insulin secretory drug (insulin secretagogues)

MoA:  stimulate release of endogenous insulin (close K channels in beta membrane which opens Ca channels to trigger insulin release; independent of level of blood glucose), only for T2DM, more potent than first-gen, metabolized by the liver, high bound to plasma proteins

ADR: too much hypoglycemia (accidental OD), weight gain

Drug-Drug Interactions: sulfonamides can increase hypoglycemic action (displace from plasma proteins)

insulin-sensitizing drug

MoA: anti-hyperglycemia (NOT hypoglycemic), improves sensitivity of peripheral tissues to insulin action/glucose uptake/storage, decreaess hepatic glucose output (primary mechanism), decreases absorption of glucose from intestine. lowers arterial BP/erum lipids (body weight not adversely affected), is rapidly excreted unchanged y kidneys (requires good kidney function)

ADR: GI (n/d, anorexia), lactic acidosis primary concern (serious but rare side effect, minimze by strict adherence to C/I such as renal impairment)

Drug Interactions: other drugs that are renally eliminated increase metformin blood levels (competitition to be removed), radio-contrast dye has similar effect

alpha-glucosidase inhibitor

MoA:  reversibly inhibits intestinal alpha-glucosidase enzymes responsible for digestion of complex carbs. taken before meals, it delays postprandial absorption of glucose (attenuation of postprandial increases in plasma glucose), "smooths out" postprandial glucose peaks. for Type 1 OR 2 DM. no direct effects on insulin secretion/sensitivity, for adjunctive therapy, wide interindividual variation (no fixed dose for everyone)

ADR: high incidence of GI disturbances (flatulence, diarrhea)

C/I: inflammatory bowel disease, intestinal obstruction

Drug interactions: adverse hypoglycemia: treat with glucose, not sucrose (sucrose breakdown to glucose may be blocked)

incretin mimetics

MoA: injective DPP-IV resistance incretin mimetic: binds to/activates human GLP-1 receptors which enhances glucose-dependent insulin secretion, inhibits glucoagon secretion, slows gastric emptying, increases sensation of satiety, for T2DM, SC admin before meals

ADR: hypoglycemia

Drug interactions: decrease absorption of PO drugs due to slowing of gastric emptying, take at least 1 hour before injecting

dipeptidyl peptidase IV inhibitors 

MoA: DPP-IV inactivates endogenous incretin. so inhibiting it causes an increase in glcuose-dependent insulin release and decreasing glucagon release from pancreas, for T2DM (adjunctive or alone with diet/exercise), taken PO QD

ADR: hypoglycemia 

Drug interactions: can increase digozin plasma levels, increase risk of ACE-I angioedema 

amylin analog

MoA: amylin is a pancreatic peptide for glucose homeostasis. as an analog, is slows gastrice mptying, inhibits glucagon secretion, increases sensation of satiety, used mainly as adjunctive for Type 1/2 DM for "smoothing out peaks/valleys of glucose fluctuations", SC admin before meas

ADR: hypoglycemia, some weight loss

Drug interactions: due to slowing of gastric emptying, may decrease absorption of PO drugs (take 1 hr before) 

rapid onset/short acting insulin

Regular: soluble, can be admin SC (maintenance) or IV (emergencies)

Lispro/Aspart: faster acting than regular

can be mixed with intermediate/long acting agents

ADR: severe hypoglycemia (can lead to brain damage)-- give glucose PO/IV or candy PO or glucagon IM/NS to sustain life, immunologic rxn (insulin antibodies, reduced systemic actions), local lipodystrophy, weight gain 

Intermediate-acting insulin

given SC, not for emergency IV

given once AM and once PM to provide basal level of insulin for 24 hours, may be supplemented with rapid/short acting forms for maintenance as needed

ADR: severe hypoglycemia (can lead to brain damage)-- give glucose PO/IV or candy PO or glucagon IM/NS to sustain life, immunologic rxn (insulin antibodies, reduced systemic actions), local lipodystrophy, weight gain 

slow onset, long-acting insulin

not soluble, not for emergency IV, given once a day for a basal level of insulin for 24 hours (can be supplemented with rapid/short acting forms throughout day as needed) 

ADR: severe hypoglycemia (can lead to brain damage)-- give glucose PO/IV or candy PO or glucagon IM/NS to sustain life, immunologic rxn (insulin antibodies, reduced systemic actions), local lipodystrophy, weight gain 

digitalis glycoside

Use:  tx of CHF by increasing myocardial contraction (inhibit cell membrane bound to N-K ATPase, which reduces Na pumped out of cell, causing increased intracellular free Ca which is responsible for inc myocardial contractility: therefore inc CO, inc excretion of salt/water, reveral in SNS-induced reflex tachycardia) and decreasing HR (vagal slowing and extravagal--high doses). Not recommended to slow heart in normal sinus tachycardia if no accompanying CHF. Some diuretic action: produces copious amounts of UO (secondary due to cardiac actions)

Drug interactions: phenybutazone displaces it from plasma proteins (increased levels), phenobarbital/phenytoin: decrease plasma levels, quinidine increases, antacids, sulfasalazine, bile acid binding resins decrease bioavailability 

ADR:  low margin of safety, can cause calcium overload, anorexia, n/v/d, clinical arrhythmia, paroxysymal atrial tachycardia, ventricular tachycardias and fibrillations (can be fatal), mental disorientation, delirium, blurried vision, white borders/halos on dark objects

digitalis glycoside: dixoxin antibodies

binds to Digoxin and forms a fab-frament-digitalis complex which is excreted

USE: life-threatening digitalis glycoside toxicity and/or OD characterized by severe hyperkalemia 

non-glycoside inotropic agent (+/- vasodilator activity), synthetic catecholamine-like beta-1 adrenergic agonist given only IV

USE: severe, refractory CHF

increased CO mainly by increased ventricular beta-1 receptor action (positive inotropic effect) 

non-glycoside inotropic agent (+/- vasodilator activity)

given only IV for sesvere, refractory CHF, exerts positive inotropic effect

can increase renal blood flue to activation of dopamine receptors

non-glycoside inotropic agent (+/- vasodilator activity), non-catecholamine positive inotropic drug, bypyridine derivatives and called phosphodiesterase inhibitors (used IV for severe, refractory CHF)

MoA: positive inotropic mechanism (inhibition of cAMP), increased free Ca availability during systole (more SR Ca uptake during diastole). No tolerance develops, cardiac effects are not highly dependent on the presence of adequate numbers of beta receptors, peripheral vasodilator effects 

ACE-I

MoA: inhibitor of angiotensinn converting enzyme (ACE), decrease preloading and afterload, increase CO and exercise capacity, decrease some of the pulmondary and peripheral congestion by those mechanisms, inhibiti production of locally produced A-II (contributes to hypertrophy in CHF) , activated by liver (which is congested in CHF)

ADR:  non-productive cough

Drug interactions: too much reduction in BP when used with diuretics/other anti-HTN agents (direct vasodilators) 

ARB

MoA: competitive antagonists of A-II receptor, local production of A-II, ACE dependent and independent, better at inhibiting A-II than ACE-I 

ADR: not as much as a productive cough as ACE-I

USE: CHF

diuretic 

USE: CHF

used because of reduced retention of sodium and water (reduce fluid volume). 

Loops for when Clcr is below 30, thiazides when above, K sparing to maintain K levels

diuretic 

direct vasodilator: primarily afterload reduction

USE: CHF

MoA:  dilating arterial resistance vessels (inhibit vasoconstriction by NE or A-II, reducing afterload)

Pts who benefit most: severe CHF refractory to other therapies, pt after acute MI (preexisting chronic CHF)

direct vasodilator: preload and afterload reduction 

MoA: dilates arterial resistance vessels (inhibit vasoconstriction produced by NE or A-II or vasopressin, reduces afterload), also decreases preload through increasing venous capacitance (venodilation)

Good for pt: severe CHF refractory to other therapies, acute MI (preexisting chronic CHF)

Note: can only be given IV, useful in intensive care, monitor hemodynamics (rapid actions may dec BP too low too fast) 

direct vasodilator and diuretic 

MoA: decreases both arterial and venous smooth muscle tone by increasing intracellular levels of cGMP, diuretic action due to natural naturiuretic capacbility as a natriuetic peptide 

Pt who benefit: severe CHF refractory to other therapies, after acute MI (preexisiting chronic CHF) 

beta-blocker

MoA: can ppt fatal exageration of low CO, prevents down regulation of beta adrenergic receptor numbers and related functions 

Class IA anti-arrhythmic drug, inhibits sodium, potassium channels 

USE: tx of various arrhythmias, supraventricular nd ventricular, inhibits ectopic atail and ventricular arrhythmias

ADR: prolong ventricular AP duration (causes other arrhythmias), n/v/d

MoA: drug inhibits sodium channels, meteabolite inhibits potassium channels, causes changes in AP

USE: Class IA, for various arrythmias

ADR: reversible lupus syndrome, CNS side effects, GI problems, ventricular arrhythmias 

MoA: Class IB drug, rapidly interacts with phase zero sodium channels. shorts phase 3 repolarization through inhibition of small population of late opening sodium channels still open during AP plaeau (opened more by ischemic conditions)

USE: ER ventricular arrhythmias (during MI), suppresses ventricular arrhythmias caused by abnormal automaticity  (decreases slope and therefore increases threshold, abolishes ventricular reentry forms of arrhythmias despite a dec in AP duration and decrease in ERP and conduction. Stops TdP because it dec Ap duration

NOTE: IV ONLY

ADR: drowsiness, slurred speech, arrythmias aggravated by hyperkalemia 

MoA: Class IC drug, interacts with sodium channnels slower, notably blocks phase zero sodium channels, markedly suppresses phase 0 slope, slows conduction, inhibits some K channels blocks some late opening sodium channels), no net effect on duration of AP, ERP, increase in threshold for phase zero, decrease in slope of phase 4

ADR:  negative inotropic effects: aggravate CHF

reduces incidence of sudden adrenergically driven arrythmic death after M I (stabilizes)

class II agent, blocks cardiac beta receptor actions on Ca channels, decreasing inward Ca currents, diminish Phase 4 depolarization, depresses automaticity, especially in nodal tissues

useful for arrhythmias caused by increased sympathetic neural activity

beta 1 specificity redices risk of bronchospasm, partial agonist activity 

class II agent, blocks cardiac beta receptor actions on Ca channels, decreasing inward Ca currents, diminish Phase 4 depolarization, depresses automaticity, especially in nodal tissues

useful for arrhythmias caused by increased sympathetic neural activity

short acting used IV in acute arrhythmias during surgery, emergency

class II agent, blocks cardiac beta receptor actions on Ca channels, decreasing inward Ca currents, diminish Phase 4 depolarization, depresses automaticity, especially in nodal tissues

useful for arrhythmias caused by increased sympathetic neural activity

Class III: inhibit potassium channels during AP, diminish outward K current (prolongs repolarization, phase 3), decreases conduction velocity by dec cell-to-cell coupling, prolongation of AP duration/ERP

USE: severe, refractory supraventricular, ventricular tachyarrhythmia

NOTE: concentrates in tissues with proloned half-life of several weeks

ADR: interstitial pulmonary fibrosis, hyper/hypo thyroidism (iodine accumulation in the skin)

Class IV antiarrhythmic drug, CCB, bind to cardiac calcium channels, decrease slope of phase 0/4, slows conduction, supreessing automaticity, less intracellular calcium, means less outward K, less repolarization

USE: supraventricular arrythmias may make WPW worse when accompanied by atrial fibriallation

ADR: decreease AV conduction too much

decreaes conduction velocity, abnormal impulse formation in AV node (inhibits Ca influx, activates Ach sensitive phase 4 K current), prolongs AV node refactory period

USE: drug of choice for paroxysmal supraventricular tachycardia (PSVT)

ADR: low toxicity, flushings, SOB, chest pain

MoA: inactivates COX (plt only have COX 2) which suppresses syntheiss of thromboxane by platelets, irreversible. 

USE: prevention of MI, ischemic attacks, ischemic stroke, arterial thrombotic events, prevent vein graft occlusion

ADR: abdominal discomfort, heartburn, nausea, GI bleeding

MoA: phosphodiesterase I, increases cAMP, plaetlet adhersion inhibitor

USE: with coumarin anticogulants, prevents thrombosis

ADR: hypotension

MoA:  irreversible inhibitor of ADP, inhibiting platelet aggregation

USE: reduction of atheroschlerotic events, MI, stroke, vascular death

ADR: bleeding

MoA: binds to antithrombin III, inactivates factor Xa, inhibits thrombin formation, negatively charged

ADR: bleeding, thrombocytopenia, hypersensitivity (aniaml origin), local capillary rupture (do not use IM)

C/I: avoid in pregnancy (teatogenic, causes intrauterine hemorrhage), use instead of oral drugs during 1st trimester

USE: venous thromboembolic disease, extracorporeal circulation, maintain patency for catheters

TREAT OD WITH PROTAMINE SULFATE

Binds and inactivates heparin, effect is instantaneous, strongly basic

ADR: transient hypotension, anaphylactic rxn (fish)

MoA: blocks synthesis of Factors II, VII, IX, X, proteins C and S, meaning they can't bind caclcium, formation of thrombin is reduced, delay of action

USE: proxphylaxis of thromboembolic (novalvular atrial fibrillation, valvular heart disease, prosthtic heart vales, acute vneous thrombosis, pulmonary embolism, acute MI, prevention of reocclusion of coronary artery bypass grafts), prevention of thrombosis 

ADR: hemorrhage, HTN, necroti clesions/gangrene (discontinue, use heparin if this happens), Gi distrubances, do not use for pregnant women! (causes severe abnormalities) 

Administereing Vitamin K1, fresh frozen plasma can be reverse effects

MoA: blocks thrombin

USE: anticoagulation in heparin-induced thrombocytopenia pt

ADR: hypersentivitity, bleeding

MoA: combines with plasminogen, converting it to plasmin (fibrinolytic) 

USE: thrombolytic, coronary artery thrombosis, MI

ADR: bleeding, hypersensitivity, fever

MoA: cleaves plasminogen to plasmin

USE; thrombolytic, coronary artery thrombosis, MI

ADR: bleeding, fever

MoA: cleaves plasminogen to plasmin

USE: thrbolytic, conary artery thrombosis, MI

ADR: bleeding, arrhythmias 

Reversal of action can happen with aminocaproic acid 

MoA: necessary for coagulationcascade: prothrombin to thrombin

USE: hemophilia A

ADR: few, dose related

MoA: necessary for coagulation cascade: prothrombin to thrombin

USE: hemophilia B

ADR: few, dose related

MoA: required for synthesis fo blood coagulation factors II, VII, IX, and X

USE: hypoprothrombinemia caused by coumarins, newborn hemorrhaic disease

ADR: nontoxic, some anaphylaxis has occurred 

MoA:  component of hemoglobin, myoglobin, stored in ferritin or hemosiderin

USE:  iron deficiency anemias

ADR anaphylaxis possible, n/v/d

MoA: cofactor required for DNA synthesis

USE: megaloblastic anemia

ADR: C/I for pernicious anemia leading to neurologic complications

MoA: cofactor for methylmalonlyl-CoA mutase, methionine synthase

USE: megaloblastic anemias

ADR: leber's disease, hypersensitivity 

MoA: growth, differentiation of stem cells into erythrocytes

USE: anemias of chronic disease (i.e. cancer chemotherapy pt, HIV)

ADR: flu-like symptoms, HTN

MoA: grwoth and differentiation of stem cells of the neutrophil lineage

USE: chemo induced neutropenia, bone marrow transplantation, HIV neutropenia

ADR: well tolerated

MoA: growth/differentiation of stem cells into granulocytes, macrophages

USE: myeloid recovery in cancer pt

ADR: well tolerated

MoA: growth/differentiation of stem cells to megakaryocytes/plt

USE: prevention of thrombocytopenia in cancer pt

ADR: well tolerated