Question cervical contractions. Since the uterus is

Question 1
Oxytocic drugs are used before birth to induce uterine contractions.
It is also used to cause an abortion or control postpartum vaginal haemorrhage.
Ergonovine, Methylergonovine, Oxytocin, Carboprost, Dinoprostone and Mifepristone are drugs under this category.
1) State the action of each oxytocic drugs that has been mentioned above.
2) Describe the use of each of the drugs and their adverse reaction.

Ergonovine is able to trigger muscles of uterine to increase level of force and frequency of contractions. This contractions, in usual doses precede in periods of relaxation but in in larger doses, the basal uterine tone will be elevated and will be decreasing the relaxation periods. Ergonovine is also inducer of cervical contractions. Since the uterus is more sensitive to oxytoxic effects towards the end of pregnancy, and the oxytocic actions of ergonovine are greater than its vascular effects, it can produces arterial vasoconstriction by stimulation of alpha-adrenergic and serotonin receptors and inhibition of endothelial-derived relaxation factor release. Therefore, ergonovine causes vasoconstriction of coronary arteries (“Ergonovine – DrugBank”, 2018). Adverse reactions of ergonovine however includes cardiovascular side effects, including blood pressure elevation (sometimes extreme), chest pain, dizziness, myocardial infarction, ventricular arrhythmias, bradycardia, and peripheral vasospasm, gastrointestinal side effects including nausea, vomiting, diarrhoea, and abdominal or stomach pain, hypersensitivity side effects including allergic reactions (including shock) have occurred with ergonovine. General side effects have included unpleasant taste, tinnitus, sweating, uterine cramps, and nasal congestion. Nervous system side effects have included headache (mild and transient). Respiratory side effects have included dyspnea (“Ergonovine Side Effects in Detail –”, 2018).

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Methylergometrine acts right on the smooth muscle of the uterus and increases the tone, rate, and fullness of rhythmic contractions over binding and the resultant antagonism of the dopamine D1 receptor. Thus, it induces a rapid and sustained tetanic uterotonic effect which shortens the third stage of labor and reduces blood loss. (“Methylergometrine – DrugBank”, 2018) More common adverse reactions to methylergometrine are abdominal pain, headache, increased blood pressure, cardiovascular side effects including palpitations, hypertension, hypotension, acute myocardial infarction, transient chest pains, arterial spasm (coronary and peripheral), bradycardia, and tachycardia and respiratory side effects have included dyspnoea and nasal congestion (“Methylergonovine Side Effects in Detail –”, 2018).
Oxytocin promotes contractions by increasing the intracellular Ca2+, which in turn activates myosin’s light chain kinase. Increases contraction amplitude and frequency, which tends to decrease cervical activity, produce dilation and effacement of the cervix, and transiently impede uterine blood flow; contractions produced by oxytocin at term are similar to those occurring during spontaneous labor. Uterine response increases with the duration of pregnancy and is greater in labor than when not in labor; only very large doses elicit contractions in early pregnancy. Contracts myoepithelial cells surrounding the alveoli of the breasts, forcing milk from the alveoli into the larger ducts and facilitating milk ejection. Minimal antidiuretic activity relative to vasopressin; water intoxication possible at high doses and/or excessive electrolyte-free fluid (“Oxytocin – DrugBank”, 2018). Cardiovascular side effects have included hypertension, premature ventricular contractions, sinus tachycardia, and other cardiac arrhythmias. Neonatal bradycardia, premature ventricular contractions and other arrhythmias have been reported. Nervous system side effects have included mania-like disturbances and seizures. Neonatal seizures and permanent CNS or brain damage has been reported. Genitourinary side effects have included pelvic hematoma. Excessive doses have produced pelvic fracture, uterine hypertonicity, spasm, tetanic contraction and rupture. Hepatic side effects have included neonatal jaundice (“Oxytocin Side Effects in Detail –”, 2018).
Carboprost is a synthetic prostaglandin that binds to prostaglandin E2 receptor, causing myometrial contractions, causing the initiation of labour or the expulsion of the placenta. Prostaglandins occur naturally in the body and act at several sites in the body including the womb (uterus). They act on the muscles of the womb, causing them to contract. Carboprost tromethamine administered intramuscularly stimulates in the gravid uterus myometrial contractions similar to labor contractions at the end of a full term pregnancy. Whether or not these contractions result from a direct effect of carboprost on the myome-trium has not been determined. Nonetheless, they evacuate the products of conception from the uterus in most cases. Carboprost tromethamine also stimulates the smooth muscle of the human gastrointestinal tract. This activity may produce the vomiting or diarrhea or both that is common when carbo-prost tromethamine is used to terminate pregnancy and for use postpartum. With the clinical doses of carboprost tromethamine used for the termination of pregnancy, some patients do experience temperature increases. In some patients, carboprost tromethamine may cause transient bronchoconstriction (“Carboprost Tromethamine – DrugBank”, 2018). Adverse reactions including diarrhea, nausea, vomiting, increased temperature and flushing are the most frequent adverse reactions observe. Adverse effects of this drug are generally transient and reversible when therapy ends. Endometritis, retained placental fragments, and excessive uterine bleeding were the most common complications after discharge from the hospital. Transient pyrexia may be due to the effect of carboprost on hypothalamic thermoregulation. Temperature elevation have been reported of the patients who received the recommended dosage regimen. In all cases, temperature returned to normal when therapy ended (“Carboprost Side Effects in Detail –”, 2018).

Dinoprostone administered by intravaginal stimulates the myometrium of uterus to contract in a manner that is similar to the contractions seen in uterus during labor, resulting in the clearing of the products of conception from the uterus. It is believed that dinoprostone exerts its uterine effects via direct myometrial stimulation, but the exact mechanism of action is unknown. Dinoprostone also appears to produce local cervical effects including softening, effacement, and dilation. Although the exact mechanism of action for this effect is also unknown, but it has been suggested that this effect may be associated with collagen degradation caused by secretion of the enzyme collagenase as a partial response to locally administered dinoprostone. (“Dinoprostone – DrugBank”, 2018). More common adverse effects may include abdominal or stomach cramps, diarrhoea, fever, nausea, vomiting, less common or rare, chills or shivering, constipation, flushing, headache, swelling of the genital area (vulva), tender or mildly bloated abdomen or stomach (“Dinoprostone topical Side Effects in Detail –”, 2018).
The abortion action of mifepristone is caused by competitive interaction with progesterone at progesterone-receptor sites. The compound hinders the activity of progesterone resulting in termination of pregnancy. For the treatment of Cushing’s syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels. Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days’ pregnancy. (“Mifepristone – DrugBank”, 2018). The most commonly reported side effects included uterine contractions/cramping, diarrhoea, and abdominal pain, uterine contractions or cramping usually occurred within hours of oral administration, heavy bleeding required haemostatic curettage and some conditions such as endometritis, heavy bleeding, pelvic inflammatory disease, cramps, dysmenorrhea, hypermenorrhoea, intermenstrual bleeding, menstrual disorder, spotting, vaginal haemorrhage (“Misoprostol Side Effects in Detail –”, 2018).

Question 2
Asthma is a respiratory condition characterized by recurrent attacks of dyspnea and wheezing caused by bronchi constriction. It is an obstructive of lower airway and can be reversible.
To treat asthma, various combination of anti asthma drugs are used.
Sympathomimetic Drug, Xanthine Derivative, Corticosteroids, Leukotriene Receptor Antagonists and Leukotriene Formation Inhibitors, Mast Cell Stabilizer
1) Explain each of the drugs mechanism of action with its uses.
Sympathomimetic drugs mimic the effects of sympathetic activation on the heart and circulation. Sympathomimetics stimulate the heart through activation of beta-adrenoceptors, and cause vascular smooth muscle contraction and vasoconstriction through activation of alpha-adrenoceptors like the sympathetic nerves innervating the heart. Sympathomimetics are used in conditions where it is appropriate to raise blood pressure by stimulating the heart and inducing vasoconstriction. Because long-term use of sympathomimetics is deleterious, they are used for short-term treatment of refractory heart failure, cardiogenic shock, and hypotension caused by hemorrhage or sepsis. Most sympathomimetics are catecholamines or analogs of catecholamines that can be divided into two mechanistic classes: 1) alpha-adrenoceptor agonists (?-agonists), and 2) beta-adrenoceptor agonists (?-agonists) (“CV Pharmacology | Sympathomimetics”, 2018).
Xanthine derivatives improves breathing by opening air passages in the lungs. It is used in the treatment of asthma, chronic bronchitis, and emphysema. This medication works best when taken on an empty stomach one hour before or two hours after meals. If stomach upset occurs, it may be taken with food. Long acting capsules and tablets must be swallowed whole. Crushing or chewing them may destroy the long action and increase the possibility of side effects (“XANTHINE DERIVATIVES – ORAL side effects, medical uses, and drug interactions.”, 2018).
Corticosteroids are steroid hormones that are either produced by the body or are man-made. Naturally occurring corticosteroids, hydrocortisone (Cortef) and cortisone, are produced by the outer portion of the adrenal gland known as the cortex (hence the name, corticosteroid). Corticosteroids are classified as either:
• glucocorticoids (anti-inflammatory) which suppress inflammation and immunity and assist in the breakdown of fats, carbohydrates, and proteins, or as
• mineralocorticoids (salt retaining) that regulate the balance of salt and water in the body.
Synthetic corticosteroids imitate the actions of naturally occurring corticosteroids and can be used to replace corticosteroids in people with adrenal glands that cannot produce enough corticosteroids, however, they are used often to treat diseases of immunity, inflammation or salt and water balance.
Some glucocorticoids also can retain salt. Fludrocortisone (Florinef), a synthetic mineralocorticoid has powerful salt retaining effects with significant anti-inflammatory actions, and is used mostly for its salt retaining capabilities (Omudhome Ogbru, 2018).
Leukotriene receptor antagonists, called LTRAs for short, are a class of oral medication that is non-steroidal. They may also be referred to as anti-inflammatory bronchoconstriction preventers. LTRAs work by blocking a chemical reaction that can lead to inflammation in the airways. Although not preferred first choice therapy. LTRAs can also be used when an inhaled corticosteroid cannot, or will not, be used. (“Leukotriene Receptor Antagonists (LTRAs) – Asthma Canada”, 2018)
Mast cell stabilizers are a group of medicines that stop the release of histamine and other chemical mediators from mast cells. Mast cells are a type of leukocyte and are involved in allergic rhinitis, allergic conjunctivitis, anaphylaxis, asthma, autoimmune diseases, eczema, itch, and reproductive disorders. The mast cell stabilizers cromolyn and nedocromil work by hindering a calcium channel that is essential for mast cell degranulation. Mast cell stabilizers may be used to prevent asthma and symptoms of seasonal or chronic allergic rhinitis (“List of Mast cell stabilizers –”, 2018).


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