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02 pharm
drugs
50
Medical
Pre-School
03/09/2014

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Term
clopidogrel (Plavix)
Definition
MOA: irreversible inhibitor of platelet aggregation (covalent modifier of P2Y12 ADP receptor)

INDICATION: secondary prevention of MI, stroke, peripheral vascular disease; coronary artery stents; coronary artery bypass grafting

PHARM EFFECTS: inhibits sustained platelet aggregation (transient aggregation can still occur)

NOTES: elective procedures should be deferred until pt has completed appropriate course of clopidogrel therapy (12 mo after drug-eluting stent implantation or 1 mo for bare-metal stent)
Term
dipyridamole (Persantine)
Definition
MOA: inhibitor of phosphodiesterase (an enzyme which degrades cAMP; high [cAMP] leads to a decrease in platelet aggregation)

INDICATION: ADJUNCT -- used with warfarin in prosthetic heart valve replacement; used with ASA to reduce stroke risk

PHARM EFFECTS: increase in [cAMP] leading to decrease in platelet aggregation

ADVERSE EFECTS: gingival bleeding
Term
aspirin
Definition
MOA: irreversible nonselective inhibitor of COX, thereby inhibiting thromboxane A2 (TXA2) formation which is a potent inducer of platelet aggregation

INDICATION: prevention of arterial thrombosis (stroke, MI, TIA)

PHARM EFFECTS: reduction in clotting inducer TXA2
ADVERSE EFECTS: gastric ulcer

NOTES: 4-10 days to recover platelet aggregation following ASA discontinuation
Term
warfarin (Coumadin)
Definition
MOA: inhibitor of vit K epoxide reductase (vit K is a cofactor for synthesis of many clotting factors)

ADVERSE EFECTS: too much: bleeding; too little: angina, blood clots
CONTRAINDICATIONS: extensive drug interactions-

NOTES: pt must avoid vit K in diet (primarily leafy greens); INR every 2 weeks
no need to abruptly discontinue warfarin prior to common dental procedures; risk of life-threatening bleeding < risk of thrombembolic event
aim for INR < 3.0
40 h half-life
can be reversed with vit K in case of emergency
Term
heparin
enoxaparin (Lovenox)
Definition
MOA: binds to and activates antithrombin III which itself covalently binds to serine protease and prevents it from participating in coagulation cascade --> inactivates thrombin, factors IXa, Xa, Xia, XIIa

INDICATION: "used by patients at home as a 'bridge to warfarin'"

PHARM EFFECTS: efficient inactivation of Xa as well as thrombin, Ixa, Xia, & XIIa

NOTES: AT III inhibits clotting; heparin binds ATIII and speeds up the anti-clotting reaction 1000x
Term
pradaxa (Dabigatran)
Definition
MOA: direct thrombin inhibitor
INDICATION: reduces risk for stroke in pts w/ atrial fibrillation

NOTES: unlike warfarin, there is no reversal agent due to its MOA. 14 h half-life compared to warfarin's 40 h half-life; therefore, a missed dose is more serious
Term
atorvastatin (Lipitor)
"statin"
Definition
MOA: competitively inhibits HMG-CoA reductase

INDICATION: hyperlipidemia

PHARM EFFECTS: inc in synthesis of hepatic LDL receptors; inc in hepatic uptake of LDL and ID

ADVERSE EFECTS: rhadbomyolysis leading to kidney failure; constipation, diarrhea, stomach pain, nausea

CONTRAINDICATIONS: EtOH increases active level of drug --> rhabdomyolysis; erythromycin, itraconazole, ketoconazole all contraindicated with lovastatin (Mevacor) especially, but w/ all statins as well --> rhabdomyolysis
Term
ezetimibe (Zetia)
Definition
MOA: selectively inhibits cholesterol uptake through a brush border protein (NPC1L1)

INDICATION: hyperlipidemia

PHARM EFFECTS: dec cholesterold absorption by 50%; dec LDL concentration in the plasma; dec cholesterol content of chylomicrons

ADVERSE EFECTS: abdominal pain, diarrhea

CONTRAINDICATIONS: hepatic impairment
Term
fenofibrate (TriCor)
gemfibrozil (Lopid)
Definition
MOA: PPARa agonist (binds to PPARa, a transcription factor controlling expression of lipid-metabolizing enzymes)

INDICATION: hyperlipidemia

PHARM EFFECTS: inc muscle expression of lipoprotein lipase, inc uptake of TG-containing lipoproteins; inc HDL; dec TGs

CONTRAINDICATIONS: warfarin (fibric acid derivatives displace warfarin from its albumin binding site)
Term
niacin (Niaspan)
Definition
MOA: inhibition of acyl-CoA acyltransferase, inc mitochondrial & peroxisomal b-oxidation in liver, dec lipogenesis in liver, and inc plasma lipoprotein lipase activity

INDICATION: hyperlipidemia
Term
colesevelam (Welchol)
Definition
MOA: non-absorbed polymer which sequesters bile acids in the intestines so that they are not reabsorbed

INDICATION: hyperlipidemia, ADJUNCT w/ statins

PHARM EFFECTS: inc conversion of cholesterol to bile acids; inc clearance of plasma LDL-cholesterol

Boys and postmenarchal girls, 10 to 17 years of age, with heterozygous familial hypercholesterolemia
Adjunct with statins
Term
albuterol (Proventil)
salmeterol
Definition
MOA: B2 adrenergic receptor agonist;
acts via G-protein-coupled receptor, ultimately leading to an efflux of Ca++ from intracellular compartment --> dec myosin light chain relaxation --> bronchodilation

INDICATION:
SHORT-ACTING - albuterol --> used for acute bronchospasm relief;
LONG-ACTING salmeterol --> used as a controller for asthma (long-term control of bronchospasm)

PHARM EFFECTS: dec inflammatory cytokine production, dec in responsiveness of airway to inflammatory mediators, dec plasma exudation

ADVERSE EFECTS: w/ long-term use, inc asthma exacerbations, loss of bronchoprotection
Term
inhaled steroids
Definition
PHARM EFFECTS: dec accumulation of macrophages and leukocytes; dec phagocytosis; dec lysosomal enzyme release; dec release of chemical mediators of inflammation

ADVERSE EFECTS: oropharyngeal candidiasis, dysphonia, leads to decreased adherence and quality of life
Term
theophylline
Definition
MOA: inhibition of phosphodiesterase; direct histone deacetylase activation

INDICATION: asthma

PHARM EFFECTS: bronchodilation; anti-inflammatory effects --> dec mediator release from inflammatory cells, dec allergen response

ADVERSE EFECTS: nausea, vomiting, headache, insomnia; overdose: persistent vomiting, cardiac arrythmias, & intractable seizures which can be lethal
Term
montelukast (Singulair)
Definition
MOA: competitive antagonist of cysteinyl leukotriene receptor

INDICATION: asthma & seasonal allergy rhinitis

CONTRAINDICATIONS: ASA & NSAIDs
Term
zileuton (Zyflo)
Definition
MOA: inhibits 5-lipoxygenase

INDICATION: prophylaxis & chronic treatment of asthma

ADVERSE EFECTS: can cause liver problems --> must monitor liver enzymes during therapy
Term
omalizumab (Xolair)
Definition
MOA: anti-IgE monoclonal antibody

ADVERSE EFECTS: nasopharyngitis, upper respiratory infection, headache; rare anaphylaxis reaction

"mab" Monoclonal AntiBody
Term
ipratropium (Atrovent)
tiotropium (Spiriva)
Definition
MOA: competitive antagonism of acetylcholine at M3 receptors in the lung

ADVERSE EFECTS: dry mouth, altered taste & coughing after administration
Term
Diuretic potency greatest to least
Definition
loop (furosemide), thiazide, potassium sparing (spironolactone)
Term
Spironolactone (Aldactone)
Definition
aldosterone antagonist and potassium sparing diuretic

-It prevents the nuclear translocation of the mineralocorticoid receptor.

-Indications
Hypertension
Edema states
Heart failure
Hepatic cirrhosis
Congestive Heart Failure
Hypokalemia
Male to female gender transformation

- decrease anti hypertension with NSAIDs

Spirono"lactate" = lactate, man boobs, gender transformation
Term
diuretics inhibit
Definition
Na reabsorption
Term
Hydrochlorothiazide (HCTZ)
Definition
Mechanism: Binds to the Na+Cl- cotransporter in the distal tubule and inhibits turnover

MOA: binds to the NaCl cotransporter in the distal tubule and inhibits turnover

INDICATION: HTN, edema (CHF, hepatic cirrhosis, renal dysfunction, corticosteroid therapy)

PHARM EFFECTS: dec in NaCl reabsorption, inc absorption of Ca++

ADVERSE EFECTS: hypokalemia, hyponatremia, gout, dry mouth, lichenoid rxns, orhtostatic hypotension

CONTRAINDICATIONS: NSAIDs -- dec anti-HTN effect
opiates -- inc orthostatic hypotension
Term
furosemide (Lasix)
Definition
MOA: inhibition of NaCl reabsorption in loop of Henle by binding to Cl- site of cotransporter

INDICATION: HTN, heart failure, acute pulmonary edema, hyperkalemia, hypercalcemia, edema states

PHARM EFFECTS: reduces extracellular fluid volume and BP with a greater magnitude than with thiazides

ADVERSE EFECTS: same as those for thiazides with respect to hypokalemia and hyponatremia

CONTRAINDICATIONS: NSAIDs -- dec anti-HTN effect
Term
Diuretics main dental concerns:
Definition
Dry Mouth, lichenoid rxs, orthostatic hypotension
Term
nitroglycerine
Definition
MOA: binds & activates guanylyl cyclase in endothelial cells
greatly decreases preload

INDICATION: acute chest pain
PHARM EFFECTS: relaxation of vascular smooth muscle leading to vasodilation and dec BP

ADVERSE EFECTS: headache, orthostatic hypotension, stroke, dizziness, reflex tachycardia,

CONTRAINDICATIONS: opiates -- inc effects of NO
Term
Which Ca channel blocker that can be used with beta blockers?
Definition
amlodipine (Norvasc)
Term
Which Ca channel blockers are contraindicated with beta blockers?
Definition
verapamil (Calan)
dilitazem (Cardizem)
Term
Digoxin
Definition
Positive ionotrope

effects contractility

Inhibition of the sodium-potassium ATPase

 in available sodium
↓ the rate of calcium-sodium exchange
More calcium is available for contraction of cardiac muscle
↑ force of contraction
↓ rate of contraction
Heart pumps more efficiently

metabolized by gut bacteria, can have a problem if pt is on antibiotics leading to digoxin toxicity --

Signs of toxicity
Excessive salivation
Headache
Fatigue and drowsiness
Abdominal pain
Visual disturbances Yellow or green haze around objects
Term
Most common heart rhythm disturbance
Definition
atrial fibrillation
Term
amiodarone (Cordarone)
Definition
MOA: alteration of the lipid membrane in which channels are receptors are located

PHARM EFFECTS: lengthens refractory period by inhibiting K+ channels, blocks Na+ & Ca++ channels, antagonizes a & b adrenergic receptors
Term
Dental Management Precautions with hypertension
Definition
Avoid the use of epinephrine-impregnated gingival retraction cord
Avoid the use of vasoconstrictors for direct hemostasis to control local bleeding
Avoid stimulating the gag reflex in patients with a history of hypertension
Term
1st line agents in HTN
Definition
Thiazide diuretics
β blockers
Term
Amlodipine (Norvasc)/ Ramipril (Altace)

Why is this an efficacious therapeutic combination?
Definition
Baroreceptor reflexes
↑sympathetic outflow
Tachycardia
Increased contractility
Vasoconstriction


Renal perfusion reflexes
↑Renin release

you are able to block the compensatory changes associated with the baroreceptor reflex, so when rein increases you inhibit that Angiotensin/Aldosterone cycle.
Term
prednisone
Definition
MOA: binds AP-1 or NK-kB intraceullar transcription factors to inhibit their pro-inflammatory action; inc expression of glucocorticoid-induced leucine zipper proteins; chromatin remodeling

INDICATION: chronic inflammatory and immune diseases (see list at right)

PHARM EFFECTS: inhibition of accumulation of macrophages and leukocytes, phagocytosis, lysosomal enzyme release, and release of chemical mediators of inflammation

NOTES: withdrawal syndrome (requires 3 day tapering period for all courses of therapy) --> joint pain, muscle pain, fatigue, fever, nausea & vomiting may cause acute adrenal crisis (low endogenous cortisol) with chronic therapy -- low BP, dehydration, confusion, tachypnea, sweating, shock, coma, seizures, delays wound healing
Term
prednisone adverse effects
Definition
Dermatologic:
impaired and delayed wound healing
Thin fragile skin
Neurologic:
Convulsions
Vertigo
Headache
Endocrine:
Development of Cushing's state
Secondary adrenocortical and pituitary unresponsiveness
Diabetes
Fluid and Electrolyte:
Sodium and fluid retention
CHF, HTN and potassium loss
Musculoskeletal:
Loss of muscle mass
Osteoporosis
Compression fractures
GI:
Peptic ulcer
Pancreatitis
Ulcerative esophagitis
Term
methotrexate
Definition
MOA: folate analog which inhibits endogenous folate synthesis --> apoptosis of CD4 & CD8 T cells

INDICATION: rheumatoid arthritis, psoriasis, graft vs. host disease, severe asthma

PHARM EFFECTS: anti-inflammatory effects

ADVERSE EFECTS: leukopenia

NOTES: once-per-week dosing
Term
mycophenolate mofetil (CellCept)
Definition
MOA: inhibitor of inosine monophosphate dehydrogenase (rate limiting enzyme in biosynthesis of guanosine)

INDICATION: not listed, but presumably the same as methotrexate's?

PHARM EFFECTS: induces activated T cell apoptosis, dec lymphocyte activation and activity, dec expression of adhesion molecules, dec production of NO by neutrophils

ADVERSE EFECTS: mout ulceration, gingival hyperplasia, gingivitis, dry mouth, dysphagia
Term
cyclosporine
tacrolimus (Prograf)
Definition
MOA: inhibits synthesis of IL-2 (responsible for activation and proliferation of activated lymphocytes) in activated T cells

INDICATION: immunosuppressant for graft survival, topical for oral lichen planus, psoriasis, rheumatoid arthritis, chronic dry eyes

ADVERSE EFECTS: renal toxicity, HTN, hyperlipidemia, neurotoxicity, gingival hyperplasia
Term
antihistamines
Definition
MOA: inverse agonist which stiblizes the inactive conformation of H1 histamine receptor; some are competitive inhibitors of H2 histamine receptor

INDICATION: DENTISTRY: conscious sedation, pre-med for general anesthesia, reduction of post-op nausea, allergic lesions of oral mucosa; OTHER: nasal allergies, symptomatic relief of common cold, motion sickness, sedation

PHARM EFFECTS: H1 blockage: anti-inflammatory effects; H2 blockage: anti-emetic effects (e.g. Phenergan)

ADVERSE EFECTS: CNS depression --> drowsiness, lethargy, dec motor coordination; anti-muscarinic effects --> dry mouth, constipation, blurred vision
Term
1st GENERATION antihistamines
Definition
diphenhydramine (Benadryl)
chlorpheniramine (Chlor-Trimeton)
meclizine (Antivert)
for vertigo
promethazine (Phenergan)
for nausea & vomiting
Term
2nd GENERATION antihistamines (less CNS depression than what is seen in 1st generation)
Definition
loratadine (Claritin)
fexofenadine (Allegra)
cetirizine (Zyrtec)
Term
adalimumab (Humira)
Definition
MOA: binds to and inactivates TNFa (cytokine which enables normal inflammatory and immune responses)

INDICATION: autoimmune diseases: rheumatoid arthritis, ulcerative colitis, Crohn's disease, psoriasis

PHARM EFFECTS: immunosuppression

ADVERSE EFECTS: inc susceptibility to opportunistic infections, inc risk for TB, invasive fungal infections, sepsis, CNS demyelination
Term
basiliximab (Simulect)
Definition
MOA: IL-2 receptor antagonist

INDICATION: autoimmune diseases: rheumatoid arthritis, ulcerative colitis, Crohn's disease, psoriasis

PHARM EFFECTS: inhibits IL-2 activation of lymphocytes

ADVERSE EFECTS: inc susceptibility to opportunistic infections
Term
colchicine
Definition
MOA: arrests mitosis in metaphase by binding to microtubular protein and preventing spindle formation, inhibits neutrophil migration and phagocytic activity in inflamed joints, inhibits inflammatory response by inhibiting neutrophil activation

INDICATION: gout

PHARM EFFECTS: dec trafficking of phagocytosed particles to lysosomes, dec release of chemotactic factors, dec motility and adhesion of neutrophils, phosphorylation of neutrophil proteins

ADVERSE EFECTS: neutropenia, diarrhea

NOTES: to treat gout, red meat is eliminated from the diet, and NSAIDs + colchicine for first 4-6 months to prevent acute episodes during beignning of chronic therapy
Term
allopuriinol (Zyloprim)
Definition
MOA: non-competitive inhibitor of xanthene oxidase
INDICATION: chronic gout
PHARM EFFECTS: dec biosynthesis of uric acid
Term
probenecid
Definition
MOA: inhibits the basolateral anion exchanger of

PHARM EFFECTS: dec [urate] in plasma

ADVERSE EFECTS: may develop urate stones in kidney or ureter, gingival soreness, nausea+vomiting, dizziness
Term
etanercept (Enbrel)
Definition
MOA: soluble TNF receptor dimer-Fc fusion protein

Rheumatoid arthritis
Term
infliximab (Remicade)
Definition
MOA: monoclonal antibodies consisting of the ligand binding portion of the TNFa receptor

Rheumatoid arthritis
Term
Proposed Roles for Tumor Necrosis Factor in Rheumatoid Arthritis
Definition
Cytokine
Central to many aspects of the inflammatory response
Stimulates macrophages to secrete phagocytic compounds
Stimulates production of acute phase proteins
Term
OSteoarthritis treatment
Definition
Drug Therapy:
Acetaminophen
NSAIDS
Duloxetine (Cymbalta)-approved indication
Glucosamine/Condroitin sulfates
Intra-articular hyaluronic acid injections
Joint replacement surgery
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