Pharmacology

Question 1

Somatropin

Answer 1

Identical to human GH (191 aa)
Somatrem (extra methionine)
PK: IM or SC 3-7x/week, depot IM 1-2x/month
MOA: activate GH receptor (cell surface, Jak-Stat pathway–>nucleus effects)
Tx: replacement tx for GH deficiency, prior to epiphysial closure, maintenance therapy (increased linear growth, bone/muscle formation, decreased fat, increased sense of well being), $$$$
Other: Turner’s syndrom, Prader-Willi syndrome, idiopathic short stature
Problems: increased mortality v. general population, abuse for anabolic effects, does not work for Laron dwarfism (GH receptor defect, requires IGF for treatment)

Question 2

Sermorelin

Answer 2

Synthetic GHRH analog (shortened version)
PK: daily IV, SC, or nasal
MOA: activates GHRH receptor (GPCR), stimulates endogenous GH release –> stimulates IGF-1 release and growth
Tx: GH deficiency
Problems: ineffective with pituitary defect (no GHRH receptors) (require GH or IGF tx)

Question 3

Octreotide

Answer 3

Synthetic analog of SST (8 aa: shorter, more stable)
Longer t1/2 than SST
Less effect on insulin (select for GH release)
PK: 2-3 SC injections/day, monthly IM depot
MOA: activates SST receptors (GPCR), selective for SST-2 and -5 subtypes (hormone-secreting tumors)
Tx: acromegaly dt GH-secreting tumor, hormone-secreting tumors with SSTRs, GI-secretion disorders
Problems: inhibition of GI motility and secretions (loose stools, nausea, malabsorption, flatulence, gallstones), $$$$

Question 4

Cabergoline

Answer 4

DA agonist analog –> inhibit PRL release
Not a peptide = orally effective
long t1/2 = 1-2x/wk dosing
Same drug used in PD (decreased PRL is a side effect)
MOA: PRL inhibition via D2 receptors (GPCR); cabergoline is D2-selective
Tx: hyperprolactinemia (and resulting infertility), prolactinoma, suppression of lactation, inhibit GH release (acromegaly; in normal patients it stimulates GH release)
Problems: Nausea, dizziness, hypotension (D2 receptors); tolerance

Question 5

Arginine vasopressin (AVP)

Answer 5

Synthetic, identical to natural hormone
Short acting
PK: IV, IM, SC, or nasal
MOA: V1 and V2 effects
Tx: V1 receptor-related applications (short duration); temporary diabetes insipidus following pituitary surgery (V2); local administration for bleeding artery constriction (rapid hydrolysis); prevent/treating hemorrhage; vasoconstriction in resuscitation of V tachycardia and fibrillation
Problems: increased blood pressure, GI/uterine contractions/cramps (cross-reactive with oxytocin receptors), headaches and nausea

Question 6

Desmopressin acetate (DDAVP)

Answer 6

Modified synthetic analog of vasopressin
Long-acting (10-20 hours)
V2 (antidiuretic)&raquo_space;» V1 (pressor) activity
PK: IV, SC, inhaled nasal, oral (first orally administered peptide hormone drug)
MOA: activate V2 vasopressin receptor
Tx: diabetes insipidus, hemophilia, vonWillebrand’s disease, oral desmopressin for nocturnal enuresis (inhaled caused hyponatremia –> seizure and death for this)
Problems: V1-side effects of AVP are minimal with DDAVP dt V2 selectivity

Question 7

Levothyroxine

Answer 7

Pure T4
Low onset, long duration (more protein bound)
Converted to T3 in body
Dose: 100 ug
Oral
Tx: Primary drug due to daily dosing, given IV for myxedema coma, slow onset/long duration (plasma stores)
Small dose for old patients or those with cardiac disease, continued use during pregnancy (requirements increase)
Adverse: overdose, hyperthyroidism

Question 8

Liothyronine

Answer 8

Pure T3
Rapid onset, short t1/2 (less protein bound)
Rapid onset, sudden dramatic physiological changes (dangerous)
Dose: 25 ug (4x more potent than T4)
Oral
Tx: rarely used in chronic therapy, used prior to surgery for thyroid cancer (maintain suppressive effects as patient tapered off T4), short-term support prior to/following radio iodine, limited use in treating depression
Adverse: overdose, hyperthyroidism

Question 9

Methimazole (MMI)

Answer 9

Thioamide: inhibit TH synthesis
Inhibit peroxidase, iodination, and coupling
More potent than PTU, longer-acting (qd dosing)
Delayed effect dt latent period from stored T3/T4
Direct anti-autoimmune effects –> disease remission (possible)
Tx: first line therapy (“non-destructive”), rapid control of thyroid hormone production, 1 year
PK: oral, cleared from circulation, concentrated in thyroid (action longer than plasma half-life), metabolism by conjugation, urine excretion
Adverse: agraunulocytosis **, rare fetal problems

Question 10

Propylthiouracil (PTU)

Answer 10

Thioamide: inhibit TH synthesis
Inhibit peroxidase, iodination, and coupling
Less potent than MMI, shorter half-life (2-4x/day dosing)
Inhibits peripheral conversion of T4 –> T3 (more rapid effect in acute thyroid storm)
Delayed effect dt latent period from stored T3/T4
Direct anti-autoimmune effects –> disease remission (possible)
Tx: first line therapy (“non-destructive”), rapid control of thyroid hormone production, 1 year, THYROID STORM, PREGNANCY (mild hyperthyroidism, treat prior to pregnancy)
PK: oral, cleared from circulation, concentrated in thyroid (action longer than plasma half-life), metabolism by conjugation, urine excretion
Adverse: agranulocytosis**, liver toxicity/failure

Question 11

Propranolol

Answer 11

Beta blocker: treat hyperthyroid (SNS) symptoms

Question 12

Potassium iodide

Answer 12

Inhibit TH synthesis
Acute inhibition of synthesis and RELEASE of T3/T4
No effect on T4–>T3 conversion
Rapid effects, short duration (gland “escapes” inhibition) (increased iodine available increases hormone synthesis)
Vasoconstrictor effect (decreased size/vascularity of gland)
Tx: “firm up” the gland for easier removal, not useful for long-term therapy, immediate pre-op period (10 days), thyroid storm (acute effect, inhibit release of preformed thyroid hormones), radiation emergencies (inhibit uptake of radioactive iodine)
Do not use before radio iodine therapy
Adverse: sore throat, burning mouth, rash, diarrhea

Question 13

Radioactive iodine

Answer 13

Non-surgical destruction of thyroid gland
t1/2 = 8 days
15% gamma radiation (diagnosis); 85% weak beta radiation (1-2 mm travel)
oral, concentrates in thyroid
Tx: large (mCi) doses for destruction of thyroid tissue, pretreat with thioamides (lower TH –> increase TSH –> increase/max radioiodine uptake; decreased TH levels lessen risk of treatment-induced thyroid storm)
Concerns: minimal radiation danger, very localized effects, contraindicated in pregnancy, nursing, and young children, high doses –> radiation thyroiditis & salivary adenitis; transient/permanent hypothyroidism (treat with replacement T4)

Question 14

Regular insulin

Answer 14

Natural
Original rapid/short-acting
Prep with physiological level of Zn (readily soluble, readily absorbed)
Onset: 30-60 min. Peak: 2-4h. Duration: 5-8h.
True solution (clear) (IV)
Use: 30 minutes before meal
Non-prescription
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 15

Isophane insulin (NPH)

Answer 15

Natural
Insulin complex with protamine (protein) at neutral pH
(Neutral Protamine Hagedorn = NPH; ISOPHane)
Slower absorption, longer action
Onset: 1-2h. Peak: 6-12h. Duration: 18-24h.
Cloudy suspension (no IV)
Use: between meals and overnight
Non-prescription
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 16

Inhaled insulin

Answer 16

Old: complications with dosing, device, and lungs
New: fewer lung problems (some cough and throat irritation), rapid-acting prep.
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 17

Insulin lispro

Answer 17

Rapid, short, synthetic
Lys(28)Pro(29) NOT Pro-Lys in B chain
PK: no dimerization = absorbed more quickly, aggregates less (monomer); similar to physiologic pattern of insulin release with meal
Shorter duration of action
Peak: 30-60m. Duration: 3-4h.
Use: immediately before meal (less danger of insulin-induced hypoglycemia)
IV
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 18

Insulin aspart

Answer 18

Rapid, short, synthetic
Pro replaced by Asp
Longer duration than Lispro
B/w regular insulin and lispro in terms of duration
Use: at meal time
IV
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 19

Insulin glulisine

Answer 19

Slow, long, synthetic
Lys replaced by Glu; Asp replaced by Lys
PK: similar to regular/lispro/aspart
Fastest onset
Use: before or immediately AFTER a meal
IV
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers--mask symptoms of hypoglycemia), surgery, pregnancy

Question 20

Insulin glargine

Answer 20

Slow, long, synthetic
Gly substitution in A chain, two Arg at C-terminus of B chain
Formulated with Zn at pH 4 (decrease aggregation, increase solubility, clear sol’n)
Hexamers form at site of injection (pH 7.4) –> slowly, variably absorbed
**Very long, low, constant action
Use: subQ qd at HS (flat PK properties)
Opposite effect of lisper and apart
Do not mix in same syringe as other insulins
May be used in combo with other insulins
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 21

Insulin detemir

Answer 21

Long-acting analog
The is deleted, Myristic acid (14C) att. at Lys(29)
PK: similar to Glargine
Binds to albumin via FA chain
Neutral pH formula
Better, less variable absorption than glargine
Do not mix in same syringe as other insulins
Use: subQ qd at HS
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 22

NPL/NPA insulins

Answer 22

Isophane (NP) versions of synthetic insulins (protamine complexed)
Synthetic rapid insulins formulated with protamine
Slows and prolongs action
PK: similar to isoprene
Available in premix combos
NPL: NP + Lispro
NPA: NP + Aspart
Adverse: insulin-induced hypoglycemia, immunologic reactions (allergy, resistance, lipodystrophy)
Interactions: agents that increase glucose/decrease insulin, agents that decrease glucose/increase insulin/increase hypoglycemia, PROPRANOLOL (B-blockers–mask symptoms of hypoglycemia), surgery, pregnancy

Question 23

Pramlintide

Answer 23

Analog of Amylin (peptide hormone from pancreatic B cells)
Effects: decrease post-prandial glucose, decrease liver glucose production, slows gastric emptying, increases satiety
Use: DMI/DMII who lack adequate control with insulin alone
Tx: subQ before meals along with insulin
Adverse: mild nausea, HA, risk of hypoglycemia (reduce dose of short-acting insulin)
Interactions: drugs that slow GI motility or decrease GI drug absorption, renal excretion (kidney disease)

Question 24

Glucagon

Answer 24

Counter-regulatory hormone to insulin
From pancreas in response to hypoglycemia
Increases glucose
Tx: IM of subQ to treat hypoglycemia

Question 25

Diazoxide

Answer 25

Inhibits release of insulin Opens ATP-sensitive K channels (opposite effect of SUs) Oral

Question 26

Glimepiride

Answer 26

Sulfonylurea Enhance insulin secretion from beta cells MOA: Block ATP-sensitive K+ channels (physiologically, glucose blocks these channels, leading to depolarization, Ca2+ entry, and Ca2+-dependent exocytosis of insulin) Decrease glucagon and increase tissue sensitivity to insulin PK: Well absorbed orally, slowed by food; protein bound; qd dosing; metabolized by liver; excreted by kidneys in bile Effects: hypoglycemia, wt gain, GI/skin/liver/blood abnormalities, c/i in pots with liver or kidney disease

Question 27

Repaglinide

Answer 27

Meglitinide Enhance insulin secretion from beta cells MOA: bind ATP-sensitive K+ channels to increase insulin secretion; not a very strong effect = not very useful PK: faster effect than SUs, but shorter duration; take 30 minutes before meal to decrease post-prandial glucose Effects: hypoglycemia (less of a risk), wt gain, safer in kidney disease

Question 28

Metformin

Answer 28

Biguanide Decreases glucose production (liver) and increases glucose uptake; increases insulin effectiveness; does not increase insulin secretion (ie. no hypoglycemia) MOA: upstream action on AMP kinase pathway (regulates glucose metabolism) Useful in insulin patients with insulin resistance Used in combo with SUs, etc. First/best drug to try in DM2 PK: oral, 2-4x/day (after breakfast and supper), absorbed from GI tract, not protein bound, renal excretion w/o metabolism Effects: c/i in kidney or liver disease (lactic acidosis), does not induce wt gain, inhibits lactate metabolism, unpleasant GI effects (metallic taste, diarrhea, nausea, vomiting, anorexia)

Question 29

Acarbose

Answer 29

Decrease glucose absorption from gut MOA: microbial sugars inhibit mammalian sugar-metabolizing enzymes (alpha-glucosidase, amylase); inhibit hydrolysis of disaccharides and complex carbs slows formation/absorption of glucose Take immediately before meals (lower post-prandial glucose) Not powerful effects (use in mild disease) Can be combined with insulin, etc. PK: Complex oligosaccharide, poorly absorbed, ie. remains in gut (site of action) Effects: no hypoglycemia, increase hypoglycemia risk when combined with insulin, glucose (not sucrose--disaccharide) required to treat hypoglycemia, flatulence, cramps, diarrhea, avoid with metformin (avoid GI effects)

Question 30

Miglitol

Answer 30

Decrease glucose absorption from gut MOA: microbial sugars inhibit mammalian sugar-metabolizing enzymes (alpha-glucosidase, amylase); inhibit hydrolysis of disaccharides and complex carbs slows formation/absorption of glucose Take immediately before meals (lower post-prandial glucose) Not powerful effects (use in mild disease) Can be combined with insulin, etc. PK: simple monosaccharide, does get absorbed Effects: no hypoglycemia, increase hypoglycemia risk when combined with insulin, glucose (not sucrose--disaccharide) required to treat hypoglycemia, flatulence, cramps, diarrhea, avoid with metformin (avoid GI effects)

Question 31

Pioglitazone

Answer 31

Thiazolidinedione MOA: bind peroxisome proliferator-activated receptor-gamma (PPAR-gamma) (nuclear TF that enhances transcription of insulin-responsive genes); AMP kinase signaling Decrease gluconeogenesis, glucose output, and TG synthesis in liver Increase glucose uptake and utilization in muscle Increase glucose uptake and decrease FA production in adipocytes Used with insulin, SU, and/or metformin PK: oral, take with food, qd, metabolized in liver, excreted in feces (safe in renal disease) Effects: hepatotoxicity, fatal liver disease (liver fxn testing), CV disease/death risk (edema, CHF, ischemia, angina MI), no hypoglycemia risk, increase fracture risk (elderly, women, osteoporosis), less effective than hoped

Question 32

Rosiglitazone

Answer 32

Thiazolidinedione MOA: bind peroxisome proliferator-activated receptor-gamma (PPAR-gamma) (nuclear TF that enhances transcription of insulin-responsive genes); AMP kinase signaling Decrease gluconeogenesis, glucose output, and TG synthesis in liver Increase glucose uptake and utilization in muscle Increase glucose uptake and decrease FA production in adipocytes Used with insulin, SU, and/or metformin PK: oral, take with food, qd, metabolized in liver, excreted in feces (safe in renal disease) Effects: hepatotoxicity, fatal liver disease (liver fxn testing), CV disease/death risk (edema, CHF, ischemia, angina MI), no hypoglycemia risk, increase fracture risk (elderly, women, osteoporosis), less effective than hoped

Question 33

Exenatide

Answer 33

Incretin-based Analog of GLP-1 (glucagon-like peptide-1)--released in response to food Potentiate insulin secretion, decrease glucagon secretion, slow gastric emptying (satiety), moderate reductions in fasting glucose, reduced post-prandial glucose Wt. loss Use: with SU and/or metformin, with insulin glargine (DMII) Inject SC from pre-filled pens (before morning/evening meals); now available in XR for weekly injection Effects: nausea, hypoglycemia risk (with SUs), renal failure, thyroid C-cell tumors and pancreatitis Alters absorption of antibiotics and contraceptives (so takes these before injection); avoid in kidney disease

Question 34

Pramlintide

Answer 34

Amylin-based Amylin analog Used in DMII who are already on insulin and who lack adequate control

Question 35

Sitagliptin

Answer 35

DPP-IV inhibitors Similar effect as GLP-1 agonist MOA: inhibits DPP-IV (degrades endogenous incretins), prolongs endogenous incretin action PK: oral, qd, effective as monotherapy Fixed-dose combo with metformin and/or pioglitazone available DMII only (and still slightly risky) Effects: no wt gain or loss, increased hypoglycemia risk when combined, increased risk of respiratory tract infection (DPP-IV important there too), renal elimination

Question 36

Canaglifozin

Answer 36

SGLT2 inhibitor MOA: inhibit sodium-glucose co-transporter 2 (SGLT2) (mediates glucose reabsorption in kidney); reduces glucose reabsorption --> increases glucose excretion PK: oral, qd in am No direct effect on insulin Effects: risk of genital and UTI, diuretic effect (dehydration, hypovolemia, hypotension)

Question 37

Hydrocortisone/cortisone (endocrine)

Answer 37

``` Cortisol Cortisone: prodrug of hydrocortisone Activity at GC and MC receptors Orally effect, IV prep available Short acting, 8-12h duration, multiple doses needed ```

Question 38

Prednisolone/Prednisone (endocrine)

Answer 38

``` Modified hydrocortisone structure Prednisone: prodrug of prednisolone More potent, slower metabolism Longer duration, 18-36h, qd dosing Selective for GC v. MC effects (important for anti-inflammatory effects) ```

Question 39

Fludrocortisone (endocrine)

Answer 39

Increased potency and selectivity at MC receptor Also retains strong GC potency and efficacy Long duration of action, qd dosing Use: when MC replacement therapy or action is primary goal (adrenal failure, 21-hydroxylase deficiency)

Question 40

Spironolactone (endocrine)

Answer 40

``` Aldosterone antagonist K+ sparing diuretic Treat aldosterone-secreting tumors Anti-androgenic effects (gynecomastia, hirsutism) Progesterone agonist activity ```

Question 41

Dexamethasone

Answer 41

Used if very high doses of Hydrocortisone/Prednisolone or their prodrugs are inadequte Reduce reddness, swelling (vasoconstriction, decreased permeability, direct effect on bv, decreased release of kinins and histamine), fever, and pain (decrease prod of AA metabolites, inhibit prostaglandin, thromboxane, and leukotriene release, decrease expression of phospholipase A2 and COX-2) Immunosuppression MOA: alter transcription (decreases pro-inflammatory genes, increase anti-inflammatory genes) Tx: arthritis, bursitis, skin inflammation, collagen vascular disorders, hypersensitivity, allergic reaction, asthma, renal disease, ulcerative colitis, IBD, eye disease, prevent organ/graft rejection, AFTER BRAIN/SC INJURY (minimize cerebral edema) Effects: MC effects (edema, low Na, low K, alkalosis, HTN,), GC effects (similar to Cushing's syndrome) C/I: heart disease, HTN, diabetes, peptic ulcer, infection, osteoporosis, glaucoma, psychoses

Question 42

Bethamethasone

Answer 42

Glucocorticoid Stimulate surfactant production for lung maturation in premature infants Give to mother before delivery (less protein bound, better delivery to fetus)

Question 43

Hydrocortisone/cortisone (infl)

Answer 43

OTC Reduce reddness, swelling (vasoconstriction, decreased permeability, direct effect on bv, decreased release of kinins and histamine), fever, and pain (decrease prod of AA metabolites, inhibit prostaglandin, thromboxane, and leukotriene release, decrease expression of phospholipase A2 and COX-2) Immunosuppression MOA: alter transcription (decreases pro-inflammatory genes, increase anti-inflammatory genes) GC receptor effects Tx: arthritis, bursitis, skin inflammation, collagen vascular disorders, hypersensitivity, allergic reaction, asthma, renal disease, ulcerative colitis, IBD, eye disease, prevent organ/graft rejection Effects: MC effects (edema, low Na, low K, alkalosis, HTN,), GC effects (similar to Cushing's syndrome) C/I: heart disease, HTN, diabetes, peptic ulcer, infection, osteoporosis, glaucoma, psychoses

Question 44

Prednisolone/prednisone (infl)

Answer 44

Reduce reddness, swelling (vasoconstriction, decreased permeability, direct effect on bv, decreased release of kinins and histamine), fever, and pain (decrease prod of AA metabolites, inhibit prostaglandin, thromboxane, and leukotriene release, decrease expression of phospholipase A2 and COX-2) Immunosuppression MOA: alter transcription (decreases pro-inflammatory genes, increase anti-inflammatory genes) Longer duration of action Decreased MC effect (reduce side effects, increase safety) Similar to methylprednisolone and triamcinolone Tx: arthritis, bursitis, skin inflammation, collagen vascular disorders, hypersensitivity, allergic reaction, asthma, renal disease, ulcerative colitis, IBD, eye disease, prevent organ/graft rejection Effects: MC effects (edema, low Na, low K, alkalosis, HTN,), GC effects (similar to Cushing's syndrome) C/I: heart disease, HTN, diabetes, peptic ulcer, infection, osteoporosis, glaucoma, psychoses

Question 45

Aspirin

Answer 45

Prototype NSAID inhibit COX IRREVERSIBLY (covalently acetylate enzyme) (therefore inhibit PG synthesis) Acetyl-salicylic acid (hydrolyzed to salicylic acid) Anti-inflammatory (salicylate metabolite) Degradation of acylated COX and new COX synthesis required to recover COX action 10x more potent on COX-1 PK: oral, well-absorbed, 325 mg (standard dose), good distribution (incl. CNS), 80-90% protein bound (slows accumulation, can displace other drugs--warfarin, methotrexate, sulfonamide) Metabolism: Low doses (2-3 tabs q 4-6h)--liver conjugation (first-order kinetics, saturable); High doses (4+ tabs q 4-6h)--kidney excretion unmetabolized, zero order kinetics, half life increases with increasing dose Reduce clotting Tx: analgesia (2-3 tabs q 4-6h), pain of inflammation (sensitize bradykinin, substance P), antipyresis (2-3 tabs q 4-6h; hypothalamus, return thermoregulatory set-point), anti-infl (4+ tabs q 4h; COX-2; rheumatic fever, rheumatoid arthritis), prevent MI/stroke (80 mg/day (1/4 tab), reduce thrombus formation, after ischemic stroke or prophylactic, effect on platelets for ~7days, platelets use COX-1 to make TXs, promote PGI formation via COX-2 to increase bleeding time, Men >45, women > 55) Adverse: GI bleeding/irritation (PGs protect stomach mucosa), avoid with blood-clotting deficiencies, high doses stimulate respiratory center (increased breathing), overdose (metabolic acidosis from renal failure, central respiratory paralysis, multi-organ system failure), salicylism (tinnitus, dizziness, HA, confusion, deafness--from mild toxicity)

Question 46

Ibuprofen

Answer 46

``` NSAID PROpionic acid derivative 200 mg q 4-6h (analgesia, antipyresis) 400 mg q 4-6h (anti-infl) Use: analgesic, anti-pyretic, anti-infl. Tx: patent ductus arteriosus Chronic use at high dose increases risk of MI and stroke Block effects of low dose aspirin (take 8h before or 30 min after) ```

Question 47

Naproxen

Answer 47

NSAID PROpionic acid derivative Use: analgesic, anti-pyretic, anti-infl. 200-250 mg bid Enteric-coaded delayed-release prep qd Chronic use may not increase risk of MI as much as ibuprofen Chronic use: greater ulcer risk

Question 48

IndomethACin

Answer 48

NSAID aCEtic Acid Derivative 10-20x more potent than aspirin Severe side effects: don't use for analgesia and antipyresis Used in SEVERE inflammation (arthritis) and PDA Related: diclofenAC (Europe, common NSAID), KetorolAC (injectable, post-op analgesia)

Question 49

Celecoxib

Answer 49

Selective for COX-2 (most infl. effects dt COX-2) Treat inflammation (Without COX-1 related effects) PK: 100-200 mg bid, rapidly absorbed, liver metabolism, t1/2 ~12h Tx: osteoarthritis, rheumatoid arthritis, FAP Equal to naproxen for arthritis; poorer than naproxen for post-dental surgery Fewer probs for asthmatics Interactions: CYP 2C9 and may inhibit 2D6 (genetic variant), slow metabolism of tricyclic antidepressants, SSRIs, antiarrhythmics Adverse: edema** (decreased kidney fxn), GI probs (fewer than ibuprofen/naproxen, slow ulcer/wound healing), cross-sensitivity with sulfonamides, not during pregnancy, [BLACK BOX] MI, increased platelet aggregation (shift balance between PGIs and TXs)

Question 50

Acetaminophen

Answer 50

Not an NSAID (technically--no anti-infl.) Inhibit COXs and PG synthesis PK: 325 mg tabs; 2-3 tabs q4h, GI absorption, uniform distribution, liver metabolism (conjugation, CYP 2E1), urine excretion, toxic metabolites accumulate at high doses Effects: analgesia, antipyresis; NO ANTI-INFLAMMATORY ACTION, CNS: relaxation, drowsiness, euphoria Effects of aspirin not seen with acetaminophen: GI, hematological, Reyes, CV, respiratory, acid-base balance Adverse: max dose set at 4 g/day, cross-sensitivity with salicylate, hepatic damage (long term, persistent, EtOH increases risk, do not use in liver disease/dmg), skin rash, drug fever, mucosal lesions, rare: neutropenia, leukopenia, pancytopenia; chronic use can lead to nephrotoxicity Overdose: 10-25 g ingestion, GI distress (after 24h), hepatotoxicity (jaundice 24-48h, reversible usually, reactive electrophile metabolite that can modify & inactivate liver proteins (glutathione)); Tx: supportive, remove drug (activated charcoal first 4h, vomiting/gastric lavage first 4h, after 4h rely on reversal of toxicity with sulfhydryl reagents

Question 51

Sodium bicarbonate

Answer 51

Toxicity Tx | Alkalization of urine (IV), trap salicylate in urine (pKa=3)

Question 52

N-acetylcysteine

Answer 52

Toxicity Tx Reactive sulfhydryl (-SH) that "captures" reactive acetaminophen and "replace" depleted glutathione Oral: 140 mg/kg + 70 mg/kg q 4h for 16 coses IV: 150 mg/kg loading dose over 15-60 min; 50 mg/kg over 4h; 6-25 mg/kg for 16hr Monitor blood levels/liver fxn in hospital for 3 days Similar: N-cysteamine Window: 8 horus but depends on level of overdose

Question 53

NSAIDs

Answer 53

Inhibit COX (converts AA into PG-G2/H2 (prescursors to other PGs and TXs)) COX-1 (PGHS-1): constitutive, platelets, stomach mucosa protection, kidneys, CNS (fever, pain) COX-2 (PGHS-2): constitutive (vasc endothelium--decrease aggregation, protect stomach mucosa, kidneys, CNS); INDUCIBLE (infl--injury, infection, stress, neurodegeneration; wound healing, cancer?) Inhibit COX-1 and 2 (stronger on COX-1) PGs at high concentrations in areas of infl. (infl, fever, pain) Non-steroidal (as opposed to GC anti-infl. steroids) Non-Non-opioid analgesics (less powerful, but adequate for mild pain, safer)

Question 54

Propionic acid derivatives

Answer 54

PRO Use: analgesic, anti-pyretic, anti-infl. Reversible inhibition of COX-1 Better for tx of dysmenorrhea and also used in gout Adverse: GI, prolong bleeding (short term), bind heavily to albumin (displace warfarin, etc.), cross-sensitivity to salicylates (i.e. don't use in pt with aspirin asthma) Toxicities: nausea, vomiting, epigastric pain, GI bleed, lethargy, drowsiness, seizure, coma (tx: activated charcoal w/i 2 hours)

Question 55

Morphine

Answer 55

Agonists for opiate receptors (GPCR); inhibitory neurotransmission (reduce activity in pathways relating to pain) Acts at Mu (strong), Kappa, and Delta receptors Schedule II PK: readily absorbed, 50% first pass metabolism (conjugation with glucuronic acid), rapid acting, max effect in 60-90 min, t1/2=2.5-3h, duration 4-5h, renal excretion Tolerance: develops to some effects, not to others, chronic pain patients have average dose of 550 mg (200 mg is often fatal in normal ppl) Analgesia: most effective drug for acute severe pain, raises pain threshold, anti-anxiety, does not depress other sensory modalities (selective), chronic use discouraged except for terminal disease Respiratory Depression: decreased sensitivity to plasma CO2, develops in parallel with analgesia Nausea and vomiting (33%): "first dose" phenomenon GI: constipation (35-40%), little or no tolerance (big prob with chronic use), give in combo with naltrexone (opioid receptor antagonist specific for GI tract) Drowsiness and sedation, clouded thinking (20%) Miosis: diagnostic sign of OD!! little/no tolerance!! Euphoria, tranquility, pruritis, CV effects (orthostasis) USE: analgesia, sickle cell crisis dyspnea in end stage lunch cancer/COPD Effects: dependence, biliary/urinary tract pressure, allergic rxn, sensitive in elderly/neonates, dysphoria, excitement (kappa receptors) Limitations: respiratory system compromise, head injuries, CNS tumors, pregnancy/delivery Interactions: CNS depressants, EtOH (spike plasma levels by 50%), MAOIs (hyperpyrexic coma, HTN)

Question 56

Mu receptor subtype

Answer 56

``` Morphine-like actions Analgesia Anti-anxiety Respiratory depression Euphoria, dependence GI actions ```

Question 57

Kappa receptor subtype

Answer 57

``` Pentazocine-Like actions (ketocyclazoine) Analgesia Miosis Sedation Dependence Dysphoria**, diuresis ```

Question 58

Codeine

Answer 58

Schedule II 120 mg = 10 mg morphine (never used at this dose) Oral reliability! (met to morphine by CYP 2D6) Mild to moderate pain (30-60mg), combo preps Cough suppressant (5-15mg), combo with promethazine More constipation! Less abuse potential (Sizzurp)

Question 59

Methadone

Answer 59

Full opioid agonist! (10mg q 6-8h) Schedule II Orally reliable! Long half life! (long duration of action means people can sleep through the night) Prolonged Q-T interval, arrhythmias (caution with CYP 3A4 inhibitors--metabolized by CYP 3A4) Analgesia (not prn): use has increased, "safe" Drug abuse treatment Can prod. euphoria/dependence (full agonist)

Question 60

Fentanyl

Answer 60

Full agonist (50 ug IV) Schedule II Very potent, short acting (except patch) (30 min IV), quick onset of action (except patch) Transdermal patch (long term use, ex. cancer pts, abuse/misuse potential) Lozenge/film/tablet (breakthrough pain, only if pt tolerant to opioids) Morphine-like effects: analgesia, euphoria, dependence, sedation, respiratory depression Maintain CV stability (+) Muscle rigidity of chest/abd wall (-)

Question 61

Hydrocodone

Answer 61

Full agonist Schedule II (new classification, used to be III) #1 prescription in USA Major abuse problem Zohydro ER: pure hydrocodone (ie. not in combo), sustained release prep that is not tamper resistant

Question 62

Oxycodone

Answer 62

Full agonist | Major abuse problem (esp timed-release prep (OxyContin))

Question 63

Loperamide

Answer 63

Full agonist at opioid receptors Anti-diarrheal agent Do not cross membranes readily (ie. no CNS action) GI effects (constipatory)

Question 64

Dextromethorphan

Answer 64

``` Not an opioid analgesic Cough suppressant (DM) Stereoisomer of levomethorphan Agonist at sigma and serotonin receptors (not at mu receptor) Abused by teenagers (robotripping) C/i with MAO-I (serotonin syndrome) ```

Question 65

Heroin

Answer 65

Full opioid agonist | Abuse is increasing exponentially

Question 66

Partial opioid agonists

Answer 66

Efficacy not equal to morphine Antagonists with combined with full agonist Respiratory depression ceiling and a parallel analgesic ceiling (partial agonist + no mu effect) KAPPA RECEPTOR AGONISTS, mu weak partial agonists/antagonists Effect: hallucinations, dysphoria Difficult to treat overdoses

Question 67

Petazocine

Answer 67

Partial opioid agonist (prototype) Schedule IV 30-50mg Kappa agonist, mu antagonist Limited analgesia, resp depression (plateaus occur simultaneously) High dose/chronic use produce dysphoria (kappa) IV: BP, HR increase (side effect) Antagonist properties in dependence More reliable orally than morphine Use: analgesia (mod to severe pain), short term use only

Question 68

Buprenorphine

Answer 68

Partial opioid agonist Schedule III .3 mg IM or IV or as a patch t1/2 = 6h Partial agonist at mu receptor, antagonist at kappa receptors Limited effects on: analgesia, resp depression, euphoria No dysphoria May prolong QT (cf. methadone) Use: analgesia (IV, IM, patch), opioid/cocaine dependence treatment (po)

Question 69

Tramadol

Answer 69

Partial opioid agonist Schedule IV Very popular drug Weak partial mu agonist, plus serotonin and NE uptake blocker Analgesic for moderate pain (due to ST and NE block?) Can produce dependence! Difficult withdrawal (paranoia, anxiety, panic, confusion, hallucinations, numbness) Adverse: seizures, serotonin syndrome, drug interactions, overdose/suicide risk Similar to Tapentadol

Question 70

Naloxone

Answer 70

Opioid antagonist Blocks mu > delta, kappa No effects on its own Use: overdose/high dose treatment Potent but short acting (1-4h) (IM, IV, subQ, nasal) (orally ineffective), must be given continuously dt short DOA Block opioid effects when opioids are on board, precipitate withdrawal in opiate dependent people, no effect on resp depression on drugs other than opiates

Question 71

Opioid overdose

Answer 71

Diagnostic triad: 1. respiratory depression (2-8/min, shallow) 2. Miosis: pinpoint pupils, lack of this indicates another drug unless pt is anoxic 3. Coma Treatment: intubate, prevent further absorbance, naloxone (.4 mg IV) Partial agonists are not very responsive to antagonists!

Question 72

Beta-2 agonist bronchodilators

Answer 72

Most widely used B2 adrenergic receptor on airway smooth muscle --> bronchodilation Stimulate AC and increase cAMP --> relax airway SM K+ channel regulation via B2 receptor (contributes to bronchodilation) Some anti-info effects (inhibit infl cells and mediator release) This is not replacement tx, we use it bc it is easy and works

Question 73

Albuterol (salbutamol)

Answer 73

Short acting b2 agonist "Rapid acting acute attack" (rescue medication) Use: relieve bronchoconstriction in acute attacks, prevent exercise-induced asthma, PRN PK: inhalation (1-5m onset of action, 2-6h duration), orally (longer DOA, 6-8h), raced mixture (D,L) Adverse: B2 receptor effects (tachy, palpitations, muscle tremor), CNS stimulation, minimized with inhalation, Overuse --> increased mortality (prob. due to "worsening of disease"; don't use bronchodilators without treating underlying inflammation) Short action makes them inconvenient and reduced compliance for maintenance use

Question 74

Salmeterol

Answer 74

Long acting b2 agonist (LABAs) Cannot be used for acute attacks (onset too slow) Highly B2 selective, long DOA (lipophilic), lipophilic "tail" that binds to "exosite" on b2 receptor Exosite: 2 sites on B2AR (catechol-binding and exo-site); lipid tail of salmeterol binds to exo-site to anchor catecholamine moiety next to receptor PK: inhalation BID Use: long-term asthma maintenance tx, overnight suppression of nocturnal asthma, use alone in COPD Effects: B2 agonist effects (reduced by local admin by inhalation) Always give with inhaled anti-infl (often in combo)(asthma)

Question 75

Formoterol

Answer 75

Long acting b2 agonist (LABAs) Cannot be used for acute attacks Highly B2 selective, long DOA (lipophilic), no specific anchor PK: inhale BID, faster onset than salmeterol Use: maintenance tx, prevent exercise induced bronchospasm, use alone in COPD Always give with anti-infl (asthma)

Question 76

Epinephrine

Answer 76

Non-seletive Beta agonist PK: fastest onset, very short duration of action Inhalation, subQ for acute attack Effects: adrenergic effects, anxiety, muscle tremors, tachycardia

Question 77

Fluticasone

Answer 77

``` Inhaled cortico-steroid (ICSs) 1-2 puffs BID Long-acting GC >>> MC Effects: minimal, hoarseness, pharyngeal candidiasis, HPA axis suppression, decreased BMD, osteoporosis, cataracts, glaucoma ```

Question 78

Budesonide

Answer 78

``` Inhaled cortico-steroids (ICSs) 1-2 puffs BID Long acting GC >>> MC Effects: minimal, hoarseness, pharyngeal candidiasis, HPA axis suppression, decreased BMD, osteoporosis, cataracts, glaucoma ```

Question 79

Inhaled cortico-steroids (ICSs)

Answer 79

Little effect on bronchoconstriction Bind GC receptors Suppressive effects on infl cells Alter transcription of genes (decrease pro-infl, increase anti-infl) Anti-infl effects (modulation of cytokine/chemokine prod, inhibit basophils, eosionphils, other leukocytes) Use: moderate persistent asthma, severe asthma, prophylaxis to prevent attacks (not to reverse attacks), control symptoms, improve lung fxn, improve quality of life, prevent exacerbations, reduce airway change Some require continuous use, others are able to stop

Question 80

Combo preps (ICS + LABA)

Answer 80

Fluticasone and salmeterol (Advair)** Budesonide and formoterol (Symbicort)** Mometasone and fomoterol (Dulera) LABAs should not be used without these GCs for asthma (but are okay for COPD)

Question 81

Prednisone (asthma)

Answer 81

Systemic GC Use: acute exacerbations with rapid-acting beta agonist, severe chronic asthma not controlled by inhaled prep Effects: GC effects, less selective for GC v. MC than fluticasone and budesonide, taper off systemic steroids when starting inhaled steroids (allow HPA axis to recover fxn)

Question 82

Theophylline

Answer 82

Methylxanthine Bronchodilators MOA: PDE inhibitor (increases cAMP), target: PDE3 (smooth muscle), antagonist at adenosine receptors (adenosine-->bronchoconstriction), alter cellular Ca2+ Analog of caffeine Natural ingredient in tea Oral admin mult times per day (short DOA), NOT available for inhalation Weak bronchodilator Use: add-on tx in acute asthma, adjunct in long-term preventative therapy (decrease symptoms) Adverse: nausea, HA, nervousness, anxiety, insomnia, toxic levels (can be fatal), altered by CYP450-altering foods/drugs

Question 83

Leukotriene modifiers

Answer 83

LT: product of 5-lipoxygenase (5-LO) from AA (LTA4) Eosinophil migration Mucus production Airway wall edema Enhanced bronchoconstriction Alt to steroids for mild persistent asthma Add-on for moderate persistent asthma Some use in allergic rhinitis, chronic sinus disease Not good for acute attacks (bronchodilation is not a major action) LTC4/D4/E4 Cys-LT1 R: mucus secretion, bronchoconstriction, edema, eosinophilia Cys-LT2 R: vascular contraction, cell adhesion USEFUL FOR ASPIRIN SENSITIVE ASTHMA (restore LT/PG balance)

Question 84

Zileuton

Answer 84

Inhibit synthesis of leukotrienes Inhibit 5-LO PK: oral BID, NOT inhaled more anti-infl because all LT are blocked Effects: HA, GI, reversible liver toxicity, less specific action

Question 85

Monotelukast

Answer 85

Block leukotriene receptors Selective for Cys-LT1 receptor (major for LTD4) PK: orally 1-2x/day, NOT inhaled, rapid absorbed, high bioavailability, CYP450 metabolism Effects: HA, GI, psychosis, depression

Question 86

Omalizumab

Answer 86

MAB= monoclonal antibody (against IgE) Anti-allergy MOA: prevent IgE from binding/activating IgE receptors PK: subQ every 2-4 weeks (peptide, not broken down quickly like other peptides b/c it's an Ab) Use: allergic asthma to a "non-seasonal" allergen, moderate to severe disease not controlled by inhaled steroids, reduce frequency/severity of exacerbations, allow reduction of anti-infl GC dose Adverse: irritation at injection site, anaphylactic rxn (observe 2h)

Question 87

Cromolyn sodium

Answer 87

"mast cell stabilizer" MOA: prevent release of histamine, etc.; not fully understood PK: inhaled as powder or aerosol, poor oral availability, 4x/day (short DOA) Use: decrease airway HYPER-responsiveness, NOT a bronchodilator, limited use overall Adverse: bronchospasm/wheezing when administered, throat irritation, cough/dry mouth, bad taste, rare (joint swelling/pain, HA, rash)

Question 88

Inhaled B2 agonist for COPD

Answer 88

Alone: salmeterol, formoterol (BID) Short-acting albuterol (intermediate symptoms/exacerbations) Nebulized: formoterol

Question 89

Indacaterol

Answer 89

COPD: inhaled LABA "Bronchodilator" (but not approved for use in asthma or in acute exacerbations of COPD) PK: qd use (first qd agent for COPD) Maintenance of COPD (chronic bronchitis and emphysema)

Question 90

Arformoterol

Answer 90

R-stereoisomer of formoterol LABA Only for COPD

Question 91

ICS drugs in COPD

Answer 91

Not approved for alone use in COPD, although COPD is viewed as an inflammatory disease Added to LABAs or other COPD drugs is recommended! (severe disease, frequent exacerbations)

Question 92

Ipratropium

Answer 92

Anti-muscarinic "bronchodilator" Derivative of atropine Non-selective of M1-M5 M3 subtype: main target for bronchodilation Reduce bronchoconstriction only due to ACh release (ie. anti-constrictor) PK: inhalation, shorter duration of action Some effect on mucus secretion Use: only for COPD, off-label use in asthma Combivent: ipratropium/albuterol combo (beta ag + musc antag) Adverse: dry mouth, pharyngeal irritation, increase IOP (glaucoma patients), classic anti-cholinergic side effects

Question 93

Tiotropium

Answer 93

Anti-muscarinic "bronchodilator" Derivative of atropine Non-selective of M1-M5 M3 subtype: main target for bronchodilation Reduce bronchoconstriction only due to ACh release (ie. anti-constrictor) PK: inhalation, qd, "LAMA" (long-acting) Some effect on mucus secretion Use: only for COPD, off-label use in asthma Adverse: dry mouth, pharyngeal irritation, increase IOP (glaucoma patients), classic anti-cholinergic side effects

Question 94

Aclidinium bromide

Answer 94

Long-acting anti-cholinergic

Question 95

Roflumilast

Answer 95

PDE4 inhibitor (COPD) Oral use, qd Reduces inflammation but does not relieve bronchoconstriction (PDE3) (NOT FOR USE IN BRONCHOSPASM) Use: reduce COPD exacerbations in adults with severe COPD, with chronic bronchitis, hx of exacerbations Adverse: diarrhea, nausea, insomnia, anxiety, depression (suicide risk), weight loss, altered liver metabolism

Question 96

Histamine reactions

Answer 96

1. Vascular smooth muscle dilation (H1--endothelium NO (fast, short acting), H2--sm muscle cAMP (slow, long lasting), flushing, hypotension, reflex tachycardia) (only partially blocked by H1 antagonists) 2. Increased vascular permeability (edema/wheal formation, endothelial cell retraction--H1--protein/plasma leaking) 3. Peripheral sensory nerve excitation (H1/H3, itching, pain) 4. Nasal congestion (H1) 5. Bronchi smooth muscle contraction (H1, bronchial hyperactivity, involves a neural response) 6. Intestinal smooth muscle contraction (H1, diarrhea)

Question 97

Epinephrine

Answer 97

Physiological antagonist of histamine alpha1: vasoconstriction (raise BP) beta2: bronchodilation Tx: anaphylactic shock

Question 98

Cromolyn sodium

Answer 98

Histamine release inhibitor Alters Cl- channel fxn; inhibits lung MAST CELL histamine release Aerosol Tx: prophylactic for asthma or hay fever

Question 99

Diphenhydramine

Answer 99

Benadryl First Generation Antihistamine Enter CNS (sedation), anti-cholinergic (atropine-like), GI problems PK: oral, 4-6h, CYP450 MOA: inhibit vasodilation, inhibit capillary permeability/edema Anti-allergic/anti-inflammatory activity (decreased infl, itching, sneezing, rhinorrhea) Use: allergic rhinitis, urticaria, motion sickness/vertigo (anti-muscarinic), insomnia/sedative Adverse: sedation (enhanced by EtOH/CNS depressants), dizziness/headache, CNS stimulation in children, GI disorders (msucarinic, adrenergic, serotonin receptors)(constipation/diarrhea, loss of appetite, nausea), anti-muscarinic (...), allergic reactions Adverse: reduce lactaion, enter breast milk, narrow angle glaucoma Avoid in children and elderly Overdose looks like atropine overdose (tacky, dry mouth, dilated pupils, hallucinations) Caution in pregnancy

Question 100

Chlorpheniramine

Answer 100

Chlor-Trimeton First Generation Antihistamine Enter CNS (sedation), anti-cholinergic (atropine-like), GI problems PK:oral, 4-6h, CYP450 MOA: inhibit vasodilation, inhibit capillary permeability/edema Anti-allergic/anti-inflammatory activity (decreased infl, itching, sneezing, rhinorrhea) Use: allergic rhinitis, urticaria, OTC cold remedies Less effect at muscarinic effectors Adverse: sedation (enhanced by EtOH/CNS depressants), GI disorders (msucarinic, adrenergic, serotonin receptors)(constipation/diarrhea, loss of appetite, nausea), anti-muscarinic (...), allergic reactions Avoid in children and elderly Overdose looks like atropine overdose (tacky, dry mouth, dilated pupils, hallucinations) Caution in pregnancy

Question 101

Promethazine

Answer 101

Phenergan First Generation Antihistamine Enter CNS (sedation), anti-cholinergic (atropine-like), GI problems PK:oral, 4-6h, CYP450 MOA: inhibit vasodilation, inhibit capillary permeability/edema Anti-allergic/anti-inflammatory activity (decreased infl, itching, sneezing, rhinorrhea) Use: allergic rhinitis, urticaria, motion sickness/vertigo, insomnia/sedative, antiemetic Adverse: sedation (enhanced by EtOH/CNS depressants), dizziness/headache, CNS stimulation in children, GI disorders (msucarinic, adrenergic, serotonin receptors)(constipation/diarrhea, loss of appetite, nausea), anti-muscarinic (...), allergic reactions, PHOTOSENSITIVITY Avoid in children and elderly Overdose looks like atropine overdose (tacky, dry mouth, dilated pupils, hallucinations) Caution in pregnancy

Question 102

Meclizine

Answer 102

Antivert First Generation Antihistamine Enter CNS (sedation), anti-cholinergic (atropine-like), GI problems PK: oral, 12-24h, CYP450 MOA: inhibit vasodilation, inhibit capillary permeability/edema Anti-allergic/anti-inflammatory activity (decreased infl, itching, sneezing, rhinorrhea) Use: motion sickness/vertigo Adverse: LESS sedation (enhanced by EtOH/CNS depressants), dizziness/headache, CNS stimulation in children , GI disorders (msucarinic, adrenergic, serotonin receptors)(constipation/diarrhea, loss of appetite, nausea), anti-muscarinic (...), allergic reactions Avoid in children and elderly Overdose looks like atropine overdose (tacky, dry mouth, dilated pupils, hallucinations) Caution in pregnancy

Question 103

Doxylamine

Answer 103

First Generation Antihistamine Enter CNS (sedation), anti-cholinergic (atropine-like), GI problems PK: oral, 4-6 h, CYP450 MOA: inhibit vasodilation, inhibit capillary permeability/edema Anti-allergic/anti-inflammatory activity (decreased infl, itching, sneezing, rhinorrhea) Use: MORNING SICKNESS (with B6 and pyridoxine) Adverse: sedation (enhanced by EtOH/CNS depressants), dizziness/headache, CNS stimulation in children, GI disorders (msucarinic, adrenergic, serotonin receptors)(constipation/diarrhea, loss of appetite, nausea), anti-muscarinic (...), allergic reactions Avoid in children and elderly Overdose looks like atropine overdose (tacky, dry mouth, dilated pupils, hallucinations) Caution in pregnancy

Question 104

Fexofenadine

Answer 104

Allegra Second Generation Antihistamine Do not enter CNS (not sedative), CYP3A4 metabolism, less muscarinic action PK: oral, 12-24h, CYP3A4 MOA: inhibit vasodilation, inhibit capillary permeability/edema USE: allergic rhinitis, dermatologic pain/itching (better prophylactically) Adverse: DO NOT TAKE WITH FRUIT JUICES (OATP inhibitor, reduces absorption) Adverse: nausea/vomiting (low incidence), dysmenorrhea, drowsiness, enters breast milk

Question 105

Cetirizine

Answer 105

Zyrtec Second Generation Antihistamine Do not enter CNS (not sedative), CYP3A4 metabolism, less muscarinic action PK: oral, 12-24h, CYP3A4 MOA: inhibit vasodilation, inhibit capillary permeability/edema Use: allergic rhinitis, dermatologic pain/itching Adverse: SEDATING, drowsiness, weak anti-muscarinic effects (ex. dry mouth), CYP3A4 drug interactions