Block 2 Drugs Flashcards
Aldosterone
Made in zona glomerulosa from desoxycorticosterone
Release by renin-angiotensin and potassium
Traditional mineralocorticoid
Cortisol
Made in zona fasciculata and reticularis
Release by ACTH
Traditional glucocorticoid
Glucocorticoid - Effects
Mediated by glucocorticoid receptor
Enhances liver gluconeogenesis
Stimulates amino acid mobilization (degrading skeletal muscle, skin, etc.)
Increases plasma glucose, liver glycogen, urinary nitrogen excretion
Reduces peripheral glucose utilization
Redistribution of body fat - moon face, buffalo hump
Fatty acid release
Mineralocorticoid - Effects
Mediated by mineralocorticoid receptor in kidney
Increases sodium reabsorption
Increase potassium and hydrogen ion excretion
Responsible for CV effects
Dexamethasone
Strong glucocorticoid, no mineralocorticoid activity
Prednisolone
Primarily glucocorticoid, weak mineralocorticoid
Fludrocortisone
Very potent mineralocorticoid (stronger) and glucocorticoid
Primary use of glucocorticoid
Anti-inflammatory and immunosuppression
Metyrapone
Synthesis inhibitor of steroids
Blocks 11-beta hydroxylation to stop synthesis at 11-desoxycortisol
Causes ACTH levels to increase
Diagnostic test
Mifepristone
Competitive antagonist at progesterone and glucorticoid receptor
Termination of pregnancy
Treat Cushings Disease
Drospirenone
Progesterone agonist - With estrogen to suppress ovulation or as HRT in post-menopausal women
Mineralocorticoid receptor antagonist - Diuretic, antagonizes salt retention of estrogen
Androgen receptor antagonist
Azathioprine
Metabolized to 6-mercaptopurine
Delivery: Orally active
Mechanism: Purine anti-metabolite inhibiting de novo and salvage
Therapeutic Use: Inhibit rejection of transplanted organs and some autoimmune disease (ex. rheumatoid arthritis)
Side effects: Bone marrow suppression (main), GI and hepatic toxicity (secondary)
Cyclophosphamide
Mechanism: Alkylating agent results in cross-linking DNA, esp toxic in B-cells
Delivery: Orally active
Therapeutic Use: Treatment of autoimmune in combination with other drugs. Not for graft rejection.
Side effects: Bone marrow depression is major side effect
Methotrexate
Mechanism: Inhibitor of dihydrofolate reductase, purine synthesis
Therapeutic Use: Autoimmune disease
Side effects: Hepatic toxicity
Mycophenolate Mofetil
Metabolized to active mycophenolic acid
Mechanism: Inhibits IMP dehydrogenase, de novo purine synthesis (GMP), targets lymphocytes
Therapeutic Use: Renal allograft rejection with cyclosporine and corticosteroids; Autoimmune diseases (rheumatoid arthritis and refractory psoriasis)
Side effects: Infection, leukopenia, anemia
Caution with: GI disease, reduced renal function, infections, pregnancy
Cyclosporine
Mechanism: Inhibition of IL-2 synthesis by blocking NFAT transcription factor, decreases T-cell helper function, proliferation, cytotoxicity
Delivery: Orally active
Therapeutic use: Rejection of transplanted organs (more effective, fewer side effects); Some autoimmune diseases
Side effect: Nephrotoxicity (major, reversible), Hepatotoxcity
Tacrolimus
Binds FK binding protein
Same mechanism as cyclosporine
50-100x extra potency
Less nephro/hepatotoxicity
Sirolimus
Mechanism: Inhibits T-cell activation and proliferation downstream of IL-2, Binds FKBP-12 to block cell cycle progression
Therapeutic Use: Same as cyclosporine, coating of cardiac stents
Zileuton
Inhibitor of 5-lipoxygenase
Pharmacokinetics: Oral administration; half-life of 2.5 hrs, CYP metabolized
Mechanism: Inhibits cys-LTs (bronchoconstriction; increases vascular permeability) and LTB4 (chemotaxis)
Therapeutic use: Prophylactic of mild asthma
Adverse effects: few, increase liver enzymes
Zafirlukast
Cysteinyl leukotriene receptor antagonist
Mechanism: Inhibits cys-LTs
Pharmacokinetics: Oral administration; half-life of 10 hrs, CYP2C9/3A4 metabolism
Therapeutic Use: Prophylactic treatment of mild asthma
Adverse effects: Minimal
Dinoprostone - Cervical use
PGE2 Analog
Mechanism: Activation of collagenase, relaxes cervical smooth muscle, EP4 receptor subtype
Therapeutic use: Cervical ripening in pregnancy
Delivery: Cervical gel
Dinoprostone - Uterine use
PGE2 Analog
Mechanism: Uterine contractions via EP1/3
Therapeutic use: Termination of early pregnancy/abortion
Delivery: Vaginal suppository
Adverse effects: GI-related (nausea, vomiting, diarrhea), fever, uterine-rupture (contraindicated in women with history of C-section, uterine surgery)
Carboprost - Pregnancy use
PGF2 Analog
Mechanism: Uterine contractility stimulated at FP receptors
Therapeutic use: Termination of pregnancy during the second trimester (wks 13-20)
Delivery: Intramuscular injection
Carboprost - Postpartum
PGF2 Analog
Mechanism: Myometrial contractions via FP receptors
Therapeutic: Postpartum hemorrhage that is not responding to traditional methods
Preparation: Intramuscular injection
Adverse effects: GI-related (nausea, vomiting, diarrhea), fever, uterine-rupture (contraindicated in women with history of C-section, uterine surgery), rare bronchoconstriction
Misoprostol
PGE1 Analog
Mechanism: Suppression of gastric acid secretion by stim. EP3 receptors on parietal cells, Decrease in cAMP. increase mucin and bicarb secretion, mucosal blood flow
Therapeutic: “Replacement therapy” for prevention of ulcers caused by long-term NSAID usage
Preparation: Oral administration
Adverse effect: Diarrhea-common, contraindicated in pregnancy
Alprostadil - Penile
PGE1
Mechanism: Increase in cAMP to relax muscle of corpus cavernosum
Therapeutic use: Impotence/ED
Preparation: Intracavernous or intra-urethral
Adverse effect: Pain at site of injection, priapism (prolonged erection)
Alprostadil - Neonate
PGE1
Mechanism: cAMP-mediated relaxation of ductus arteriosus smooth muscle
Therapeutic: Maintenance of patent ductus arteriosus
Mechanism of action: cAMP-mediated relaxation of ductus arteriosus smooth muscle
Adverse effect: Apnea in about 10% of neonates; <2 kg
Epoprostenol
PGI2
Mechanism: cAMP-mediated dilation of pulmonary artery vascular smooth muscle
Therapeutic effect: Primary pulmonary HTN (rare)
Bimatoprost - Non-cosmetic
PGF2
Mechanism: Increases outflow of aqueous humor
Therapeutic use: Glaucoma
Preparation: Opthalmic solution
Adverse effects: eye redness, itching, increased brown pigment, eyelid skin; increase length and number of eyelashes
Bimatoprost - Cosmetic
PGF2
Mechanism: Increase the percent and duration of hairs in the growth phase
Therapeutic use: Eyelash hypotrichosis
Preparation: Opthalmic solution
Adverse effects: Excess. unwanted hair growth, brown iris pigmentation, eye redness, itching
Acetylsalicylic Acid (Aspirin)
Irreversible inhibitor of both COX (Aspirin specific) via acetylation of serine group
Pharmacokinetics: Plasma half-life is dose-dependent (with OD has zero-order kinetics), absorbed from stomach and small intestine, highly bound to plasma proteins and crosses BBB/placental barriers, renally eliminated
Delivery: Oral tablet, buffered (anti-stomach acid) vs enteric (passes stomach unaltered) coating
Pharmacological Effects:
NSAID
Uric acid excretion: low doses decrease/high dose increase
CNS: high dose/toxic effects of stimulation followed by depression, tinnitus, high-tone deafness, confusion, dizziness, delirium, psychosis, coma, nausea and vomiting
Respiration
Adverse reactions (Most NSAID related): GI, Platelet (irreversibility of aspirin requires new platelets to overcome), Hypersensitivity (less with non-acetylated salicylates), Kidney, Uterus/Fetus, Reye’s syndrome (Specific)
Therapeutic Use: Low dose - CVD; Intermediate Dose - Fever, Pain; High Dose - Inflammatory Disease; Cancer?
General NSAIDs
Pharmacological effects: Anti-inflammatory, Analgesia, Anti-pyretic
Adverse reactions:
GI - Ulceration and irritation due to loss of cytoprotective PGs
Platelets - Increase bleeding time by inhibiting platelet
Hypersensitivity - Respiratory, not IgE, more common with asthmatics/nasal polyps
Kidney - Decrease renal blood flow, promote salt and water retention especially on elderly who are more dependent on vasodilatory PGs
Uterus/Fetus - Prolonged gestation, labor, increased postpartum hemorrhage, intrauterine closure of PDA, avoid in 3rd trimester
Ibuprofen
Proprionic NSAID
Mechanism: Reversible COX1/2 inhibitor
Pharmacokinetics: Shorter half-life than naproxen
Pharmacological effects: NSAID
Adverse effects/toxicity: NSAID (less GI than Aspirin)
Therapeutic: Inflammatory diseases, rheumatoid disorders, mild-to-moderate pain, fever, dysmenorrhea, osteoarthritis, injection to induce patent ductus arteriosus in premature infants
Naproxen
Proprionic NSAID
Mechanism: Reversible COX1/2 inhibitor
Pharmacokinetics: Longer half-life than ibuprofen
Pharmacological effects: NSAID
Adverse effects/toxicity: NSAID (less GI than Aspirin)
Therapeutic: Management of ankylosing spondylitis, osteoarthritis, rheumatoid disorders, acute gout, mild-to-moderate pain, tendonitis, bursitis, dysmenorrhea, fever
Indomethacin
Acetic Acid NSAID
Mechanism: Reversibly COX1/2 inhibitor
Pharmacokinetics: Plasma half-life 3 hrs, 90% bound to plasma proteins
Pharmacological effects: NSAID
Adverse effects/toxicity: Frequent, GI toxicity, CNS - severe frontal headache
Therapeutic: Acute gouty arthritis, acute bursitits/tendonitis, moderate-to-severe osteoarthritis, rheumatoid arthritis, ankylosing spondylitis; IV for closure of patent ductus arteriosus
Unlabeled use: Pre-term labor
Kertolac
Acetic Acid NSAID
Mechanism: Reversibly COX1/2 inhibitor
Pharmacokinetics: Absorbed orally and intramuscularly, highly plasma protein bound
Pharmacologic effects: Analgesic and anti-pyretic, less anti-inflammatory activity
Therapeutic applications: Oral, injection for short term management of moderate-to-severe acute pain requiring analgesia at the opioid level
Nabumetone
Acetic Acid NSAID
Mechanism: Active metabolite is a reversible of COX1/2 (predominantly 2)
Pharmacokinetics: Converted to active metabolite, 6-methoxy-2-naphthylacetic acid, long half-life
Pharmacologic effects: Anti-inflammatory, analgesic
Adverse effects/toxicity: Well tolerated, less GI effects, mainly only COX2 effects
Therapeutic applications: Osteoarthritis, rheumatoid arthritis
Piroxicam
Oxicam NSAID
Mechanism: Reversible of COX1/2
Pharmacokinetics: Plasma half-life 50 hours, 99% bound to plasma proteins
Pharmacologic effects: NSAID
Adverse effects/toxicity: GI toxicity
Therapeutic: Symptomatic treatment of acute and chronic rheumatoid arthritis and osteoarthritis, advantageous of long half-life
Sulfasalazine
Salicylate NSAID, Mesalamine (5-ASA) is active component
Mechanism: No clear COX inhibition, possibly inhibition of IL-1, TNFa, lipoxygenase pathway, NF-kB
Pharmacokinetics: Oral which reaches distal GI due to azo linkage
Pharmacological effects: Local effect in GI to inhibit the inflammatory response
Adverse effects/contraindications: Sulfa moiety related. Headache, nausea, fatigue, hypersensitivity, reversibly decreases the number and motility of sperm, inhibits folate absorption
Therapeutic uses: Mild or moderately active ulcerative colitis, Rheumatoid arthritis and ankylosing spondylitis
Celecoxib
Selective COX-2 Inhibitor
Mechanism: Binds to side pocket in COX-2 obstructing active site
Pharmacokinetics: Oral administration (peak conc. 3 hrs), highly bound to plasma proteins, metabolized by CYP2C9 to inactivate
Pharmacologic effects: NSAID
Adverse: NSAID, GI irritation, Adverse CV thrombotic events (MI, stroke), Anemia - rare cases
Contraindications: Sulfonamide toxicity, prior NSAID hypersensitivity, pre-existing CV risk, post-coronary artery bypass graft surgery, caution in patients that have a def. of CYP2C9
Therapeutic applications: Signs/symptoms of rheumatoid arthritis, osteoarthritis, primary dysmenorrhea, acute pain management, polyp reduction in familial adenomatous polyposis
Acetaminophen
Mechanism: Not well understood, no affinity for COX1/2 activity site, prevents COX from reaching peroxidase form, more selective for COX in brain? COX-3?
Pharmacokinetics: Oral administration, effectively absorbed from GI tract, plasma half-life is 2 hours, little binding to plasma proteins, metabolism by phase I enzymes important for toxicity
Pharmacologic effects: Analgesic, antipyretic, NOT anti-inflammatory
Adverse: Primarily due to excessive use, no GI effects, Hepatotoxicity: Due to large doses, symptoms include vomiting, nausea, abdominal pain, treatment is with N-acetylcysteine, mechanism: glutathione substitute, risk with EtOH
Therapeutic applications: Mild-to-moderate pain and fever
Cromolyn Sodium
Inhaled Anti-Inflammatory Agent
Mechanism: Stabilizes mast cell membranes and prevents release of histamine
Delivery: Inhalation
Adverse Effects: Few
Therapeutic Uses: Preventative management of asthma, allergic rhinitis, conjunctivitis, food allergies
Omalizumab
Monoclonal Ab
Mechanism: Decreases amount of Ag specific IgE that binds to mast cells
Delivery: Subcut.
Adverse Effects: Major ones include life-threatening anaphylaxis and also bleeding related effects
Therapeutic uses: Allergic asthma
Diphenhydramine
First generation ethanolamine H1 Blocker
Delivery: Nasal/ophthalmic
Adverse reactions: Strong sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain
Therapeutic use: Allergies, motion sickness, nonprescription sleeping tablets, early stage Parkinson’s
Dimenhydrinate
First generation ethanolamine H1 Blocker
Delivery: Nasal/ophthalmic
Adverse reactions: Strong sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain
Therapeutic use: Motion sickness, vestibular disturbances
Chlorpheniramine
First generation alkylamine H1 Blocker
Delivery: Nasal/ophthalmic
Adverse reactions: Sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain
Therapeutic use: Allergies
Promethazine
First generation phenothiazine H1 Blocker
Delivery: Nasal/ophthalmic
Adverse reactions: Strong sedative, dry mouth, dry respiratory passageways, loss of appetite, nausea, vomiting, GI distress, rarely weight gain
Therapeutic use: Motion sickness, chemotherapy-induced nausea/vomiting
Fexofenadine
Second generation piperdine H1 Blocker
Delivery: Nasal/ophthalmic
Metabolism: Metabolized from terfenadine
Adverse reactions: Loss of appetite, nausea, vomiting, GI distress, rarely weight gain
Therapeutic use: Allergies
Loratadine
Second generation piperdine H1 Blocker
Delivery: Nasal/ophthalmic
Metabolism: Metabolized to desloratadine by 3A4, 2D6
Adverse reactions: Loss of appetite, nausea, vomiting, GI distress, rarely weight gain
Therapeutic use: Allergies
Desloratadine
Second generation piperdine H1 Blocker
Delivery: Nasal/ophthalmic
Metabolism: Metabolized from loratadine
Therapeutic use: Allergies
Cetirizine
Second generation piperazine H1 blocker
Delivery: Nasal/ophthalmic
Metabolism: Active metabolite of hydroxyzine
Adverse reactions: Loss of appetite, nausea, vomiting, GI distress, rarely weight gain
Therapeutic use: Allergies
Cimetidine
H2 Blocker (Least potent)
Pharmacology: Competitive inhibitors of histamine at H2 receptors, inhibit gastric acid secretion from parietal cells, reduce volume of gastric acid and H+ concentration
Pharmacokinetics: Rapidly absorbed following oral administration, small amounts undergo liver metabolism, parent drug & metabolites: excreted by kidneys
Adverse reactions (H2 blocker general): Minor diarrhea, headache, drowsiness, CNS effects with IV use or in elderly
Adverse reactions (Cimetidine specific): Inhibits P450 enzymes, decreases testosterone binding and inhibits a CYP enzyme that hydroxylates estradiol, gynecomastia, reduced sperm count, impotence in men
Therapeutic use: Major - GERD, Minor - healing of gastric and duodenal ulcers
Ranitidine
H2 Blocker (Moderately potent)
Pharmacology: Competitive inhibitors of histamine at H2 receptors, inhibit gastric acid secretion from parietal cells, reduce volume of gastric acid and H+ concentration
Pharmacokinetics: Rapidly absorbed following oral administration, small amounts undergo liver metabolism, parent drug & metabolites: excreted by kidneys
Adverse reactions (H2 blocker general): Minor diarrhea, headache, drowsiness, CNS effects with IV use or in elderly
Adverse reactions (Ranitidine specific): Inhibits P450 enzymes minorly
Therapeutic use: Major - GERD, Minor - healing of gastric and duodenal ulcers
Famotidine
H2 Blocker (Most potent)
Pharmacology: Competitive inhibitors of histamine at H2 receptors, inhibit gastric acid secretion from parietal cells, reduce volume of gastric acid and H+ concentration
Pharmacokinetics: Rapidly absorbed following oral administration, small amounts undergo liver metabolism, parent drug & metabolites: excreted by kidneys
Adverse reactions (H2 blocker general): Minor diarrhea, headache, drowsiness, CNS effects with IV use or in elderly
Therapeutic use: Major - GERD, Minor - healing of gastric and duodenal ulcers
Lysergic Acid Diethylamide (LSD)
Potent hallucinogen
Full or partial agonist at 5-HT2 receptors
Buspirone
Partial agonist at 5-HT1A receptors
Antianxiety agent
Sumatriptan
Agonist at 5-HT1D receptor
Used in the treatment of migraine headaches, stop existing headache
Side effects include nausea and vomiting, angina, dizziness, flushing
Fluoxetine
Serotonin specific reuptake inhibitors (SSRI)
Increase amount of serotonin at synapse
Treatment of affective disorders, OCD, panic attacks
Pheneizine
Monoamine oxidase inhibitor (MAOI)
Treatment of depression and narcolepsy. Side effects include food include food induced hypertensive crisis
Cyproheptadine
5-HT2 receptor antagonist, also H1 antagonist
Used in treatment of skin allergies (pruritus and urticaria)
Treatment of carcinoid
Ondansetron
5-HT3 receptor antagonists
Very effective in treatment of chemotherapy-induced nausea and vomiting
Acts both at GI and brain receptors
IV and oral forms
Alosetron
Selective 5-HT3 antagonists
Treat with diarrhea-predominant IBS who don’t respond to normal treatment
Produce severe GI adverse effects
Restricted prescribing program
Nitroglycerin
Nitrate
Mechanism: Relaxation of arterial and venous smooth muscle
Therapeutic use: Heart failure
Toxicity: Hypotension
Nitroprusside
Nitrate
Mechanism: Relaxation of arterial and venous circulations
Therapeutic use: Heart failure; Hypertensive (HTN crisis)
Toxicity: Hypotension
Hydralazine
Direct Vasodilators
Mechanism: Arterial circulation
Therapeutic use: Heart failure
Toxicitiy: Hypotension
Minoxidil
Direct vasodilator: ATP-sensitive K+ Channel Opener
Mechanism: Arterial circulation
Therapeutic use: Heart failure and hypertension
Diazoxide
Potassium channel dilator
Mechanism: Cell membrane actions
Therapeutic: Hypertension
Phosphodiesterase 3 Inhibitors
Bolded drugs: Milrinone, Inamrinone, Cilostazol
Intracellular Signaling
Heart Failure
Phosphodiesterase 5 Inhibitors
Bolded drugs: Sildenafil, Tadalafil
Intracellular signaling
Erectile dysfunction
Prazosin
Alpha-adrenergic blocker
Arterial and venous circulation
B2 Agonist
Bronchodilators
Bolded drugs: Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol
Mechanism: Intracellular Signaling - Cyclic AMP/PKA
Adverse reactions: Cardiotoxicity
Anti-cholinergic
Bronchodilators
Bolded drugs: Ipratropium, tiotropium
Mechanism: Muscarinic receptors
Adverse effects: Mucous secretion
Methylxanthine
Bronchodilators
Bolded drugs: Theophylline, aminophylline
Mechanism: Phosphodiesterase inhibition
Adverse effects: Adenosine receptor antagonism
Aliskiren
Mechanism: Renin inhibitor, potent active site, non-peptide inhibitor
Delivery: Orally active, long acting (24 h)
Therapeutic use: Treating HTN (Lowers BP with no change in HR)
Adverse reactions: Fatigue, headache, GI symptoms (comparable to placebo)
Losartan
AT1 receptor blocker
Mechanism: Prevents Angiotensin II action
Delivery: Orally active
Therapeutic use: Reduces BP w/o increasing HR, Improves heart failure
Adverse reactions: Contraindicted in pregnancy, dizziness, cough, angioedema
Other Notes: No hyperkalemic effects, concentration increases in patients with reduced liver function, does not alter lipid profile
Captopril
Mechanism: Angiotensin I Converting Enzyme (ACE) to block AT2 formation and bradykinin degradation
Therapeutic use: Reduce BP without increasing HR, Improves heart failure
Adverse reactions: Rash, proteinuria and neutropenia, cough angioedema
Enalapril
Mechanism: Angiotensin I Converting Enzyme (ACE) to block AT2 formation and bradykinin degradation
Therapeutic use: Reduce BP without increasing HR, Improves heart failure
Delivery: Pro-drug conversion to enalaprilate
Adverse reactions: Cough angioedema
Lisinopril
Mechanism: Angiotensin I Converting Enzyme (ACE) to block AT2 formation and bradykinin degradation
Therapeutic use: Reduce BP without increasing HR, Improves heart failure
Delivery: Pro-drug conversion to lisinoprilate
Adverse reactions: Cough angioedema
Spironolactone
Potassium Sparing Diuretic
Mechanism: Competitive aldosterone antagonists at mineralocorticoid receptor
Therapeutic use: Diuretics, reduce mortality from heart failure, decreases cardiac hypertrophy, fibrosis, sodium retention, treat HTN or edema with thiazide or loop diuretic
Delivery: Orally active
Adverse Reaction: Hyperkalemia, gynecomastia
Eplerenone
Potassium Sparing Diuretic
Mechanism: Competitive aldosterone antagonists at mineralocorticoid receptor
Therapeutic use: Diuretics, reduce mortality from heart failure, decreases cardiac hypertrophy, fibrosis, sodium retention, treat HTN or edema with thiazide or loop diuretic
Delivery: Orally active
Adverse Reaction: Hyperkalemia
Verapamil
Phenylalkylamine
Therapeutic use: Supraventricular arrhythmias
Mechanism: Inhibition of conduction of L-type Ca channels, heart rate moderation, cardiac vasodilation, use-dependent binding
Delivery: Oral but extensive first-pass effects
Adverse reactions: Constipation, exacerbate CHF, 2nd or 3rd degree AV block
Diltiazem
Benzothiazepine
Therapeutic use: Angina pectoris, Supraventricular arrhythmias
Mechanism: Inhibition of conduction of L-type Ca channels, heart rate moderation, cardiac vasodilation, use-dependent binding
Delivery: Oral, not much first-pass effect
Adverse reactions: 2nd or 3rd degree AV block (less than verapamil), best tolerated of original calcium channel blockers
Nifedipine
1,4-Dihydropyridines
Therapeutic use: HTN, Angina pectoris
Mechanism: Inhibition of conduction of L-type Ca channels, peripheral vasodilation, voltage-dependent binding
Delivery: Oral, not much first-pass effect, high protein binding
Adverse reactions: Hypotension, headache, flushing, peripheral edema
Amlodipine
1,4-Dihydropyridines
Therapeutic use: HTN, Angina pectoris
Mechanism: Inhibition of conduction of L-type Ca channels, peripheral vasodilation, voltage-dependent binding
Delivery: Oral, not much first-pass effect, high protein binding
Adverse reactions: Hypotension, headache, flushing, peripheral edema, better tolerated than nifedipine
Fenoldopam
Vasodilator Diuretic (DA1 Agonist) Mechanism: Increase RBF without reducing GFR, reduces net reabsorption Pharmacological Use: Increase RBF in shock
Dopamine
Vasodilator Diuretic (DA1 Agonist) Mechanism: Increase RBF without reducing GFR, reduces net reabsorption Pharmacological Use: Increase RBF in shock
Atriopepins
Vasodilator Diuretic (Atrial Natriuretic Peptides) Mechanism: Increase RBF without reducing GFR, reduces net reabsorption Pharmacological Use: Limited
Mannitol
Osmotic Diuretic
Mechanism: Non-reabsorbed solute to prevent water reabsorption
Delivery: IV, limited to inpatients
Therapeutic use: Prophylaxis of acute renal failure, edematous conditions in which a volume load is not detrimental, glaucoma
Adverse Reactions: Related to volume overload and expansion of IV fluid volume, rare hypersensitivity
Acetazolamide
Inhibitor of Carbonic Anhydrase (Diuretic)
Mechanism: Decreases bicarbonate reabsorption and therefore sodium reabsorption
Therapeutic Use: Glaucoma (reduction of aqueous humor formation), alkalinize urine to decrease drug toxicity, treat symptoms of acute altitude sickness
Adverse reactions: Metabolic acidosis to reduce renal response to drug, generally safe
Furosemide
Loop or high ceiling diuretics
Mechanism: Inhibit active chloride reabsorption, ruining Na/K/2Cl symporter, extremely potent
Therapeutic uses: Rapid diuresis (15 mins) and short in duration (2-3 hrs), management of edema due to cardiac, hepatic or renal disease, acute pulmonary edema, hypertension
Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia, ototoxicity, volume depletion
Bumetanide
Loop or high ceiling diuretics
Mechanism: Inhibit active chloride reabsorption, ruining Na/K/2Cl symporter, extremely potent
Therapeutic uses: Rapid diuresis (15 mins) and short in duration (2-3 hrs), management of edema due to cardiac, hepatic or renal disease, acute pulmonary edema, hypertension
Adverse reactions: Hypokalemia, hyperuricemia, ototoxicity (least), volume depletion
Ethacrynic acid
Loop or high ceiling diuretics
Mechanism: Inhibit active chloride reabsorption, ruining Na/K/2Cl symporter, extremely potent
Therapeutic uses: Rapid diuresis (15 mins) and short in duration (2-3 hrs), management of edema due to cardiac, hepatic or renal disease, acute pulmonary edema, hypertension
Adverse reactions: Hypokalemia, hyperuricemia, ototoxicity (most), volume depletion
Chlorothiazide
Thiazide and related diuretics
Mechanism of Action: Na/Cl symport inhibitor
Therapeutic uses: Rapid diuresis (1 hr) and long in duration, edema management due to congestive cardiac failure, hypertension, hypercalciuria in patients with renal calculi from calcium salts
Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia (decreased insulin secretion)
Contraindication: GFR < 25 ml/min
Hydrochlorothiazide
Thiazide and related diuretics
Mechanism of Action: Na/Cl symport inhibitor
Therapeutic uses: Rapid diuresis (1 hr) and long in duration, edema management due to congestive cardiac failure, hypertension, hypercalciuria in patients with renal calculi from calcium salts
Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia (decreased insulin secretion)
Contraindication: GFR < 25 ml/min
Metolazone
Thiazide and related diuretics
Mechanism of Action: Na/Cl symport inhibitor
Therapeutic uses: Rapid diuresis (1 hr) and long in duration, edema management due to congestive cardiac failure, hypertension, hypercalciuria in patients with renal calculi from calcium salts
Adverse reactions: Hypokalemia, hyperuricemia, hyperglycemia (decreased insulin secretion)
Contraindication: GFR < 25 ml/min
Triamterene
Potassium-Sparing Diuretics
Mechanism of Action: Sodium channel inhibitor, aldosterone independent
Therapeutic use: Edema, HTN, paired with thiazide or loop diuretic
Adverse Reactions: Hyperkalemia, azotemia
Amiloride
Potassium-Sparing Diuretics
Mechanism of Action: Sodium channel inhibitor, can also block Na-H exchange, aldosterone independent
Adverse Reactions: Hyperkalemia, azotemia
Heparin
Anti-coagulant
Mechanism: Catalyzes antithrombin’s suicide activity against coagulation factors (Xa, IXa, Thrombin) by providing a binding scaffold
Therapeutic Use: DVT, Pulmonary Embolism, Management of unstable angina or acute MI, low dose prophylaxis against DVT, hemodialysis, anticoagulant during pregnancy
Delivery: IV or Sub-q, Half-life is dose dependent, Cleared by reticuloendothelial system and liver
Adverse reactions: Bleeding, thrombocytopenia
Contraindications: Active bleeding, recent surgery, severe uncontrolled HTN
Low molecular weight heparins (LMWH)
Bolded ones to know: Enoxaparin, Dalteparin
Anti-coagulant, Same as heparin except when noted
Mechanism: More targeting for Xa, too short for thrombin
Therapeutic use: Same as heparin but specifically used for hip surgery also
Delivery: Cannot be absorbed through GI mucosa, absorbed more uniformly than heparin via Sub-q, longer half-life than heparin, cleared via kidney
Adverse effects: Less severe than heparin
Lepirudin
Anti-coagulant
Mechanism: Binds tightly to catalytic site and exosite I of thrombin
Therapeutic use: Alternative to heparin for coronary angioplasty or cardiopulmonary bypass
Delivery: Administered IV, excreted by kidneys, Half-life is 1.3 hrs
Adverse reactions: Bleeding, cautiously in renal failure patients due to risk of accumulation in kidney
Contraindications: Active bleeding, recent surgery, sever uncontrolled HTN, Renal Disease
Bivalirudin
Anti-coagulant
Mechanism: Binds tightly to catalytic site of thrombin until thrombin cleaves the linkage
Therapeutic use: Alternative to heparin for coronary angioplasty or cardiopulmonary bypass
Delivery: Administered IV, excreted by kidneys; Half-life of 25 minutes
Adverse reactions: Bleeding, cautiously in renal failure patients due to risk of accumulation in kidney
Contraindications: Active bleeding, recent surgery, sever uncontrolled HTN, Renal Disease
Fondaparinux
Anti-coagulant
Mechanism: Synthetic pentasaccharide that causes an antithrombin-mediated selective inhibition of Xa
Therapeutic use: FDA approved - prophylaxis of DVT for hip, knee, or abdominal surgeries; treatment of PE and DVT
Off-label - Prophylaxis of DVT in patients with history of heparin-induced thrombocytopenia, acute thrombosis in patients with a past history of HIT; acute symptomatic superficial vein thrombosis of legs
Delivery: Sub-q injection, excreted in urine, half-life of 17 hours
Adverse reactions: Hemorrhage anywhere
Contraindications: Active bleeding, recent surgery, severe uncontrolled HTN, renal impairment
Protamine Sulfate
Heparin antagonist
Mechanism: Binding of heparin to inactivate, high affinity for negatively charged molecules, minor anti-coagulant if used alone
Therapeutic use: Used to reverse heparin following cardiopulmonary bypass
Adverse reactions: Anaphylactic reactions with bradycardia, cutaneous vasodilation, hypotension; severe pulmonary HTN
Warfarin
Anti-coagulant
Mechanism: Vitamin K antagonist by blocking Vitamin K reductase (VKORC1), leaving Vitamin K in the oxidized state, prevents PTM of factors II, VII, IX, X
Therapeutic use: Long-term treatment of venous thromboembolic disease, prophylaxis against thromboembolism in atrial fib, prosthetic heart valve, and dilated cardiomyopathy
Delivery: Oral - rapid and completely absorbed after administration, 99%+ bound to albumin, inactivated by CYP2C9, delayed for several hours to days because it does not affect circulating factors
Adverse reactions: Variable dosing window due to variations of CYP2C9, tetrogenic in pregnancy, skin necrosis (rare), blue-tinged discoloration of plantar surfaces
Contraindications: Prolonged activity in liver/kidney disease, Vit K def
Dabigatran
Anti-coagulant
Mechanism: Prodrug dabigatran etexilate is converted to dabigatran: specific, reversible, direct thrombin inhibitor (including fibrin-bound thrombrin)
Therapeutic use: Post-op thromboprophylaxis for hip and knee replacements; stroke and systemic embolism prevention in patients with nonvalvular A-fib
Delivery: Orally available prodrug, half-life is 14 to 17 hrs, renal excretion. Dabigatran etexilate is a substrate for the Pgp transporter in gut and kidneys; Pgp inducers decrease plasma dabigatran
Adverse reactions: No worse than warfarin for bleeding, but risk with patients with renal bleeding. No antidote for overdose.
Rivaroxaban
Anti-coagulant
Mechanism: Selective direct-acting factor Xa inhibitor.
Therapeutic use: Post-op thromboprophylaxis for hip and knee replacements; stroke and systemic embolism prevention in patients with nonvalvular A-fib
Delivery: Oral bioavailability > 80%, 1/3 excretion by kidney unchanged, 2/3 metabolized by liver and split between renal and fecal excretion, Pgp efflux transporter substrate
Adverse reactions: Related to bleeding, but less than other anticoagulants, no hepatotoxicity
Endogenous Tissue-type Plasminogen Activator
Endogenous Thrombolytic
Mechanism: Binds to fibrin to activate fibrin-bound plasminogen to plasmin. Low t-PA at early stage clot formation, because of plasminogen activator inhibitors (PAI-1/2)
Relatively non-specific plasminogen activation
Alteplase
Thrombolytic Agent
Mechanism: Fibrin-bound plasminogen specific activator
Therapeutic use: Management of ST-elevation MIs for coronary thrombi, acute ischemic strokes, acute pulmonary emoblism
Delivery: Continuous IV administration, half-life of 1 to 4 minutes, liver elimination
Contraindications: Active bleeding, recent surgery within 10 days (major surgery, organ biopsy, trauma, CPR), GI bleeding within 3 months, cerebralvascular problems, hemorrhagic disorder, known hypersensitivity, severe uncontrolled HTN, pregnancy or postpartum
Aminocapronic Acid
Procoagulant Drugs
Mechanism: Lysine analog that binds to plasminogen and plasmin, prevents plasmin activation
Therapeutic use: Reverse states associated with an excessive breakdown of fibrin, effective in decreasing hemorrhage with surgical procedures
Dipyridamole
Anti-platelet
Mechanism: Phosphodiesterase inhibition, block adenosine uptake, increase cAMP, inhibits platelet aggregation
Therapeutic Use: Prevention of thromboemboli with warfarin in patients with prosthetic heart valves
Delivery: Oral
Adverse Reactions: Headache, GI upset, Dizziness
Clopidogrel
Anti-platelet
Mechanism: Irreversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation
Therapeutic use: Unstable angina or NSTEMI with aspirin, STEMI, recent MI, stroke, established peripheral arterial disease
Delivery: Prodrug activated mainly by CYP2C19
Adverse effects: Bleeding, less neutropenia, drug interactions with PPIs: competes for CYP2C19 activation
Prasugrel
Anti-platelet
Mechanism: Irreversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation
Therapeutic use: Reduce rate of thrombotic CV events (stent thrombosis) for percutaneous coronary intervention (PCI) management of UA, NSTEMI, STEMI
Delivery: Prodrug, undergoes esterase-mediated hydrolysis and then activation by CYP oxidation, higher potency, faster honest, and more consistent level of platelet inhibition than clopidogrel
Adverse effects: Bleeding, less neutropenia
Ticlopidine
Anti-platelet
Mechanism: Irreversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation
Therapeutic use: Not often used, largely replaced by clopidogrel, prasugrel, and ticagrelor
Delivery: Prodrug activated mainly by CYP2C19
Adverse effects: Bleeding, high neutropenia
Ticagrelor
Anti-platelet
Mechanism: Reversible ADP-P2Y12 antagonists, prevents platelet activation and aggregation
Therapeutic use: Conjunction with aspirin for secondary prevention of thrombotic events in patients with UA, NSTEMI, or STEMI managed medically with PCI or coronary artery bypass graft
Delivery: Not prodrug
Adverse effects: Bleeding, less neutropenia
Abciximab
Anti-platelet
Mechanism: Fab fragment binding to platelet GP IIb/IIIa receptors to prevent fibrinogen binding and cross-linking of platelets
Therapeutic use: Percutaneous cornary interventions (i.e. coronary angioplasty and stent placement) in combination with aspirin and heparin/LMWH; Adjunct to thrombolysis with alteplase
Delivery: IV, biphasic plasma half-life of 10 minutes and 30 minutes, functional half-life due to slow clearance is 7 days
Adverse effects: Bleeding, thrombocytopenia, hypotension, bradycardia
Eptifibatide
Anti-platelet
Mechanism: Preventing cross-linking of fibrinogen via competitive, reversible inhibition of GP IIb/IIIa receptors. Highly specific KGD sequence
Therapeutic use: Unstable angina and MI often in combination with LMWH
Delivery: IV with maximum effect by 15 minutes, lasts up to 4-8 hours after discontinuation, renal clearance
Adverse effects: Bleeding, thrombocytopenia, hypotension, bradycardia
Contraindications: Renal disease
