Pharmacodynamics refers to what compared to pharmacokinetics?
Pharmacodynamics: What the drug does to the body (effect)Pharmacokinetics: What the body does to the drug (absorption and distribution)
In what form are drugs able to cross biomembranes?
Nonionized (uncharged)Ionized form is best excreted renally as it is water soluble
What would be used to treat a salicylate, phenobarbital, or methotrexate toxicity? Why?
Sodium bicarbonate; works to alkalinize urine to promote excretion of acidic drugs
What would be used to treat a TCA or amphetamine toxicity? Why?
Ammonium chloride; works to acidify urine to promote excretion of basic drugsUsually sodium bicarbonate is used for TCA toxicity to overcome sodium channel blocking activity rather than by accelerating drug elimination.
Aside from inhibiting protective prostaglandin synthesis, why do NSAIDs cause GI irritation?
Ion trapping: unionized form absorbed in gastric mucosa. After progressing through GIT, becomes ionized in the higher pH of the intestine, trapping NSAID ions (can't be absorbed while ionized) and causing cellular damage
On a graph, how is oral bioavailability defined?
Area under the concentration time curve aka AUC PO divided by AUC IVCompares bioavailability orally to IV administration to derive a fraction which represents the oral availability of a drugF = AUC (PO) / AUC (IV)
How is the distribution of medication related to the degree of plasma protein binding?
Inverse: greater the plasma protein, the less distribution of medicationImportant consideration in situations where patients will have differing levels of protein in the plasma such as liver disease.
What 3 characteristics of drugs makes them safe to give in pregnant women?
-Large-Water soluble-Highly plasma protein-bound
Many acidic drugs are bound to _____. Drugs in the bound/unbound form are pharmacologically active?
Albumin; unboundBinding sites on albumin bind many drugs which creates competition between them which is responsible for drug interactions
Drugs with what characteristic are able to cross the BBB?
Highly lipid solubleExamples: propofol or levodopaException: Lithium, ethanol
What type of drugs occupy about 50% of albumin binding sites causing harmful effects by displacing other drugs? How can this impact newborns?
Sulfonamides; displaces bilirubin leading to kernicterus
When the volume of distribution is high, a drug is being sequestered where? What about when the volume of distribution is low?
Tissue; plasma proteinsWhen Vd is high, the possibility of displacing the drug is high which can lead to toxicity (such as verapamil and quinidine which can displace digoxin from tissue binding sites)
Drug molecules that have a low Vd (3-5L) and are sequestered to intravascular compartments share what 3 characteristics?
-Large-Charged-Plasma protein-boundLarge and in charge!
Drug molecules that have a high Vd and are sequestered to extravascular compartments share what 3 characteristics?
-Small-Lipophilic-Tissue protein-bound
Starting in the highly vascularized area and terminating in the poorly vascularized area, thiopentone sodium and propofol act rapidly because they share what characteristic? What is this concept called?
Highly lipid soluble; Redistribution
Inactivation of a drug without enzymes due to molecular rearrangement describes what? What is an example?
Hoffman's elimination; Atracurium Safe, short duration of action
CYP450 are embedded in what organelle and are often called what type of enzymes?
Smooth ER; microsomal enzymes
Succinylcholine and mivacurium are metabolized how?
Hydrolysis
Grapefruit juice is a CYP enzyme _____.
Inhibitor (inhibits drug metabolism)Statins are affected
Name 6 enzyme inducers:Good photo resolution on Sarah's cell phone
GriseofulvinPhenytoinRifampicinSmokingCarbamazepine PhenobarbitoneAlso:Chronic alcoholSt. John's Wort
Name 6 enzyme inhibitors:Vitamin K cannot cause enzyme inhibition
ValproateKetoconazoleCimetidineCiprofloxacinErythromycinIsoniazidAlso:OmeprazoleRitonavir (HIV)Grapefruit juiceMetronidazole
How does disulfiram work?
Inhibits acetaldehyde dehydrogenase to cause a vomiting/sick reaction by accumulation of metabolite acetaldehyde (derived from ethanol by alcohol dehydrogenase)
TB is treated with what? What interaction can occur?
Rifampicin; Induction of enzymatic activity breaks down oral contraceptives more rapidly, allowing pregnancy to occur Typically presents following a case of TB (tested with purified protein derivative (PPD))
Which five drugs may induce SLE by slow acetylation?SHIPD
SulfonamideHydralazineIsoniazidProcainamide/penicillimide Dapsone
What drug can cause gray baby syndrome?
Chloramphenicol; deficiency of glutathione inhibiting metabolism of the drug
What is a prodrug?
Drugs that must be metabolized before it is pharmacologically active
Is lipid solubility important for glomerular filtration? How about for tubular reabsorption? Tubular secretion?
-No, fenestrated glomerular membrane is regulated by charge and size-Yes, lipid soluble substances are more readily reabsorbed in the tubules-No, separate pumps are available for acidic and basic substances (drugs using same transporter may show interactions like probenecid and penicillin)
What is the significance of drugs excreted via bilirubin in the form of glucoronides?
Glucoronides are hydrolyzed in the intestine by bacterial flora allowing the drug to be liberated and reabsorbed if it is lipid soluble.AmpicillinRifampicinEstrogenMorphineDoxycyclineCefoperazone
How much of a drug is remaining in the body at the fourth half life?
6.25%; 93.75% has been eliminated and the patient should receive another dose of the drugThis point is also known as the "steady state"If a half-life is 9 hours, simply multiple that by four to determine the amount of time it takes to reach 6% remaining in the blood
What is the formula to calculate the half-life?
T1/2 = 0.7 * Vd/CL0.7 = constantVd = volume of distributionCL = clearance rate
Which four drugs are eliminated by zero order kinetics? What does this refer to?PETA
PhenytoinEthanolTheophyllineAspirin (at high doses)A constant amount of a drug is eliminated per unit of time. Elimination does not scale up such as in first order kinetics which eliminates drugs by 50% every half-life
In a patient with renal or liver disease, what occurs to maintenance dose and loading dose?
MD decreases, LD remains the same
How do you calculate the loading dose?
LD = Vd x CpssVd = volume of distributionCpss = target concentrationDivide by "F" if bioavailability is <100% (oral)
How do you calculate the maintenance dose?
MD = CL x CpssCL = clearanceCpss = target concentrationExample:MD = 5g/L x 5L/minMD = 25g/min
What is the role of IP3 in cellular signaling?
Second messengerG protein receptor activates phospholipase C which acts on DAG to release IP3 which acts as a second messenger on IP3-gated calcium channels. Ca+ activates calmodulin which activates various proteins
What type of receptor is a glutamate receptor?
Ligand gated and voltage gated cation channelGlutamate is stimulatory and GABA is inhibitory
Insulin and growth factors acts through which enzyme receptor?
Tyrosine kinase receptors (autophosphorylation -> gene transcription)
The fastest acting channel is which?
Ionic channels
What does the Emax of a drug represent?
Efficacy: maximal response a drug can produce
What does the ED50 of a drug represent?
Potency: Amount of drug needed to produce 50% maximal response
What is the significance of the therapeutic index?
It represents the margin of safety.Low therapeutic index means a only a small amount is required for a lethal doseaka margin of safety
What is the difference between an agonist and an allosteric activator in regard to receptors?
Agonist binds to the same receptor as the normal substance (like a competitive inhibitor), whereas an allosteric activator binds to a separate site to stimulate the receptorMay be combined to increase response, for example, an agonist given with an allosteric activator will elicit a much larger response than one alone
What drugs are partial agonists and which receptors do they bind to?
-Pindolol/acebutolol (old antihypertensives, b1 receptors)-Buprenorphine (pain/opioid addiction, mu receptors)-Clomiphene (estrogen for infertility or PCOS, estrogen receptors in hypothalamus)
What is an inverse agonist?
Binds to receptor to produce the opposite effect of the normal substance Not useful in therapeutics
What is an antagonist?
Binds to receptor without producing a response and blocks the receptor from being sitmulatedAffinity = 1Efficacy = 0Physiologic antagonist is different as a substance will bind to a different receptor. Example: epinephrine is an antagonist to histamine due to their opposite effects on vessels even though they bind to different receptor
Give three examples of competitive antagonism.
-Acetylcholine and atropine: muscarinic receptor-Morphine and naloxone: mu receptor-Propanolol and NE: b2 receptor
What is tachyphylaxis? In what drugs is this seen?
Rapidly diminishing response to successive doses of a drug, rendering it less effective.Ephedrine, tyramine, niacin, phenylephrine, amphetamine, LSD, MDMA
What is Vmax?
the maximum rate of reaction when the enzyme is saturated with substrate
What is Km?
Concentration of substrate required to react at 1/2 Vmax (maximum rate)An enzyme with a high Km has a low affinity for its substrate and requires more substrate to reach Vmax.An enzyme with a low Km has a high affinity for its substrate and requires less substrate to reach Vmax.
What is the effect on a given drug when taken with an enzyme inhibitor?
Inhibitors result in exacerbated effects of a drug due to slow metabolism and increased time in the bodyExample: Valproate is an inhibitor which increases the effects of morphine
What is the effect on a given drug when taken with an enzyme inducer?
Inducers result in therapeutic failure of a drugExample: Smoking is an inducer which could decrease the efficacy of oral contraceptives
What type of medication can cause pseudoallergy by directly triggering mast cell degranulation?
Opioids
What is the difference between type A and type B adverse drugs reactions (ADR)?
Type A: known side effectType B: exaggerated reaction, immunologic, or idiosyncratic (one-off patient, not the healthy population e.g. G6PD deficiency).
What is serum sickness?
Type III hypersensitivity: antibodies to foreign drug proteins are made and deposited in tissues, where they fix complement and damage tissue
A genetic polymorphism in what enzyme can cause an ADR when given succinylcholine?
Pseudocholinesterase deficiency: Decreased hydrolysis of esters of choline May lead to prolonged apnea/muscle relaxation
At phase 3 of a clinical trial, what attributes of a drug are being evaluated?
Both effectiveness and safetyPhase 1: safety and dosagePhase 2: effectivenessPhase 3: bothPhase 4: Common and rare side effects
Phocomelia is a teratogenic effect associated with the use of what drug?
Thalidomide: causes malformations of the arms and legsPreviously used to treat nausea
During pregnancy, what period is most vulnerable to teratogenic effect?
Organogenesis: 18-55 days
What teratogen can result in the following issues:Craniofacial: microtia (small ears), anotia (no ear), cleft palateCardiac: conotruncal/outflow tract defectsCNS: hydrocephalusThymus: aplasia, hypoplasia
Isotretinoin/retinoic acid
What three findings characterize Ebstein's anomaly and what teratogenic drug can cause this?
Right-sided heart issues:-Apical displacement of tricuspid leaflet-Decreased RV volume-Atrialization of right ventricleCaused by lithium
Name the syndrome and causative teratogen:-Microcephaly-Intrauterine growth retardation-Heart defects -Cleft lip-Short upturned nose -Nail hypoplasia
Fetal hydantoin syndrome; Phenytoin
Indomethacin is what and can cause what teratogenic effect?
NSAID; Premature closure of ductus arteriosus
What antibiotic used to treat TB can be a teratogen and cause ototoxicity?
Streptomycin (aminoglycosides- a mean guy hit a baby in the ear)
Cocaine and smoking can cause what in pregnant women?
Premature birth
Which antibiotic can cause yellowing of the teeth as a teratogen?
Tetracycline (doxycycline)
What drug is a teratogen causing bone and cartilage abnormalities marked by stippled epiphyses and small, round densities in bones on x-ray?
Warfarin
What teratogenic effect is expected from taking methotrexate?
NTDs, cleft palate, hydrocephalus, and limb anomalies
Methimazole can cause what teratogenic effect?
Cutis aplasia
Valproate causes what embryonic defects?
NTD's like myelomeningocele
Oligohydramnios can be caused by taking what type of drug during pregnancy?
ACE inhibitorsAlso causes underdeveloped skull bones and shortened limbs
G6PD deficiency leads to an absence of what? What does this cause and how is it triggered?
NADPH; hemolysis, infections, drugs, fava beansH2O2 cannot be degraded and is toxic to RBCsX-linked recessive
What drugs typically cause hemolytic anemia due to G6PD deficiency?
Antibiotics: Sulfa drugs, dapsone, isoniazid (these drugs also cause drug-induced SLE)Antimalarials: Primaquine, chloroquine, quinidineAspirin and rarely acetaminophen
Which cytochrome metabolizes codeine?
CYP2D6: activates codeine to morphineCYP2D6 is a subtype of CYP450 mono-oxygenase
Warfarin and phenytoin are metabolized by what enzyme? What gene is this found on?
CYP2C9, a subset of CYP450; VKORCIWarfarin typically inhibits vitamin K epoxide reductase which is required to produce clotting factors
Patients with enzyme CYP2C9 deficiency leads to what manifestation when treated with phenytoin?
Gingival hyperplasia
Presence of what HLA allele predisposes someone to a Stevens-Johnson syndrome reaction after given carbamazepine?
HLA-B*1502
Which HLA allele is associated with an increased risk of abacavir hypersensitivity?
HLA-B*5701Abacavir is a nucleoside reverse transcriptase inhibitor, associated with SJS
Thyroid releasing hormone stimulates what?
TSH and prolactin release
Which proteins use the JAK/STAT pathway?
-Cytokines-Bone marrow products-Growth hormone-Prolactin
Which hormones act through the cAMP pathway?
Anterior pituitary hormones:-FSH-LH-ACTH-TSH And:-PTH-Glucagon-ADH-Histamine-hCG-MSH (melanocyte)
Which proteins act through the cGMP pathway?
All vasodilators:-BNP (brain)/ANP (atrial)-Nitric oxide-Endothelium-derived relaxing factor (EDRF)Activates smooth muscle relaxation -> vasodilation
Which hormones act through the DAG/IP3 pathway?
Posterior pituitary:-Oxytocin-ADHAnd:-Histamine-Angiotensin II-Gastrin-GnRH-TRH
What is MEN1 syndrome and how does it differ from MEN2?
3 P's:-Pituitary Adenomas-Parathyroid Adenomas-Pancreatic AdenomasMEN2 presents with Marfanoid habitusStrong association with gastric ulcers (Zollinger-Ellison syndrome from the pancreatic adenomas), hypoglycemia (Insulinoma), and hypercalcemia (PTH).An AD mutation of MEN1 gene
What is the first-line treatment for beta-blocker overdose?
Glucagon: activates cAMP to release calcium to increase chronotropy and inotropy.
What is the relationship between growth hormone and IGF-1? What else inhibits growth hormone?
Growth hormone causes release of IGF-1 and IGF-1 is an allosteric inhibitor of growth hormone. (negative feedback)Somatostatin (GH-IH)
What is the treatment of acromegaly and esophageal varices?
Octreotide (somatostatin)For varices, inhibits glucagon preventing splanchnic vessel vasodilation to lower pressure.Also inhibits glucagon, insulin, and gastrin releaseAlso block TSH release
What drug can be used to treat hyperprolactinemia or galactorrhea?
Bromocriptine (dopamine agonist)Cabergoline has the same MOAAlso used in Parkinsonism (adjuvant)
Oxytocin helps induce labor by stimulating uterine contraction. For what other two reasons might it be used?
-Breast engorgement-Post partum hemorrhage (2nd choice)
What might be used to treat male infertility or cryptorchidism? What is a side effect of this drug when used in women? What is the name of the analogue?
Gonadotropins (Pulsatile release in response to GnRH); Multiple pregnancies Continuous infusion of GnRH suppresses gonadatropin secretion by desensitization and down regulation of receptorsAnalogue: Leuprolide acetate, and others include suffix "-relin
What analogue of GnRH can be used to treat prostate/breast cancer? What is a side effect in women?
Leuprolide acetate (administered continuously, will trigger flare up followed by decrease in androgen levels); Women may experience endometriosis or uterine leiomyomas (fibroids)
GnRH receptor antagonists include drugs that end in what suffix? What is a major advantage of using these drugs?
-relix; can be combined with GnRH analogue to avoid the initial flare in hormone production
In what area and which receptor of the kidney does ADH act? What drug is used as an agonist of these receptors and when would it be used?
Collecting tubules V2 receptor; Desmopressin (ADH agonist); central diabetes insipidusDesmopressin also used to treat von Willebrand disease
Drugs ending in what suffix are used to treat SIADH?
-vaptanBlocks action of ADH at V2 receptor Demeclocyline may also be used as an ADH antagonist
Why does resperidone cause amenorrhea/galactorrhea?
Blockade of D2 receptorsD2 receptor stimulation typically inhibits cAMP to release dopamine which usually inhibits prolactin
Which drug inhibits desmolase? What is this drug used to treat and why? What is a side effect of this drug?
Ketoconazole; Cushing's disease by inhibiting ergosterol synthesis needed for first step in cortisol synthesis; gynecomastia (androgen synthesis inhibitor)
What medication is a glucocorticoid antagonist? What is this used for?
Mifepristone (antiprogestin)Competitive for progesterone and glucocorticoid receptors causing abortion. May also be used in Cushing's as GC antagonist
Annexin-1 (lipocortin) inhibits what? What drug stimulates lipocortin?
Phospholipase A2; corticosteroids
Why is hyperpigmentation seen with increased ACTH?
ACTH is a precursor for MSHHigh in Cushing's syndrome
What drug is used to prevent respiratory distress in premature infants?
Betamethasone or dexamethasone
Corticosteroids inhibit all inflammatory cells except...?
Neutrophils
What is the most common systemic side effect of prolonged corticosteroid use?
Osteoporosis by decreasing precursor differentiation to osteoblasts and decreasing renal/GI Ca+ reabsorption (stimulating osteoclasts), decreased osteoprotegerin (OPG) which usually inhibits osteoclast genesisLocal side effects include dysphonia and oropharyngeal candidiasis (which is why rinsing mouth after using inhaler is suggested)
In what viral infection are corticosteroids contraindicated?
HSV keratitis
In what GI pathology are corticosteroids contraindicated?
Peptic ulcer disease
Why are corticosteroids useful in treating ALL?
Lymphotoxic effects
Why is it important to taper corticosteroids?
To prevent precipitation of acute adrenal insufficiencyNot necessary if course is less than 5 days
What may occur after long term use of topical corticosteroids?
Dermal atrophy and skin thinning
Following adrenalectomy, what drug would be given to replace mineralcorticoids?
Fludrocortisone
Synthetic androgens are what type of steroid? Name examples and side effects.
Anabolic steroids; end in -olone; acne, increased HCT and LDL, and gynecomastia-Nandrolone propionate/decanoate-Testosterone undecanoate/enanthate-Stanazolol -Ozandrolone
What adverse effects are associated with anabolic steroids?
-Premature epiphyseal long bone closing-Increased risk of thrombosis-Oligospermia-Risk of hepatic tumors
What enzyme converts testosterone to DHT and what medications inhibit it?
5-a-reductase; finasteride/dutaserideThis can also be used to treat alopecia/balding by inhibiting conversion of testosterone
Flutamide MOA? When is it used?
Nonsteroidal competitive inhibitor at androgen receptors; used in prostate cancer along with GnRH agonists to skip the initial flare period (instead of a -relix drug)
How is hyperglycemic hyperosmolar syndrome different from DKA? How is it treated?
-Usually seem in DM2 instead of DM1-Few or no ketone bodies-No acidosis-Severe dehydration-Mental status changes due to very high serum osmolarityTreated with IV regular insulin
Which three insulins are rapid acting?GAL Gadot is really fast
-Glulisine-Aspart-LisproAction in a few minutes, falls by 4 hours. Regular insulin peaks at 2 hours and falls after 8 hours.
Which three insulins are long acting?
-Glargine (peak-less)-Detemir-Degludec~24 hours+ of action
What is the basal bolus regimen for insulin? What is this for?
Long acting insulin with multiple boluses of rapid acting insulin; to meet mealtime requirements (postprandial)
How is hyperkalemia in DKA treated?
Insulin given with glucose encourages K+ uptake into skeletal muscle
What three types of drugs are contraindicated with insulin?
-Beta blockers (in poorly controlled DM) can mask symptoms of hypoglycemia: propranolol -Ethanol potentiates hypoglycemia-Salicylates potentiate hypoglycemia
What do sulfonylureas do? What is the MOA?
Increase insulin production from pancreas; blocks K-ATP channel modulatorsLeads to reduced K+ conductance leading to membrane depolarization and influx of Ca+ to release insulinMost common ADRs:HypoglycemiaWeight gain
What do meglitinides do? What is the MOA and what drug is similar?
Same as sulfonylureas but does not bind to the SU-receptor
What is the MOA of metformin (biguanides)? What ADR's are possible?
1. ↓ hepatic gluconeogenesis2. ↑ glucose uptake and use in periphery3. ↓ glucose absorbtion in GIT4. ↓ plasma glucagonADR:-B12/folate malabsorption -Lactic acidosis in renal/liver failure patientsShould check renal function (creatinine) before starting
Glitazones/thiazolidinediones do what? MOA? ADR? Sites of action?
Increased insulin sensitivity in peripheral tissue "euglycemics". Binds to PPAR-gamma nuclear transcription factor Use: Type 2 diabetesADR: fluid retention, weight gain, CHFSite of action: adipose tissue and skeletal muscleExamples:-Pioglitazone-Rosiglitazone (side effect: CV disease)-Troglitazone (side effect: hepatotoxicity)Hepatotoxic: LFTs prior to prescribing
Alpha-glucosidase inhibitors target what? Name three examples of this type of drug.
Surface membrane-bound enzymes (a-glucosidase) (disaccharide converted to monosaccharide) to reduce GI absorption of starch, dextrin, and disaccharides AcarboseMiglitolVogliboseSide effect: GI symptoms & rash
What is the role of GLP-1? What is the name of an analogue?
GLP-1 secreted from intestine to stimulate glucose-dependent insulin secretion; Exenatide given SQ prior to mealOther GLP-1 analogues end in "-tide" as well
What is the role of DPP-4? List inhibitor drugs and an ADR.
Inactivates GLP-1; can be inhibited by DPP-4 inhibitors (oral):-Sitagliptin-Linagliptin-SaxagliptinADR: Upper respiratory tract infection
What is pramlintide (Symlin)?
-Indication: for type 1 and insulin-using type 2 patients (used as preprandial supplement to insulin) and weight loss-MOA: mimetic of human amylin. Slows gastric emptying, suppresses glucagon secretion, promotes satiety (prevents postprandial hyperglycemia)
Sodium Glucose Co-Transporter-2 (SGLT2) inhibitors include what drugs? What is the MOA?
-Canagliflozin-Dapagliflozin-EmpagliflozinBlocks reabsorption of glucose from PCT encouraging glucose excretion for DM2 patients and leads to mild weight lossADRs:-UTI-Hypotension (intravascular volume contraction)-Genital infections
What is the MOA of bile acid resins?
Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more
Hypoglycemia is treated how?
Glucagon (↑ cAMP):-Increases HR and inotropy-Increases hepatic glycogenolysis and gluconeogenesis-Relaxes smooth muscles
Hyperthyroidism is treated with what drugs?
-Thioamides (propythiouracil)-Iodide (Lugol solution)-Beta blockers (propanolol)
What is the role of thyroid peroxidase?
Forms MIT and DIT from iodide after oxidation and iodination of tyrosine residues Also forms T4 and T3 by combining two DIT (T4), or 1 DIT and 1 MIT (T3)T4 is converted to T3 in the peripheral tissues by deiodination (inhibited by beta blockers, steroids, amiodarone, and radio contrast, and PTU)
Which drugs inhibit the conversion of T4 to T3 in peripheral tissues?
-PTU-Beta blockers-Corticosteroids -Amiodarone-Radio contrast
In treating hyperthyroidism, what drugs can impair the iodide transport channel?
Complex anions (-ate):-Perchlorate-Fluoborate-Pertechnetate-Thuocynate
In treating hyperthyroidism, what drugs can impair coupling of iodotyrosine residues? Name examples.
Thioamides and iodide block conversion of iodide to MIT/DIT (T3 and T4) (organification)Thioamides:-Propylthiouracil (also inhibits peripheral conversion)-Carbimazole (prodrug of methimazole)-MethimazoleIodide also inhibits proteolysis (release of T3/t4 from thyroid gland)
Agranulocytosis is an ADR of what thyroid medication? Is this drug safe in pregnant women?
Propylthiouracil (thioamide)HepatotoxicPreferred in first trimester of pregnancy as does not cross placenta or BBB, highly protein bound.Methimazole preferred in 2-3 trimester but risks cutis aplasia/esophageal atresia
What is the Wolff-Chaikoff effect?
High levels of iodide will inhibit the formation of MIT and DITPotassiumiodide given as a saturated solution to induce this effect in hyperthyroidism
What is the treatment for thyroid storm (complication of thyrotoxicosis)?
-Propanolol-Thioamides (propythiouracil preferred, methimazole)
Why is iodide given prior to thyroidectomy? What else is it useful for?
To induce the Wolff-Chaikoff effect making the gland avascular and firm.Also used to protect the thyroid from damage following radioactive exposure
What is the preferred treatment for thyrotoxicosis? What may occur as a result and what is given to reduce ADRs?
Radioactive iodine; hypothyroid occurs in 80% of patients; Pretreatment with perchlorate, or pertechnetate decrease negative effects by competitive inhibition
How is thyroid hormone replacement dosed? What is a possible side effect?
Titrate until TSH is normal; myxedema coma (dilution of blood, hypoglycemia, hyponatremia, shock)
What is the MOA of iodides in treating hyperthyroidism?
Iodides block proteolysis/release of T3/T4 to the blood
Continuous use of estrogen is associated with what complications?
Hypertrophy of endometrium causing abnormal bleeding patterns and can result in endometrial cancerEstrogen also increases coagulability of blood (increased risk of thromboembolism)
What substance is needed for proper closure of epiphyseal growth plates?
Estrogen
What drug is most effective at preventing osteoporosis? What else can this prevent?
Hormone replacement therapy (estrogens) used for 21 days at a time; Also prevents hot flashesCannot restore, only prevent bone lossMust use estrogen and progesterone to decrease chance of endometrial carcinoma
What is a possible teratogenic effect of estrogen therapy?
Vaginal adenocarcinoma in the baby later in life
What drug used to treat infertility by inducing ovulation is a partial estrogen receptor agonist and antagonist? Where are these receptors located and what is secreted as a result?
Clomiphene citrate; Hypothalamus: increases gonadotropin secretion and ovulationBlocks negative feedback to the hypothalamus and pituitary to stimulate FH/LSH release
What two drugs would be used to treat estrogen receptor positive breast cancer? Which one is associated with endometrial cancer?
Tamoxifen and Raloxifene: antagonist in the breast, agonist in the bone (good for osteoporosis). aka SERMsTamoxifen can cause endometrial cancer due to agonistic effects on uterus and pituitary. Raloxifene is an antagonist in the endometrium, avoiding the risk of endometrial cancerADR: Thromboembolic events
In the treatment of breast cancer resistant to tamoxifen, what drug would be used? What are the advantages of this drug and ADRs?
Aromatase inhibitors:-Letrozole-Anastrozole-ExemestaneAdvantages:-No endometrial hyperplasia-No uterine cancer risk-No thromboembolic riskADR:Accelerates bone loss (predisposes to osteoporosis, fracture, and arthritic symptoms)
How do progestins work?
Neuroendoccrine action: increases amplitude of LH pulses released from pituitary at low dosesWorks by inhibiting further endometrial growth, converting proliferative to secretory endometrium; The withdrawal of progestin mimics the involution of corpus luteum and creates the sloughing
What substance is important to the maintenance of pregnancy?
Progesterone: abrupt decline of progesterone release is the main determinant of onset of menstruation Also causes proliferation of acini in mammary gland and is a CNS depressant/hypnotic and increases body temperature by about 1 degree F
What is the MOA of OCPs?
1. Suppresses LH and FSH levels2. Midcycle surge of LH is absent3. Endogenous steroid levels diminished4. Ovulation does not occurCombined estrogen and progestin most common and most effective
Side effects of OCPs include...
-Thromboembolism-Hepatic adenoma (cycling metabolism)-Breakthrough bleeding-Weight gain-Acne-Hirsutism
What OCP is indicated during lactation?
Mini pills aka lactational pill containing progestins only. Taken without interruption during lactationVery low dose
Subdermal implants for contraceptive typically contain what? How about injectable? Intrauterine?
L-norgestrel and etonogestrel (Norplant)Injectable: Medroxyprogesterone acetate (MDPA)Intrauterine:Progestasert
What four drugs are given as "plan B" contraceptives?
-Mifepristone (within 3 days)-Ulipristal (within 5 days)-Levonorgestrel (within 3 days)-Ethinyl estradiol with levonorgestrel
What drug is used in the treatment of endometriosis and inhibits gonadal function by inhibiting the mid cycle surge of LH and FSH?
Danazol: suppresses ovarian function by inhibiting FSH and LH
What drug is indicated to treat hirsutism?
Spironolactone by blocking androgen receptorsTypically used as a diuretic by blocking aldosterone-dependent sodium-potassium exchange sites in the DCT.
What is the MOA of bisphosphonates and when are they usually used? What drugs work in this way?
Inhibits osteoclasts by phosphonate groups binding to calcium (hydroxyapatite); Postmenopausal osteoporosisBisphosphonates inhibit cholesterol biosynthesis which is important for osteoclast functionAlendronatePamidronateIbandronateZoledronateAnalogues of pyrophosphate (POP)
What drugs work on osteoblasts to increase bone formation?
Teriparatide (recombinant segment of PTH, enhances osteoblasts)FluorideCalcitriolCalcium
What is the side effect of taking calcium?
Constipation
What drug is used to decrease levels of PTH? What is the MOA?
Cinacalcet; Activates Ca+ sensing receptors (CaR) lowering PTHApproved to treat secondary hyperparathyroidism in CKD and parathyroid carcinoma
Insulin and glucose is given to correct hypoglycemia and hyperkalemia. What is another drug that can correct hyperkalemia? What is given to reduce the cardiotoxic effects of hyperkalemia?
Calcium gluconate; salbutamol (beta 2 agonist)
In the kidney, PTH decreases excretion of ____ and increases excretion of ____. What is the effect of vitamin D in the kidney?
Calcium (decreases excretion); phosphate (increases excretion)Vitamin D increases reabsorption of both calcium and phosphateIn the intestines and bone, both PTH and vit. D increase both Ca+ and PO4-
What drug is used to increase bone formation and by what MOA? What is a potential ADR?
Teriparatide by stimulating osteoblasts; increased risk of osteosarcoma Teriparatide is a recombinant segment of PTH
What is the active form of vitamin D and where does activation occur? By what enzyme?
1, 25-dihydroxyvitamin D (calcitriol) in the kidney; 1a-hydroxylase
Which important substances bind to nuclear receptors to modulate transcription?
-TSH-Estrogen-Vitamin D-Vitamin A
What form of vitamin D is used to treat psoriasis? What is the MOA?
Calcipotriene (calcipotriol) inhibits keratinocyte proliferation by acting on nuclear receptorsApplied topically
Where is calcitonin produced?
Parafollicular cells of thyroid (C-cells)
Bisphosphonates bind to ____ found in ________ on the bony surface. They then impair _____ by reducing _____ to the surface of the bone.
Calcium; hydroxyapatite; osteoclasts; adherenceAlso increases osteoclast survival Prevents formation of the ruffled border required for adhesion and bone resorption
Usually bisphosphonates (-dronates) are given IV. When given orally, what must be considered? What ADRs are possible with IV administration?
Patient should remain upright for 30 minutes to prevent damage to GI mucosa ADRs with IV administration: -Flu-like symptoms-Osteonecrosis of the jaw
Aside from bisphosphonates, what drug can help treat osteoporosis? What is the MOA?
Denosumab; monoclonal antibodies bind to RANKL preventing osteoblast activation of osteoclastsRemember, the RANKL receptors are on osteoBLASTS which then trigger osteoclasts to resorb bone when stimulated
Para-aminobenzoic acid (PABA) blocks what type of UV light?
UVBPABA is a precursor of folic acid, which is involved in metabolism of one-carbon compounds and nucleic acid synthesis.
Agranulocytosis is a side effect of what thyroid medication?
Propylthiouracil (PTU)
What is the MOA of propylthiouracil (PTU)?
Iodination of thyroglobulin and decreased peripheral conversion of T4 to T3