Block 1 Beeds

• To prevent acute reactions to tissue transplants.
• Also used to treat auto immune diseases
• Most non selectively inhibit immune system components

• Intensive induction therapy for prophylaxis (usually antibodies)
• Then Maintenance therapy with calcineurin inhibitors, antimetabolites and steroids

Cyclosporine and Tacrolimus

Sirolimus

• Calcineurin Inhibitors
• mTOR inhibitors
• Antiproliferative/antimetabolites
• Antibodies
• Steroids

• A calcineurin inhibitor immunosuppressant.
• Preferentially suppresses cell mediated immunity by binding to cyclophilin of T Cells. This complex inhibits calcineurin phosphatase which prevents dephosphorylation of NF-AT which normally activated transcription of IL-2 genes
• reduces function of T cells
• Metabolized by P450 so if given with p450 inhibitor it will be at higher levels

• Big drug for prevention of organ rejection- Kidney, liver, and heart
• Also used for rheumatoid arthritis and psoriasis
• Used as a drop in sever eye dryness
• Often administered with steroids

• Nephrotoxic
• It can also induce hypertension, hyperlipidemia, and hirsutism. Gingival hyperplasia

• A calcineurin inhibitor that is 10-100x more potent than cyclosporine with less pronounced side effects
• Binds to immunophilin FKBP-12 and the complex binds calcineurin and blocks its phosphatase activity
• Standard prophylactic for graft vs host disease (combined with methotrexate or mycophenolate)

• Used mainly in liver and kidney transplant patients but can also be used in heart and lung transplantation
• Used as an ointment for atopic dermatitis and psoriasis
• Tox: Nephrotoxic, Neurotoxic, and causes diabetes

• An immunosuppressant of the mTOR inhibiting class.
• Works by binding FKBP-12(like Tacrolimus) the complex then blocks mTOR action which is needed for the cell to progress through G1 so there is no proliferation.
• Also inhibits several T cell kinases/phosphatases preventing the transmission of signals that lead to cycle progression

• Decreases the RESPONSE to IL-2
• prevents B cell differentiation into plasma cells-> lowering antibodies
• Affects second phase of T lymphocyte activation (signal transduction and clonal proliferation
• (cyclosporine and tacrolimus affect 1st phase- activation)

• Low nephrotoxicity
• Used to inhibit re stenosing of cardiac vessels by reducing proliferation of endothelial cells- SRL coated stent used to do this

Hyperlipidemia, myelosuppression, hepatotoxicity, and slow wound healing

• Methotrexate
• Azathioprine
• Cyclophosphamide
• Mycophenolate Mofetil
• Leflunomide

• Autoimmune disease dreatment and to help treat against transplant rejection.
• folic acid analogue- inhibits DHFR

• An immunosuppressive cytotoxic agent. Used to control transplant rejection and to treat autoimmune disease.
• It is cleaved wit 6-mercaptopurine which acts as a purine analogue inhibiting DNA Synthesis
• Affects Cell mediated and humoral immunity since it prevents proliferation of lymphocytes in the immune response.

• 80+% is metabolized by Xanthine oxidase to 6-thiouracil. The rest by TPMT and HPRT
• Allopurinol is an XO blocker so it can increast levels of 6-MP increasing toxicity. Reduce dose to 1/4-1/3 if giving with allopurinol

• An immunosuppressant that has lowered the incidence of acute rejection- often used in place of azathioprine b/c of less marrow suppression, less infection, and better results.
• Works by blocking inosine monophosphate dehydrogenase which is used to synthesize guanine in B and T lypmhocytes
• Can be used alone for kidney and liver transplants
• Steroid sparing agent in immune mediated responses like psoriasis and lupis nephritis

• An inhibitor of pyrimidine synthesis used to treat rheumatoid and in prevention of organ rejection.
• Orally available with a long half life of its active metabolite.
• Toxicity: renal impairment and liver damage

• Very effective immunosuppressant
• can be used for autoimmune disease like SLE or autoimmune hemolytic anemia
• Larger doses to treat transplant rejection

• Polyclonal
• Anti Thymocyte Globulin
• Rh(D) immunoglobulin
• Monoclonal
• T cell receptor directed antibodies- muromonab- CD3 or OKT3
• IL-2 receptor directed antibodies- Daclizumab or Basiliximab
• these block t cell surface signaling

• A polyclonal antibody used in prevention/treatment of acute organ rejection
• Also used in treatment of aplastic anemia in patients who can't have BM transplant
• Starting to be replaced by anti IL-2R antibodies Basiliximab and Daclizumab b/c they cause less cytokine release

• Human IgG against Rh(d) antigen of the red cell. Given to Rh negative mothers pregnant with Rh+ babies.
• The Ab will bind to the baby Rh antigen blocking the mother's immune system from spotting them and attacking.
• DO NOT give to Rh + mothers or newborns
• Can also be used to prevent sensitization

• Abs directed at a single toxin- used in diagnostic tests, immuneosuppression, and cancer treatment
• Human mAbs have reduced serum sickness
• better kinetics
• Less chance of eliciting human anti mous antibodies

• Murine monoclonal antibody that binds CD3 receptor on human T lymphocytes- blocking them from making the signal for proliferation
• Used to treat acute rejection of kidney, liver, and heart transplant
• Cause severe cytokine release syndrome and CNS disturbances
• Steroids can be used to reduce the symptoms of cytokine release

• Basiliximab is a chimeric mAb against CD 25 on Tcells (IL2 R alpha chain) thus blocking the activation of T lymphocytes by IL-2
• Daclizumab is humanized mAb against Tcell CD25
• Both used for prophylaxis against organ rejection
• Well tolerated with less risk of opportunistic infections and lymphomas
• Lymphocyte depleting

• mAb that blocks VEGF from binding it's receptoron endothelial cells
• Approved for first line treatment of metastatic colon cancer

mAb to TNF alpha receptor used to treat RA and chrons

mAb to IGE used to treat bronchial asthma

• mAb that blocks RSV fusion protein.
• Used as prophylaxis to RSV

• mAb to CD20 on B cells
• Used to treat NHL

• Both immunosuppressants and anti inflammatories
• Suppression of cell mediated immunity by blocking genes for cytokines 1-6, 8, and TNF-1 reducing T cell proliferation
• Humoral immunity also suppressed by causing Bcells to express lesser IL-2R diminishing both Bcell clone expansion and antibody synthesis
• Used to treat rejection, autoimmune diseases, and to limit allergic reactions that occur with muromonab and other Abs

• Recombinant IL-2 that promotes the production of cytotoxic T lymphocytes and activates NK cells.
• Used for Renal cell carcinoma and malignant melanoma.
• Immunomodulatory agent

• Immunostimulant used in the prevention and treatment of superficial bladder cancer- given intravesicularly
• Live attenuated form of mycobacterium bovis. When administered causes a local immune response that has anti tumor activity. helps decrease the need for cyctectomy

• Interferon-a-2a used in CML, malignant melanoma, and hep B and C
• Interferon-B-1b- used to treat multiple sclerosis

Prednisone

• Inhibitors of Na K 2Cl co transport in the ascending loop of henle.
• Furosemide is the prototype- has vasodilator action
• Torsemide- a longer acting with less K wasting
• Bumetanide, and Ethacrynic acid

• when sodium absorption is blocked it makes it further down the tube to the collecting duct. Here there will be larger Na absorbption which will also cause increased K+ and H+ secretion.
• If you block the Na channel in the collecting duct you stop secretion of K+ and H+= potassium sparing

• Inhibitors of NA-Cl co transport
• Chlorothiazide, Chlorthalidone, Metolazone, and Indapamide(thiazide like diuretic)

• Carbonic anhydrase inhibitors- Acetazolamide
• Potassium Sparing- Aldosterone antagonist: spironolactone, Eplerenone
• Inhibitors of renal epithelial Na channel- Trimaterene, Amiloride
• Osmotic Diuretics- Mannitol, Glycerol

• A high ceiling loop diuretic- inhibits Na K 2Cl co transport
• Action on prox convuluted tubule- weak carbonic anhydrase activity
• Causes mild alkylosis at high dose
• Given in high dose it causes vasodilator decreasing TPR decreasing left ventricular pressure- for pulmonary edema
• can cause up to 10L of urine
• still works in pts with renal failure

• Increased Calcium secretion b/c block of the NaK2Cl channel causes K to stop leaking into the lumen so no + charge maintained to keep Ca and Mg out of urine.
• also can cause hyperglycemia, and hyperuricemia
• Ototoxicity more frequent with IV admin

A high ceiling loop diuretic (blocks Na K 2Cl) that is 40x more potent than furosemide.

• A high ceiling loop diuretic that is similar to furosemide.
• An irritant, given orally it produced diarrhea and can cause hearing loss and hepato toxicity.
• Uricosuric diuretic decreases thereabsorption of uric acid in the PCT increasing uric acid secretion.

• Edema
• Acute pulmonary edema
• Forced diuresis
• Hypertension
• Hypercalcemia

• Thiazides decrease Ca secretion and increase prox tubule reabsorption due to volume depletion. Then in the distal tubule due to the direct effects of the drugs
• Diuretic causes more Na to make it to the distal nephron where Na is exchanged for K+ and H+ increasing k+ and H secretion
• Only moderate efficacy

• Chlorothiazide, Chlorthalidone (thiazides)
• Metazolone, and Indapamide( not thiazides)
• These are good for preventing urinary stones.

increase both

• in low GFR
• Metalozone and Indapamide are still good in moderate renal failure. (not thiazides)

• Edema
• Hypertension
• Nephrogenidc diabetes insipidus
• Treatment of calcium containing renal stones.

The fluid contraction due to the thiazides causes less sodium to be excreted so the macula densa contracts to bring GFR down to keep water in.

• Hypokalemia
• Hearing loss
• Hyperuricemia
• Hyperglycemia
• Hypercalcemia- thiazides
• Hypocalcemia- Furosemide

• Block the action of carbonic anhydrase so the cells in the kidney can not make bicarb from H20 and CO2
• If losing Na in uring also losing bicarb

• A carbonic anhydrase inhibitor it prohibits Bicarb reabsorption in the PCT
• also inhibits H+ secretion
• There will be more sodium in the DCT which will push in causing K to come out

• Lower intraocular tension by decrease in aqueous humor formation
• Decrease gastric acid secretion
• Raise levels of CO2 (acidosis) lowering pH and increasing seizure threshold
• Acidosis can be helpful in treating alkylosis from hyperventilation

• Glaucoma
• To alkalinize urine to get rid of acidic substances like uric acid
• Epilepsy
• Acute mountain sickness
• Adverse effects: acidosis, hypokalemia, paraesthesia

Liver disease because it interferes with elimination of ammonia

Potassium sparing diuretics- Spironolactone and eplerenone

Potassium sparing diuretics- Amiloride and Triamterene

• An aldosterone antagonist that works by conversion to Canrenone and combining with intracellular receptors causing formation of proteins that promote reabsorption of Na+ and secretion of K+
• Action dependent on adosterone
• Indicated in conditions of hyperaldosteronism (cirrhosis and heart failure)

• Weak Diuretic that is useful in cirrhotic edema and nephrotic syndrome.
• Can be used to counteract the K+ loss due to thiazide use
• reduces heart failure mortality
• Anti androgenic effects causing impotence and menstrual irregularities.

Gynecomastia, menstrual irregularities, impotence, hyperkalemia

• A new Aldosterone receptor antagonist- better tolerated than spironolactone
• Effective for hypertension and decreases mortality in cardiac failure

• Triamteren and Amiloride
• Similar action to spironolactone but independent of aldosterone.
• Block Na channels of the principal cells in the late distal tubule and collecting duct.
• Usually given along with thiazides and loop diuretics
• Can cause hyperkalemia when used with ACE inhibitors

• 10x more potent than triamterene
• Decreases calcium and magnesium excretion
• Longer acting than triamterene
• Blocks entry of lithium into renal cells and stop lithium induced diabetes insipidus
• Given as an aerosol to help with cystic fibrosis- increases fluidity of resp secretions
• Triamterene impairs glucose tolerance and causes photo sensitivity.

• An osmotic diuretic
• Not metabolized and freely filtered in glomerulus
• blocks water and electrolyte reabsorption
• Ecpands ECF and increases GFR
• Primary action is to increase urinary volume
• Must be given IV

• maintain GFR and urin flow in renal failure
• Reduce intracranial tension and intraocular tension

• NSAIDS
• Carbamazepine
• Chlorpropamide
• Inhibitors of vasopression action- Demeclocycline, lithium, and conivaptin

• Desmopressin
• Chlorpropamide
• Carbamazepine

• Adequate water intake
• Amiloride for Li induced
• Thiazides for non Li
• Indomethacin

They are both shortened which can lead to a ischemic condition for the myocardium.

• Reduce whatever it is that is causing decreased blood flow to the myocardium. If tachycardia is the problem, slow the heart down so diastole is long enough to nourish the muscle.
• Can use coronary vasodilators or anti thrombotic drugs to increase O2 delivery
• or use vasodilators/ cardiac depressants to decrease the O2 demand of the heart

• Nitrates
• Beta Blockers
• Calcium Channel Blockers
• Ranolazine, Trimetazidine, Nicorandil are some others

• Isosorbide Dinitrate- metabolized to isosorbide mononitrate- long acting
• Nitroglycerine- sublingual for acute attacks
• Isosorbide momonitrate- same as di but shorter acting- both are weak and good for prophylaxis

• Method of administration- sublingual/inhaled is short.
• others are long acting

• Venous dilation decreasing the preload on the heart.
• If give too much can get a dangerous reflex tachycardia

• They release NO which increased cGMP which leads to muscle relaxation
• If given with a phosphodiesterase (breaks down cGMP) inhibitor can cause dangerous drops in BP.

• venous dilation> arterial dilation
• Reduced preload and afterload on the heart as a result
• Decreased O2 demand as a result of reduced load
• Prevents or reverses vasospasm, improved subendocardial perfusion and increased O2 delivery.

• Lipid soluble
• denitrated by glutathione reductase creating less active but longer acting metabolites
• Hypotension, headache
• Tolerance- can cause sympathetic activation and colume expansion (due to hypotension)need to have them not on the drug for 10-12 hours per day
• NitRITES can cause methemoglobinemia
• Contraindicated with drugs like PDE inhibitor Sildenafil citrate

• Angina
• Congestive Cardiac Failure
• Left Ventricle Failure
• Cyanide poisoning (nitrites)- Hydroxyl cobolamine is DOC

• Cardiac- decrease contractility, decrease relaxation rate, decrease heart rate, and decrease conduction rate
• Vascular- can cause vasoconstriction through B2 receptor block
• Big story is lowering the O2 demand of the heart.

• Prinzmetal angina
• Heart failure

• Reduce the work of the heart
• Reduce the heart's response to exercise
• Can cause feeling of cold in the extremeties due to lack of blood flow

• Smooth muscles, SA node, and AV node
• Smooth muscle relaxation
• Negative chronotropic
• Negative Inotropic
• Negative dromotropic

• L type calcium channel blockers (non DHP)
• They decrease AV conduction, relax vascular SM, and decrease or leave heart rate alone.
• Verapimil is centrally acting
• Used to treat arrhythmia and angina- can use with prinzmetal since there is less vascular action

• A DHP L type calcium channel blocker that works in the periphery.
• Causes reflex increase in HR
• No effect on AV conduction
• Big relaxation of vascular SM
• Good for HTN and Angina but no good for arrhythmias

Patients already on beta blockers.

• Calcuum channel blocker that is used for the prevention of cerebral vasospasm and reluctant ischemia which is a complication of subarachnoid hemorrhage.
• Cerebral Specific

Nifedipine because it works in the periphery

• SM relaxation in vascular and visceral tissues.
• Nicorandil is an example needs cold storage- a vasodilatory drug used to treat angina.

Anti anginal drug used to treat chronic angina pectoris

Anti angina pectoris drug- it improves myocardial dlucose utilization by blocking fatty acid metabolism.

• Reduction of mortality due to HT induced diseases
• Stroke, CHF
• CAD
• Nephropathy
• Peripheral Artery disease
• Retinopathy

• All by recuction of conversion of angiotensin 1 to A2 which triggers vasoconstriction and aldosterone secretion
• Reduction in arterial pressure
• Reduction in venous tension
• Reduction in aldosterone
• Captopril, Lisinopril, Enalapril, Ramipril, Benazepril, Fosinopril

• CHF
• Hypertension
• Left ventricular dysfunction
• Prevention of nephropathy in diabetes- best choice
• decrease mesangium exposure to factors that may induce mesangial proliferation

• Constrict efferent arteriole raising GFR
• Avoid ACE inhibitors in bilateral renal artery stenosis because this constriction maintains normal GFR

• Dry irritating cough via increase in bradykinin
• decrease in GFR in states of decreased cardiac output- monitor K+/renal function
• Hypotension
• Hyperkalemia from low aldosterone

• When patients are unable to tolerate ACE inhibitors.
• Losartan, Erbesartan, Candesartan are AT1 receptor blockers
• Competitive antagonist of Angiotensin 2
• No bradykinin increase or inhibition of ACE

• Renin inhibitor
• by blocking renin it blocks the conversion of angiotensinogen to angiotensin 1
• Can be used in combo with hydrochlorothiazide
• Advers effects are angioedema, hyperkalemia, and hypotension

• reduction of cardiac output
• Inhibition of renin release ( block of B1 receptor in JG cells)
• Inhibition of NE release from presynaptic adrenergic terminals
• Reduction of central adrenergic tone.

They can worsen asthma or other airway obstructions with non selective blockers

• Alpha 2 receptor agonists.
• Work by reducing Sympathetic outflow
• Clonidine can cause hypertensive crisis if withdrawn too quickly
• Methyldopa is the preffered drug for HTN in pregnancy

No reflex tachycardia

• A direct arteriolar vasodilator
• Releases NO
• Can cause reflex tachycardia
• NorEpi release can increase myocardial contractility as part of the reflex
• Adverse effects- HEadache, palpitatione
• Can cause SLE in slow acetylators or in prolonged use of higher dose
• Precipitation of angina and MI

• Hypertension that is not well controled by first line drugs
• Can use in pregnancy HTN
• Hypertensive emergencies

• K channel activator that vasodilates arterioes
• Chronic therapy can cause excess hair growth
• Used for life threatening HTN and HTN with renal failure

• Diuretics to keep sodium retention from happening (as reflex of lower bp with Vasodilator)
• Beta blockers to block reflex increase in heart rate etc as well as peripheral resistance and renin release

• in acute hypertensive emergencies- releases NO
• this decreases TPR and venous return lowering load on the heart so it can be used in Cardiogenic heart failure.
• Adverse effect is that it is metabolized to make Cyanide which can cause severe lactic acidosis
• Signs of thiocyanate (cyanide metabolite) tox include nausea, disorientation and psychosis.

Give sodium thiosulfate or hydroxocobalamin.

• Rapid/long acting arterial dilator that can be used in hypertensive emergencies
• Opens K channels
• Tox is excessive hypotension that can cause stroke and MI
• Can also cause hyperglycemia by inhibiting insulin secretion.

• Anti hypertensive agent that is used post op and for hypertensive crisis
• Selective peripheral D1 receptor weak agonist
• Tox is reflex tachy, headache, and flushing

• Bosentan and Sitaxentan
• endothelin is a vasoconstrictor
• Used for pulmonary HTN

Phosphodiesterase type 5 inhibitor used in pulmonary HTN

• Epoprostenol and Iloprost
• Both from PGI 2

Ace inhibitors

Beta blockers

Ca channel blockers

• BNP
• >400pg/ml is likely heart failure
• BNP is secreted by ventricles in response to excessive stretch

• Shortness of breath, edema, fatigue
• Causes include CAD, HTN, Diabetes, Mitral valve disease, and chronic alcohol use

• ARB
• ACE inhibitors
• Beta Blockers

signs and symptoms of heart failure, but ejection fraction is normal. Use BNP level when EF is normal and there are symptoms of heart failure

• ACE inhibitors #1
• Beta blockers
• Cardiac glycosides- digoxin
• Diuretics
• Vasodilators
• Use inotropes for acute heart failure

• Improve exercise tolerance and left ventricular ejection fraction.
• Reduce arterial resistance
• Reduce venous tension
• Reduce aldosterone
• BLOCK cardiack and vascular remodeling
• Captopril, Lisinopril, Enalapril, Ramipril, and Quinapril

• Cough
• Hyperkalemia
• Angioedema
• Fetal Toxicity

• Isosorbide Dinitrate and hydralazine used in pts who can't tolerate ACE inhibitors.
• Amlodipine and prazosin are also vasodilators that can be used in CCF
• Also use in low renin patients where ACE inhibitors have little effect.

• Reduction of volume overload
• decrease of Extra cellular volume
• Decreasing venous return.
• Loop diuretics are the most effective
• Thiazides only good for mild cases

• Aldosteron blockade is key for post infarction survival.
• Minimizes potassium loss and prevents sodium/water retention
• Also prevents endothelial dysfunction and myocardial fibrosis

• aldosterone level correlates with degree of fibrosis and remodeling
• Also causes production of inflammatory factors

• A synthetic B type natriuretic peptide that has arterial and venous dilation as well as diuretic and natriuretic properties
• Used to treate decompensated CHF with dyspnea at rest
• Increases cardiac output by venous dilation but no chance in heart reate or Oxygen demant
• Modulates the effect of other Na retaining hormones

• Inhibition of sympathetic system
• Increases Beta receptor sensitivity
• Anti arrhythmic
• Anti oxidant
• Lowering these things lowers apoptosis, necrosis, fibrosis and hypertrophy
• Must start with a low dose and monitor
• Most commonly use Carvedilol and Metoprolol in CCF

• Na/K ATPase pump inhibitor that increases intracellular Na concentration increasing intracellular Calcium
• Restores Vagal tone and abolishes sympathetic over activity

• Decreased conduction through the AV node which decreases ventricular response to rate increase
• First line drug in CCF patients with atrial fibrilation

• Nausea, vomiting, Gynecomastia, psychosis, yellow vison
• Can cause ventricular arrhythmia, AV block and bradycardia
• Amiodarone and verapamil can increase plasma Digoxin concentration by blocking its excretion
• Hypokalemia enhances tox
• can treat mild tox with K+, digibind (mAb to digoxin) for OD

similar compound to digoxin with a longer half life and eliminated in the liver so it can be used with poor kidney function.

• synchronizing the ventricles with the atria so that they function at optimal levels
• necessary when there is normal sinus rhythm but a wide QRS interval

• Phosphodiesterase III inhibitors- Milrinone- positive inotropic and vasodilatory action
• Dobutamine- beta 1 agonist that increases contractility and cardiac output

Hypokalemia

• Depolarizations that interrupt phase 3 (Early After-depolarization) during bradycardia or phase 4
• DAD- delayed after-depolarizations- happen when intracellular load is increased
• Hypercalcemia can cause ventricular cells to deplolarize on their own.

Type A Quinidine, Procainamide, Disopyramide

• Lidocaine, Mexiletine, Phenytoin
• Work with rapid ventricular rhythmslike tachy and fib
• No effect on atrial arrhythmia

Flecainide, and propafenone

Beta blockers- propranalol, esmolol, and sotalol

Widening of action potential duration- K Channel blockers- Amiodarone, Bretylium, Sotalol,and Ibutilide

Calcium channel blockers- Verapamil, Diltiazem

• They block sodium channels delaying their recovery time before a new action potential can happen.
• Prolong the effective refractory period and the action potential duration
• Quinidine, Procainamide, Disopyramide

• Class 1A anti arrhythmic drug
• An alkaloid dextro isomer of quinine that blocks the sodium AND potassium channels on cardiac cells
• Also has anti muscarinic and alpha blocking action.
• Can use for Atrial fib treatment but must first block the AV node so there is not progression to VFib
• Can cause Cinchona(tinnitus)

• Bitter irritant
• Inhibition of Cytochrome P450
• Increases plasma levels of digoxin by displacing it from tissue binding sites- decreases digoxin clearance
• Used to treat A fib and V fib

• Diarrhea, nausea, vomit, and tinnitus(cinchonism)
• thrombocytopenia
• Precipitate Torsades de Pointes (ventricular arrhythmia) by prolonging QT interval

• A class 1A anti arrhythmic drug with less anti muscarinic action than quinidine
• Used for suppression and treatment of Vtach
• Can cause SLE like symptoms of arthralgia, arthritis, especially in slow acetylators

• Class 1A anti arrhythmic drug with prominent anti cholinergic activity
• Not used with heart failure (has negative inotrope action)
• Only used (not first line) for ventricular arrhythmia

• A class 1B anti arrhythmic drug- least cardiotoxic anti arrhythmic
• Blocks Na channels in partially depolarized cells in ischemic area and does not delay channel recovery time, also decreases APD
• Not given orally
• Used for ventricular arrhythmia and digoxin induced arrhythmia
• Tox: Neurological drowsiness, nystagmus, and seizures

• Block sodium channels in the purkinje His system.
• Negative inotropic and high pro arrhythmogenic potential
• Used in life threatening Vtach
• Flecainide is indicated for Afib and refractory ventricular arrhythmia
• Contraindicated in structural heart defects

• Beta receptor blockade
• diminish phase 4 depolarization- decreasing automaticity
• Prolong AV conduction time
• Given in post MI and supra ventricular tachy
• Can use Sotalol in life threatening Ventricular arrhythmia
• Metoprolol, Esmolol, Sotalol, Acebutolol(dardio selective)

• Amiodarone
• Works by blocking potassium channels and inactivated Na channels
• also inhibits Ca channels
• Can cause thyroid problems

By blockin potassium channels they prolong phase 3 repolarization and refractory period.

• Used for recurrent vfib and hemodynamically unstable Vtach
• Tox: pulmonary fibrosis, Hepatotoxicity
• Skin pigmentation, Corneal deposits
• Interference with thyroid function
• Risk of rhabdomyolysis leading to kidney damage with simvastatin use because it inhibits CYT P450

• Bretylium- used in ventricular arrhythmia after lidocaine has failed
• Sotalol- Also class 2- Ventriculat arrhythmia
• Dofetilide- used for Afib and atrial flutter
• Ibutilide- same as Dofetilide
• side effect of dofetilide, ibutilide and sotalol therapy is torsades de pointes

• Calcium channel blockade
• Decrease AV conduction and shorten the plateau of cardiac potential
• Reduce contractility so not to be used in heart failure
• Verapamil and Diltiazem

• Important in supraventricular tachycardia
• Can also be used in all types of angina as well as migraine prophylaxis

• Adenosine
• Works by activating the K channels in the AV node causing hyperpolarization reducing the Ca currents
• Slowing of AV conduction and terminating the paroxysmal SVT
• Can cause bronchospasm

• Increases Vagal activity decreasing conduction through the AV node
• Can be used in the treatment of SVT

Treatment of Torsades De Pointes as well as digoxin induced arrhythmia

• —Anesthesia – is a reversible condition of comfort, quiescence and physiological stability in a patient before, during and after performance of a procedure.
• —General anesthesia – for surgical procedure to render the patient unaware/ unresponsive to the painful stimuli.

• Decrease in systemic BP- myocardial depression and vasodilation
• Decrease components of surgical stress response( surgery activates HPA axis and sympathetics and tissue damage causes coagulation factor/platelet activation leading to hyper coagulable state.

• Amnesia
• Adequate muscle relaxation
• Adequate ventilation
• Pain control
• No single drug takes care of all of these

• Reduction of post op pain
• Nausea and vomiting control- antiemetics
• Amnesic effect
• Reduction of anxiety- Benzodiazepines
• Prevention of allergic rxns- anti histaminics
• Analgesia- Opioids
• Prevention of Bradycardia and secretions(effect of anesthetic)- atropine

• 1. Analgesia
• 2. Excitement/combative- dangerous
• 3. Surgical Anesthesia
• 4. Medullary paralysis- respiratory and vasomotor control decreases

• Increase GABA-A- potentiated by halothane, propofol, and etomidate
• Blockage of NMDA (glutamate) receptors- Ketamine

• Inhalational- for maintenance- advantages are control of depth of anesthesia, minimal metabolism, excretion by exhalation
• IV for induction and short procedured

• Non halogenated gas- Nitrous oxide
• Halogenated hydrocarbons- Halothane
• Enflurane
• Isoflurane- most common
• Desflurane Sevoflurane used for short procedures/ day surgery
• Methoxyflurane- causes nephrotoxicity

• The ratio of the amount of anasthetic in the blood to the amount in gas
• The more in the gas the more effective the drug
• so the lower the coefficient the more in the gas phase
• Determines the rate of induction and recovery- lower # = faster induction and recovery

• Solubility in the blood (blood gas partition coefficient)
• Solubility in fat (oil gas partition coefficient)

• Measure of the drug's lipid solubility
• Lipid solubility correlates strongly with potency of the anasthetic
• Higher lipid solubility= higher potency

• Measure of the inhalational potency of a drug
• The higher the MAC (minimum alveolar concentration) the less potent the drug so we need a higher inhaled concentration for it to work
• MACs are additive and lower in the presence of opioids
• Higher oil: gas partition coefficient = lower MAC

• Very safe inhalational anasthetic
• Weak anasthetic but good analgesic effect
• Not toxic to Heart liver or kidney
• Usually given with more powerful anasthetics to hasten the uptake of the other agent
• No metabolism- removed by exhalation
• Should not be used in pregnancy

• Dental procedures
• can cause diffusional hypoxia and megaloblastic anemia
• Must continue O2 for a time after removing N2O to prevent diffusional hypoxia

• Potent anasthetic with pleasant induction
• Sensitizes heart to catecholamines
• Dilates bronchus- prefferential in asthmatics
• Inhibition of uterine contractions- can lead to bleeding- do not use for obstetrical anasthesia
• Can cause hepatitis and malignant hyperthermia
• also has dose dependent hypotension
• Only inhalational anasthetic that is metabolized significantly

• Halogenated anasthetic similar to halothane
• does not sensitize heart to catecholamines
• Sweet odor
• Causes seizures at deeper levels- do not use with epilepsy
• Can cause renal failure

• Inhalational anasthetic that is given with N2O because it is not rapidly inducing.
• does not sensitize the heart to catecholamines
• Can irritate the respiratory system
• Used toe maintain anesthesia induced by some other drug

• Inhalational anasthetic given through a special vaporizer
• Popular for Day surgery
• Induction and recovery is quick so mental and motor impairment are short
• Irritates airways causing cough and laryngospasm
• Can also cause malignant hyperthermia

• Another fast acting inhalational anasthetic.
• Induction and recovery faster than desflurane
• Not irritating to the airway
• Can cause nephrotoxicity

• Induction of anasthesia
• Rapid onset of action (seconds)- reduce stage 2 of anasthesia
• Recovery occurs mostly by redistrobution of the drug
• Require reduced amount of inhaled anasthetic for maintenance

• Thiopental
• Midazolam
• Propofol
• Etomidate
• Ketamine

• Ultra short acting barbituate IV anasthetic
• Pt will regain consciousness in 10-20 minutes as the drug redistributes to skeletal muscle
• Does not increase Intra cranial tension
• Eliminated slowly from the body by metabolism- can produce hangover with myalgias and garlic smell.
• Barbituates induce P450
• Can be used for rapid seizure control

• Commonly used IV anasthetic for induction and maintenance
• unconscious in 45 seconds then out for 15 minutes.
• Recovery is rapid and clearer than with thiopental
• Anti emetic action
• Good for day surgery since residual impairment is low

• Not an analgesic so opioids like fentanyl need to be used to alleviate pain.
• frequent pain on injection- even more so in smaller veins
• Mild myoclonic movements are common like with other IV hypnotic agents

• a non popular IV anasthetic
• short acting
• suppresses steroid production from adrenal
• Pro convulsant and emetic
• Better Cardiovascular stability over other anasthetics

• IV anasthetic that causes dissociative anasthesia
• Profound analgesic, cataleptic state, immobility, amnesia with light sleep
• Blocks NMDA receptors
• HR and BP elevated due to sympathetic stimulation
• Respiration is not depressed and reflexes are not abolished

• Burn dressing and trauma surgery
• Dangerous in hypertensive and ischemic heart disease patients
• Can cause emergence delirium, hallucinations, and involuntary movements during recovery

• IV anasthetic used for open heart surgery due to lack of cardiac depression.
• Antagonist nalmefene and naloxone reverse opioid overdose
• can be given IV, Patch, or by lozenge

• Used for induction, short procedures, and dental procedures
• good for prevention of seizures induced by local anasthetics
• FLumazenil can reverse OD of benzodiazepines
• Midazolam- fastest onset of action, greatest potency, and most rapid elimination
• Cause anterograde amnesia

• Antipsychotic
• General quiescence, psychic indifference and intense analgesia
• NO loss of consciousness
• Combination of Fentanyl and Droperidol= innovar
• Good for debilitated or seriously ill patients

• Decreased motor function
• Suppressed autonomic reflexes
• cardiovascular stability with mild amnesia
• drowsy but respond to commands
• used for endoscopy, angiography, and minor operations
• can add N2O to make it anasthesia instead of analgesia

• activate inflammatory response
• inhibit gastric acid secretion and increase mucus secretion
• involved in the induction and maintenance of labor
• Maintenance of renal blood flow
• Maintain patent ductus arterious
• TXA2 vasoconstriction and aggregation of platelets
• PGI-2 vasodilation and anti platelet action

• large family of drugs that block COX enzymes blocking formation of prostaglandins from arachadonic acid
• anti pyretic, analgesic, and anti inflammatory

• Aspirin- acetlysalacylic acid
• Ibuprofen, Fenoprofen, ketoprofen, Naproxen- propionic acid derivatives
• Indoethacin, Etodolac, Sulindac- acetic acid derivatives
• Proxicam and Meloxicam- Oxicam derivative
• Ketorolac, diclofenac, Nambumetone

• COX-2 selective inhibitor, has analgesic, antipyretic, and anti inflammatory effects but with less GI tox than traditional NSAIDs
• Normal dose has no effect on platelet aggregation
• Can result in renal toxicity
• at higher doses can cause HTN and thrombosis

• Prototype NSAID
• IRREVERSIBLY acetylates COX enzymes
• anti inflammatory, analgesic, and anti pyretic
• Inhibits mucus secretion in stomach and increases acid secretion-> ulcer-> hemorrhage
• Misoprostol, a PGE-1 analog can be given to treat NSAID induced gastric ulcers

• Low dose (60mg) can irreversibly inhibit thromboxane production in platelets and since platelets have no nuclei can't resynth TX
• Endo cells can make new COX enzymes giving them anti platelet properties
• Decreases secretion of Uric acid into the urine at low doses-gout
• medium doses might not effect uric acid
• High dose can block reabsorption of uric acid increasing secretion- Stones

• Inhibition of PGE2 synthesis and PGI2 decreases blood flow in the kidneys, long term use can cause nephro tox
• High dose can uncouple oxidative phosphorylation leading ti increased CO2, hyperventilation, and respiratory alkalosis
• VERY high dose can cause respiratory paralysis and acidosis
• can precipitate bronchial asthma (hypersensitivity)
• Prolonged bleeding time
• Reye's syndrome- fatal hepatitis

• Salicylate intoxication- nausea, vomiting, hyperventilation, and tinnitus
• Sever salicylate intox- hallucinations, restlessness, convulsions, and acidosis
• Treatment of aspirin OD is with bicarbonate and dialysis

• Propionic acid derivatives - used to treat rheumatoid and osteoarthritis
• Ibuprofen is equally effective as indomethacin in closing patent ductus arteriosus in preterm infants

• Oxicam derivatives used to treat rheumatoid and osteoarthritis, and ankylosind spondylitis
• Long half life
• Meloxicam is somewhat cox 2 selective at theraputic doses

• Indomethacin, Etodolac, and Sulindac
• Indomethacin used in acute gouty arthritis and ankylosing spondylitis
• Can also be used to clos patent ductus arteriosus
• causes serious hematological tox

• used for osteo and rheumatoid arthritis
• Cox 2 inhibitors lower risk of ulcers and no effect on platelets
• can cause nephrotoxicity and HTN at high dose

• Tylenol
• analgesic and anti pyretic no anti inflammatory activity
• inhibits COX in the CNS but not periph (anti pyretic)
• blocks generation of pain impulses

• Mostly metabolized to produce non toxic metabolites gets glucuronidated in liver and excreted in the urine
• Small amount made into highly reactive intermediate that can cause liver tox
• At toxic levels liver glutathione is depleted causing more of the reactive intermediate reacting with sulfhydryl groups on hepatic proteins
• Renal tubular necrosis
• Treatment for OD is acetylcysteine

• Familial metabolic diseas that causes recurrent acute arthritis episodes due to urate crystals
• can cause calculi and nephritis

• NSAIDs, Glucocorticoids, or Colchicine
• Indomethacin, celecoxib, naproxen also effective
• Aspirin not used because of inhibition of urate secretion
• Glucocorticoids provide rapid relief- within hours- commonly prednisone or betamethasone
• IV Methylpredisolone and intraarticular triamcinolone are equally effective

• good if given early in attack
• inhibits MT formation
• reduces leukocyte migration and phagocytosis
• can be given in low dose as prophylaxis for chronic gout
• Diarrhea common, can severely damage kidney and liver