Heparin:

• Inhibits blood coagulation by forming complexes with an α2-globulin (Antithrombin III) and each of the activated proteases of the coagulation cascade (Kallikrein, XIIa, XIa, IXa, Xa, and Thrombin). After formation of the heparin-ATIII-coagulation factor, heparin is released and becomes available again to bind to free ATIII.
• Blocks conversion of Prothrombin to Thrombin and thus inhibits the synthesis of Fibrin from Fibrinogen.
• Inhibits platelet function and increases vascular permeability. May induce moderate to severe thrombocytopenia.
• Is prescribed on a “unit” basis.
• Heparin is not effective after oral administration and is generally administered by intravenous or subcutaneous injection. Intramuscular injections should be avoided.
• Heparin does not cross the placenta and does not pass into the maternal milk.
• is contraindicated in any situation where active bleeding must be avoided.

Ulcerative lesions, intracranial hemorrhage, etc.

Overdosage:

• Simple withdrawal.

• Protamine sulfate: Highly basic peptide that binds heparin and thus neutralizes its effects.

PSEUDOEPHEDRINE

Pseudoephedrine appears to have less pressor activity and weaker central nervous system effects than ephedrine. It has agonist activity at both β1  and β2 adrenoceptors, leading to increased cardiac output and relaxation of bronchial smooth muscle.

Pseudoephedrine is rapidly absorbed throughout the body. It is eliminated largely unchanged in urine by N-demethylation.

It is indicated in symptomatic relief from stuffed nose, respiratory tract congestion, bronchospasm associated with asthma, bronchitis and other similar disorders.

Indomethacin

commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms.

Indications

ankylosing spondylitis, rheumatoid arthritis, osteoarthritis, juvenile arthritis, psoriatic arthritis, Reiter's disease, Paget's disease of bone, Bartter's disease, pseudogout, dysmenorrhea (menstrual cramps), pericarditis, bursitis, tendonitis, fever, headaches, nephrogenic , diabetes insipidus (prostaglandin inhibits vasopressin's action in the kidney)

Indomethacin has also been used clinically to delay premature labor, reduce amniotic fluid in polyhydramnios, and to treat patent ductus arteriosus.

Mechanism of action

Indomethacin is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation.

Prostaglandins also cause uterine contractions in pregnant women. Indomethacin is an effective tocolytic agent, able to delay premature labor by reducing uterine contractions through inhibition of PG synthesis in the uterus and possibly through  calcium channel blockade.

Indomethacin easily crosses the placenta, and can reduce fetal urine production to treat polyhydramnios. It does so by reducing renal blood flow and increasing renal vascular resistance, possibly by enhancing the effects of vasopressin on the fetal kidneys.

Adverse effects

Since indomethacin inhibits both COX-1 and COX-2, it inhibits the production of prostaglandins in the  stomach and intestines which maintain the mucous lining of the

gastrointestinal tract. Indomethacin, therefore, like other nonselective COX inhibitors, can cause ulcers.

Many NSAIDs, but particularly indomethacin, cause lithium retention by reducing its excretion by the kidneys.

Indomethacin also reduces plasma renin activity and aldosterone levels, and increases

sodium and potassium retention. It also enhances the effects of vasopressin. Together these may lead to:

edema (swelling due to fluid retention)

hyperkalemia (high potassium levels)

hypernatremia (high sodium levels)

hypertension (high blood pressure)

Sulindac:  Is a pro‐drug closely related to Indomethacin. 

Converted to the active form of the drug. 

Indications and toxicity similar to  Indomethacin

Megltinides

nateglinide
repaglinide

Mechanism

binds to K+ channels on β-cells → postprandial insulin release

Clinical use
type 2 diabetes mellitus
may be used as monotherapy, or in combination with metformin

SGLT-2 Inhibitors

canagliflozin
empagliflozin

Mechanism

glucose is reabsorbed in the proximal tubule of the nephron by the sodium-glucose cotransporter 2 (SGLT2)
SGLT2-inhibitors lower serum glucose by increasing urinary glucose excretion
the mechanism of action is independent of insulin secretion or action

Clinical use

type II DM

Gabapentin (Neurontin): newer; for generalized tonic-clonic seizures and partial seizures (partial and complex)

Mechanism: unknown but know doesn’t mimic GABA inhibition or block Ca currents

Side effects: dizziness, ataxia, fatigue; drug well-tolerated and no significant drug interactions