Pharmacology MD4 Flashcards
Vancomycin
glycopeptide, tx vs gram +, MRSA
- binds to D-ala-D-ala terminus on precursor peptide units, inhibits peptidoglycan polymerase, prevents peptidoglycan cross-linking in 2nd stage of bacterial cell wall synthesis-> incr permeability, apoptosis
- use sparingly to prevent development of bacterial resistance
- nephrotoxicity, ototoxicity, phlebitis (vein inflam), red man syndrome (flushing, erythema of face, neck, torso d/t mast cell degranulation)
- not absorbed well via intestines, only given PO for pseudomembranous colitis (c. diff) since the med doesn’t get absorbed and just sits in the gut
Piperacillin-Tazobactam
(Zosyn)
extended spectrum penicillin + B-lactamase inhibitor
IV, tx of nosocomial, polymicrobial infxn (diabetic foot), activity vs gram +/-, pseudomonas aeruginosa
MoA:
Piperacillin: binds PBP, prevents peptidoglycan crosslinking in 3rd/final phase of bacterial cell wall synthesis-> cell lysis
Tazobactam: competitive, irreversable binding to active site of beta-lactamases (intra, extracellular, bound)-> inactivation
- vs clavulanate: has activity vs certain enterobacteriaceae spp. and pseudomonas aeruginosa (gram -)
- not able to be given PO
Amoxicillin-Clavulanate
(Augmentin)
beta-lactam:beta-lactamase inhibitor combo, extended activity vs gram + beta-lactamase containing bacteria (NOT MRSA or bacteria w/ altered PBPs (penicillin resistance))
MoA:
Amoxicillin: binds PBP-1A preventing peptidoglycan cross-linking in 3rd/final phase of bacterial cell wall synthesis-> cell lysis
Clavulanate: competitively & irreversibly binds active site of beta-lactamases (extracellular, intracellular, bound)-> inactivation
- is a beta-lactam itself, however, has little to no antibacterial activity
- able to be given PO
- AE: hepatotoxcitiy
Propranolol
competitive, non-selective B-blocker
- B1 blockade (heart, vascular SM): negative chrono & inotropic effects-> decr HR, contractility, CO, BP
- B2 blockade: prevents vasodilation, unopposed alpha stim-> incr reflex peripheral vasoconstriction (in response to low BP)-> more modest BP decr vs B1 selective antagonists (no AE of hypotension)
- b2 blockade can cause bronchoconstriction (CI in asthma, COPD)
- in tx of thyrotoxicosis:
- block sympathetic activity (L-isomer) (tremor, anxiety, heat intolerance), AE: dizzy, fatigue, weakness, depression
- prevent conversion of T4 to T3 in periphery (D-isomer)
Methimazole
- thioamide vs hyperthyroidism
- MoA: concentrates in thyroid, binds thyroid peroxidase, inhibits oxidation, organification, coupling-> decr synthesis of new thyroid hormones
- doesn’t affect pre-formed/existing hormones, may take weeks-mo. to produce effect
- short half-life (5-9 hr), frequent dosing
- freely crosses placenta and into breast milk
- high risk of congenital malformations (aplasia cutis (missing skin) on scalp, esophageal atresia w/ tracheoesophageal fistula, choanal atresia), CI in pregnancy during organogenesis in 1st trimester
- lower risk of agranulocytosis/leukopenia, aplastic anemia (can be fatal, s/sx sore throat) vs. PTU
- lower risk of liver failure/tox vs. PTU (methimazole used first)
Propylthiouracil (PTU)
- thioamide vs hyperthyroidism
- MoA: concentrates in thyroid, binds thyroid peroxidase, inhibits oxidation, organification, coupling-> decr synthesis of new thyroid hormones
- @ higher doses: prevents peripheral conversion of T4 -> T3, may have rapid effects (tx in thyroid storm)
- short half-life (1 hr), frequent dosing
- less readily crosses placenta, no proven risk of congenital malformations (vs methimazole), used in pregnancy during 1st trimester (then switched back to methimazole)
- higher risk of liver failure/tox vs methimazole (used as 2nd line tx)
- higher risk of agranulocytosis/leukopenia, aplastic anemia vs methimazole (s/sx sore throat, can be fatal)
Levothyroxine
- tx of hypothyroidism, IV for myxedema coma
- synthetic/exogenous L-isomer of T4 is converted/deiodinated to T3 in peripheral tissues-> actions of T3
- AE: hyperthyroidism (L-isomer mediated) like palpitations, tachycadia, wt loss, nervousness, heat intolerance = inappropriate dosage of hormone
- 6-10 day half life
- AE: can cause acute adrenal crises (correct w/ glucocorticoids prior in pts w/ uncorrected adrenal insuff.)
Liothyronine
- synthetic/exogenous T3
- used in tx of myxedema coma, faster onset vs levothyroxine (doesn’t need to be converted from T4)
- more cardiotoxic than levothyroxine (HF), not used primarily in hypothyroid tx
- half life 2.5 days
Fludrocortisone
- mineralocorticoid >>> glucorticoid effects
- pharmacologically similar to aldosterone
- salt retaining effect is much higher than other corticosteroids, tx in adrenal insufficiency, classic CAH
- no appreciable glucocorticoid effects @ therapeutic doses, administered along w/ a glucocorticoid for adrenal insufficiency, classic CAH
- 18-36 hr half life
- AE: mostly d/t mineralocorticoid effects: fluid & electrolyte imbalance (esp. hypokalemia), edema/CHF, hypertension
Hydrocortisone
- glucocorticoid & mineralocorticoid actions (anti-inflam & salt retention) in 1:1
- suppress release of CRH & ACTH-> decr androgen synthesis & adrenal hyperplasia in CAH
- low potency tx for adrenal insufficiency
- topical, safest for infants/children and chr use
- 8-12 hr half life, crosses into breast milk & placenta
- AE: Cushing’s syndrome (hypercortisolism)
- prednisone (glucocorticoid)- has more anti-inflam effect, less salt retaining effect
Lactulose
synthetic derivative of lactose, disaccharide formed from one galactose + one fructose
Pharmacokinetics: per os or rectum. Not digested by GI enzymes.
MoA:
Tx of hepatic encephalopathy
- reaches colon unchanged, where normal bacterial flora degrade it into acids (lactic primarily, + formic & acetic), causes acidic environment that ionizes ammonia to ammonium, ammonium is unable to diffuse across colonic membrane-> excretion in feces-> decr serum ammonia by 25-50%-> improves mental status
- incr ammonia diffusion from blood into gut, where it can be converted to ammonium and excreted
Tx constipation (laxative)
- breakdown of lactulose in colon-> incr osmotic pressure-> fluid accumulation-> softens stool & distends colon, enhances peristalsis
- may take 1-2 days for nml BM
AE: @ initiation of tx, 20% have gaseous abdominal distension, flatulence, belching, abdominal cramping/discomfort. Diarrhea suggests excessive dose.
Tiotropium (bromide)
anticholinergic, long-term COPD management
- more potent (10 x, dissociates more slowly), once daily dosing vs. ipratropium bromide
- competitive, reversible binding to muscarinic receptors, preventing acetylcholine binding.
Binds to:
-M1: preventing parasympathetic cholinergic neurotransmission
M2: prevents negative feedback for Ach release.
M3 on bronchial smooth muscle & mucous glands: decr bronchoconstriction & mucus secretion
Pharmacokinetics:
- selective for M1 & M3 (dissociates slowly), dissociates rapidly from M2
- bronchodilation for 24 h duration of action (half lives for release from M1 in 14 h, M2 in 3 h, M3 in 36 h)
- dry powder via oral inhalation or inhalation spray
- AE: anticholinergic: dry mouth, constipation, urinary retention, paradoxical bronchospasm, CI in acute bronchospasm, also not shown to be effective in asthma
Haloperidol
high-potency antipsychotic
-tx for psychotic disorders, tics, Tourette’s syndrome, behavioral problems in children
MoA: blocks postsynaptic D2 (dopamine) receptors in the mesolimbic system
incr dopamine turnover by blocking D2 somatodendritic autoreceptors
After 12 wks/chronic tx, blocks depolarization in dopamine tracts
decr dopamine neurotransmission correlates w/ antipsychotic effects
very weak anticholinergic & a1-adrenergic receptor blocking (AE: sedation, muscle relaxation, hypotension, reflex tachycardia, minor ECG changes)
AE: extrapyramidal sx d/t D2-R blockade: dystonia (sustained muscle contractions), akathisia (motor restlessness), pseudoparkinsonism (slowing of movements, resting tremor, postural instability, rigidity), tardive dyskinesia (involuntary repetitive movements)
More AE: leukopenia, neutropenia, agranulocytosis, neurologic malignant syndrome (NMS): life threatening reaction to antipsychotics
Pharmacokinetics: oral, IM, IV, 1/2 life 12-22 h (16 h)
Spironolactone
K+ sparing diuretic, oral, tx of heart failure and HTN (weak, used in combo to prevent hypokalemia)
-competes w/ aldosterone for mineralocorticoid receptor, prevents DNA activation & downstream protein synthesis-> decr Na/K ATPase activity in DCT/collecting duct-> incr Na & Cl excretion, decr K & PO4 excretion-> incr H2O excretion
-competes w/ DHT @ androgen receptors, excess testosterone-> estrogens via aromatase, incr estrogen:testosterone), decr androgens production (@ higher doses) can cause AE: gynecomastia, testicular atrophy, decr libido, impotence (males), menstrual irregularity, postmenapause bleeding (females)
-high doses, interferes w/ steroidogenesis in adrenal glands & gonads
has been used off label to tx PCOS, female hirsutism
- AE: hyperkalemia
- Pharmacokinetics: 1-2 h half life
Furosemide
- loop diuretic, tx HF & BP
- binds to Cl- site on Na+/K+/2 Cl- cotransporter in ascending loop of Henle, incr excretion of Na, K, Cl, also Ca2+, Mg2+ and H2O
- incr Ca2+ excretion
- most effective diuretic
- incr natriuresis & FENa
Pamidronate
bisphosphonate, tx of Pagets disease of bone, hypercalcemia of malignancy, osteolytic metastases, osteoporosis, off label for hyperparathyroidism
MoA: decr serum Ca2+ & osteoclast bone resorption, incr bone mass & decr risk of fx via:
bind to calcified bone matrix (hydroxyapatite) preventing binding of osteoclast precursors, preferentially in areas of high bone turnover
1) decr osteoclast formation/activation, 2) incr osteoclast apoptosis, 3) inhibit cholesterol biosynthesis which is required for osteoclast formation
Pharmacokinetics: IV, intermediate potency
oral bisophosphonate absorption is interfered w/ significantly by food
AE: osteonecrosis of the jaw (recommend dental work prior to starting, prevents normal healing of bone), esophageal erosions in oral, hypocalcemia
Calcitonin
-salmon calcitonin, peptide hormone, 40 x more potent and longer duration than human
-only used for short-term/acute (1-2 days) tx of hypercaclemia (then body gets resistant/adjusts to it)
- tx of Pagets disease of bone, adjunct in postmenopausal osteoporosis
- decr efficacy vs bisphosphonates in incr bone density & decr fx
MoA: directly inhibits osteoclasts by binding to membrane receptors-> decr bone resorption (decr serum Ca2+ and PO4)
decr renal reabsorption of Ca2+ & PO4
*relieves bone pain d/t osteoporotic fx
Pharmacokinetics: intranasal (osteoporosis only) or parenteral, 1 h half life
AE: rhinitis or other nasal sx d/t intranasal admin
CI: fish hypersensitivity
Insulin Glargine (Lantus)
- long-acting insulin analog, AA modifications of regular human insulin
- equipotent w/ regular insulin (Novolin)
- consistent, basal 24-hr insulin coverage = once daily admin., no significant peaks, more closely resembles endogenous basal insulin release
- forms hexamer precipitate in neutral pH subQ tissue-> delay in onset & constant insulin release over 24-hr
- long acting effects are dependent on subQ admin.
- soluble in acidic environments
MoA: insulin incr storage and inhibits breakdown of glucose, lipids, proteins, incr uptake of glucose in skeletal muscles & adipocytes, inhibits hepatic gluconeogenesis/glycogenolysis
- AE: decr risk of nocturnal and severe hypoglycemia, hypokalemia (incr Na/K ATPase), weight gain (decr glucosuria, incr anabolic effects)
- CI: emergencies req rapid onset (DKA), hepatic/renal impairment
- Pharm: subQ admin., onset 1.5 h, duration of action 24 h
Insulin Lispro (Humalog)
- rapid acting insulin analogs
- equipotent w/ regular insulin (short acting, Novolin)
- more closely mimics endogenous postprandial insulin release, better postprandial glycemic control
Pharmacokinetics: subQ or IV admin., more rapid onset (15-30 min), faster peak plasma concentrations (30-90 min), shorter duration (3-5 h)
*given 15 min prior to or immediately after meals d/t faster onset
AE: decr risk of nighttime/severe hypoglycemia, weight gain, hypokalemia
CI: similar efficacy to regular insulin in tx of hyperglycemic crisis (DKA), however, regular insulin is recommended, hepatic/renal impairment
- only rapid acting insulins used in insulin pumps (CSII)
- insulin aspart (NovoLog)
Metformin
- 1st line tx in DM T2
- cheap, synergistic w/ sulfonylureas
- MoA?:
- decr hepatic gluconeogenesis
- incr peripheral insulin sensitivity
- improve lipid profile
- anorexia (wt loss)
*does not cause weight gain (d/t anorexic effects), does not cause hypoglycemia (doesn’t incr insulin secretion, just incr sensitivity to it)
- AE: lactic acidosis, GI upset
- CI: renal failure, liver failure, (conditions that incr risk of lactic acidosis), DM T1 (DKA)
Sulfonylureas
-secretagogue, glyburide & glipizide
MoA:
- close ATP-sensitive K+ channels on membrane of pancreatic B cells-> depolarization-> open voltage-gated Ca2+ channels-> influx of Ca2+-> release of insulin granules
AE: weight gain, hypoglycemia (incr insulin secretion)
Enoxaparin
- anticoagulant, low MW heparin
- tx of MI, blood clot prophylaxis
MoA: binds to and accelerates action of ATIII-> inhibition of factors Xa > IIa-> anticoagulation
AE/CI: bleeding
Novolin N
- NPH (neutral protamine Hagedorn), zinc and protamine forms a neutral non soluble complex, decr absorption, incr duration of action
- intermediate acting (4-12 h duration), used as basal insulin BID
Cimetidine
- oral/parental tx of PUD, mild GERD (~50% of pts)
- competitive, reversible blocker @ H2 receptors on the basolateral membrane of gastric mucosal parietal cells->
decr histamine-induced secretion of gastric acid volume and acidity (basal and nocturnal), lesser effect on gastrin & ACh-stimulated (food-stimulated)
*gastric acid can still be secreted d/t other stimuli (smaller decr in acid output vs PPIs)
- pharm:
- 2 h 1/2 life, takes
- 45 min to provide sx relief in GERD d/t MoA (decr release of new gastric acid)
- can cross placenta, breast milk
- AE:
- weak antiandrogenic:
- inhibits DHT binding to androgen receptors, decr estradiol metabolism (gynecomastia, decr libido), incr PRL (galactorrhea)
- -OR- inhibition of CYP450-> decr breakdown of estrogen-> gynecomastia
- decr renal Cr clearance-> incr serum Cr
- cross BBB: headache, dizziness, confusion
- inhibitor of hepatic CYP450: multiple drug-drug interactions, slows metabolism and potentiates warfarin, B-blockers (propranolol), etc.
