Antagonizes the vasoconstrictive effects of angiotonin II, relaxes vascular smooth musculus advancing vasodilation, increasing nephritic salt H2O elimination, cut down plasma volume and lessening cellular hypertrophy, prevent ACE mediated debasement of bradykinin and substance P.
Hydrochlorothiazide: Decreases extracellular volume by interaction with thiazide sensitive Na-CL- cotransporter in kidney so there is autumn in cardiac end product and the hypotensive consequence remains maintained in long term intervention because of decreased vascular opposition. .Hydrochlorothiazide opens Ca2+ activated K+ channels, taking to hyperpolarization of vascular smooth musculus cells that causes shutting of L type Ca2+channel and diminish its gap so decreased Ca2+ entry and decreased vasoconstriction, inhibits vascular carbonic anhydrous which alter systolic Ph and do gap of Ca2 activated K+ channels
Adverse drug reactions:
Irbesartan: Hypotension, hyperkalemia, reduced nephritic map, cough incidence is less and angioedema occurs seldom, contraindicated in gestation
Hydrochlorothiazide: Gout due to hyperurecemia, quickly developing terrible hypernatremia, hypercalcaemia due to suppression of Ca elimination, K+ depletion taking to polymorphic ventricular tachycardia and other cardiac jobs, ischaemic ventricular fibrillation taking to sudden cardiac decease, alteration in plasma lipoid and glucose tolerance, crosses placenta but no direct consequence on fetus.
Relevant Drug Interaction:
Irbesartan: Hyperkalemia occur in concurrence with other factors that alter K+ homeostasis such as nephritic inadequacy, consumption of extra K+ and drugs that cause keeping of K+ .
Hydrochlorothiazide: Linear with other antihypertensive, K+ , Mg+ consuming action potentiate arrhythmias with digitalis toxicity, corticoids amplify hypokalemia, lessening Li clearance, NSAIDS lessening antihypertensive action of Microzide
Irbesartan: Largely used 150 to 300mg one time day-to-day.
Hydrochlorothiazide: 12.5 to 25 milligrams one time day-to-day
Rationale for usage in Mrs. AB
Hydrochlorothiazide are the most of import category of drug to cut down blood force per unit area and in most instances normally combined with other drugs like angiotonin receptor adversary that has cardio protective consequence every bit good as better control of blood force per unit area with limited side effects. ( Goodman Gilman 11th edition )
Metformin ( Biguanide group ) and Glibenclamide ( sulfonylurea group ) are unwritten hypoglycaemic drugs that are used in the intervention of diabetes and hence used for Mrs. AB as she is a known instance of diabetes.
Mechanism of action:
Metformin: Suppress hepatic gluconeogenesis and glucose end product from liver.
Enhance insulin mediated glucose disposal in musculus and fat by impacting GLUT 1 conveyance.
Retard enteric soaking up of glucose
Interfere with mitochondrial respiratory concatenation so promote peripheral glucose use by anaerobiotic glycolysis
Glibenclamide: Provoke brisk release of insulin from pancreas, act on sulfonylurea receptor, on the pancreatic beta cell membrane cause depolarisation by cut downing conductance of ATP sensitive k+channels, enhances calcium inflow and degranulation. Extrapancreatically they sensitize the mark tissues to the action of insulin.
Metformin: lactic acidosis, abdominal hurting, anorexia, sickness, metallic gustatory sensation, diarrhoea, fatigue.
Glibenclamide: Hypoglycemia, sickness, purging, flatulency, diarrhoea, concern, weight addition, hypersensitivity
To look into the blood sugar degree often, educate the patient sing symptoms of hypoglycaemia which may mime cardiovascular event in aged. In instance of experiencing giddiness or tired patient is educated to maintain something eat something Sweet to rectify hypoglycaemia like cocoa or glucose or honey but if the patient is unconscious it & amp ; acirc ; ˆ™s better to give endovenous glucose extract
Rationale for its usage in Mrs. AB
Sulfonylurea reduced incidence of micro vascular complications in type 2 Diabetes Mellitus but did non hold important consequence on macro vascular complications. Metformin nevertheless can cut down macro vascular complications as good, it decreased decease and other diabetes related end points in Type 2 Diabetes corpulent patients- its anorexic action AIDSs in weight decrease and has the potency to take down myocardial infarction and shot. Metformin is largely used to supplement sulfonylureas in patient non adequately controlled by sulfonylureas entirely. ( K.D.Tripathy, 6th edition )
Metoprolol is eta sympathomimetic receptor agonist which reduces frequence and badness of onslaught inexertion angina and improves endurance in patients who have had MI. It decreases myocardial O demand and increase blood flow to ischemic ground. It reduces arterial blood force per unit area, negative chronoscopic and negative inotropic consequence.
Curative benefit in Mrs. AB: It will cut down perennial episodes of ischaemia and hazard of patterned advance to MI. In presence of equal antiplatelet therapy and vasodilation by angiotonin receptor adversary beta adregernic receptor adversary is helpful.
Adverse effects of Metoprolol: Bradycardias, complain of cold appendages, may do or worsen bosom failure in patients with remunerated bosom failure, acute MI or megalocardia.
Nursing safeguards: Metoprolol should ne’er be stopped suddenly after long-run intervention because hazard of angina or sudden decease is increased.
Warfarin: Adversary of vitamin K so factors II, VII, IX, X are inhibited. Warfarin is effectual in forestalling venous thrombosis or systemic embolization in patients with acute myocardial misdemeanor. INR is international normalized ratio which is calculated from the patient & A ; acirc ; ˆ™s factor II clip to supervise efficaciousness and patient conformity, targeted INR is between 2 to 3.
Adverse Effectss of Coumadin: Bleeding is the major inauspicious consequence of Coumadin, so careful monitoring of the patients is required. Hazard of shed blooding is extremely increased when INR becomes 4. Patient is educated sing marks and symptoms of shed blooding. Warfarin during gestation causes birth defects and abortion, may do skin mortification, reversible and sometimes painful bluish tinged stain of the plantar surfaces, precipitates assorted syndromes of limb sphacelus etc.
INR is international normalized ratio: a fasting blood sample is obtained 8-14 hour after last Coumadin dosage and patients PT is determined along with a normal pooled plasma.
INR=PTpt/PT ref ( Goodman Gilman 11th edition )
Glyceryl Trinitrate ( GTN ) is a pro-drug that leads to formation of free extremist azotic oxide ( NO ) . NO activates Guanyl Cyclase addition cellular degree of cGMP, activate PKG and modulate the activities of cyclic nucleotide phosphodiesterases. Ultimately the smooth musculuss are relaxed taking to vasorelaxation. Low dose GTN cause relaxation of venas more than arteriolas which decrease the left and right ventricular chamber size and stop diastolic force per unit areas but consequences in small alteration in vascular opposition. The Systemic arterial force per unit area falls somewhat and bosom rate is unchanged or may increase somewhat. Pneumonic vascular opposition and cardiac end product are somewhat reduced. Dose that do non change systemic arterial force per unit area frequently produce arteriolar dilation in face and cervix so there is blushing. Higher doses cause farther venous pooling and may diminish arteriolar opposition every bit good. Thereby systolic and diastolic blood force per unit area is reduced. Cardiac end product is reduced and that may do lividness, failing, giddiness and activation of compensatory mechanisms. The automatic tachycardia and peripheral arteriolar vasoconstriction tend to reconstruct systemic vascular opposition that is superimposed on sustained venous pooling. In patients with autonomic disfunction and an inability to increase sympathetic outflow the autumn in blood force per unit area consequent to veno distension in can non be compensated. In these clinical context nitrates may cut down arterial force per unit area and coronary perfusion force per unit area significantly bring forthing life endangering hypotension and even worsening angina.
The hemodynamic mechanism responsible for have focused on the ability of organic nitrates to do distension and prevent vasoconstriction of big epicardial vass without impairing car ordinance in the little vass which are responsible for 90 % of overall coronary vascular opposition. Vessels larger than 200micrometer in diameter are extremely antiphonal and those less than 100 microns respond minimally. Analysis of coronary angiograms in worlds has shown that sublingual glyceryl trinitrate dilates epicardial vass and reduces the opposition to flux to such countries. The ensuing addition in blood flow would be distributed preferentially to ischemic myocardial parts as a effect of vasodilatation induced by car ordinance.
Untoward response to the curative usage of organic nitrates is about all secondary to actions on the cardio vascular response. Severe concern, transeunt episodes of giddiness, failing due to postural hypotension may develop peculiarly in patients standing immobile, may on occasion take to loss of consciousness.
Dose and path:
Sublingual path is used to end an onslaught, the tablet is crushed under the dentition and spread over buccal mucous membrane, it acts within 1 to 2 proceedingss, plasma T1/2 is 2 proceedingss and action depends on its handiness on buccal mucous membrane, staying portion is spit or swallowed when no longer needed.
Paths of disposal:
Sublingual tablet, sublingual spray, unction to be applied on tegument, transdermic spot, endovenous extract. In instance the sublingual GTN does non work so aspirin tablet can be chewed and swallowed. ( Goodman Gilman 11th edition ) .