Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm Block 2 > Drug List Block 2 - Sheet1 > Flashcards

Drug List Block 2 - Sheet1 Flashcards

1
Q

Synthetic analog of PGE2

Therapeutic uses:

  1. Cervical ripening
  2. Terminating early pregnancy/abortion

Mechanism:
1. Activation of collagenase also relaxing cervical smooth muscle EP4 receptor subtype (for cervical ripening)

  1. Uterine contractions via EP1/3 receptors

SE:
GI related (nausea, vomiting, diarrhea)
Fever
Uterine rupture: contraindicated in women having history fo cesarean section or other uterine surgery

A

Dinoprostone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Analog of PGF2alpha

Therapeutic use:

  1. Termination of pregnancy in 2nd trimester
  2. Control postpartum hemorrhage that is not responding to conventional treatment methods

Mechanism:

  1. Stimulates uterine contractility by action at FP receptors
  2. Postpartum, the drug cause myometrial contractions via FP receptors. This provides hemostasis at the stie of placenta formation
SE: 
GI related (nausea, vomiting, diarrhea)
Fever
Uterine rupture (contraindicated in women having history of cesarean section or other uterine surgery)
Rare case of bronchoconstrictino
A

Carboprost

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

PGE1 analog

Therapeutic use:
Replacement therapy for prevention of ulcers caused by long term NSAIDS

Mechanism:
Suppresses gastric acid secretion by stimulating EP3 receptors on parietal cells; causes decrease in cAMP
Increase mucin and bicarbonate secretion
Increase mucosal blood flow

SE: Diarrhea-common and contraindicated in pregnancy

*(Misoprostol used with methotrexate or mifepristone for termination of early pregnancy)

A

Misoprostol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

PGE1

Use:

  1. Impotence/ED
  2. Maintenance of patent ductus arteriosus

Mechanism of action

  1. Increase in cAMP which relaxes smooth muscle fo corpus cavernosum
  2. cAMP mediated relaxation of ductus arteriosus smooth muscle

SE:
1. Pain at site of injection (reason for intra-urethral formulation)
Priapism: prolonged erection
2. Apnea in 10% of neonates,

A

Alprostadil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

PGI2 agonist

Therapeutic use: Primary pulmonary hypertension.

Mechanism: cAMP mediated dilation of pulmonary artery vascular smooth muscle

SE: Nausea, vomiting, headache, flushing

A

Epoprostenol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Prostaglandin PGF2alpha analog

Uses: glaucoma and eyelash hypotrichosis

Mechanism: Increases outflow of aqueous humor and Increases the percent and duration of hairs in the growth phase.

Pharmacology: administered as opthalmic drops

SE: Eye redness, itching, permanent changes in eye color (increased brown pigment), eyelid skin; may increase length and number of eyelashes

A

Bimatoprost

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Mechanism: Blocks 11 beta hydroxylation so synthesis is stopped at 11-desoxycortisol. Does not inhibit ACTH release, so plasma ACTH increases stimulating synthesis and excretion of 17-hydroxycorticoids as 11-desoxycortisol.

Used as a diagnostic test

A

Metyrapone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Competitive antagonist at progesterone and glucocorticoid receptors

Progesterone antagonist- Termination of pregnancy
Glucocorticoid antagonist- Treat cushing syndrome etc.

A

Mifepristone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Competitive antagonists at mineralcorticoid receptor

Uses: diuretics, cardiac fibrosis/hypertrophy, HTN

A

Spironolactone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Competitive antagonists at mineralcorticoid receptor

Uses: diuretics, cardiac fibrosis/hypertrophy, HTN

A

Eplerenone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Progesterone and Mineralocorticoid and Androgen receptor antagonist

Mineralcorticoid antagonist-diuretic, antagonizes the salt retaining effects of estrogen
Progesterone Agonist- Used with estrogen to suppress ovulation and as hormone replacement therapy in post menopausal women
Androgen receptor antagonist

A

Drospirenone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Responses: 1. Lymphocytopenia and monocytopenia, Prevent neutrophil adherence to endothelium, Inhibit action of chemotactic factors
2. Interferes with macrophage antigen processing, blocks the actions of lymphokines, inhibits binding to Fc receptors

Toxicity: 1. Suppression of adrenal-pituitary axis (acute adrenal insufficiency on abrupt withdrawal
2. Cushing’s syndrome

Contraindication: in presence of existing infection

Uses: in combination with other drugs in autoimmune diseases and to prevent graft rejection

A

Prednisolone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Mechanism: Metabolized to 6-mercaptopurine, a purine antimetabolite that inhibits purine biosynthesis thereby inhibitng DNA synthesis, inhibits De novo AND salvage pathways.

Pharmacology: Orally active

Used to inhibit rejection of transplanted organs and some autoimmune diseases such as rheumatoid arthritis

SE: Bone marrow depression, GI and hepatic toxicity

A

Azathioprine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Mechanism: alkylating agent that cross links DNA to kill replicating and nonreplicating cells.

Pharmacology: Toxic effect more pronounced on B cells so more effective in suppressing humoral immunity.
Orally active.

Use: treatment of autoimmune diseases in combination with other drugs.
NOT EFFECTIVE IN PREVENTING GRAFT REJECTION

SE: Bone marrow depression

A

Cyclophosphamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mechanism: inhibitor of dihydrofolate reductase, inhibits folate dependent steps in purine synthesis, inhibiting DNA synthesis

Use: treat autoimmune diseases

SE: Hepatic toxicity

A

Methotrexate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Mechanism: Lymphocyte selective immunosuppressant by inhibiting IMP dehydrogenase (necessary for de novo purine synthesis w no effect on salvage pathway). Lymphocytes cannot make GMP via salvage. More selective than AZA or methotrexate but equally effective

Pharmacology: Orally active
Used with cyclosporine and corticosteroids to prevent renal allograft rejection (allowing lower dose of cyclosporine)

Use: treat autoimmune diseases– rheumatoid arthritis and refractory psoriasis

Contraindications: Active GI disease, reduced renal function and infections. Also pregnancy (loss and congenital malformations)

SE: infection, leukopenia, anemia

A

Mycophenolate Mofetil

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Mechanism: binds to cellular receptor Cyclophilin and inhibits calcineurin (a calcium dependent phosphatase), blocking activation of transcription factor NFAT necessary for IL 2 production. Blocks T cell helper function.

Pharmacology: Orally active

Use: Prevent rejection of transplanted organs. some autoimmune diseases. more effective than other agents used with fewer side effects

SE: nephrotoxicity. Hepatotoxicity

A

Cyclosporine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Mechanism: binds FK binding protein a cyclophilin related protein, same mechanism as cyclosporine. Spectrum is same but 50-100 more potent

SE: less nephro and hepatotoxicity

A

Tacrolimus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Mechanism: Inhibits T cell activaiton and proliferation downstream of IL-2. Binds FKBP-12, binds and inhibits mTOR (not calcineurin), this mTOR is a kinase involved in cell cycle progression blocking G1->S transition

Use: Same as cyclosporine. Coating of cardiac stents.

A

Sirolimus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Mechanism: Irreversible inhibitor of cyclooxygenase 1 and 2.

Uses:
Cancer?
CV disease (low dose)
Fever, pain, (intermediate dose)
Chronic inflammatory disease/rheumatoid arthritis (high dose)

SE: Typical NSAIDs side effects + Salicylism + Reye’s Syndrome

Pharmacology:
Non COX inhibition effects (1. Uric acid excretion 2. CNS 3. Respiration)

  1. At low dose decrease uric acid secretion. at high dose increase uric acid excretion.
  2. CNS (b/c crosses BBB) delirium psychoses, nausea, vomiting.
  3. Respiration (Direct stim of respiratory center to increase RR, leading to respiratory alkalosis, compensated by a renal excretion of bicarbonate.
  4. Salicylism
  5. Reye’s syndrome (liver failure and death related to viral epidemics
A

Acetylsalicylic Acid/Aspirin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Mechanism: Reversible inhibitor of COX 1 and COX 2. Naproxen has a much longer plasma half life (14 hr vs. 2) than ibuprofen

Uses:
Both: Rheumatoid disorders (including juvenile rheumatoid arthritis), osteoarthritis, mild-to-moderate pain, dysmenorrhea, fever,
Ibuprofen: Inflammatory diseases, IV preparation to induce closure of PDA in premature infants less than 32 wk gestational age when usual treatments ineffective.
Naproxen: manage ankylosing spondylitis, acute gout/bursitis/tendonitis,

SE: Less GI effects than Aspirin

A

Ibuprofen and Naproxen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Mechanism: Reversible inhibitor of COX 1 and COX 2

Uses:
gout
preterm labor (investigational)
IV form used for closure of patent ductus arteriosus in neonates,
not routinely used to treat pain or fever.

SE: Frequent adverse rxns, CNS severe frontal headache, better tolerated if given at night

A

Indomethacin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Mechanism: Reversible inhibitor of COX 1 and COX 2

Uses:
Alternative for opioid analgesics in treatment of post-operative pain (short term, and much more effective for pain than inflammation)

SE: Serious adverse effects

A

Ketorolac

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Mechanism: Active metabolite (6methoxy2naphthylacetic acid) is reversible inhibitor of COX2 moreso than COX-1.

Uses:
Osteoarthritis
Rheumatoid arthritis

SE: Well tolerated with less GI effects

A

Nabumetone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Mechanism: Reversible inhibitor of COX 1 and COX 2. SUPER LONG HALF LIFE plasma T1/2 50 hours

Uses:
Symptomatic treatment of acute and chronic rheumatoid arthritis and osteoarthritis, advantage in osteoarthritis treatment because of LONG HALF LIFE.

SE: GI toxicity

A

Piroxicam

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Mechanism: 5-aminosalicylic acid (mesalamine) active component linked to sulfapyridine (a sulfa antibiotic) by azo bond (which prevents absorption in upper GI tract). NOT CYCLOOXYGENASE INHIBITION. Possibly inhibition of IL-1, TNFalpha, lipoxygenase pathway, scavenging of free radicals oxidants, inhibition of NF-kappaB.

Uses:
Mild or moderately active ulcerative colitis (b/c of mesalamine)
Rheumatoid arthritis and ankylosing spondylitis (b/c of sulfapyridine)

SE:
High % for b/c sulfa moiety
Allergic rxns (rash, fever, hepatitis, pneumonitis, hemolytic anemia, bone marrow suppression)
Decreases number and motility of sperm

Therapeutic application: mild or moderately active ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis

A

Sulfasalazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Mechanism: COX-2 selective inhibition. Metabolized by CYP450 2C9

Uses:
Rheumatoid arthritis and osteoarthritis
Primary dysmenorrheal
Management of acute pain
reduce # of intestinal polyps in familial adenomatous polyposis (COX2 contributory to certain cancers)

SE:
Hypersensitivity
Increase risk in GI irritation, ulceration, bleeding
Increased risk of adverse CV thrombotic events
Anemia (rare)

Contraindications:
Sulfonamide toxicity
Prior NSAID hypersensitivity
CV risk factors/disease
GI disease
Coronary artery bypass graft surgery
CYP2C9 deficiency
A

Celecoxib

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Mechanism: No aff for COX1 or COX2 active site. inhibits reduction of COX to peroxidase form, brain selective? COX3?
Metabolized partially by liver microsomal system (CYP2E1, CYP1A2, CYP3A4), but mostly by glucoronidation and sulfation (95%)

Uses:
Treatment of mild-to-moderate pain and fever; does not have antirheumatic or anti-inflammatory effects

SE:
Well tolerated with little to no GI issues at normal doses. But with excessive use results in hepatic toxicity… evidenced by elevated liver enzymes like aminotransferase.
NAPQI (N-acetyl-p-benzoquinoneimine toxicity if glutathione reduced), covalently binds amino acids in proteins and enzymes.
N-acetylcysteine used to replenish glutathione stores to manage toxicity.

Contraindication:
Ethanol use, as alcohol induces CYP450 (producing NAPQI) and depletes glutathione.

A

Acetaminophen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

1st generation with most sedative effect

Uses: Allergies, Motion sickness, Sleeping, Early stage Parkinson’s disease

A

Diphenhydramine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

1st generation

Uses: Allergies, Motion sickness, Vestibular disturbances

A

Dimenhydrinate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

1st generation

A

Chlorpheniramine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

1st generation

Uses: Allergies, Motion sickness, Chemotherapy induced nausea and vomiting

A

Promethazine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

2nd generation

NOT metabolized by P450

A

Fexofenadine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

2nd generation

Metabolized by CYP450 to desloratadine

A

Loratadine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

2nd generation with most sedative effect

Active metabolite of hydroxyzine

A

Cetirizine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

H2 receptor antagonist

Has the most potential for adverse effect due to inhibiting P450 metabolism

A

Cimetidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

H2 receptor antagonist

A

Famotidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

H2 receptor antagonist

Also inhibits P450 metabolism but to less of an extent than Cimetidine

A

Ranitidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Mechanism: Stabilizes mast cell membrane to prevent release of histamine.

Uses:
Chronic control of asthma and prophylaxis of bronchospasm (allergen or exercise induced). NOT A RESCUE MEDICINE
Nasal formulation for allergies
Opthalmic formulation for conjunctivitis
Oral formulation for systemic mastocytosis (significant increases in mast cell numbers in the skin and internal organs)
Off label uses for food allergy and irritable bowel syndrome

SE: Safe drug/few side effects

A

Cromolyn sodium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Mechanism: IgG monoclonal antibody for which the antigen is the Fc region of the IgE antibody. Forms omalizumab-IgE complexes ergo no affinity for FcRI

Uses: Decreases amount of antigen specific IgE that normally binds to and sensitizes mast cells,

SE: Injection site reaction, anaphylaxis after the first dose and in some cases >1 year after initiation of regular treatment.

A

Omalizumab

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

5-HT2 receptor agonist. Hallucinogen

A

lysergic acid diethylamide

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

5-HT1A receptor partial agonist- antianxiety

A

buspirone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Agonist for 5-HT1D receptor on cerebral blood vessels.

Promote vasoconstriction. Treatment of migraine headaches, stops existing ones.

SE: nausea, vomiting, angina, dizziness, flushing

A

sumatriptan

44
Q

5-HT4 partial agonist. Releases other enteric transmitters. Normalizes impaired intestinal motility, stimulates intestinal secretion

Uses: For irritable bowel syndrome with constipation in women.

SE: Taken off market 2007 due to CV effects, but restored with limited prescribing program

A

Tegaserod

45
Q

Selective 5-HT2C receptor agonist. activation of receptors in the hypothalamus activate spropiomelanocortin (POMC) production

Uses: Treatment of obesity with BMI greater than 30. Promotes weight loss through satiety

A

Lorcaserin

46
Q

Serotonin specific reuptake inhibitors (SSRIs), block active reuptake of serotonin. Increases amount of transmitter in synapse.

Uses: Treatment of affective disorders,, OCD, panic attacks.

SE:Sexual dysfunction nausea etc.

A

fluoxetine

47
Q

Monoamine oxidase inhibitor, block metabolism of serotonin, NE, and DA. Increased synaptic serotonin.

Uses: Treatment of affective disorders and narcolepsy

SE: hypertensive crisis

A

phenelzine

48
Q

5-HT2 antagonist, also histamine H1 antagonist.

Uses: Treatment of allergies, pruritis, urticaria. Carcinoid.

A

cyproheptadine

49
Q

5-HT3 antagonist, CNS and GI action

Uses: Treatment of chemotherapy induced nausea and vomiting, post op and x ray therapy induced nausea and vomiting

A

ondansetron

50
Q

Selective 5-HT3 antagonist

Uses: treat diarrhea predominant IBS in women.

SE: Can produce severe GI adverse effects. A restricted prescribing program must be followed

A

alosetron

51
Q

Syntheized from serotonin in pineal. Own receptors M1, M2- Gi associated

Uses: Entrains circadian clock, target for insomnia treatment.

A

Melatonin

52
Q

Vasodilator drugs

A

Nitroglycerin, Nitroprusside, Hydralazine, Minoxidil, Diazoxide, Ca2+ channel blockers, Verapamil, Diltiazem, Milrinone, Inamrinone, Cilostazol, Sildenafil, Tadalafil, ACE inhibitors, Fenoldopam, Prazosin

53
Q

Bronchodilator drugs:

A

Albuterol, Pirbuterol, Terbutaline, Salmeterol, Formoterol, Ipratropium, Tiotropium, Theophylline, Aminophylline

54
Q

Mechanism: Generation of nitric oxide, activating guanylate cyclase, increasing cGMP, resulting in relaxation. Venous dominant,

Uses: Heart failure

Effects: hypotension

A

Nitroglycerin/Isosorbide Dinitrate/Isosorbide-5-mononitrate

55
Q

Mechanism: NO releasing, guanylate cyclase action, increase cGMP, relaxation. Arterial/venous both affected

Use: hypertensive emergencies

SE: hypotension

A

Nitroprusside

56
Q

Mechanism: Unknown. Direct vasodilator

Uses: Heart failure patients, pill with Isosorbide dinitrate (works on venous circulation), working on arterial circulation. Severe/emergencies hypertension.

A

Hydralazine

57
Q

Mechanism: K+ATP channel opening. Works on arterial circulation. Direct vasodilator

Uses: Severe hypertension and hair growth for males.

SE: Fluid retention (so use with diuretics)

A

Minoxidil

58
Q

Mechanism: K+ channel opener, efflux of K+ leads to hyperpolarization, closing Ca2+ channel, preventing contraction

Uses: in hypertensive emergencies (and hypoglycemia) and in hypoglycemia

A

Diazoxide

59
Q

Ca2+ Channel blockers

A

Examples: Nifedipine, Verapamil, Diltazem

Mechanism: Block the L-type Ca2+ channels. Non selective, and affect arterial circulation, block Ca2+ influx.
Heart vs. Vascular Smooth Muscle: PKA phosphorylates Ca2+ channel causing influx and contraction. Versus. PKA phosphorylates and inactivates MLCK, normally activating by phosphorylation Myosin light chain.

60
Q

PDE3 inhibitors

A

Milrinone, inamrinone, cilostazol

Intracellular signaling

Used for heart failure (and dilate vacular smooth muscle)

61
Q

PDE5 inhibitors

A

Sildenafil, tadalafil
Intracellular signaling
Erectile dysfunction

62
Q

Mechanism: Vasodilator on endothelial through action on B2 receptor through release prostaglandins, nitric oxide, and epoxygenase metabolites. Increased by ACE inhibitor. (because ACE breaks down bradykinin). SO A LITTLE DIFF THAN AT1 RECEPTOR BLOCKER. Works on both arterial and venous circulation

A

Bradykinin

63
Q

Mechanism: Dopamine 1 receptor agonist. Arterial and venous circulation

Use: Good for hypertensive crisis. Renal blood flow and Na excretion increased

A

Fenoldopam

64
Q

Mechanism: Vasodilator that blocks NE acting on Alpha-adrenergic receptors. Arterial and venous circulation

A

Prazosin

65
Q

Mechanism: Oxytocin antagonist, inhibit uterine contractions
Works through PLC, increasing Ca2+, causing contraction

Use: Preventing pre term labor

A

Atosiban

66
Q

B2 adrenergic agonists

A

Bronchodilators
Examples: Albuterol (most widely used), Pirbuterol, terbutaline, Simeterol, Formoterol

Mechanism: Beta 2 agonist causes rise in cAMP/PKA resulting in relaxation. Also acts on Calcium activated potassium channels to cause Potassium efflux and hyperpolarization and relaxation.

SE: Cardiotoxicity-tachycardia (Beta 2 on the cardiac smooth muscle)

67
Q

Anti cholinergic bronchodilator

A

Bronchodilators
Examples: Ipratropium, tiotropium

Mechanism: Block muscarinic receptors, blocking a contraction pathway. (Acetylcholine acting on M3 receptor typically causes contraction)

Use: Can also be used for inhibiting mucous secretion

68
Q

Methylxanthine

A

Bronchodilator
Examples:Theophylline, aminophylline

Mechanism: Adenosine receptor antagonism and phosphodiesterase inhibition. Increasing cAMP leading to bronchodilation. Also inhibits Adenosine from causing bronchoconstriction.

Use: Good for mucous clearance, antiinflammatory actions, prevent edema by decreasing permeability.

69
Q

ACE inhibitors

A

Examples: captopril, enalapril, lisinopril

Improves CHF survival, regardless of BP
Increases Bradykinin levels, resulting in increase in Nitric oxide and Prostaglandins

Decreases MAP when Angiotensin I given
Does not change MAP when Angiotensin II given
Does not change MAP when NE given
Increases decrease in MAP when Brady kinin given (enhances bradykinin response)
Does not change loss in MAP when other vasodilators given

SE: Cough and rash (due to elevation in bradykinin), Taste disturbance, rarely an allergic reaction resulting in angioedema (life threatening, and thus CANNOT USE ACE INHIBITOR. CONTRAINDICATION)

Pharmacology:
Racial differences in antihypertensive response (Blacks less response to ACE inhibition or angiotensin renin system. Thus the first antihypertensive you would prescribe is diuretic. Cauc/asian have same response to either)

70
Q

Renal Vasodilators

A

Examples: Dopamine, Fenoldopam, Caffiene, Atriopeptins

Mechanism: Selectively dilates renal vasculature that modifies proximal tubular function. Increases RBF with no change to GFR, decreasing filtration fraction, resulting in decreased proximal tubular sodium reabsorption which is compensated by more distal nephron segments limiting diuretic effect

Therapeutic uses: Limited, hypertensive crisis and shock

71
Q

Osmotic Diuretics

A

Examples: Mannitol

Mechanism: (1. Freely filtered. 2. Not reabsorbed. 3. Metabolically inert)
Given IV, act in tubular lumen as nonreabsorbable solute, Urine volume and Na+ excretion are proportional to osmotic load. Thus increased urinary excretion of sodium, potassium, chloride, water, and mannitol.

Therapeutic uses: Edema, glaucoma, acute renal failure

SE: Related to volume overload and expansion of intravascular fluid volume. Also a rare hypersensitivity

72
Q

Inhibitors of carbonic anhydrase

A

Examples: Acetazolamide

Mechanism:
Weak diuretic
Inhibited by acidosis-limits clinical use
Filtered and secreted by Organic Acid Transporter, acts from tubular lumen
Inhibits Carbonic anhydrase in the proximal distal tubule (which normally provides H+ ions for bicarbonate reabsorption)
Increases excretion of Na+, K+, bicarbonate, H2O
Alkalinize the urine

Therapeutic uses: 
Glaucoma
Alkalize the urine for decreasing drug toxicity
Altitude sickness
Anticonvulsant

SE: Metabolic acidosis and Hypokalemia

73
Q

Loop diuretics

A

Examples: Furosemide, Bumetanide, Etharynic acid

Mechanism:
High efficacy (20-30%)
Rapid in onset and short duration of action (20 min)
Na+ K+ 2Cl- Symport inhibitors
Filtered and secreted by the OAT
Acts on the cortical and medullary segments of the ascending limb of the loop of Henle
Increase the excretion of sodium, potassium, chloride, and water
Increases the renal blood flow and GFR
Enhances calcium excretion
Large urine volume

Therapeutic uses:
Edema of cardiac, hepatic, or renal origin,
Acute pulmonary edema
Hypertension

SE: 
Hypokalemia
Alkalosis
Hypovolemia
Hyperuricemia
Hyperglycemia (furosemide only)
Ototoxicity
74
Q

Thiazide diuretics

A

Examples: Chlorothiazide, Hydrochlorothiazide, Metolazone

Mechanism:
Intermediate efficacy
Moderate onset (60 min)
Long duration
Filtered and secreted by the OAT
Inhibits Na-Cl symporter
Acts on cortical segment of distal tubule
Increases excretion of Na+ K+ Cl- H2O
Urine is hypertonic-unable to dilute
Increases K= secretion
Enhances urate reabsorption (PT)

Therapeutic uses:
Edema due to CHF
Hypertension
Hypercalcinuria/Ca salt-renal caliculi

SE:
Hypokalemia
Alkalosis
Hyperuricemia
Hyperglycemia
Decrease in GFR
75
Q

Potassium sparing diuretics

A

Examples:
Spironolactone, Eplerenone (Aldosterone antagonists): Block aldosterone action on collecting duct
Triamterene, Amiloride (Na+ channel inhibitors): Block Na+ entry into principal cells of the collecting duct

Mechanism:
Low efficacy
Weak diuretic
Increases Na+ excretion without K+ loss
Increase Na+ excretion
Decrease K+ excretion
Increase urinary excretion of sodium, chloride, and H2O

Therapeutic uses:
Edema
Hypertension
Seldom used alone but with thiazide or loop diuretics to enhance naturesis without potassium loss
Aldosterone antagonism improves survival in heart failure

SE:
Low efficacy
Hyperkalemia if used alone, thus usually used with thiazide
Gynecomastia (spironolactone»eplerenone)
Triamterene decreases RBF and GFR
Na+ channel inhibitors-mild azotemia

76
Q

Heterogeneous mixture of sulfated polysaccharides
Large and highly negatively charged (must be IV or subcutaneous injection)
DOES NOT: affect synthesis of clotting factors or lyse existing clot
DOES: Prevent further clot formation and further extension of the clot

Cleared and degraded by the reticuloendothelial system (monocytes and macrophages in reticular connective tissue) and liver

Mechanism: Catalyzes antithrombin’s inhibition of several coagulation proteases.

Therapeutic use:
Deep venous thrombosis or pulmonary embolism. (USE IV INFUSION FOR INITIAL TREATMENT, also administer warfarin)
Low dose used as prevention in surgical patients
Initial management of unstable angina or acute myocardial infarction
Coronary angioplasty or stent replacement
Surgery requiring cardiopulmonary bypass
In Vitro with: 1. hemodialysis, 2. blood samples drawn for lab, 3. Maintain patency of indwelling arterial catheters
Does not cross placenta, so used in pregnancy for anticoagulation

SE:
Bleeding/hemorrhage (treat with protamine sulfate)
Heparin induced thrombocytopenia (immune response decreasing platelet counts by 50% due to IgG antibodies formed against complex of heparin-platelet factor 4 a chemokine released during platelet activation binding to FcgammaIIa receptors on platelet). Discontinue heparin and use LMWH or lepuridin

CI:
active bleeding
Severe uncontrolled HTN
Recent surgery of eye, brain, spinal cord

A

Heparin (UFH)

77
Q

Suicide substrate for thrombin, 10a, 9a, 11a, 12a
Because activated coag factors attack specific Arg-Ser peptide bond in the reactive site, becoming trapped and inactivated.
1000 fold increase in rxn rate in presence of heparin. 3x D-glucosamines and 2x uronic acid residues bind to AT making reactive site more accessible to proteases.

A

Antithrombin function

78
Q

Examples: Enoxaparin/Dalteparin

Fragment of standard MW Heparin.

Administered subcutaneously, with longer half life than heparin so advantage in hospital setting.

Poorly catalyze inhibition of thrombin by ATIII because it can no longer ALSO bind to the thrombin (in addition to the ATIII). You end with somewhat more specificity for 10a,9a,11a,12a.

Therapeutic Use:
Acute DVT
Prophylaxis of DVT
Hip replacement surgery, during, and following hospitalization
Acute unstable angina and MI

SE:
Risk in patient with renal disease due to renal elimination
Less risk of bleeding compared to heparin
Lower risk of thrombocytopenia compared to heparin

CI:
Active bleeding
Severe uncontrolled hypertension
Recent surgery for eye, brain, spinal cord
Renal impairment
A

Low molecular weight heparins (LMWH)

79
Q

LMWH

A

Enoxaparin/Dalteparin

80
Q

Direct thrombin inhibitor

Mechanism: Inactivates thrombin by blocking the substrate binding site 1:1 complex. Bind to both the catalytic site and exosite 1

IV administration (as compared to dabigatron, which is oral)

Renal excretion

Therapeutic use: alternative to heparin in patients with heparin-induced thrombocytopenia

A

Lepirudin/Bivalirudin

81
Q

Direct Factor 10a inhibitor
Synthetic pentasaccharide

Subcutaneous administration (as compared to rivaroxaban, which is oral)
Renal excretion

Therapeutic use:
Prevention of DVT in patients undergoing surgery
Treatment of acute PE
Treatment of acute DVT w/o PE

A

Fondaparinux

82
Q

Heparin antagonist Low MW, + charged.
1:1 binding with heparin

SE:
Weak anticoagulant properties in high doses or when alone
Anaphylactic reaction from fish hypersensitivity and previous exposure from insulin products
Severe pulmonary hypertension

Therapeutic use:
Heparin overdose with acute bleeding that cannot be controlled by stopping heparin
Reverse heparin following cardiopulmonary bypass

A

Protamin sulfate

83
Q

Oral anticoagulant

Structural analog of Vitamin K. 3 types, racemic/S/R…
Administered as racemic but S is more active form.
Metabolized differently KNOW MORE FOR S: (S uses CYP2C9) (R uses CYP1A1, 1A2, 3A4)

Mechanism: (Moreso S-warfarin) Blocks VKORC1 (vitamin K reductase), preventing the recycling of oxidized Vitamin K (epoxide) to the reduced form (hydroquinone). This results in preventing the gamma-carboxylation of several glutamate residues in
prothrombin, 7,9,10, and endogenous anticoagulalant proteins C and S.

This is a competitive inhibition because Vit K administation will displace warfarin.

Therapeutic effect not seen for several hours to days
Peak plasma at 24 hours

CI: 
same as heparin, also
CYP2C9 polymorphisms
Genetic variations in VKORC1
Pregnancy/teratogenic, boen metabolism is vit k dependent
Liver, kidney disease, vit k deficiency

Adverse reactions that are rare
Purple toe syndrome
Skin necrosis/gangrene

A

Warfarin

84
Q

PT, prothrombin time

  1. Blood sample collected with citrate to inactivate calcium and prevent clotting
  2. Add thromboplastin, a saline extract of brain containing tissue factor and phospholipids
    NORMAL CLOTTING in 12-14 seconds

Tests extrinsic and common pathway.

*There is a variability in thromboplastin, so ratio of patient PT to a control PT is obtained by standard method using WHO primary standard thromboplastin. So you actually measure INR

Normal INR between 0.8-1.2

Warfarin is therapeutic when PT betwen 15-26
INR usually 2-3

*Therapeutic effect of warfarin delayed because… blocks synthesis of clotting factors. The circulating factors are not inhibited by warfarin. so These active factors are still aorund while no longer able to synthesize any more active factors

A

How to test for warfarin function

85
Q

If INR at therapeutic 2-3: Stop drug

If INR>5: give Vitamin K

For immediate reversal: transfusion with fresh frozen plasma

A

How to reverse warfarin

86
Q
  1. CYP2C9*2 and *3 have decreased activity so wafarin not inactivated so use less warfarin
  2. VKORC1 variants. If produce less, then use less warfarin. If produce more, use more warfarin
A

Why might the dosage of warfarin be varied among individuals

87
Q

Oral anticoagulant.a direct thrombin inhibitor.
Lepirudin is the IV equivalent

Given as a pro-drug, metabolized to active dabigatran

Mechanism: interacts with active site of thrombin thus potent, reversible, competitive direct thrombin inhibitor that inhibits BOTH FIBRIN-BOUND AND FREE THROMBIN

Pharmacokinetics:
Predictable
Oral
Rapid onset (2 hours peak plasma)
Short half life (14-17 hr)
Not substrate for CYP450
Excreted by kidney
Must be carefully stored since administered as pro-drug can breakdown if exposed to moisture (30 days of stability)

P-glycoprotein can limit oral absorption of drugs by transporting them back into GI.

SE:
Less for bleeding compared to warfarin
No antidote!! Depends on excretion with plasma halflife of 14 hr
Upset GI

CI:
Renal impairment
Advanced liver disease
Valvular heart disease (bioprosthetic heart valves). More dangerous than with warfarin.
Drug interactions with P-glycoprotein efflux transporters. (If used with P-gp inducer, plasma conc and half life reduced. If used with P-gp inhibitor, increased plasma concentration)

Therapeutic Use:
Patients with nonvalvular atrial fibrillation at risk for stroke or systemic embolism
Prophylaxis in patients with knee or hip replacement

A

Dabigatran

88
Q

Oral anticoagulant, a direct 10a inhibitor
Fondaparinux is the subcutaneous equivalent

(notice the Xa in the name..)

Good because Xa is primary site of amplification (1000 cul thrombin per 1 cul Xa)
Also good because you wouldn’t affect existing thrombin levels

Unlike heparin, capable fo gaining access to clotbound factor 10a. Inhibits both free factor 10a and factor 10a in the prothrombinase complex. This prevents extension of the thrombus by blcoking further generation of thrombin within the clot

Pharmacokinetics:
1/3 renal eliminated unchanged
2/3 metabolized in liver, half of which renal half of which hepatobiliary route
CYP450 metabolized. 
Substrate for P-glycoprotein

No significant between group difference in risk of major bleeding ALTHOUGH INTRACRANIAL AND FATAL BLEEDING OCCURRED LESS FREQUENTLY WITH RIVAROXABAN GROUP

SE:
Bleeding
Drug interactions with CYP3A4 inhibitors/inducers AND P-glycoprotein inhibitors/inducers

No good monitoring

Therapeutic Use:
Similar to dabigatran
(patients with nonvalvular atrial fibrillaiton at risk for stroke or systemic embolism)
(Prophylaxis in patients with knee or hip replacement)

A

Rivaroxaban

89
Q

Thrombin bound to fibrin within a thrombus remains enzymatically active and protected from inactivation by antithrombin.

Fibrin-bound thrombin can locally activate platelets and trigger coagulation thereby causing thrombus growth

A

Importance of free thrombin vs. fibrin-bound thrombin

90
Q

None. little effect on PT or INR

A

Monitoring of dabigatran and rivaroxaban

91
Q

Aminocaproic acid
Tissue plasminogen activator (t-PA)
Alteplase

A

Thrombolytic drugs

92
Q

Plasminogen converted to plasmin by cleavage of single peptide bond Arg560-Val561). Generates a towo chain disulfide linked molecule exposing the kringles. N terminus/heavy chain has 5 disulfide bonded loops to bind lysine residues in polymerized fibrin. C terminus/light chain, contains the active catalytic site

t-PA (endogenous) and Alteplase (exogenous) cleaves the ARG-VAL bond to form plasmin from plasminogen

Plasmin is fibrin-specific due to alpha2-antiplasmin

A

Mechanism for fibrinolysis

93
Q

t-PA recombinant

Activates bound plasminogen several hundred fold more rapidly than free plasminogen
Very short half life, requires IV
Limits systemic lytic state only at low phys concentrations.

SE: Hemorrhage

Therapeutic Uses:
Acute MI (STEMI)
Treatment of pulmonary embolism/DVT
Stroke within first 3 hours

A

Alteplase

94
Q

Inhibitor of Fibrinolysis

A lysine analog that binds to lysine binding sites on plasminogen and plasmin blocking binding of plasma to fibrin

Reverse states assoc with excessive fibrinolysis

Concentration in urine can be 100x that in plasma; useful for treating urinary tract bleeding

A

Aminocaproic acid

95
Q

Aspirin

Dipyridamole

Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor

Abciximab, Eptifibatide

A

Antiplatelet drugs

96
Q

GlycoProtein receptor proteins (integrins) binding collagen, vWF causing platelets to adhere to subendothelium: GPIb, GPIa/IIa,

GPIIb/GPIIIa: glycoprotein receptor binding fibrinogen

PAR1/PAR4: protease activated receptors; thrombin (IIa) binds to these receptors

P2Y/P2Y12: purinergic receptors for ADP

Activation of PAR1/PAR4 or P2Y1/P2Y12 receptors: stimulates COX and GPIIb/IIIa: fibriongeon binding results in cross linking of adjacent platelets

COX mediated production of TXA2/PGI2

A

Important platelet receptors

97
Q

Low dose aspirin. Irreversible inhibitor of COX-1 in platelets, inhibit platelet production of TXA2 preserves PGI2

SE: GI irritation/bleeding
low dose aspirin could haeve potentially adverse effects assoc with aspirin/nsaids like hypersensitivity

Therapeutic uses:
MI prophylaxis
alone or in comb with thrombolytics in acute MI
Acute phase of ischemic stroke
Stroke prophylaxis
Unstable angina/acute coronary syndrome (unexpected chest pain at rest)
Preeclampsia prophylaxis- remains controversial

A

Aspirin

98
Q

A vasodilator and inhibitor of platelet aggregation

Main mechanism: Inhibition of phosphodiesterase (PDE3 and PDE5), increasing cAMP in platelet, inhibits platelet aggregation

SE: headache/GI upset

Therapeutic use:
Primary prophylaxis of thromboemboli in patients with prosthetic heart valves, given in combination with warfarin
In combination with aspirin for secondary prevention of MI or TIA

A

Dipyridamole

99
Q

Mechanism:
Act through ADP receptor (P2Y1/P2Y12) receptors to inhibit ADP induced platelet aggregation
2 different GPCR that mediate platelet aggregation
P2Y1 couples to Gq, increases PLC, increases calcium
P2Y12 couples to Gi, decreases AC, decreases cAMP, decreases PKA

IF stimulate ADP receptor=get platelet aggregation
If block ADP receptor=block platelet aggregation

All are irreversible except ticagrelor

Oral drugs
Prasugrel prodrug with 2 step process: esterase mediated hydrolysis, then CYP3A4 and 2B6 to active cmpd
Clopidogrel and Ticlopidine are prodrugs metabolized to active compound by CYP2C19

Advantage of reversible anti platelet drug?

A

Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor Mechanism

100
Q

SE:
Bleeding-all drugs
Ticagrelor specific-dyspnea
Ticlodipine-neutropenia (so used much less often if at all)

A

Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor SIDE EFFECTS

101
Q
  • DRUG INTERACTION BETWEEN ASPIRIN AND CLOPIDOGREL
    CYP2C19 polymorphisms, poor metabolizers, meaning not as much active drug
    also
    Patient taking both aspirin and clopidogrel complianing of GI irritation. Prescribed proton pump inhibitor omeprazole which is also a substrate for CYP2C19. Leading to less active metabolite of clopidogrel
A

Clopidogrel mechanism importance…

102
Q 
Clopidogrel:
Unstable angina
NSTEMI (non-occlusive thrombus) in comb with aspirin
STEMI (occlusive thrombus)
Recent myocardial infarction, stroke
Established peripheral arterial disease

Prasugrel:
Manage patients undergoing percutaenous coronary intervention (PCI) for UA, NSTEMI, STEMI

Ticagrelor:
Used with aspirin for secondary prevention in patients with UA, NSTEMI, STEMI
To manage patients undergoing PCI a/o coronary artery bypass CABG

A

Clopidogrel, Ticlopidine, Prasugrel, Ticagrelor THERAPEUTIC INDICATIONS

103
Q

GbIIb/IIIa antagonist, IV preparations

Abciximab: quick onset but delayed clearance. Effective up to 7 days

Eptifibatide: Quick onset, quick offset (normal platelet aggreg within 8 hr of stopping) renal clearance

SE:
Bleeding
Thrombocytopenia, hypotension, bradycardia
Eptifibatide, caution in patients with renal disease

Clinical use:
Abciximab:
Patients undergoing PCI, including angioplasty or stent placement
In comb with aspirin and heparin (or LMWH)
Also used with alteplase for thrombolysis

Eptifibatide:
Patients with unstable angina and myocardial infarction, often with LMWH
Patients undergoing PCI, including angioplasty or stent placement

A

Abciximab/Eptifbatide pharmacokinetics, SE, Use

104
Q

Fab fragment of the chimeric human murine monoclonal antibody

Prevents binding of fibrinogen, vW factor, and other adhesive molecules

Blocks access of the molecules to the receptor. Not a direct interaction with the binding site of the GPIIa/IIIb receptor. noncompet

A

Abciximab

105
Q

Cyclic heptapeptide
Derivative of Disintegrins, proteins from snake venoms inhibiting platelet aggregation
Contains KGD (Lys,-Gly, Asp) sequence motif binding specifically to GpIIb-IIIa receptors ont he platelet surface blocking binding of fibrinogen activated platelets
Competitive and reversible inhibitor
Binds specifically to the receptor

A

Eptifibatide

Pharm Block 2 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions