peptic ulcer disease, prolonged bleeding time, hypersensitivity and respiratory depression (Bullock & Manias, 2016).

Question 7

Morphine

It interacts with CNS opioid receptors to cause nerve cell hyperpolarization which inhibits both nerve firing and transmitter release. Its interaction with kappa receptors decreases the release of substance P – a modulator of pain receptors. Adverse effects include respiratory depression, dysphoria and acute urinary retention (Tripathi, 2015)

Methadone

Its actions are mediated by the mu receptor and its analgesic role is equivalent to that of morphine. It is also an agonist of NMDA hence effective in the management of neurogenic pain. Adverse effects include torsades de pointes and presents with multiple drug-drug interactions (Tripathi, 2015).

The major effects of aspirin are analgesia, anti-inflammation and anti-pyrexia. This makes it qualify to be an anti-inflammatory drug as well. It converts the enzyme responsible for COX pathway (cyclooxygenase) to acetylated cyclooxygenase which is inactive. It decreases PGE2 synthesis leading to desensitization of the nerve endings to most of the chemical mediators. It manages pain of low to moderate intensities. The common adverse effects include gastrointestinal effects, reduction of platelet thromboxane levels, depression of the respiratory system, Reye’s syndrome, uncoupling of oxidative phosphorylation and hypersensitivity reactions (Tripathi, 2015).

Celecoxib

This is an anti-inflammatory drug that inhibits majorly the COX-2 pathway rather than the COX-2. This inhibition is reversible and time-dependent. Fortunately, it does not result into GIT bleeding and ulcers as aspirin do. This drug produces the following adverse effects: headache, abdominal pain, diarrhea, dyspepsia and anaphylactic reactions. It should also be avoided in patients with cardiovascular and CNS disorders (Tripathi, 2015).

Acetaminophen

It is best used in the management of pyrexia and pain together with stomach problems (GIT bleeding). It can also be used for those who need to manage the two conditions without effects on inflammation. Chicken pox in children can be best managed using acetaminophen to alleviate pain and fever associated with the viral infection. It can be taken together with probenecid and glutathione without any drug interactions. The main adverse effect of acetaminophen is Hepatotoxicity (Tripathi, 2015).

Question 8

Neonates and Children

Absorption in the very young is altered due to variation in gastric emptying time, microbial flora, intestinal motility, bile salt formation, length of bowel available for absorption and gastric acid secretion. All these are present in children in low amounts. Injected drugs are also variably absorbed due to their muscle mass and chemical characteristics. This is why IM injection is often avoided in children.

In regard to distribution, children should be given higher doses of water soluble drug formulations since most of their body weight comprises of water. Children may also have an increased free circulation of drug molecules due to inappropriate binding of drugs to plasma proteins. Children have lower concentrations of these proteins; at the same time, other molecules such as bilirubin compete for the binding site leading to higher frequencies of adverse effects.

Plasma half-lives in children are longer than in adults (more than two times). This is attributed to the reduction in efficiency of Phase I activity of drug metabolism. Elimination is also compromised due to a reduction in GFR, Renal blood flow, tubular secretion and plasma protein binding (Limbird et al., 1996).

Absorption is relatively reduced in the elderly due to reduced small-bowel surface area, reduced gastric acid emptying leading to an increase in pH

Distribution is compromised by increased fat content hence there will be increased volume for distribution of highly lipid soluble drugs such as diazepam. Their elimination half-lives may also be elevated. A rapid drop in serum albumin increases unbound drug in circulation that potentiates the adverse effects of drugs such as warfarin.

There is an evident alteration in metabolism quality and rate due to a reduction in the the cytochrome P450 enzyme activities. Hepatic clearance is also altered due to prolongation of Phase I reactions of metabolism. First pass metabolism also reduces by 1% per year for after clicking 40 years of age. Renal elimination of drugs is also reduced significantly since creatinine clearance reduces with advancement of age (Limbird et al., 1996).

References

Bullock, S., & Manias, E. (2016). Fundamentals of pharmacology. clinical nurses’ perceptions and experiences of graduate nurses’ medication knowledge. International Journal of Nursing Studies, 39(8), 773-784.

Limbird, L. E., Ruddon, R. W., Goodman, L. S., Gilman, A., Hardman, J. G., Molinoff, P. B., & Gilman, A. G. (1996). Goodman & Gilman’s CD-ROM: Goodman & Gilman’s the pharmacological basis of therapeutics, 9/e. New York: McGraw-Hill Health Professions Division.

Tripathi, K. D. (2013). Essentials of medical pharmacology. Indian Journal of Pharmacology, 26(2), 166.