Pharm III Test 2 Drugs
what drug is this: Clonidine and methyldopa Used for hypertension that are not controlled by other drugs Reduce CO and PVR Methyldopa can be used for pregnant women AE:drowsiness, fatigue, withdrawal slowly =>clonidine
Alpha 2 agonists
what drug is this: -reduce the viscosity of sputum and ease the release of it -effective for cystic fibrosis and COPD -antagonist of the cough center in the lungs
Mucolytic agents
what drug is this: -corticosteroids -hydrocortisone and prednisone=>systemic steroids -beclomethasone, fluticasone, budesonide=>inhaled steroids -limit transcription of mediators and cytokines -decrease inflammatory cells -inhalation -used more for Asthma *not effective for steroids* AE: candiasis and dysphonia
Anti-Inflammatory agents
what drug is this: MOA: They bind to β2 receptors on bronchial smooth muscles to achieve bronchodilation via stimulating the formation of cAMP. Selective β2 agonists: albuterol, Salmeterol Nonselective: epinephrine, ephedrine, isoproterenol (short acting) Short acting beta agonists (SABAs): albuterol, pirbuterol, metaproterenol Long acting beta agonists (LABAs): Salmeterol, Formoterol indacaterol, olodaterol. Clinical uses: Asthma and COPD (primarily inhaled or oral administration) Adverse effects: · Particularly for non-selective adrenoceptor agonists with oral administration: tachycardia, skeletal muscle tremor, and decreases in serum potassium levels. · Long-acting β-agonists (LABA: salmeterol and formoterol) received "black box" warnings.
Adrenoreceptor agonists
what drug is this: Inhibit renin production Doesn't get used that much due to not being better than other drugs in this pathway
Aliskiren
what drug is this: Prazosin,Terazosin Used to treat moderate to severe hypertension when you cant use another drug Used for BPH All cause orthostatic hypotension
Alpha 1 blockers
what drug is this: MOA: Drugs in this class block the binding of angiotensin II to type 1 angiotensin II (AT1) receptors. They have no effect on bradykinin metabolism and are therefore more selective blockers of angiotensin effects than ACE inhibitors. They also have the potential for more complete inhibition of angiotensin action compared with ACE inhibitors because there are enzymes other than ACE that are capable of generating angiotensin II. Prototype drugs: Losartan, valsartan Clinical uses: · Therapeutic uses similar to ACE inhibitors and provide benefits in patients with heart failure and chronic kidney disease. · ARBs are most commonly used in patients who have had adverse reactions to ACE inhibitors. · Less effective in African-American patients UNLESS combined with a thiazide-like diuretic or a calcium channel blocker (just like ACEi) Adverse effects: Similar to ACE inhibitors including contraindication for pregnant women, BUT no cough.
Angiotensin receptor-blockers (ARBs)
what drug is this: MOA: Drugs in this class inhibit the converting enzyme peptidyl dipeptidase that hydrolyzes angiotensin I to angiotensin II. Thus, Angiotensin II inhibitors lower blood pressure principally by decreasing peripheral vascular resistance. Cardiac output and heart rate are not significantly changed. Unlike direct vasodilators, these agents do not result in reflex sympathetic activation and can be used safely in persons with ischemic heart disease. The absence of reflex tachycardia may be due to downward resetting of the baroreceptors or to enhanced parasympathetic activity. Peptidyl dipeptidase also inactivate bradykinin, a potent vasodilator that works at least in part by stimulating release of nitric oxide and prostacyclin. Thus, ACEs also function through activating bradykinin. Prototype drugs: Lisinopril, captopril Clinical uses: · ACE inhibitors have a particularly useful role in treating patients with chronic kidney disease because they diminish proteinuria and stabilize renal function (even in the absence of lowering of blood pressure). This effect is particularly valuable in diabetes, and these drugs are now recommended in diabetes even in the absence of hypertension. These benefits probably result from improved intrarenal hemodynamics, with decreased glomerular efferent arteriolar resistance and a resulting reduction of intraglomerular capillary pressure. ACE inhibitors have also proved to be extremely useful in the treatment of heart failure and as treatment after myocardial infarction, and there is evidence that ACE inhibitors reduce the incidence of diabetes in patients with high cardiovascular risk. · Combines well with thiazides and CCBs and are available in fixed-dose combination Adverse effects: · Dry cough due to bradykinin accumulation · Contraindicated during pregnancy due to risk of fetal hypotension, anuria, and renal failure hyperkalemia · Drug interactions include those with potassium supplements or potassium sparing diuretics because of risk of hyperkalemia; · Combination of ACE inhibitors and ARBs or aliskiren are not recommended due to toxicities · Less effective in African-American patients UNLESS combined with a thiazide-like diuretic or a calcium channel blocker
Angiotensin-converting enzyme (ACE) inhibitors
what drug is this: -treats asthma -mepolizumab, reslizumab -stops the activations of eosinophils -inhibit the binding of the major interleukin that is responsible for the asthma response -this interleukin develops the creation of eosinophils
Anti-IL-5 therapies
what drug is this: -omalizumab -used for allergic asthma, chronic urticaria and nasal polyps -antiinflammatory drug -inhibits the binding of the immunoglobulin that starts asthma -binds to the immunoglobulin -SC injection
Anti-IgE
what drug is this: 3 known vasopressin receptors - V1a, V1b, V2. Ø V1a and V1b found in CNS and vasculature Ø V2 found in kidney Agonists - Vasopressin (Pitressin), desmopressin (DDAVP) Have antidiuretic properties Increase water reabsorption by kidney by inserting aquaporins (water channels) in luminal membranes of renal tubule cells in collecting duct Used in treatment of central diabetes insipidus Antagonists Nonselective (older) - Lithium, demeclocycline Ø Interfere with ADH activity Ø Mechanism not known Ø Demeclocycline used more often (less adverse effects) Ø Both may cause acute renal failure Ø Now being replaced by vaptans Conivaptan (IV only, V1a and V2), tolvaptan selective against V2 receptor. Therapeutic Uses Used to treat Euvolemic and hypervolemic hyponatremia Used to manage SIADH (syndrome of inappropriate ADH secretion) Used in treatment of congestive heart failure Adverse Effects If not monitored, may cause Ø Hypernatremia Ø Nephrogenic diabetes insipidus In the wings: Lixivaptan, a potent, selective vasopressin V2 receptor antagonist was in development as a treatment for hyponatremia. It is now in clinical trials as a treatment for autosomal dominant polycystic kidney disease (ADPKD).
Antidiuretic Hormone and Antagonists
what drug is this: H1 receptor antagonists, first vs. second generations, side effects, indications in treating bronchospasm and allergic rhinitis.
Antihistamines
what drug is this: -treats bronchospasm and allergic rhinitis -blocks histamine response -bronchodilation and vasoconstriction *reverse of what histamine does* AE: drowsy, sedation
Antihistamines (H1 Antagonists)
what drug is this: -counteract parasympathetic pathway -SAMAs=>Ipratropium -LAMAs=>Tiotropium -atropine -M3 Antagonists -used more for COPD -inhalation -tiotropium
Antimuscarinic agents
what drug is this: Codeine, Hydrocodone; Dextromethorphan; Gabapentin; Benzonatate MOA: They work by inhibiting a coordinating region for coughing located in the brain stem, disrupting the cough reflex arc.
Antitussives: Cough Suppressants
what drug is this: Guaifenesin MOA: It acts by stimulating the secretion of respiratory tract fluid and reducing the viscosity of secretions to facilitate expectoration.
Antitussives: Expectorants
what drug is this: Acetylcysteine (Mucomyst) MOA: used to reduce the viscosity of sputum and facilitate their removal (making it easier to cough it up).
Antitussives: Mucolytic agents
what drug is this: Prototype drugs: Hydralazine, Minoxidil MOA: · Hydralazine causes the release of nitric oxide from drug or endothelium · Minoxidil leads to hyperpolarization of cell membranes through opening of potassium channels. Clinical uses: · Very efficacious orally active vasodilator. · Dilates arterioles but not veins. · Used in combination with a β blocker and loop diuretic. Adverse effects: · The most common adverse effects of hydralazine are headache, nausea, anorexia, palpitations, sweating, and flushing. · Adverse effects of Minoxidil are tachycardia, palpitations, angina, and edema when β blockers and diuretic dosing is inadequate; headache sweating and hypertrichosis are common.
Arterial Dilators
what drug is this: MOA: The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. The result is increased intracellular cGMP, which relaxes vascular smooth muscle. Prototype drugs: Sodium Nitroprusside Clinical uses: Sodium nitroprusside is a powerful parenterally administered vasodilator that is used in treating hypertensive emergencies as well as severe heart failure. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. Adverse effects: Other than excessive blood pressure lowering, the most serious toxicity is related to accumulation of cyanide; metabolic acidosis, arrhythmias, excessive hypotension.
Arterial and venous dilator
what drug is this: -Bind to B2 receptor in lungs and activate adenyl cyclase and increase the formation of cAMP -result in bronchodilation and inhibiting the mediators from the mast cells -Used more for asthma than COPD -Nonselective->epinephrine, ephedrine and isoproterenol -Selective→albuterol -there are short acting (albuterol) and long acting forms (salmeterol, formoterol) *black box warning of asthma related death due not treating inflammation of asthma* -LABAs should never be used alone and should be combined with steroids -AE: Tachycardia or tremors
B2 agonists
what drug is this: MOA: They decrease blood pressure primarily as a result of a decrease in cardiac output. Other mechanism may include Inhibition of renin secretion. Metoprolol and atenolol, which are cardioselective, are the most widely used β blockers in the treatment of hypertension. Metoprolol is approximately equipotent to propranolol in inhibiting stimulation of β1 adrenoceptors such as those in the heart but 50- to 100-fold less potent than propranolol in blocking β2 receptors. Relative cardioselectivity is advantageous in treating hypertensive patients who also suffer from asthma, diabetes, or peripheral vascular disease. Prototype drugs: Metoprolol, Atenolol Clinical uses: They are useful for lowering blood pressure in mild to moderate hypertension. In severe hypertension, β blockers are especially useful in preventing the reflex tachycardia that often results from treatment with direct vasodilators. Beta blockers have been shown to reduce mortality after a myocardial infarction and some also reduce mortality in patients with heart failure; they are particularly advantageous for treating hypertension in patients with these conditions. Other things to remember: They are less effective in the elderly and African-American population
Beta Blockers
what drug is this: Metoprolol, Atenolol, Lebetalol.Carvedilol Used to treat mild to moderate hypertension Inhibit renin secretion *beta receptors on kidney* and Cardiac output Doesn't cause hypotension in normal individuals Often used in combination with other things Less effective in elderly and african american population Beta blocking and vasodilation effects=>lebetalol and carvedilol Lebetalol for pregant women B2 selective=>metoprololo and atenolol
Beta Blockers
what drug is this: Bind to bile acid and secrete through feces Results in more cholesterol being converted to bile acids Decrease LDL levels Increase in col-7a-hydroxylase levels *rate limiting enzyme in bile acid synthesis* Used for hypercholesteremia AE: GI distress
Bile acid-binding resins
what drug is this: MOA: 1) Bile acids, metabolites of cholesterol, are normally efficiently reabsorbed in the jejunum and ileum. Excretion is increased up to tenfold when resins are given, resulting in enhanced conversion of cholesterol to bile acids in liver via 7α-hydroxylation, which is normally controlled by negative feedback by bile acids. 2) Increase uptake of LDL and IDL from plasma results from upregulation of LDL receptors, particularly in liver. Prototype drugs: Colestipol, cholestyramine, and colesevelam Clinical uses: The resins are used in treatment of patients with primary hypercholesterolemia, producing approximately 20% reduction in LDL cholesterol in maximal dosage. Adverse effects: Probably safest lipid-lowering drugs, because they are not absorbed systematically, recommended for patients of 11-20 yrs, constipation and bloating, usually relieved by increasing dietary fiber should be avoided in patients with diverticulitis
Bile acid-binding resins
what drug is this: Amlodipine, Verapamil, Diltiazem Block calcium channels DHPs=>amlodipine *much more selective for vasculature* *decrease PVR* Non-DHPs=>verapamil and diltiazem Safe for pregnancy Do not combine beta-blockers with non-DHPs because you can substantially decrease heart rate and blood pressure AE: peripheral edema due to excessive vasoconstriction
Calcium Channel Blockers
what drug is this: MOA: calcium channel blockers reduce peripheral resistance and blood pressure. The mechanism of action in hypertension is inhibition of calcium influx into arterial smooth muscle cells. Prototype drugs: Amlodipine, Verapamil, Diltiazem Clinical uses: They are all equally effective in lowering blood pressure, and many formulations are currently approved for this use in the USA. However, hemodynamic differences among calcium channel blockers may influence the choice of a particular agent. Amlodipine and the other dihydropyridine (DHP) agents are more selective as vasodilators and have less cardiac depressant effect than verapamil and diltiazem (non-DHP). Adverse effects: · Generally considered safe for use during pregnancy. · Most side effects due to excessive vasodilation: peripheral edema · Combination of verapamil (non-DHPs) with β blockers are contraindicated due to increased propensity for AV block or severe depression of ventricular function
Calcium channel blockers
what drug is this: -Acetazolamide -amide group drugs -used for glaucoma more than diuretics -used for acute mountain sickness, idiopathic intracranial hypertension and epilepsy -Work on proximal tubule -secreted into PCT -Inhibit the buffering system of HCO3- and H+ -This results in a increase in sodium being excreted out due to loss of sodium/H+ antiporter and also result in more HCO3- being excreted out due to not being able to convert to CO2 and water and diffused into kidney cells. -this results in more K in the collecting duct due to sodium exchanging with potassium in the collecting duct via ENAC and ROMK. AE: hypokalemic, hyperchloremic metabolic acidosis (due to loss of bicarb) and alkalinized urine (due to increased excretion of bicarb), kidney stones Contradicted if allergy to sulfa or cirrhosis pts.
Carbonic Anhydrase Inhibitors
what drug is this: Mechanism of action: Inhibit carbonic anhydrase. Cause inhibition of NaHCO3 reabsorption in the proximal convoluted tubule. Cause urinary alkalinization, metabolic acidosis Efficacy decreases with use over days. Carbonic anhydrase inhibitors increase excretion HCO3-, Na+, K+ and (slightly) phosphate. Therapeutic Uses FDA approved indications Glaucoma (most common use) High levels of HCO3- in the aqueous humor; these agents reduce aqueous humor formation and thus â intraocular pressure Prevention and treatment of acute mountain (high altitude) sickness Promote mild metabolic acidosis which counteracts the respiratory alkalosis that results from hyperventilation in this condition Idiopathic intracranial hypertension (Pseudotumor cerebri), decrease CSF production Epilepsy (increase CO2 level in brain, increase seizure threshold) Off -label use: Sleep apnea, Hydrocephalus, Metabolic Alkalosis, Cystine renal calculi, uric acid kidney stone ↑PH in urine Acid toxicity (aspirin, Methotrexate), ↑PH in urine Prevention contrast -induced nephropathy Pharmacokinetics Well absorbed after oral administration Diuresis seen at 30 min, maximal at 2 hours, persists 12 hours (single dose) Excreted by kidney - reduce dose in renal insufficiency Adverse Effects Metabolic Acidosis Renal Stones Hypokalemia Other: drowsiness, paresthesia (large doses) In patients with renal failure may accumulate leading to nervous system toxicity Contraindications Patients allergic to sulfas Cirrhosispatients, ↑PH in urine ↓ excretion of NH3hyperammonemiahepatic encephalopathy
Carbonic Anhydrase Inhibitors
what drug is this: MOA: These agents reduce sympathetic outflow from vasomotor centers in the brain stem but allow these centers to retain or even increase their sensitivity to baroreceptor control. Methyldopa (L-α-methyl-3,4-dihydroxyphenylalanine) is an analog of L-dopa and is converted to α-methyldopamine and α-methylnorepinephrine. Its antihypertensive action appears to be due to stimulation of central α2 adrenoceptors by α-methylnorepinephrine or α-methyldopamine. Clonidine appears to exert antihypertensive action at α adrenoceptors in the medulla of the brain. Clonidine reduces sympathetic and increases parasympathetic tone, resulting in blood pressure lowering and bradycardia. Prototype drugs: Methyldopa, Clonidine Clinical uses: · Methyldopa was widely used in the past but is now used primarily for hypertension during pregnancy. It lowers blood pressure chiefly by reducing peripheral vascular resistance, with a variable reduction in heart rate and cardiac output. · Blood pressure lowering by clonidine results from reduction of cardiac output due to decreased heart rate and relaxation of capacitance vessels, as well as a reduction in peripheral vascular resistance. Adverse effects: Methyldopa · Sedation, particularly at the onset of treatment. · With long-term therapy, patients may complain of persistent mental lassitude and impaired mental concentration Clonidine · Drowsiness · Fatigue · Dry mouth and sedation · Withdrawal of clonidine after protracted use, particularly with high dosages (more than 1 mg/d), can result in life-threatening hypertensive crisis mediated by increased sympathetic nervous activity.
Centrally Acting Sympatholytic Drugs
what drug is this: MOA: Ezetimibe selectively inhibits intestinal absorption of cholesterol and phytosterols. A transport protein, NPC1L1, is the target of the drug. It is effective in the absence of dietary cholesterol because it also inhibits reabsorption of cholesterol excreted in the bile. Prototype drugs: Ezetimibe Clinical uses: 1) For treating hypercholesterolemia. Ezetimibe is synergistic with reductase inhibitors, producing decrements as great as 25% in LDL cholesterol beyond that achieved with the reductase inhibitor alone. 2) Specific therapeutic for Sitosterolemia which is caused by homozygous or combined heterozygous ablative mutations in ABCG5/G8, resulting in elevated levels of LDL enriched in phytosterols, tendon and tuberous xanthomas. Adverse effects: a low incidence of reversible impaired hepatic function with a small increase in incidence when given with a reductase. contraindicated in pregnancy
Cholesterol Absorption Inhibitor
what drug is this: MOA: block all the known pathways of eicosanoid synthesis. They do not relax airway smooth muscle directly but reduce bronchial hyperreactivity and reduce the frequency of asthma exacerbations. Systematic drugs: Hydrocortisone, Prednisone Inhaled corticosteroids: Fluticasone, Beclomethasone, Budesonide Clinical uses: Asthma ( Not effective for COPD) Adverse effects: Inhaled forms can cause candidiasis and dysphonia
Corticosteroids
what drug is this: -largely ineffective -NMDA antagonists or GABA agonist -antagonists at the medullary cough center in the brain -treats cough AE: sedative
Cough Suppressants
what drug is this: Reduce plasma cholesterol levels Inhibits absorption of cholesterol in lumen of intestine in which results in lower cholesterol levels in the blood Used for hypercholesteremia Inhibits sterol transporter (NCPC1L1)
Ezetimibe
what drug is this: Agonist for PPAR-alpha Activates fatty acid metabolism and creates more lipoproteins as well Decrease VLDL levels Increase HDL levels due to increasing A-1 Increase oxidation of fatty acids Used for hypertriglyceridemia AE: rashes, hypokalemia and myopathy,hepatotoxicity
Fibrates
what drug is this: MOA: 1) Ligands for the nuclear transcription receptor, PPAR-α, thus transcriptionally up-regulate LPL and other genes involved in lipid metabolism. 2) Increase oxidation of fatty acids in liver and striated muscle. 3) Increase lipolysis of lipoprotein triglyceride via LPL. 4) Levels of VLDL decrease, in part as a result of decreased secretion by the liver. 5) Only modest reductions of LDL occur in most patients. Prototype drugs: Gemfibrozil and fenofibrate Clinical uses: Fibrates are useful drugs in hypertriglyceridemias in which VLDL predominate and in in type 3 hyperlipoproteinemia (dysbetalipoproteinemia, mutantion in Apo E). Adverse effects: Rashes gastrointestinal symptom Myopathy syndrome Should be avoided in patients with hepatic or renal dysfunction
Fibrates
what drug is this: PPAR-alpha agonist Activate fatty acid metabolism and also creates more lipoproteins Decreases triglyceride levels by decreasing synthesis from fatty acid omega -3
Fish oil
what drug is this: MOA: Excess dietary lipid generally leads to fat deposition and impaired glucose homeostasis, but consumption of this alleviates many of these detrimental effects. The beneficial effects of FO are thought to be mediated largely via activation of the nuclear receptor peroxisomal-proliferator-activated receptor α (PPARα) by omega-3 polyunsaturated fatty acids and the resulting upregulation of lipid catabolism. Prototype drugs: omega-3 fatty acid ethyl esters Clinical uses: 1) reduce hepatic triglyceride synthesis (reduces TG by 20-50%); 2) Used as an adjunctive therapy to treat hypertriglyceridemia, Side effects: 1) dyspepsia, after-taste ("fish burps"), 2) inhibit platelet aggregation, 3) worsen glycemic control in diabetic patients.
Fish oils (omega-3 fatty acids)
what drug is this: Arterial dilator Formation of NO and activation of cyclic GMP, opening of potassium channels, blocking calcium channels antihypertensive Oral Give beta blocker for tachycardia and diuretic for fluid retention AE: lupus like sx,tachycardia and fluid retention
Hydralazine
what drug is this: Decrease PVR Increase sodium excretion Lower blood volume Can be paired with alot of other antihypertensive drugs Most frequently used antihypertensive diuretic Blocks NCC (sodium chloride cotransporter) in distule tubule Enhances calcium reabsorption AE: hypokalemic metabolic alkalosis, hyperglycemia, hyperurcemia, hyperlipidemia etc.
Hydrochlorothiazide,Clorthalidone *Thiazide diuretics*
what types of drugs are these: Renin, angiotensin, and aldosterone play important roles in some people with essential hypertension. Approximately 20% of patients with essential hypertension have inappropriately low and 20% have inappropriately high plasma renin activity. Blood pressure of patients with high-renin hypertension responds well to drugs that interfere with the system, supporting a role for excess renin and angiotensin in this population. Angiotensin II has vasoconstrictor and sodium-retaining activity. Angiotensin II and III both stimulate aldosterone release. Angiotensin may contribute to maintaining high vascular resistance in hypertensive states associated with high plasma renin activity, such as renal arterial stenosis, some types of intrinsic renal disease, and malignant hypertension, as well as in essential hypertension after treatment with sodium restriction, diuretics, or vasodilators. However, even in low-renin hypertensive states, these drugs can lower blood pressure
Inhibitors of angiotensin
what drug is this: -montelukast, zafirlukast or zileuton -Zileuton=>5-lipoxygenase inhibitor -lukast drugs=>leukotriene receptor antagonists -inhibits 5-lipoxygenase on arachidonic acid -bronchodilation -reduce mucus production -has some anti-inflammatory effects as well -much safer than steroids
Leukotriene pathway inhibitors
what drug is this: ACE inhibitors Inhibits the formation of the vasocontrictor angiotension II Decreases PVR Prevents the breakdown of bradykinin Pairs well with thiazides and CCBs Dont pair in the same pathway (ARBs or renin antagonists) Used for Ischemic heart disease, chronic kidney disease, and diabetes AE: dry cough due to the accumulation of bradykinin, hyperkalemia, DO NOT use in pregnancy, contradicted with NSAIDs and potassium sparring diuretics
Lisinopril, Captopril
what drug is this: Furosemide, bumetanide, torsemide and ethacrynic acid Work on the thick ascending loop of henle Secreted into tubule by active transporter (acid) and compete with uric acid secretion Used for CHF, renal failure, pulmonary edema, hypercalcemia, hyperkalemia, anion overdose and hypertension Inhibit NKCC2 transporter Lose sodium and water this results in more K in the collecting duct due to sodium not exchanging with potassium in the collecting duct via ENAC and ROMK along with increased excretion of H+. AE: hypokalemia, metabolic alkalosis, ototoxicity, hyperuricemia, hypomagnesemia *decreased effect with NSAIDs*
Loop Diuretics
what drug is this: Increases HDL levels by inhibiting uptake or removal of apoA-I Antagonist of the DGAT2 that is responsible for making triglycerides in the intestine from fatty acid and glycerol and therefore decreases triglyceride levels Antagonist of HDL Catabolism receptor in which results in more HDL Decrease triglyceride levels AE: flushing due to increasing prostaglandins and vasodilation
Niacin
what drug is this: Are the most efficacious diuretic agents available (high ceiling) Act on thick ascending limb of loop of Henle. Mechanism of Action Inhibit NKCC2, the luminal Na+/K+/2Cl- co-transporter in the thick ascending limb (TAL) of the loop of Henle. As a result, decrease NaCl reabsorption, diminish positive potential that drives divalent cation absorption. Therefore, also get increased excretion of Ca2+ and Mg2+ Therapeutic Uses Edema, including Ø Chronic renal insufficiency Ø Acute pulmonary edema Renal failure Congestive heart failure Acute hypercalcemia (together with isotonic saline) Hyperkalemia Pharmacokinetics Rapidly absorbed from GI tract. Extensively plasma protein bound - but rapidly secreted into tubule (proximal) by acid transport system. NSAIDs and probenecid may reduce secretion of loop diuretics if given simultaneously (compete for weak acid secretion such uric acid in proximal tubule) t1/2's 1-2 hours, duration of action 3-6 hours - for furosemide it is 2-3 hours Adverse Effects Hypokalemia Metabolic alkalosis Ø Increased delivery of salt and water to the collecting duct enhances the renal secretion of K+ and H+ Ototoxicity - dose-related; reversible Ø More common with ethacrynic acid Hyperuricemia (compete secretion, hypovolemia enhances uric acid reabsorption) Hypomagnesemia Cross sensitivity with other sulfonamides (ethacrynic acid not a sulfonamide) Allergic reactions - Less with ethacrynic acid Rashes Other - dehydration, hyponatremia, mild hyperglycemia (possibly due to a hypokalemic induced insulin resistance) Drug Interactions Diminished effect if given with NSAIDs Bile acid sequestrants - reduce bioavailability of diuretics Digoxin - hypokalemia may predispose to digoxin toxicity Reduced renal clearance of lithium (acidic urine decreases excretion of lithium) Ototoxic drugs Contraindications/Precautions Sulfa-allergy Exception: ethacrynic acid
Loop or high ceiling Diuretics
what drug is this: Angiotensin II receptor blocker (ARBs) Block the binding of angiotensin II to type 1 angiotensin II receptors Reduce PVR No bradykinin side effect do to where in the pathway it acts on Contradicted in pregnancy Less effective in african american population Used for ischemic heart disease, chronic kidney disease and diabetes
Losartan, Valsartan
what drug is this: -form of caffeine -theophylline (tea product) -used for asthma -theophylline -inhibit phosphodiesterase -used in pts who asthma isnt controlled by beta agonists -very narrow therapeutic index AE: anxiety, tremor,nausea, insomia
Methylxanthines
what drug is this: Arterial dilator Formation of NO and activation of cyclic GMP, opening of potassium channels, blocking calcium channels Oral Used for hair growth but can act as an antihypertensive Rarely drop BP Give beta blocker for tachycardia and diuretic for fluid retention AE: tachycardia and fluid retention
Minoxidil
what drug is this: MOA: They antagonizes both alpha-1 and beta-receptors. Prototype drugs: Labetalol, Carvedilol Clinical uses: Labetalol is used for emergency treatment in pregnant women
Mixed Adrenergic Antagonists
what drug is this: -spironolactone, eplerenone -Work on the collecting duct -used for hyperaldosteronism, hypokalemia, systolic heart failure, drug-resistant hypertension, can be used for transgender women for hirsutism. -Act on principle cells -Aldosterone receptor antagonists -Block ENAC and decrease Na influx -Loss of sodium and water -Decrease exchanges of K and H AE:hyperkalemia metabolic acidosis, gynecomastia
Potassium Sparing Diuretics
what drug is this: MOA: They target interleukin 5 (IL-5) ) or its receptor . IL-5 is a major cytokine responsible for development of eosinophils which are associated with severe asthma. Clinical uses: As add-on, maintenance therapy of severe asthma in patients with an eosinophilic phenotype. Side effects: Injection site reactions.
Monoclonal antibodies: Mepolizumab, Reslizumab, and Benralizumab
what drug is this: MOA: It inhibits the binding of IgE and activation of IgE receptor-expressing inflammatory cells (reducing circulating IgE) Clinical uses: Reduces frequency of asthma exacerbations Side effects: 1) Anaphylaxis (rare), 2) Possible increase in malignancies; 3) Injection site reactions.
Monoclonal antibodies: Omalizumab
what drug is this: MOA: They competitively inhibit the action of acetylcholine at muscarinic receptors (M3) on bronchial smooth muscles to achieve bronchodilation. Short acting muscarinic antagonists (SAMA): Ipratropium Long acting muscarinic antagonists (LAMAs): Tiotropium, Aclidinium Clinical uses: · Combination inhalers of SAMA and SABA, such as ipratropium/albuterol, for treating Asthma and COPD · LAMA/LABA (tiotropium/olodaterol) for treating COPD · Longer-acting antimuscarinic agents, tiotropium and aclidinium, are approved for maintenance therapy of COPD. Adverse effects: Dryness of oropharynx, Cough
Muscarinic antagonists
what drug is this: Topical (nasal mucosa) agents: Phenylephrine Oxymetazoline, Xylometazoline- longer acting Corticosteroids: Nasal spray: Budesonide, Fluticasone propionate MOA: constrict dilated vessels in the nasal mucosa and reduce hyperemia- relieve nasal and sinus congestion.
Nasal Decongestants
what drug is this: -afrin -stimulate alpha 1 receptors -constrict dilated vessels in the nasal mucosa -relieve nasal and sinus congestion
Nasal decongestants
what drug is this: MOA: 1) inhibits VLDL secretion, in turn decreasing production of LDL. 2) inhibits HDL-Apo-A-I degradation, and thus increasing in HDL levels. Clinical uses: 1) In combination with a resin or reductase inhibitor, niacin normalizes LDL in most patients with heterozygous familial hypercholesterolemia and other forms of hypercholesterolemia. 2) In severe mixed lipemia that is incompletely responsive to diet, niacin often produces marked reduction of triglycerides, an effect enhanced by marine omega-3 fatty acids. 3) is clearly the most effective agent for increasing HDL and reduces Lp(a) in most patients. Adverse effects: Most persons experience a harmless cutaneous vasodilation and sensation of warmth after each dose when niacin is started or the dose increased. Reversible elevations in aminotransferases up to twice normal may occur, usually not associated with liver toxicity. Rarely, true hepatotoxicity may occur. should be avoided in patients with significant peptic disease. contraindicated in pregnancy
Niacin (nicotinic acid)
what drug is this: Arterial and venous dilator Formation of NO and activation of cyclic GMP, opening of potassium channels, blocking calcium channels IV Used for hypertensive emergencies Give beta blocker for tachycardia and diuretic for fluid retention AE: cyanide poisoning,tachycardia and fluid retention
Nitroprusside
what drug is this: Mannitol Used for head injury, glaucoma, kidney injury, removal of uremic toxins Used to decreased pressure of things throughout the body Filtered by glomerulus Aquaretic Work on the descending loop of henle and proximal convoluted tubule Block aquaporin 1 channel AE:dehydration, hypernatremia Contradicted for heart failure, pulmonary edema or severe renal impairment
Osmotic Diuretics
what drug is this: Mechanism of action Filtered by glomerulus Water retained in segments of the kidney that are freely permeable to water - the proximal tubule and the descending limb of the loop of Henle Pharmacokinetics Not metabolized. Excreted unchanged Therapeutic Uses To increase water excretion in preference to sodium excretion To maintain urine volume in conditions in which glomerular filtration is greatly reduced Reduction of intracranial and intraocular pressure Adverse effects Headache, nausea, and vomiting - common Worsening of heart failure and pulmonary edema secondary to extracellular volume expansion If not with adequate water replacement may get dehydration, hypernatremia and hyperkalemia
Osmotic Diuretics
what drug is this: MOA: bind to PCSK9 to block degradation of LDL receptors Prototype drugs: alirocumab and evolocumab (monoclonal antibodies), Inclisiran (siRNA) Clinical uses: Use of these agents is restricted to patients who have familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease who require additional reduction of LDL. Side effects: 1) injection reactions, 2) nasopharyngitis, 3) myalgia, 4) cognitive impairment
PCSK9 inhibitors
what drug is this: Alirocumab and evolocumab Reduces LDL levels Block degradation of LDL receptors Used for high risk patients who are not lowering LDL levels via statins
PSCK9 inhibitors
what drug is this: MOA: Diuretics lower blood pressure primarily by depleting body sodium stores. This class of drugs reduces Na+ absorption in collecting tubules. Spironolactone is a synthetic steroid that is a competitive inhibitor of aldosterone. Prototype drugs: Spironolactone Clinical uses: Potassium-sparing diuretics are useful both to avoid excessive potassium depletion and to enhance the natriuretic effects of other diuretics. Aldosterone receptor antagonists in particular also have a favorable effect on cardiac function in people with heart failure. Adverse effects: (also described in diuretics lecture) · Hyperkalemia · Hyperchloremic metabolic acidosis · Endocrine abnormalities · Contraindicated with patients with chronic renal insufficiencies
Potassium-sparing diuretics
what drug is this: MOA: The mechanism of action of this drug is unique in that it blocks the RAAS by binding to a pocket in renin itself, preventing it from cleaving angiotensinogen to angiotensin I. Prototype drugs: Aliskiren (the first and only approved direct renin inhibitor). Clinical uses: Aliskiren is used for the treatment of hypertension in children above 6 years and adults. This drug may also be used in conjunction with antihypertensives such as calcium channel blockers and thiazides in products form to provide additional blood pressure control. Adverse effects: · Body aches or pain · chills · cough
Renin inhibitors
what drug is this: Decrease PVR Increase sodium excretion Lower blood volume Can be paired with alot of the other antihypertensive drugs Potassium sparring diuretics Reduce sodium absorption in collecting tubules Competitive inhibitor of aldosterone Combine alot with thiazides due to balancing out the potassium drop and elevation AE:hyperkalemia, endocrine abnormalities,contradicted in pts in renal insufficiencies
Spironolactone
what drug is this: Block the enzyme that creates cholesterol in the liver prodrug HMG-COA reductase inhibitors Should be taken in the evening due to synthesis being highest at this particular time Reduce LDL effectively Used for hyperlipidemias, hypercholesterolemia and acute coronary syndromes Levels will be increased by drinking at least 1 liter of grapefruit juice AE: hepatotoxicity, myopathy, and rhabdomyolysis, contraindicated in pregnant women
Statins
what drug is this: Chlorthalidone Work on the distal convoluted tubule Used for hypertension*first line*,heart failure, kidney stones, nephrogenic DI Secreted into tubule by active transporter (acid) and compete with uric acid secretion Chlorthalidone has high half-life due to binding to RBCs Inhibit Na-Cl cotransporter (NCC) -increase sodium and water excretion -increase Ca reabsorption due to more sodium being secreted into the lumen -this results in more K in the collecting duct due to sodium not exchanging with potassium in the collecting duct via ENAC and ROMK along with increased excretion of H+. AE: hypokalemia, metabolic alkalosis, hyperuricemia, hyperglycemia, hyperlipidemia, hyperatremiaia, allergy (sulfa)
Thiazide Diuretics
what drug is this: MOA: Diuretics lower blood pressure primarily by depleting body sodium stores. Initially, diuretics reduce blood pressure by reducing blood volume and cardiac output; peripheral vascular resistance may increase. After 6-8 weeks, cardiac output returns toward normal while peripheral vascular resistance declines. Sodium is believed to contribute to vascular resistance by increasing vessel stiffness and neural reactivity, possibly related to altered sodium-calcium exchange with a resultant increase in intracellular calcium. These effects are reversed by diuretics or dietary sodium restriction. Prototype drugs: Hydrochlorothiazide, Chlorthalidone Clinical uses: Thiazide diuretics are appropriate for most patients with mild or moderate hypertension (Lowering BP 10-15 mm Hg) and normal renal and cardiac function. They are often used in initial treatment of hypertension. In patients with more severe hypertension, diuretics are used in combination with other antihypertensive drugs. Adverse effects: (also described in diuretics lecture) · Hypokalemic metabolic alkalosis · Hyponatremia · Hyperglycemia · Hyperlipidemia · Increase uric acid concentrations (hyperuricemia) and may precipitate gout
Thiazide Diuretics
what drug is this: Mechanism of Action Act by blocking the Na+/Cl- transporter (NCC) in the distal convoluted tubule thus inhibiting Na+ and Cl- reabsorption. The thiazides increase Na+, Cl-, K+ and H2O excretion. Increase Ca2+ reabsorption. Therapeutic Uses Hypertension Heart failure Nephrolithiasis (due to idiopathic hypercalciuria) Nephrogenic diabetes insipidus Pharmacokinetics All the thiazide diuretics are absorbed after oral administration (chlorothiazide poorly ~10%). There are differences in metabolism, t1/2, etc. Plasma protein binding varies. Adverse Effects Hypokalemia Metabolic alkalosis Hyperuricemia Secreted by organic acid transport in proximal tubule - compete with secretion of uric acid Hypercalcemia Hyperglycemia Due to impaired insulin secretion and decreased tissue utilization of glucose Hyperlipidemia - 5-15% increase in total serum cholesterol Hyponatremia Allergy. Thiazides have a sulfonamide structure Borderline renal and/or hepatic insufficiency may be aggravated. Don't use if creatinine level is >2.5mg/dL or if creatinine clearance is <30mL/min.
Thiazide Diuretics
what drug is this: Conivaptan and tolvaptan Used to treat hypoatremia (euvolemic, hypervolemic), SIADH, CHF, PKD Aquaretic Work on the collecting duct Inhibit the insertion of aquaporin 2 to the apical cell membrane No sodium loss AE: hypernatremia, nephrogenic DI, liver toxicity (tolvaptan), inhibits CYP3A4 system (conivaptan)
Vasopressin receptor or ADH antagonist
what drug is this: MOA: They produce most of their antihypertensive effects by selectively blocking α1 receptors in arterioles and venules, thus lowering BP by dilated blood vessels and decreasing peripheral vascular resistance. These agents produce less reflex tachycardia when lowering blood pressure than do nonselective α antagonists. Prototype drugs: Prazosin, Terazosin Clinical uses: These drugs are more effective when used in combination with other agents, such as a β blocker and a diuretic, than when used alone. Owing to their beneficial effects in men with prostatic hyperplasia and bladder obstruction symptoms, these drugs are used primarily in men with concurrent hypertension and benign prostatic hyperplasia. Adverse effects: A precipitous drop in standing blood pressure develops in some patients shortly after the first dose is absorbed (we discussed this in Pharm I). For this reason, the first dose should be small and should be administered at bedtime. Aside from the first-dose phenomenon, the reported toxicities of the α1 blockers are relatively infrequent and mild.
alpha 1 blockers
what drug is this: MOA: They inhibit leukotriene-related enzyme (5-lipoxygenase) or function as leukotriene receptor antagonist. Prototype drugs: · Zileuton: a 5-lipoxygenase inhibitor · Zafirlukast and Montelukast: LTC,D, E4-receptor (Cys-LT1) antagonists Clinical uses: Alternative treatments in asthma and can be of benefit for children when oral therapy is preferred over inhalers: these are effective in the treatment of allergic rhinitis but are less effective than intranasal corticosteroids. Adverse effects: 1. Zafirlukast may increase prothrombin time in patients on warfarin. 2. Hepatotoxicity.
leukotriene pathway inhibitors
what drug is this: MOA: cause an intracellular increase in levels of cAMP through inhibition of the phosphodiesterase enzyme (PDE),. Prototype drugs: theophylline, theobromine, caffeine Clinical uses: Asthma and COPD; mainly in patients whose symptom is difficult to control by beta agonists Adverse effects: 1. Nausea, vomiting 2. Insomnia, restlessness 3. Tremors, palpitations, cardiac arrhythmias, tachycardia, tachypnea. 4. Convulsions
methylxanthines
what drug is this: Aldosterone is a mineralocorticosteroid that enhances Na+ reabsorption and K+ secretion in distal tubule. Potassium sparing diuretics inhibit the action of aldosterone. This may be by competitive antagonism (spironolactone and eplerenone), or by inhibition of Na+ influx through ion channels and interference with transport in distal tubule (triamterene, amiloride). Amiloride not metabolized, triamterene is and some of the metabolites are active. Therapeutic Uses Hyperaldosteronism Ø Spironolactone and eplerenone more effective Ø Hypokalemia (may be used with other diuretics for this purpose) Ø Heart failure Adverse Effects Hyperkalemia Metabolic acidosis Spironolactone, which has a steroid structure, has endocrine effects Ø Males - gynecomastia, decreased libido, impotence Ø Females - menstrual irregularities, amenorrhea, postmenopausal bleeding, breast soreness Drug Interactions Medications that increase potassium e.g., ACE inhibitors, ARBs(angiotensin II receptor blockers) NSAIDs - decrease the effect Note: All diuretics may cause xerostomia(dry mouth), thirst.
potassium sparing diuretics
what drug is this: MOA: 1) The active forms of this are structural analogs of the HMG-CoA intermediate that HMG-CoA reductase mediates the first committed step in sterol biosynthesis. Thus, these drugs competitively inhibit HMG-CoA reductase and impair the synthesis of cholesterol. 2) clearly induce an increase in high-affinity LDL receptors. This effect increases both the fractional catabolic rate of LDL and the liver's extraction of LDL precursors (VLDL remnants) from the blood, thus reducing LDL. Prototype drugs: mevastatin, lovastatin, atorvastatin, simvastatin, rosuvastatin (which ones are prodrugs?) Clinical uses: They are most effective and best tolerated agents in treating dyslipidemias, especially in reducing LDL. It has become standard practice to initiate reductase inhibitor therapy immediately after acute coronary syndromes, regardless of lipid levels. Adverse effects: Myopathy hepatic dysfunction Interactions: CYP-dependent metabolism (3A4, 2C9) interacts with CYP Other things to remember: Best administered in evening, why? Half-life differences among these
statins
what type of drug is this: All are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Sodium nitroprusside also relaxes veins. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system, as well as renin, angiotensin, and aldosterone. Because sympathetic reflexes are intact, vasodilator therapy does not cause orthostatic hypotension or sexual dysfunction. Vasodilators work best in combination with other antihypertensive drugs that oppose the compensatory cardiovascular responses.
vasodilators
