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A type III hypersensitivity reaction is mediated by immune complex deposition. In lupus, auto-antibodies are formed and these complexes are deposited in other tissues, especially in the kidneys, skin, and joints. Graves disease and myasthenia gravis are examples of type II but in some classification systems they are called type V reactions. The auto-antibodies created in Graves attack TSH receptors in the thyroid, whereas in

Myasthenia the target is the acetylcholine receptor. Hashimoto’s thyroiditis is usually considered an example of a combination of type II and IV reactions, as T cells are directed at thyroid antigens and antibodies are also produced. Allergic rhinitis is a classic example of a type I, IgE mediated reaction.

Thiazolidinediones Sulfonylureas work in beta cells in the pancreas that are still functioning to enhance insulin secretion. Alpha-Glucosidase Inhibitors stop α-glucosidase enzymes in the small intestine and delay digestion and absorption of starch and disaccharides which lowers the levels of glucose after meals. DPP4 blocks the degradation ofGLP-1, GIP, and a variety of other peptides, including brain natriuretic peptide. Glucagon-like peptide-1 receptor agonists work in various organs of the body. Glucagon-like peptide-1 receptor agonists enhance glucose homeostasis through: (i) stimulation of insulin secretion; (ii) inhibition of glucagon secretion;

(iii) direct and indirect suppression of endogenous glucose production; (iv) suppression of appetite; (v) enhanced insulin sensitivity secondary to weight loss; (vi) delayed gastric emptying, resulting in decreased postprandial hyperglycaemia. Thiazolidinediones are the only true insulin-sensitising agents, exerting their effects in skeletal and cardiac muscle, liver, and adipose tissue. It ameliorates insulin resistance, decreases visceral fat. Biguanides work in liver, muscle, adipose tissue via activation of AMP-activated protein kinase (AMPK) reduce hepatic glucose production. SGLT2 inhibitors work in the kidneys to inhibit sodium-glucose transport proteins to reabsorb glucose into the blood from muscle cells; overall this helps to improve insulin release from the beta cells of the pancreas.

Clopidogrel and ticlopidine are ADP receptor pathway inhibitors. The irreversible inhibition of the ADP- dependent pathway of platelet activation is thought to be the result of covalent modification and inactivation of the platelet P2Y ADP receptor. This receptor is coupled to the inhibition of adenylyl cyclase. Both drugs are prodrugs and undergo conversion to active metabolites in the liver. However, clopidogrel must undergo oxidation by hepatic P450 enzymes to its active form. This is significant because many drugs are metabolized the hepatic P450 enzymes, including statins, and clopidogrel may interact with these medications. Clopidogrel is a second-generation thienopyridine and ticlopidine is a first-generation thienopyridine. Both drugs are indicated in combination with aspirin to prevent stent thrombosis. Eptifibatide is a GPIIb-IIIa receptor antagonist that is used to treat unstable angina and non-ST segment elevation myocardial infarction. Eptifibatide is also used to reduce ischemic events in patients who are undergoing percutaneous coronary intervention. The drug is a synthetic peptide that directly antagonizes the GPIIb-IIIa receptor on the platelet. Aspirin is an antiplatelet drug that works by inhibition of synthesis of prostaglandins. Prostaglandin G2 is the result of a synthesis pathway that is activated by platelets and endothelial cells, and results in localized

vasoconstriction and induction of platelet aggregation, as well as causing release of platelet granules. Warfarin is an anticoagulant that acts on vitamin K-dependent reactions in the coagulation pathway. Vitamin K is necessary for hepatic synthesis of coagulation factors II, VII, IX and X, protein C and protein S. Vitamin K- dependent carboxylation is necessary for induction of enzymatic activity of these coagulation factors. Take- home message: Clopidogrel, a second-generation thienopyridine ADP receptor pathway inhibitor, is indicated in combination with aspirin to prevent stent thrombosis in patients who undergo percutaneous coronary intervention after myocardial infarction. Clopidogrel is a prodrug that must undergo oxidation by hepatic P450 enzymes, and therefore may affect the activity of statins and other drugs dependent on the hepatic P450 enzymes.

Dexamethasone is associated with psychiatric disturbances. Corticosteroids may exacerbate pre-existing psychiatric conditions.