Pharm-Part 5

Front 1

theopyhylline
-site of action?

Back 1

Note: aminophylline works just like theophylline

-site of action: direct effect b/c works inside cell, thus it dilates normal lungs and if pt has taken propanolol (B blocker) b/c theophylline doesn't need B-receptor to work

S/E: seizures

MOA: (~sildenafil)
inhibits PDEase
==>inhibits degradation or cAMP
==>cAMP becomes cAMP protein kinase
==>cAMP protein kinase adds phosphate to MLC-K to become MLCK-P (inactive)
==>less MLCK-P to convert MLC to MLC-P, which is req for bronchial SmM contraction
==>less bronchial SmM contraction (easier to breathe)

S/E: seizures

Note: theo is metabolized by CYP450, so if person on theo develops a sinus infxn which req Tx with AB, which AB would require decr in daily dose of theo?
==>erythromycin (inhibits CYP450)

-similarly, asthmatic on theo develops seizure after taking OTC drug for heartburn. Rx?
==>Cimetidine (blocks CYP450, which metabolizes theo)

Front 2

person is treated w/propanolol. which drug will still bronchodilate?

Back 2

theophylline or aminophylline b/c their MOA=inhibits PDEase (in which intracellular, does not act via Beta receptors, which would be blocked by propanolol)

S/E: seizures

Front 3

asthmatic pt taking theophylline develops sinus infxn that req Tx with AB. What AB would require lowering of daily dose of theo?

Back 3

Erythromycin (b/c it blocks CYP450, which metabolizes theo)

Front 4

asthmatic pt taking theophylline develops seizures after taking OTC drug for heartburn. drug?

Back 4

cimetadine (b/c it blcoks CYP450, which metabolizes theophylline)

Front 5

aminophylline

Back 5

Note: aminophylline works just like theophylline

-site of action: direct effect b/c works inside cell, thus it dilates normal lungs and works even if pt has taken propanolol (B blocker) b/c theophylline doesn't need B-receptor to work

MOA: (~sildenafil)
inhibits PDEase
==>inhibits degradation or cAMP
==>cAMP becomes cAMP protein kinase
==>cAMP protein kinase phosphorylates MLC-K to MLCK-P (inactive)
==>less MLCK-P to phosphorylate MLC to MLC-P, which is req for bronchial SmM contraction
==>less bronchial SmM contraction (easier to breathe)

Note: theo is metabolized by CYP450, so if person on theo develops a sinus infxn which req Tx with AB, which AB would require decr in daily dose of theo?
==>erythromycin (inhibits CYP450)

-similarly, asthmatic on theo develops seizure after taking OTC drug for heartburn. Rx?
==>Cimetidine (blocks CYP450, which metabolizes theo)

Front 6

cromolyn sodium
-site of action

Back 6

inhibits mast cell degranulation by preventing Ca++ influx into mast cells when no IgE bridges form
==>no mast cell degran
==>no histamine release to bind H1-R

Normally:
H1-R activates IP3 (Inosine TriPhosphate (P3)), which activates MLCK, which converts MLC==>MLCK-P, which contracts bronchial SmM (hard to breathe)

Front 7

ipratropium
-site of action

Back 7

muscarinic antagonist
==>no muscarinic message
==>easier to breathe

Normally:
muscarinic receptor activates IP3 (Inosine Triphosphate (P3)), which activates MLCK, which converts MLC==>MLCK-P, which contracts bronchial SmM (hard to breathe)

Front 8

zafirlukast

Back 8

LTC4 and LTD4 receptor antagonist

Normally:
LTC4 and LTD4 receptors activates IP3, which activates MLCK, which converts MLC==>MLCK-P, which contracts bronchial SmM (hard to breathe)

Front 9

beclamethasone

Back 9

"--sone"=corticosteroid

Corticosteroids inhibit production of Arachidonic Acid, which is the precursor of leukotrienes and prostaglandins (which induce bronchial SmM contraction=harder to breathe).

Thus, corticosteroids make it easier to breathe (ICS lecture: Long-term Tx for Asthma=corticosteroids)

[Recall how corticosteroids decr all inflammatory substances, including LT's & PG's).

Normally:
LTC4 and LTD4 receptors (leukotrienes) & PGD4 receptor (prostaglandin) activates IP3, which activates MLCK, which converts MLC==>MLCK-P, which contracts bronchial SmM (hard to breathe)

Front 10

albuterol

Back 10

Tx: Asthma
("AST" drugs for Asthma:
Albuterol
Selmeterol
Terbutaline)

B2-agonist==>bronchial SmM relaxation (easier to breathe)

Front 11

terbutaline

Back 11

Tx: Asthma
("AST" drugs for Asthma:
Albuterol
Selmeterol
Terbutaline)

B2-agonist==>bronchial SmM relaxation (easier to breathe)

Front 12

what drug causes biggest incr FEV1 with smallest incr HR?

Back 12

albuterol

Front 13

pt with exercise induced asthma uses cromolyn sodium prophylactically? MOA?

Back 13

cromolyn prevents Ca++ influx into mast cells when IgE bridges form = no mast cell degranulation

Front 14

glucocorticoids

Back 14

*inhibits production of IL-1 and IL-6 by macrophages and monocytes
==>inhibits Ig synthesis by B cells (d/t decr IL-1 & IL6)
==?prevents fxns of cytotoxic T-cells (d/t decr IL-1)

*inhibits production of PG's and LT's (inflammatory substances)

*NO BM depression

Note: glucocorticoids INCR # neutrophils in blood (stim their release from BM and prevents them from moving out of blood into lymphoid tissue), but it does the opposite for all other WBC's (L, M, E, B): glucocort decr # of other WBC's in the blood by stimulating them their mvmt from blood to lymphoid tissue

S/E:
-glaucoma
-osteoporosis
-GI ulcers (d/t decr PG in stomach)
-psychosis

Front 15

which drug suppresses cellular immunity, blocks synthesis of PG's and LT's, and incr #neutrophils in blood?

Back 15

glucocorticoids

Note: glucocorticoids INCR # neutrophils in blood (stim their release from BM and prevents them from moving out of blood into lymphoid tissue), but it does the opposite for all other WBC's (L, M, E, B): glucocort decr # of other WBC's in the blood by stimulating them their mvmt from blood to lymphoid tissue

Front 16

cyclosporine

Back 16

(immunosuppressant)

inhibits calcineurin
==>prevents prod of IL2 by helper T cells

Front 17

mycophenolate

Back 17

(immunosuppressant)

inhibits inosine monophosphate
==>prevents purine synthesis in T and B lymphocytes

Front 18

azathioprine

Back 18

(cytotoxic immunosuppressant)

MOA: converted to 6-mercaptoPURINE, which is a PURINE analog
==>cannot make nucleic acids req for T and B cell prolif

Front 19

cyclophosphamide

Back 19

(cytotoxic immunosuppressant)

alkylates DNA

s/e: hemorrhagic cystitis

Front 20

Sx:
-hypercalcemia
-hypercalcinuria;
-hyperphosphatemia
- anorexia, nausea, weight loss, weakness; dehydration

-what's the problem
-how Tx?

Back 20

problem=Vit D toxicity

[dehydration develops because
hypercalcemia impairs the renal concentrating ability of the kidney]

Tx:
*aggressive hydration w/isotonic saline (goljan: first step is to restore fluids via nl saline)
*furosemide (elim Ca++)
*plicamycin (mithramycin) = cytotoxic antibiotic that prevents bone resorption

Front 21

pt with renal failure has low plasma Ca++. Tx?

Back 21

1,25 (OH)2 Vit D

Front 22

Patient w Paget’s disease (a localized bone dx w uncontrolled osteoclastic bone
resorption and secondary in the formation of poorly organized bone) exhibits hearing loss,
bone pain, bone deformity, increased serum alkaline phosphatase, increased urinary hydroxyproline, high output HF and immobilization hypercalcemia. TX w ?

Back 22

Tx w calcitonin to decrease bone pain, bone deformity, hearing loss and hypercalcemia.
Calcitonin will decrease serum Ca++ and PO4- by inhibition of osteoclastic bone resorption and
decreasing the reabsorption of Ca++ and PO4- by the kidney.

Front 23

alendronate

Back 23

=bisphosphanate (alendronate & etidronate)

Tx:
-glucocorticoid-induced osteoporosis
-post-meno osteoporosis
-Paget's dz (+calcitonin)

MOA: inhibit bone resorption by inhibiting osteoclasts' ability to break down hyroxyapatite crystals

Front 24

post-menopausal woman requires tx to maintain bone mass, but cannot take estrogen bx her mother and sister had breast cancer. Tx w ?

Back 24

alendronate or etidronate (bisphosphanates)

Front 25

etidronate

Back 25

=bisphosphanate (alendronate & etidronate)

Pat's mneum: Lazy 'dro smokin (hydro is a type of weed) guy named nate (smokes so much his boys call him "dro-nate") doesn't ever want to do any work or goto class--"class?? Mann fuck class!!!! I'll smoke some 'dro instead!!!"
(-dronate, “CLASS”=osteoCLASTS)


Tx:
-glucocorticoid-induced osteoporosis
-post-meno osteoporosis
-Paget's dz (+calcitonin)

MOA: incorporated into bone and inhibit osteoclast bone resorption

Front 26

A patient tx with steroids develops hypocalcemia. Why?

Back 26

steroids (-) Vit D's absorption of Ca++ from GI
==>low serum Ca++
==>incr PTH
==>incr renal Ca++ excretion
==>hypocalcemia & osteoporosis

Front 27

Sx=pallor, fatigue, feel light-headed; craving for clay

-what's the prob?
-Tx?

Back 27

Fe-def anemia

-caused by blood loss, decr GI abs of Fe, incr Fe req

-Tx:
*ferrous iron
*Vit C (incr GI abs of ferrous iron)

Front 28

folate def:
-Sx?
-Tx?

Back 28

Sx=
diarrhea
anorexia
sore tongue
irritability
forgetfulnes (but no neurologic Sx)

Tx?
-po folate

Front 29

Sx:
-diarrhea
-anorexia
-sore tongue
-irritability
-distal parasthesias
-sensory disturbances

-Dx?
-Tx?

Back 29

(mneum: think Haley)

Dx=Vit B12 def
(it's B12 def and not folate def b/c paresthesias & sensory disturbances=neurologic Sx)

-Vit B12 def causes neurologic Sx b/c B12 req to convert methylmalonyl acid==>succinyl CoA, which is req for synthesis of myelin.
-If no myelin==>demyelination of dorsolateral spinal column (dorsal column==>sensory abnl;
corticospinal tract==>UMN problems like paresthesias)

Tx: cyanocobalamin or hydroxycobalamin (cobalamin=Vit B12)

Front 30

Clinical: A patient with normochromic, macrocytic anemia has distal paresthesias. The patient
is treated with p.o. folate and the anemia disppears, but the neurological S/S worsens. What happened?

Back 30

Folate will correct the megaloblastic anemia, but the neurological syndrome
results from B12 deficiency because B12 is needed for the synthesis of myelin.

Front 31

what Rx cause normochromic macrocytic anemia?

-why?
-how tx?

Back 31

*Phenytoin
*Isoniazid
(these inhibit abs of folate in GI tract)

*TriMETHOprim (trim)
*pyramidine
*METHOtrexate
(these these inhibit DHF reductase)

--Tx with leukovorin (=folonic acid) for BM rescue

Front 32

pt on hemodilaysis develops normochromic, macrocytic anemia.

-why?
-how tx?

Back 32

hemodialysis clears folate out of system.

Thus, all pts on hemodialysis must be tx with:
-folate
-EPO
-ferrous iron

Front 33

pt with Hct=24 is started on hemodialysis. After tx w/EPO, folate, and ferrous iron, the pt develops HTN. why?

Back 33

-EPO, folate, and ferrous iron all incr viscosity of blood
==>incr viscosity of blood==>incr resistance (Poiseuille's law)

==>inct BP

Front 34

what drugs can be used for "blood doping" (incr Hct) in competitive cycling?

Back 34

-EPO (erythroPOETIN)
-ePOETIN alfa
-darbePOETIN

Front 35

Clinical: Which synthetic glucocorticoid is used to differentiate bilateral adrenal hyperplasia from
adrenal carcinoma?

Back 35

dexamethasone

(BILATERAL adrenal hyperplasia==>pituitary Cushing's
(incr ACTH causes hyperplasia of BILATERAL adrenal glands; vs. adrenal tumor usually only affects one side)

Remember the dexamethasone suppression test that you use for Cushing's! High-dose DEXA will suppress cortisol in pituitary Cushing's, but it will not suppress but will not suppress cortisol in other causes of Cushing's (adrenal carcinoma or ectopic ACTH tumor). Goljan: There are only 2 instances when an endocrine tumor can be suppressed:
-pituitary Cushing's (suppressed by high-dose DEXA)
-prolactinoma (suppressed by DOPA analogs)

Front 36

which drug increases urinary excretion of 17-ketosteroids (testosterone) in pt with bilateral adrenal hyperplasia (i.e. adrenal Cushing's) hyperplasia) without incr urnary excretion of 17-OH-steroids (cortisol) in pt with adrenal carcinoma?

Back 36

Metyrapone

17-ketosteroid=testosterone
17-OH-steroid=11-deoxycortisol; cortisol


Metyrapone inhibits the CYP450scc that converts 11-deoxycortisol to 11-cortisol.
==>no cortisol for negative feedback on pit
==>incr ACTH
==>stimulates entire steroidogeneis pathway
==>incr testosterone and thus urinary testosterone excretion (but no incr excretion of cortisol b/c can't convert 11-deoxycortisol to 11-cortisol)

*But in pt with adrenal carcinoma, the cortisol produced by the tumor caused negative feedback on pit
==>decreased ACTH
==>adrenal has already atrophied and thus cannot respond to incr ACTH caused by metyrapone w/incr testosterone (as in bilateral adrenal hyperplasia)
==>decr cortisol (d/t adrenal atrophy), thus no incr in urinary excretion of cortisol

Front 37

what drug suppresses plasma cortisol in pt with nl pit-adrenal fxn?

Back 37

ketoconazole (blocks CYP450scc)
--note, this is on Adrenal steroid genesis chart in FA Endocrine section

Front 38

which drug causes "medical adrenalectomy?"

Back 38

aminogluthethimide (blocks conversion of chol==>pregnenolone==>no adrenal steroidogenesis)

Tx: Cushing's

Front 39

pt tx with steroids develops GI ulcer. MOA?

Back 39

inhibit production of PG's to coat stomach

Front 40

a patient with breast tenderness is on a drug to enhance fertility.

rx?

Back 40

[breast tenderness=Sx of hyperestrogenism)

clomiphene


Blocks estrogen receptors in hypothalamus and pituitary
==>↓feedback inhibition of GnRH and gonadotropins
==>↑GnRH secretion
==>↑FSH secretion
==> ovulation

Front 41

why is estradiol contraindicated in a patient w a history of thromboembolic dx (DVT's)?

Back 41

estradiol incr synthesis of clotting factors

Front 42

Tx breast cancer

Back 42

tamoxifen (blocks est receptors)

Front 43

Why do OCP's which contain an estrogen also contain a progestin?

Back 43

progestin also blocks endometrial hyperplasia d/t est

Front 44

Which compound can be used to maintain bone mass in a postmenopausal woman who
has had breast cancer?

Back 44

raloxifene (SERM) or alendronate (bisphosphanate)

Front 45

fluoxymesterone

Back 45

androgen

*used for anabolic effects
*prevent catabolic action of cortisol
*stimulate erythropoiesis and protein synthesis

Front 46

nandrolone

Back 46

nANDROlone=ANDROgen

*used for anabolic effects
*prevents catabolic action f cortisol
*stimulates erythropoiesis and protein syn

Front 47

A body builder treats himself w fluoxymesterone (an anabolic steroid). How his
spermatogenesis be affected?

Back 47

suppressed

fluoxymesterone (androgen) suppress hypothalamic release of GnRH
==>less FSH from pituitary
==>less development of sperm

Front 48

Clinical: A body builder has an enlarged heart and spleen, borderline DM and mild HT, but
androgenic steroids are not present in his urine. What drug is he abusing?

Back 48

GH
==>increases production of IGF

Front 49

Clinical: What drug will suppress the secretion of GH hormone in a patient with acromegaly?

Back 49

octreotide (somatostatin analog)

or bromocriptine (DOPA analog)

Front 50

Older man has arthralgia, fluid retention and hyperglycemia. What drug has the effect?

Back 50

GH

Front 51

Tx BPH

Back 51

finasteride
==>inhibits 5α-reductase
==>decr DHT

Front 52

Tx hair loss

Back 52

finasteride
==>inhibits 5α-reductase
==>decr DHT

Front 53

androgen receptor antagonist?

Back 53

flutamide

("Unmanly men play the flute.")

Front 54

Clinical: How to tx a young boy w cryptorchidism?

Back 54

hCG

Front 55

leuprolide

Back 55

Tx:
-prostatic cancer
-endometriosis
-leiomyomas (uterine fibroid tubors)

continuous infusion via IM densensitizes GnRH receptors
==>inhibit release of LH/FSH

Tx: for in vitro

Rx is used to suppress GnRH (and thus suppress LH/FSH) Then administer exogenous gonadotropins (hCG, which looks like LH)
==>synchronized follicular development

Front 56

goserelin

Back 56

Tx:
-prostatic cancer
-endometriosis
-leiomyomas (uterine fibroid tumors)

=GnRH analog

("GO"nadotropin "Rel"easing Hormone= "GO"se"REL"in)

continuous infusion via IM densensitizes GnRH receptors
==>inhibit release of LH/FSH


Tx: In vitro fert

Rx is used to suppress GnRH (and thus suppress LH/FSH) Then administer exogenous gonadotropins (hCG, which looks like LH)
==>synchronized follicular development

Front 57

nafarelin

Back 57

*GoseRELIN
*nafeRELIN
*Leuprolide

GnRH analogs

Tx:
-prostatic cancer
-endometriosis
-leiomyomas (uterine fibroid tubors)

continuous infusion via IM densensitizes GnRH receptors
==>inhibit release of LH/FSH

Tx: for in vitro

Rx is used to suppress GnRH (and thus suppress LH/FSH) Then administer exogenous gonadotropins (hCG, which looks like LH)
==>synchronized follicular development

Front 58

Tx prostatic cancer

Back 58

*Leuprolide
*GoseRELIN
*NafeRELIN

Tx:
-prostatic cancer
-endometriosis
-leiomyomas (uterine fibroid tubors)

continuous infusion via IM densensitizes GnRH receptors
==>inhibit release of LH/FSH

Tx: for in vitro

Rx is used to suppress GnRH (and thus suppress LH/FSH) Then administer exogenous gonadotropins (hCG, which looks like LH)
==>synchronized follicular development

Front 59

Tx endometriosis

Back 59

*Leuprolide
*GoseRELIN
*NafeRELIN

=GnRH analog
("GO"se"REL"in= "GO"nadotropin "REL"easing Hormone)

Tx:
-prostatic cancer
-endometriosis
-leiomyomas (uterine fibroid tubors)

continuous infusion via IM densensitizes GnRH receptors
==>inhibit release of LH/FSH


Tx: in vitro vert

Rx is used to suppress GnRH (and thus suppress LH/FSH) Then administer exogenous gonadotropins (hCG, which looks like LH)
==>synchronized follicular development

Front 60

Tx leiomyomas

Back 60

*Leuprolide
*GoseRELIN
*NafeRELIN

Tx:
-prostatic cancer
-endometriosis
-leiomyomas (uterine fibroid tubors)

continuous infusion via IM densensitizes GnRH receptors
==>inhibit release of LH/FSH

Tx: for in vitro

Rx is used to suppress GnRH (and thus suppress LH/FSH) Then administer exogenous gonadotropins (hCG, which looks like LH)
==>synchronized follicular development

Front 61

glucagon

Back 61

secreted by pancreatic alpha cells; 29 AA protein

MOA:
*converts hepatic glycogen==>plasm glucose (no effect on SkM glycogen)
*cardiac effects: incr dp/dt d/t incr cAMP

PE:
*use to Dx T1DM; glucagon SHOULD stimulate release of insulin and C-peptide in non-diabetics; no C-peptide release in T1DM

Tx:
*severe hypoglycemia
*poisoning with BB: increases dp/dt independent of B-receptors

Front 62

insulin--onset, peak, duration:
-Lispro
-Regular
-NPH (protamine)
-ultralente
-glargin

Back 62

onset; peak; duration

Lispro: 10m, 60m, 3-4h
Regular: 15m, 2-4h, 5-8h
NPH (protamine):
1-2h, 6-12h,18-24h

ultralente:4-8h, 16-18h, 20-36

glargine (very slow absorption with no peak, duration=24 h)

Front 63

Tx: DKA

Back 63

-lispro or regular insulin IV
-IV fluids for rehydration
-K+ to prevent hypokalemia as insulin drives glucose into liver, SkM, and fat cells

Front 64

sulfonylureas

Back 64

"hypoglycemics"

*tolbutamide
*chlorpropamide
*glyburide
*glipizide

Tx: T2DM

MOA: blocks ATP-sensitive K+ channels in beta cells
==>depol beta cells
==>release insulin

S/E: hypoglycemia

Front 65

tolbutamide

Back 65

Tx: T2DM

MOA: blocks ATP-sensitive K+ channels in beta cells
==>depol beta cells
==>release insulin

S/E: hypoglycemia

Front 66

chlorpropamide

Back 66

Tx: T2DM

MOA: blocks ATP-sensitive K+ channels in beta cells
==>depol beta cells
==>release insulin

S/E: hypoglycemia

Front 67

glyburide

Back 67

Tx: T2DM

MOA: blocks ATP-sensitive K+ channels in beta cells
==>depol beta cells
==>release insulin

S/E: hypoglycemia

Front 68

glipizide

Back 68

Tx: T2DM

MOA: blocks ATP-sensitive K+ channels in beta cells
==>depol beta cells
==>release insulin

S/E: hypoglycemia

Front 69

metformin

Back 69

Tx: T2DM

MOA: decr insulin resistance primarily in SkM and fat cells

FirstAid: decr gluconeogenesis
S/E: lactic acidosis

Front 70

rosiglitazone

Back 70

(a glitazone)

Tx: T2DM

MOA: decr insulin resistance primarily in SkM and fat cells

Front 71

which drug decr hepatic glucose production in a T2DM without enhancing the pancreatic secretion of insulin?

Back 71

metformin

Front 72

ipecac

Back 72

ipecac induces vomiting by an action at the CTZ and by an irritant action in the stomach which is not blocked by antihistamines

(bulimics use)

Front 73

Clinical: What drug induces emesis by stimulating D2-receptors in the CTZ?

Back 73

apomorphine (morphine works via dopamine receptors)

Front 74

lactulose

Back 74

lactulose (synthetic disaccharide) – slow-acting laxative which is converted to small organic acids in the bowel; these acids exert an osmotic effect to slowly draw water into the feces.

Front 75

Clinical: A patient with S/S (confusion/coma) of hepatic portal encephalopathy needs tx.
Drug =

Back 75

Drug = lactulose which acidifies the bowel to trap ammonia as ammonium ion; ammonium lost in feces

==>plasma [ammonia] falls
==>coma and confusion disappear

Front 76

docusate sodium

Back 76

= a stool softener = an anionic surfactant: detergent action (~soap) allows water to enter feces; softens the stool wo increasing its bulk

Front 77

Diarrhea – tx w

Back 77

DOC=loperamide (Imodium)

-or diphenoxylate which stimulate mu opiate receptors

Front 78

Ulcers – tx

Back 78

*H2-receptor blockers (cimetidine)
*antacids, (Al and/or Mg hydroxides)
*PGE-receptor agonists (misoprostol)
*proton pump inhibitors (omeprazole)
*sucralfate (mixture of sucrose ("sucr") & AlOH ("al"), which forms a viscous gel at acidic pH; gel coats ulcerated tissue)

*modern tx is to eradicate Helicobacter pylori w triple AB tx =
1. clarithromycin,
2. amoxacillin,
3. omeprazole

Front 79

Which antiulcer drug does not alter stomach pH? =

Back 79

sucralfate

Front 80

Clinical: Patient on propranolol takes cimetidine for heartburn and develops severe bradycardia.
Why?

Back 80

Bx cimetidine inhibits CYP450 and thus blocks the metabolism of propranolol

Front 81

antacids and GI tract

Back 81

AlOH = constipation; MgOH = diarrhea

Front 82

Pat being tx w doxycycline; which drug contraindicated?

Back 82

Al/Mg antacids

Front 83

Patient needs emergency surgery; need to empty stomach/prevent reflux. Drug = ?

Back 83

metoclopramide = prokinetic in stomach and bowel and tightens the LES

FA:
MOA: prokinetic, D2-R antagonist

Tx: Diabetic and post-surgery gastroparesis

S/E: Park effects

Front 84

Clinical: Cancer chemo patient has n/v and noctural acid reflux Tx w = ?

Back 84

metoclopramide= prokinetic in stomach and bowel and tightens the LES

Front 85

Patient has post-operative paralytic ileus Tx w = ?

Back 85

A: metoclopramide, bethaneCHOL, cisapride

Front 86

Patient treated with drug for Crohn’s disease or ulcerative colitis develops hepatic damage or bone marrow depression. Drug = ?

Back 86

sulfasalazine=SHIP drug; patient is a slow acetylator.

SULFASALAzine consists of SULFApyridine conjugated to 5-aminoSALIcyclic acid (5-ASA).

Bacterial E's in the large bowel hydrolyze SULFASALAzine to free SULFApyridine and free 5-aminoSALIcyclic acid.

-5-ASA = NSAID ==>hepatic damage
-sulfaPYRIdine, which is metabolized by acetylation,
suppresses BM (Kat's note: recall Tx malaria: "trim-PYRImethamine: the PYRImethamine part inhibits DHF-R==>inhibits THF formation (this would probly suppress BM)

Front 87

constipation, hypokalemia, muscle weakness, abnormal architecture inner GI wall

suggests what?

Back 87

laxative abuse with castor oil or bisacodyl

Front 88

NSAIDS

Back 88

1. Inhibits platelet aggregation by acetylating & irreversibly inhibiting COX1 & COX2
==>prevents conversion of AA to PG's (TxA is a PG)
==>nl platelet count but incr BT b/c platelets don't work! (no effect on PT, PTT)

2. Aspirin blocks platelet aggregation caused by arachidonic acid but not the aggregation caused by PGG2 and PGH2 (cyclic endoperoxides)

3. Inhibition of platelet aggregation relieves chest pain in unstable angina: platelet count is normal, but bleeding time is increased

4. Aspirin converted to salicylate during first-pass metabolism in the liver

Front 89

NSAIDS: how recog non-linear kinetics

Back 89

Note:

Linear kinetics=1st order kinetics

**Most drugs
-[drug] falls by constant PERCENTAGE/FRACTION
-Most drugs operate this way b/c the enzymes resp for drug elimination are NEVER saturated
--------------------

Non-linear kinetics=Zero Order Metabolism

-[drug] falls by constant AMOUNT (called "nonlinear" b/c does not fall by constant fraction/percentage like most drugs do)
-Enzymes resp for drug elimination are saturated
--------------------


Large doses of aspirin exhibit nonlinear kinetics - how to recognize non-linear kinetics?

I. the disappearance of plasma salicylate:
1. plasma [salicylate] falls by constant AMOUNT during zero-order elim b/c enzymes resp for hepatic Cl are saturated with substrate

2. plasma [salicylate] falls by 50% during 1st-order elim (constant PERCENTAGE/FRACTION)

(Most drugs operate this way)

II. the apperance of plasma [salictylate] during po dosing:


When the dose is doubled, the plasma concentration should double.

If the doubling the dose causes [salicylate] to increase more than two-fold, the hepatic enzymes have become saturated and elimination has changed from first-order to zero-order; the decr in Clearance will cause the half life to incr

Front 90

aspirin OD:
Sx
Tx

Back 90

- n/v, tinnitus

*Respiratory alkalosis: aspirin uncouples oxidative phosphorylation in skeletal muscle
==>thus form lactic acid
==>incr pCO2
==>increases respiration
==>resp alkalosis

*metabolic acidosis: as CO2 production increases, a metabolic acidosis develops

- children skip the alkalosis step and go directly to acidosis w low blood pH and low bicarbonate

TREATMENT: make urine alkaline (acetazolamide or NaHCO3) to enhance the renal clearance of salicylate and infuse bicarbonate to correct acidosis

Front 91

Clinical: half-life of aspirin as only 1 h, why does it inhibit platelet inhibition for a longer period

Back 91

Aspirin irreversibly acetylates active site of COX-1 in platelets

Front 92

Clinical: How does aspirin prevent platelet aggregation when it is not taken in doses large enough to maintain a steady-state plasma concentration?

Back 92

Aspirin irreversibly acetylates active site of COX-1 in platelets

Front 93

Clinical: patient has intermittent episodes of hemiplegia which resolve spontaneously; would like
to treat with aspirin, but patient has aspirin “hypersensitivity”;

Back 93

ticlopidine:

irreversibly blocks ADP receptors
==>no GP2b/3a receptors to bind fibrinogen and cause platelet aggregation

Front 94

Clinical: What is the causative compound in aspirin hypersensitivity? =

Back 94

leukotrienes

Front 95

Clinical: DOC for menstrual cramps

Back 95

ibuprofen

Front 96

Clinical: Baby has patent ductus arteriosus

Tx?

Back 96

close w/indomethacin

Front 97

Clinical: Want to keep ductus arteriosus open prior to surgery: what drug will do this ?

Back 97

alPROSDTAdil = PGE1 (PROSTAglandin) analog dilates the ductus arteriosus

Front 98

Clinical; pat tx with NSAID develops GI ulceration. MOA =

Back 98

inhibit gastric PG syn

Front 99

Clinical: A patient with nasal polyps who has wheezing with aspirin needs a antipyretic drug

Back 99

DOC = acetaminophen

Front 100

Acetaminophen

Back 100

antipyretic but not antiinflammatory

Front 101

Clinical: Drug OD; initially blood chemistries normal, but 36 h later see increase in AST and ALT.

Q: what is the drug?
-how tx OD?

Back 101

acetaminophen; treat with n-acetylcysteine to replenish glutathione

Front 102

Adverse effects of NSAID’s

Back 102

*gastric ulceration – results from decreased PG synthesis in stomach; prevent or tx with misoPROstol (methyl-PGE1; PRO=PROstaglandin)

*interstitial nephritis – hematuria, proteinuria, flank pain

*decreased RBF and GFR causing oliguria

Front 103

Clinical: Patient on NSAID for tendonitis for 2 weeks develops fever and hematuria: diagnosis?

Back 103

acute interstitial nephritis

Front 104

Clinical: Patient with CHF takes ibuprofen; effect on kidney = ?

Back 104

1. Constriction of afferent arteriole lowers RBF and GFR ==>salt/water retention

2. no PG's to partially inhibit the effects of ADH in the collecting duct = water retention.

Front 105

Clinical: Patient tx with NSAID for arthritis exhibits decr [Hb] and Hct and has occult blood in his stool.

Which drug could be addded to tx to reverse this pathology?

Back 105

misoPROSTol (PROSTaglandin PGE analog
==>incr gastric mucosal lining
==>less bleeding from ulcer)

Front 106

Colchicine

Back 106

binds to tubulin to block the formation of microtubules and thus inhibit phagocytosis of urate crystals by WBC’s; used to tx the pain of acute attacks

Front 107

Allopurinol

Back 107

inhibits xanthine oxidase (purine degradation pathway: degrades purines==>uric acid)

Front 108

Clinical: Patient with a renal transplant is taking the immunosuppressant drug azathioprine.
Patient develops gout. Which gout drug is contraindicated?

Back 108

allopurinol bx azathioprine is converted to the cytotoxic agent 6-mercaptopurine (6-MP; kills antigen presenting cells and T- and B-lymphocytes). 6-MP is inactivated (metabolized) by xanthine oxidase.

Allopurinol==>inhibit xanthine oxidase
==>incr levels of cytotoxic agent 6-MP

Front 109

Clinical: Patient with lymphoma tx with chemo. Which drug will prevent decr in renal function?

Back 109

allopurinol--prevents the formation of urate

Chemo kills lymphoma cells ==>release nucleic acids which are converted to urate (Degredation Pathway of purines)
==>xs urate in urine crystalizes to occlude the collecting ducts, pelvis and ureters
==>rapid, progressive renal dysfunction

Front 110

Probenacid

Back 110

Probenecid and large doses of aspirin enhance the renal clearance of urate

==>urate (urate=uric acid=acidic) stones may form, so keep the urine alkaline with sodium citrate

Front 111

Clinical: Which gout drug is not uricosuric?

Back 111

colchicine, allopurinol

Front 112

Clinical: patient takiing a small daily dose of aspirin may develop gout whereas a large daily dose of aspirin is used to treat gout. Why the discrepancy?

Back 112

Small doses of aspirin enhance urate
reabsorption in the renal tubule whereas large doses of aspirin are uricosuric

Front 113

Clinical: Patient being tx for gouty arthritic develops leukopenia. Which drug ?

Back 113

colchicine (House episode)

Front 114

Clinical: Pg woman develops hyperthyroidism. How to treat

Back 114

PTU

Front 115

Clinical: What are the usual causes of hyperprolactinemia and their treatment?

Back 115

A: blockade of D2-dopamine receptors and increased TRH in hypothyroidism cause hyperprolactinemia.

A: in hypothyroidism, tx w thyroxine to suppress plasma [prolactin]
(incr T4==decr TRH==>decr PRL)

Front 116

Clinical: patient w recurrent v. tach/v. fib. develops hyper- or hypothyroidism while taking
amiodarone. Why?

Back 116

AmIODaroNE (Tx V tach/V fib) is 37% iodide by weight (IODiNE). This iodide can either prevent the conversion of T4 to T3 (hypothyroidism), or it can serve as a substrate for the synthesis of T3 by thyroid peroxidase (hyperthyroidism)

Front 117

Central DI – tx with

Back 117

desmoPRESSIN (~vasoPRESSIN=ADH)
(=DDAVP (VP=VasoPressin))

-long half-life b/c resistant to degradation by peptidases;
-very selective for renal V2-receptors

Front 118

Nephrogenic DI – tx w

Back 118

HCTZ;

if that doesn’t work, try indomethacin

Front 119

Li+-induced DI – tx w

Back 119

*DOC=amiloride (prevents entry of Li+ into principal cells of LDT/CD)

*or HCTZ

Front 120

Carcinoid syndrome =

-desc
-tx

Back 120

bronchospasm, GI cramping and diarrhea, "odd" flushing of the skin, hypotension and increased urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid)

*tx w:
-cyproheptadine (blocks 5-HT1 and 5-HT2 receptors) or
-the somatostatin analog octreotide, which inhibits the release of 5-HT from the tumor.

Front 121

increased urinary excretion of 5-HIAA (5-hydroxyindoleacetic acid

Back 121

carcinoid syndrome

Front 122

metoclopramide

Back 122

1. Blocks D2-receptors in CTZ (block CTZ)=anti-emetic– prevents nausea;

S/E’s = EPS, hyperprolactinemia

2. Blocks 5-HT3 receptors in CTZ and at vagal afferents – prevents nausea/emesis

3. Stimulates 5-HT4 receptors on prejunctional cholinergic neurons to amplify the release of ACh, ACh stimulates muscarinic receptors in the GI tract
==>empty the stomach prior to emergency surgery

4. Tx GERD (via incr LES tone)

Front 123

ondansetron

Back 123

antiemetic drug which blocks 5-HT3 receptors in CTZ and at vagal afferent fibers

(“—setron”= antiemetic, blocks 5-HT3 in CTZ)

Front 124

cisapride

Back 124

Tx:
-GERD
-empty stomach prior to emergency surgery

agonist at 5-HT4 receptors on prejunctional cholinergic neurons - amplifies the release of ACh to increase tone in the LES

Front 125

sumatriptan

Back 125

agonist at 5-HT1B and 5-HT1D receptors to inhibit the release of inflammatory peptides

*used to treat migraine headache and cluster headache

Front 126

buspirone

Back 126

-a partial agonist at 5-HT1A (serotonin) receptors;

-opens K+ channels to hyperpolarize neurons; used to tx anxiety, slow onset of action, no drug dependence

Front 127

histamine H1-receptors

Back 127

-dilate arterioles
==>"rubor" & "calor" of acute inflamm

-contracts vascular endothelial cells
==>increase capillary permeability

-contract GI smooth muscle==> diarrhea

-contracts bronchial SmM==>asthma

-stimulates afferent pain receptors==>pain/itch ("dolor" of acute inflam)

Front 128

H2-R

Back 128

-dilate arterioles
-increases gastric H+ secretion

Front 129

cromolyn sodium

Back 129

inhibits mast cell degranulation by preventing incr in intracellular Ca++

Front 130

olopatidine

Back 130

inhibits mast cell degranulation and blocks histamine H1-receptors, used
to tx conjunctivitis assn with seasonal allergy

Front 131

Sedating antihistamines =

Back 131

-diphenhydramine (benadryl)
-meclizine (prophylaxis against motion sickness and n/v during pregnancy)

Front 132

Non-sedating antihistamines =

Back 132

terFENADINE
fexoFENADINE
clemastine

Front 133

Prophylaxis of motion sickness

Back 133

Prophylaxis of motion sickness (need to block central muscarinic ACh receptors)

= dimenhydrinate, meclizine and scopolamine

Front 134

Tx of Meniere’s disease

Back 134

Meniere’s disease (hearing loss, vertigo, tinnitus from nonsuppurative disease of the labyrinth of ear)

DOC=meclizine (prophylaxis for motion sickness & n/v during pregnancy)

Front 135

H2-receptor blockers =

Back 135

cimeTIDINE
famoTIDINE
raniTIDINE

(Every girl wants "to dine" (TIDINE) w/a guy who owns an H2 (Hummer))

blocks gastric acid secretion,
also blocks allergic responses in the skin

Front 136

Sedating antihistamines =

Back 136

diphenhydramine, meclizine (H1 blockers)

Front 137

Non-sedating antihistamines =

Back 137

= terfenadine, fexofenadine, clemastine

Front 138

Prophylaxis of motion sickness

Back 138

PROPHYLAXIS of motion sickness (need to block central muscarinic ACh receptors):

*dimenhydrinate
*meclizine
*scopolamine (“Give Scop to ppl on a Ship”)

(mneum:

“2 men (dimen) hydrate (hydrinate) their pregnant wives to prevent motion sickness.”

“The “2 men” (dimen) are named “mec” and “liz”.”

Front 139

Tx of Meniere’s disease

Back 139

Meniere’s disease (hearing loss, vertigo, tinnitus from nonsuppurative disease of the labyrinth in ear)

DOC=meclizine

Front 140

H2-receptor blockers =

Back 140

cimetidine, famotidine, ranitidine – blocks gastric acid secretion,
also blocks allergic responses in the skin

Front 141

Clinical: A patient exposed to poison oak - how tx?

Back 141

; To completely block the vasodilation, must give both H1 blocker (diphenhydramine) and H2 blocker (cimetidine)

Front 142

Clinical: A patient w GERD is being treated with cimetidine requires allergen testing by a dermatologist.

Back 142

Must d/c cimetidine to ensure accuracy of skin tests. Tx GERD w
omeprazole during allergy testing.

Front 143

Clinical: Patient has insomnia from depression; tx with a TCA but patient still has insomnia. what happens if give antihistamien (i.e. diphenhydramine)

Back 143

patient gets urinary retention
from combined atropine-like effect of the drug combination