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