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I.
The "Top 200 Drugs" – ranked by number of Rx's written – from
www.pharmacytimes.com
a. More rx's are written for hypertension than any other condition (12 of the top
50 drugs are for HTN – combining beta-blockers, calcium channel blockers,
ACE inhibitors, angiotensin receptor blockers, and diuretics)
b. Five of the top 50 are for hyperlipidemia
c. Four of the top 50 are for depression or antibiosis
d. Three of the top 50 are for pain, gastroesophageal reflux disease (GERD),
asthma, thyroid supplementation, or diabetes
e. Two of the top 50 are for warfarin
f. One of the top 50 drugs is for anxiety, allergy, or osteoporosis
g. So, doctor, what do you make of these commonly prescribed drugs, and what
do they imply about the conditions occurring in your patients? Should you be
concerned about ocular manifestations? What about drug side effects?
II.
Depression
a. Very common – 2nd only to HTN as the most commonly seen condition
b. Major depression = depressed mood or anhedonia for 2+ weeks, plus 3+ of
the following: insomnia, feeling worthless or guilty, fatigue, diminished
concentration, change in appetite, psychomotor retardation, recurrent suicidal
thoughts
c. 50-6% respond to initial therapy (either meds or psychotherapy)
d. Serotonin- and norepinephrine-reuptake inhibitors are
i. tertiary amine tricyclics (Elavil, Sinequan, Tofranil)
ii. secondary amine tricyclics (Norpramin, Pamelor)
iii. bicyclic (Effexor)
e. SSRIs are Celexa, Prozac, Paxil, Zoloft
f. Serotonin antagonist is Remeron
g. Norepinephrine- and dopamine-reuptake inhibitor is Wellbutrin
III.
Hypertension
a.
Present in 1 in 4 adults in the US; classic defn. = systolic > 140, diastolic > 90
b.
Risk factor for CVA, MI, renal failure, CHF, progressive atherosclerosis, and
dementia; each 20 mm syst or 10 mm diast doubles the risk of CV disease
c.
The JNC 7 Report from 2003
d.
NEW – normal is systolic < 120 and diastolic < 80
e.
NEW – pre-hypertension is systolic 120-139 or diastolic 80-89
f.
NEW – Stage I HTN is systolic 140-159 or diastolic 90-99
g.
NEW – Stage II HTN is systolic ≥ 160 or diastolic ≥ 100
h.
Lifestyle modification = diet (BMI 24.9 or less), reduced sodium, increased
fruit/vegetable, reduced fat, 30 minutes/day aerobic exercise, ≤ 2 drinks/day
i.
Pre-HTN treatment: lifestyle modification
j.
Stage I HTN treatment: Diuretic (still preferred drug per ALLHAT), ACEI, ARB,
k.
CCB, or combinations (beta blockers less in favor now)
l.
Stage II HTN treatment: 2-drug combinations
IV.
Pain Control
a.
Drugs include NSAIDs, opioid combinations, and meds for neuropathy
b.
Neuropathic pain is quite common; related to diabetes, infection (herpes,
HIV), nerve trauma, stroke, or occurring idiopathically
c.
Neuropathy: both "negative" and "positive" symptoms
d.
Pain control is both local (local analgesia, capsaicin) and CNS
e.
Blockade of calcium channels (gabapentin), sodium channels (amitriptyline)
f.
Both gabapentin and amitriptyline have many side effects
V.
Anxiety
a. Generalized anxiety disorder is common: 6 months of symptom duration
(prominent worrying and impairment) plus 3 or more of the following on most
b.
c.
d.
e.
days: fatigue, restlessness, poor concentration, irritability, muscle tension,
and unsatisfying sleep (but not anhedonia, which is seen in depression)
Other anxiety disorders are panic disorder, obsessive compulsive disorder,
social anxiety disorder, and PTSD.
Symptoms are physical, cognitive, behavioral, affective, and uncontrollable
worry
Benzodiazepines are the cornerstone of therapy
Physical dependence can occur with long-term therapy, but provide rapid relief
V.
Gastro-esophageal reflux disease (GERD)
a. Classic symptoms of heartburn and/or acid reflux
b. Laxness of the esophageal sphincter
c. Common in the US – 20% or more with symptomatology
d. GERD = non-erosive reflux disease, erosive esophagitis, and Barrett's
esophagus
e. Barrett's demonstrates cellular metaplasia; risk of adenocarcinoma
f. Parietal cells produce acid in response to acetylcholine (d/t sight/taste/smell of
food), gastrin, or histamine (both released by presence of food in stomach).
g. Proton pump inhibitors bind within pumps in the secretory canaliculi of parietal
cells, resulting in reduced acid production
VI.
Hyperlipidemia
a. National Cholesterol Education Program (NCEP) released Adult Treatment
Panels; latest (ATP III) was released in 2003.
b. Optimal levels of LDL are now < 100 mg/dL, triglycerides < 150 mg/dL
c. Patients are stratified into 3 risk groups, with varying levels of LDL
d. Highest risk patient has: CHD/CAD or other atherosclerotic disease (PAD,
abdominal aortic aneurysm, symptomatic carotid disease) or diabetes or >
20% risk of CHD within 10 years (per Framingham projection system); goal is
LDL < 100
e. Middle risk patient does not have CHD/CAD or atherosclerotic disease, but has
2+ risk factors from among the following: cigarette smoking; HTN (> 140/90)
or tx for HTN; low HDL (< 40 mg/dL); family h/o premature CHD (men < 55,
women < 65); age (men over 45 years of age, women over 55 years of age);
goal is LDL < 130.
f. Low risk patient has 0 or 1 risk factors; goal is LDL < 160.
g. Steps to reducing cholesterol are (1) dietary counseling and increased activity;
(2) addition of high fiber diet; and (3) drug therapy
VII.
Anti-platelet and anticoagulant drugs
a. Factors increasing stroke risk are (1) non-modifiable (age, male gender, nonwhite ethnicity, family history, and past CVA); and (2) modifiable (HTN, DM,
a-fib, carotid artery disease, hyperlipidemia, cigarette smoking, obesity, and
high alcohol use.
b. Types of strokes are either (1) hemorrhagic strokes, caused by saccular
aneurysm of large/medium intracranial arteries or hypertensive intracerebral
hemorrhage; or (2) ischemic strokes, resulting from large vessels
(atherosclerosis drives thrombus formation at carotids and aortic arch), small
vessels (middle cerebral artery, circle of Willis, basilo-vertebral arteries), or
cardioembolic phenomena (A-fib, mechanical valve, cardiomyopathy, or
valvular or rheumatic heart disease).
c. Prevention of strokes requires treating modifiable factors for atherosclerosis
(HTN, systolic HTN in the elderly, hyperlipidemia).
d. Prevention of strokes also uses anti-platelet aggregation drugs (reduces
thrombus formation by reducing aggregation of platelets on diseased arteries);
strategy reduces risk by 25-30%; ASA, Plavix, or Aggrenox
e. Anticoagulation with warfarin reduces risk of cardioembolic phenomena in
patients with A-fib or mechanical heart valves
VIII.
Postmenopausal osteoporosis
a. Bone mass or mineral density is reduced, causing "microarchitectural
deterioration" and increased bone fragility with increased susceptibility to
fractures.
b. Women at age 50+ = lifetime risk of vertebral fracture is 1 in 3, and risk of hip
fracture is 1 in 6.
c. Osteoporosis is clinically silent until a fracture occurs
d. Tested by DEXA (dual-energy X-ray absorptiometry
e. Risk factors for osteoporosis are environmental (cigarette smoking, alcoholism,
inactivity, thin or low body weight), drug therapy (steroids, antiepileptic drugs,
anticoagulant drugs), endocrine disease (hyperparathyroidism, Cushing's
disease), rheumatologic disease (RA, ank spondylitis), genetics
f. Drug therapy works to reduce bone resorption
g. Biphosphonates inhibit the normal function of osteoclasts (which is absorption
and removal of bone); the result is increased bone mineral density
h. Biphosphonates are associated with ocular inflammation. The worst offender
(pamidronate/Aredia) is used for tumor-induced hypercalcemia or Paget's
disease; alendronate/Fosamax and risedronate/Actonel are less toxic.
IX.
Allergy management
a. Allergy, whether seasonal or perennial, is a very common condition in the US.
b. Traditional strategies of oral antihistamines have been augmented markedly
by other drug modalities, often with fewer side effects.
c. First generation antihistamines remain effective, but their sedating and anticholinergic side effects are well known (Acrivastine/Semprex,
brompheniramine OTC, carbinoxamine/Palgic, chlorpheniramine OTC,
clemastine/Tavist, cyproheptadine, diphenhydramine, hydroxyzine/Atarax,
and triprolidine/Actifed)
d. Second generation antihistamines cause less sedation (cetirizine/Zyrtec,
desloratadine/Clarinex, fexofenadine/Allegra and generic, loratadine/Claritin
OTC, and levocetirizine/Xyzal).
e. Nasal steroids are increasingly popular (beclomethasone/Beconase,
budesonide/Rhiocort, flunisolide/Nasarel, fluticasone/Flonase and generic,
mometasone/Nasone/Nasacort.
f. Mast cell stabilizer nasal spray (cromolyn/Nasalcrom)
g. Antihistamine nasal spray (azelastine/Astelin – aka Optivar for eyes)
h. Leukotriene antagonist (montelukast/Singulair)
i. With such a profusion, plus crossover from asthma treatment, which is best?
X.
Erectile Dysfunction
a. Erectile dysfunction (ED) due to many causes: major cause is aging, but risk
factors include DM, HTN, hyperlipidemia, CAD, trauma, post-prostatectomy,
cigarette smoking, depression, antidepressants (particularly SSRIs).
b. ED is very common, increasing with age – 52% in men 40-70 years old, and
67% in men older than 70.
c. Sexual stimulation involves release of nitric oxide (NO) in corpus cavernosum,
with stimulation of cGMP synthesis, which relaxes smooth muscle in the corpus
and penile arteries; end result is increased penile blood flow and an erection.
d. Phosphodiesterase type 5 inhibitors (PDE5 inhibitors) enhance the effect of NO
by inhibiting phosphodiesterase 5, which would otherwise degrade cGMP
e. PDE5 inhibitors are sildenafil (Viagra), vardenafil (Levitra), and tadalafil
(Cialis)
f. All PDE5 inhibitors are contraindicated with nitrates (ie, NTG) due to
exaggerated vasodilation; normal side effects include headaches, facial
flushing, and nasal congestion from arterial vasodilation.
g. Viagra side effects include blue color distortion and blurred vision.
h. NAION has been tenuously associated with PDE5 use but most patients have
had other risk factors (including DM, HTN, CAD, hyperlipidemia, nocturnal
i.
hypotension) or the "disc at risk." Many of the 25 reports of NAION did not
have the episode occurring within the 4-hr plasma half-life of the drug.
The only men who must avoid these drugs are those with a history of NAION
in one eye already.
XI.
Conclusions - some of these very commonly managed conditions have little impact
on eye health or the visual system, and the drugs used for their treatment have similarly little
ocular impact. Other conditions (HTN, hyperlipidemia, stroke risk and prevention) have
tremendous inter-relationships with the visual system. Finally, other conditions may have
little direct impact but the medications used in management may have marked ocular
toxicities associated with their use.
The Top 50 of the Top 200 List
1. Lipitor
2. generic Vicodin
(MKR)
3. Toprol XL
4. Norvasc
5. amoxicillin
6. generic Vicodin
(WTS)
7. Synthroid
8. Nexium
9. Lexapro
10. albuterol
11. Singulair
12. levothyroxine
(SDZ)
13. lisinopril (TEV)
14. Ambien
15. Zyrtec
16. Prevacid
17. Zoloft
18. warfarin
19. Advair Diskus
20. furosemide
21. Fosamax
22. Protonix
23. azithromycin
24. Effexor XR
25. Zocor
26. Plavix
27. levothyroxine
(MYN)
28. generic Percoset
29. Vytorin
30. cephalexin
31. Diovan
32. lisinopril (SDZ)
33. metformin
34. atenolol (SDZ)
35. prednisone
36. Levaquin
37. Lotrel
38. atenolol (MYN)
39. metoprolol
40. Zetia
41. Seroquel
42. Wellbutrin XL
43. Celebrex
44. Avandia
45. hydrochlorothiazide
46. Actos
47. Diovan HCT
48. Premarin
49. Altace
50. Crestor