Pharm Iii

Front 1

how many men have some degree of ED:

Back 1

10 to 30 million

Front 2

On arousal, parasympathetic activity triggers a series of events starting with the release of ________ and ending with increased levels of the intracellular mediator _______________________, which causes penile vascular and trabecular smooth muscle relaxation.

Back 2

nitric oxide (NO)
cyclic guanosine monophosphate (cGMP)

Front 3

The rapid filling of the cavernosal spaces compresses venules resulting in decreased venous outflow, a process often referred to as the

Back 3

corporeal veno-occlusive mechanism

Front 4

Diseases that typically cause ED:

Back 4

DM, kidney disease, neurologic disease, vascular disease, hormonal imbalances

Front 5

what do these have in common:
• Alcohol
• Amphetamines
• Barbiturates
• Cocaine
• Marijuana
• Nicotine
• Opiates

Back 5

cause or lead to ED

Front 6

It is believed that psychological factors such as stress, anxiety, guilt, depression, low self-esteem, and fear of sexual failure cause _________ of ED cases.

Back 6

10-20%

Front 7

All act to increase intracavernosal cyclic GMP levels, which leads to relaxation of smooth muscle of the corpus cavernosum and penile arteries. Each drug has been proven to be effective in restoring erectile function, allowing for satisfactory sexual intercourse in many men with erectile dysfunction.

Back 7

PHOSPHODIESTERASE-5 (PDE-5) INHIBITORS

Front 8

they inherently have the potential to cause hypotension

Back 8

PDE-5 inhibitors

Front 9

side effects include:
headache, lightheadedness, flushing, syncope, dyspepsia, and "blue vision" due to weak inhibition of type 6 phosphodiesterase, and when combined with nitrates BP can drop 50/25 mg

Back 9

Sildenafil

Front 10

Alpha adrenergic antagonists, which are commonly used for the treatment of benign prostatic hyperplasia, are contraindicated (due to potential hypotension with combination therapy)

Back 10

PDE-5 inhibitors

Front 11

should be avoided in patients taking drugs that can prolong the half-life by blocking CYP3A4 (including erythromycin & ketoconazole); on the other hand, drugs that induce CYP3A4 such as rifampin and phenytoin can be expected to reduce the effectiveness of a dose of ________

Back 11

sildenafil

Front 12

this ED drug can be taken without regard to meals.
Effect may last up to 36 hours after a single dose.

Back 12

Tadalavil (Cialis)

Front 13

Used for treatment of pulmonary arterial hypertension (PAH)

Back 13

Ravatio (sildenafil)

Front 14

only _________ of men actually develop any symptoms due to BPH.

Back 14

40 - 50%

Front 15

The density of ___ receptors is increased in hyperplastic prostatic and bladder tissues. When ____ receptors are occupied by EPI/NE, detrusor muscle tone in the bladder is increased along with muscle tone in the prostate. In other words, the bladder wall is very "contractile". This, of course, leads to the frequent and urgent need to urinate.

Back 15

alpha 1 sub A

Front 16

act against the dynamic component of bladder outlet obstruction by reducing bladder and prostatic smooth muscle tone. There are two types:

Back 16

non-selective alpha1-adrenergic blockers
o Alfuzosin (Uroxatral)
o Doxazosin (Cardura)
o Terazosin (Hytrin)

alpha1 sub A adrenergic blockers
o Tamsulosin (Flomax

Front 17

what are these:
• Eye: pupil constriction (prevention of alpha 1-mediated pupil dilation)

• Small arterioles: dilation (prevention of vasoconstriction)

o lowers BP, total peripheral resistance (hence, an anti-hypertensive)

o indirectly (reflexly) triggers reflex tachycardia

o accounts for orthostatic hypotension

• Mucus, salivary, lacrimal secretions increased

o occurs because of increased blood flow (vasodilation) to secretory cells

• Impaired ejaculation in males

Back 17

side effects of non-selective alpha 1 receptor blockade

Front 18

often produce a "first dose phenomenon" – which includes dizziness, headache, weakness, excessive secretions, blurred vision, nausea and vomiting; this reaction can cause syncope due to severe symptomatic postural hypotension.

Back 18

non-selective alpha 1 receptor blockade

Front 19

What are these:
• Preexisting hypotension and/or tachycardia (or tachyarrhythmias)

• Ischemic heart disease (history or risk of MI; tachycardia and hypotension exacerbate ischemia)

• Ischemic brain disease (history or risk of stroke; hypotension that these drugs can cause underperfuses brain, favoring ischemic stroke)

• The hypotensive effect can be potentiated by concomitant use of PDE-5 inhibitors (sildenafil, vardenafil & tadalafil) used for ED

Back 19

main CI of non-selective alpha 1 blockers

Front 20

These drugs act by reducing the size of the prostate gland

Back 20

5alpha-Reductase Inhibitors

Front 21

catalyzes the conversion of testosterone to dihydrotestosterone in prostatic and other androgen-sensitive tissues.

Back 21

type 2 form of 5 alpha reductase inhibitor

• Finasteride (Proscar)
• Dutasteride (Avodart)

Front 22

slowly reduce the serum dihydrotestosterone level. As a result, prostatic volume decreases by about 20% over 3-6 months of treatment. The alpha 1-adrenergic antagonists have no effect on prostate size.

Back 22

5 alpha reductase inhibitor

• Finasteride (Proscar)
• Dutasteride (Avodart)

Front 23

Typically, PSA levels are monitored to follow the effectiveness of treatment. Serum PSA concentrations typically decrease by about 50%, a change that must be kept in mind in interpreting the results of serum PSA measurements in men treated with this drug.

Back 23

5 alpha reductase inhibitor

• Finasteride (Proscar)
• Dutasteride (Avodart)

Front 24

The major side effects are decreased libido and ejaculatory or erectile dysfunction (in approx. 4-6% of men). Headache, drowsiness, and dizziness could also occur with finasteride.

Back 24

5 alpha reductase inhibitor

• Finasteride (Proscar)
• Dutasteride (Avodart)

Front 25

has been shown to have an effect on disease progression, leading to a reduction in the need for BPH-related surgery. Is most effective in men with larger prostates ( > 40 ml) or higher PSA levels ( > 1.4 ng/ml) and may be the most appropriate treatment for those men who wish to reduce their risk of needing BPH-related surgery.

Back 25

Finasteride (Proscar)

5 alpha reductase inhibitor

Front 26

diuretics work on what side of the tubular epithelium

Back 26

luminal

Front 27

These block Na+Cl- symporters in the DCT of the nephrons responsible for Na+Cl- reabsorption.
•Hence, Na+Cl- is excreted along with H2O, thereby lowering blood volume
•__________ maximally increase the excretion of filtered Na+ load by only around 5%

Back 27

thiazides

Front 28

exhibit a flat-dose response curve in regards to a desired therapeutic effect – a marked increase of dose does NOT lead to a marked increase of desired response; in fact, increasing the dose is more likely to increase the risk and severity of side effects & adverse responses.

Back 28

thiazides

Front 29

are one of the "Big 5" drug groups for initial therapy of "mild" essesential hypertension. They are the "preferred" agents for initiating therapy unless patient-related factors/co-morbidities weigh against using this drug class(e.g. – because of side effects) or favor choosing a drug from a different class (beta-blocker, calcium-channel blocker, ACEI or ARB).

Back 29

thiazides

Front 30

o Hydrochlorothiazide has a duration of action of about 12-18 hours, while ________________ duration is approximately 24 hours. The duration of action makes once-daily dosing feasible --- a huge convenience to the patient, which ultimately favors compliance.

Back 30

chlorthalidone’s

Front 31

counteract the sodium & water retention observed with other anti-hypertensive agents and can be useful in combination therapy with beta-blockers, ACE inhibitors and angiotensin receptor blockers (ARBs).

Back 31

thiazide diuretics

Front 32

Most patients will respond to thiazide diuretics with a reduction in blood pressure within _______ weeks, although a minority will not achieve maximum reduction in arterial pressure for up to ___ weeks on a given dose. Therefore, doses should not be increased more often than every 2-4 weeks.

Thiazide diuretics are particularly useful in the treatment of _____________ or elderly patients. These patients tend to respond best to thiazide diuretics compared to other anti-hypertensives – why is unclear.

Back 32

2 - 4 weeks
12 weeks
African Americans

Front 33

clinical indications:
HTN
CHF
Nephrolithiasis due to idiopathic hypercalcemia
diabetes insipidus (particularly nephrogenic)

Back 33

thiazides

Front 34

adverse effects/contraindications:
sexual impotence
hypovolemia
hypokalemia
hyperuricemia
hypercalcemia
dyslipidemia
hyperglcemia and increase A1C

Back 34

thiazides

Front 35

All of the _______ cross the placenta, but they have not been found to have direct adverse effects on the fetus. However, if administration of a ________ diuretic is begun during pregnancy, there is a risk of transient volume depletion that may result in placental hypoperfusion. Since the ___________ appear in breast milk, they should be avoided by nursing mothers.

Back 35

thiazides

Front 36

drug interactions:
increase risk of digoxin toxicity (via hypokalemia)
serious Na, K, Cl, H2O depletion
increase risk of lithium toxicity

may slow bone demineralization in osteoporosis

Back 36

thiazides

Front 37

act in the ascending LOH to block the Na+-K+-2Cl- symporters – this is where approx. 25% of the filtered Na+ load normally gets reabsorbed

• The site and MOA impair the formation of a concentrated urine by diminishing the interstitial osmotic gradient

Back 37

loop diuretics

Furosemide (Lasix)
Torsemide (Demadex)
Bumetanide (Bumex)

Front 38

have a rapid response and a steep dose-response relationship; high doses can cause an approx. 8X increase of baseline urine output

Back 38

loop diuretics

Furosemide (Lasix)
Torsemide (Demadex)
Bumetanide (Bumex)

Front 39

clinical indications:
edema (chronic or acute)
HTN
acute renal failure

Back 39

loop diuretics

Furosemide (Lasix)
Torsemide (Demadex)
Bumetanide (Bumex)

Front 40

Adverse Effects/Contraindications:
hyponatremia
hypovolemia
hypokalemia
hypocalcemia (the opposite of what occurs with thiazides)
ototoxicity (can cause dose-related hearing loss that is usually reversible)
GI disturbances (nausea, anorexia, vomiting, diarrhea)

Back 40

loop diuretics

Furosemide (Lasix)
Torsemide (Demadex)
Bumetanide (Bumex)

Front 41

can increase risk of digoxin toxicity (via hypokalemia)
K levels must be monitored carefully

Back 41

thiazides and
loop diuretics

Furosemide (Lasix)
Torsemide (Demadex)
Bumetanide (Bumex)

Front 42

These diuretics antagonize the effects of aldosterone at the late DCT and cortical collecting duct. Inhibition can occur by direct pharmacologic antagonism of aldosterone receptors (spironolactone) or by inhibition of Na+ influx through Na+ channels (amiloride, traimterene). Bottom line is that either mechanism leads to an increase in Na+ excretion and a decrease in K+ excretion.

Back 42

K+-Sparing Diuretics / Aldosterone Receptor Blockers

Amiloride (Midamor)– K+-sparing
Triamterene (Dyrenium) -- K+-sparing
Spironolactone (Aldactone) – Aldosterone receptor blocker

Front 43

is used for symptomatic management of hyperaldosteronism, whether primary or secondary

Back 43

spironolactone

K sparing diuretic

Front 44

The main use of __________ diuretics is as adjunctive treatment of HTN and CHF. These drugs are seldom used alone; they are not very efficacious anti-hypertensive drugs when used as monotherapy. But, as stated earlier in the notes, they are often used in combination with a thiazide diuretic, mainly to counteract thiazide-induced potassium loss

Back 44

K+-Sparing Diuretics / Aldosterone Receptor Blockers

Amiloride (Midamor)– K+-sparing
Triamterene (Dyrenium) -- K+-sparing
Spironolactone (Aldactone) – Aldosterone receptor blocker

Front 45

Gynecomastia, altered libido, impotence, hirsutism and BPH have been reported with

Back 45

Spironolactone

K sparing diuretic

Front 46

the enzyme responsible for catalyzing the breakdown of H2CO3 into H+ and HCO3-. In Medical Physiology, we discussed the presence of this enzyme in RBCs and also the CSF. Well…………it's also found in the cells lining the PCTs of nephrons. When H2CO3 is filtered by the kidneys, CA converts it into HCO3-. The HCO3- is then reabsorbed along with Na+. By blocking CA, these drugs block Na+ and HCO3- reabsorption and cause a diuresis.

Back 46

Carbonic Anhydrase Inhibitors

Acetazolamide (Diamox)
Brinzolamide or Azope (Dorzolamide or Trusopt) for glaucoma

Front 47

When used topically in the eye, these can lower the pH of the aqueous humor. This affects the ciliary body in such a way that it secretes less aqueous humor, thereby lowering intraocular pressure.
Likewise, they can also cause a decrease in CSF production by the choroid plexus.

Back 47

Carbonic Anhydrase Inhibitors

Acetazolamide (Diamox)
Brinzolamide or Azope (Dorzolamide or Trusopt) for glaucoma

Front 48

clinical indications:
acute, mild, periodic edema
glaucoma
adjunctive management of hydrocephalus

Back 48

Carbonic Anhydrase Inhibitors

Acetazolamide (Diamox)
Brinzolamide or Azope (Dorzolamide or Trusopt) for glaucoma

Front 49

adverse effects:
metabolic acidosis
hyponatremia
hypokalemia

Back 49

Carbonic Anhydrase Inhibitors

Acetazolamide (Diamox)
Brinzolamide or Azope (Dorzolamide or Trusopt) for glaucoma

Front 50

drug interactions:
Salicylates displace __________ from plasma protein binding sites – this raises free _____________ levels and raises risk of toxicity, particularly metabolic acidosis

Back 50

acetazolamide

Carbonic Anhydrase Inhibitor

Front 51

As we learned in Medical Physiology, the PCT and descending LOH reabsorb lots of H2O. An ___________ that is NOT reabsorbed causes H2O to be retained in these segments of the nephron and promotes

Back 51

osmotic diuretic

mannitol (osmitrol)

Front 52

Main clinical indications include:
prompt removal of renal toxins
reduction of intracranial pressure (ICP) in neurologic conditions
reduction of intraocular pressure before ophthalmologic procedures

Back 52

osmotic diuretic

mannitol (osmitrol)

Front 53

This is rapidly distributed in the ECF and extracts H2O from cells. Prior to the diuresis, this leads to expansion of the extracellular volume and hyponatremia. This effect can complicate heart failure and may produce pulmonary edema. Headache, nausea and vomiting are commonly observed in patients treated with these.
Excessive use of __________ without adequate H2O replacement can ultimately lead to severe dehydration, free H2O losses, and hypernatremia.

Back 53

osmotic diuretic

mannitol (osmitrol)

Front 54

Before 12 years of age, migraine is more common in boys than girls, but prevalence increases more rapidly in girls after puberty; after age 12, females are _______ more likely than males to suffer from migraine.
Prevalence is highest in both men & women between ____ years of age

Back 54

2-3X
35-45

Front 55

Regardless of what the triggers are, it’s believed they somehow impact various neurons within the cerebral cortex, particularly neurons releasing serotonin and norepinephrine. These neurons form synapses with other neurons that appear to project to the brainstem and terminate in an area known as the:

Back 55

trigeminal nucleus caudalis

Front 56

Migraine pain is believed to result from activity within the _________________. When the trigeminal nucleus caudalis receives “input” from a triggering event occurring in the cerebral cortex, neurons within it send signals to pain-sensitive, intracranial, extracerebral structures – things like blood vessels, venous sinuses, and the dura mater. This signaling occurs via the trigeminal nerves (particularly the ophthalmic branch). Research has shown the neurotransmitters released on these structures include _________, __________ and ______ (calcitonin gene related peptide).

Back 56

trigeminovascular system
substance P
neurokinin A
CGRP

Front 57

substance P, neurokinin A and CGRP (calcitonin gene related peptide). The bottom line with these neurotransmitters is that they appear to interact with dural blood vessels to promote vasodilation and dural plasma extravasation, resulting in perivascular inflammation. Signals are sent back from these areas via the trigeminal nerve to the ____________, where the information is relayed further to higher cortical pain centers.

Back 57

trigeminal nucleus caudalis

Front 58

Aspirin

• Is widely used for treatment of migraine (and also tension headache) both alone and in combinations such as Fiorinal, which contains caffeine and ___________(a short-acting, weak barbiturate)

• __________ is used for its sedative effects; caffeine has vasoconstrictive properties

• Fiorinal is also available with codeine (schedule III)

Back 58

Butalbital

Front 59

• Has also been shown to be effective for treatment of migraine (and also tension headache)

• Is available in combination such as Fioricet and Esgic, which also caffeine and butalbital; Fioricet is also available with codeine (schedule III)

• Esgic-Plus has more _________ than Esgic (500 vs 325 mg)

• Phrenilin is a combination of 50mg butalbital/325mg APAP (no caffeine); Phrenilin Forte has 650 mg APAP

Back 59

Acetaminophen

Front 60

•__________ nasal spray (recall, this is an opioid agonist-antagonist) has been rapidly effective for relief of moderate to severe migraine, but drug dependence and abuse have been reported

Back 60

Butorphanol

Front 61

a non-specific serotonin agonist and a vasoconstrictor, has been used for many years for treatment of moderate to severe migraine headache. It is available alone in sublingual tablets and combined with caffeine in oral tablets (Cafergot) and suppositories (Cafergot suppositories).

Dihydroergotamine (DHE) mesylate, which can be injected SC, IM or IV or sprayed intranasally (Migranal), is also effective in treating migraine attacks.

Back 61

Ergot Alkaloids (Ergotamines)

Front 62

• Serious adverse effects (_________), such as vascular (including coronary) occlusion gangrene & rebound headache, are rare and usually associated with overdosage (more than 6 mg in 24 hours or 10 mg per week)

• Liver disease or fever can accelerate development of __________

• C/I in peripheral vascular disease, coronary artery disease, hypertension and pregnancy

Back 62

Ergot Alkaloids (Ergotamines)

ergotism

Front 63

• Nausea & vomiting are fairly common, but can be prevented by pre-treatment with or concurrent use of an anti-emetic such as prochlorperazine (Compazine, and others)

Back 63

Ergot Alkaloids (Ergotamines)

Front 64

• Long-term continuous use (on the order of years) has been associated with retroperitoneal, pleural, and pericardial fibrosis and fibrotic thickening of the cardiac valves

Back 64

Ergot Alkaloids (Ergotamines)

Front 65

• The effects of __________ may be potentiated by triptans, beta-blockers, dopamine or CYP3A4 inhibitors (e.g. – erythromycin, verapamil). _______ and triptans should not be taken within 24 hours of each other

Back 65

Ergot Alkaloids (Ergotamines)

Front 66

5-HT1 Receptor Agonists

Back 66

triptans

Front 67

The ______ are considered to be “specific” therapies for acute migraine since, in contrast to analgesics, they act at the pathophysiological mechanism of the headache. All of the ____________ inhibit the release of vasoactive peptides (substance P, neurokinin A and CGRP), promote vasoconstriction, and block pain pathways in the brainstem.

Back 67

triptans

Front 68

The advantages of the triptans over the ergotamines include not requiring pre-medication with potentially sedating anti-emetics, and their beneficial effects upon other phenomena of migraine, particularly __________ and ________. Many patients have been able to use triptans either at home or in the workplace without significant problems

Back 68

nausea and photophobia

Front 69

Adverse Effects, CIs & DDIs
burning at injection site
Tingling, flushing, dizziness, drowsiness, fatigue and a feeling of heaviness, tightness or pressure in the chest may occur with all _______, but most commonly with injectable __________. Most of these reactions occur soon after the injection and resolve spontaneously within 30 minutes. Angina, MI, cardiac arrhythmia, stroke, and death have occurred rarely with these drugs.

Back 69

triptans

sumatriptan

Front 70

They are contraindicated in patients with coronary or other arterial disease or uncontrolled hypertension. It may be prudent to give the first dose of the drug under medical supervision for patients with risk factors but no known coronary heart disease

Back 70

triptans

Front 71

None are FDA-approved for pregnant women.

Overuse (typically more than 2-3 days a week) of analgesics, ergotamine tartate (not DHE) or
__________ can cause a daily dull headache. _________ overuse can also cause a migraine-like daily headache or an increase in migraine headache frequency.

Back 71

triptans

Front 72

IV metoclopramide (Reglan) and IV or IM prochlorperazie (Compazine) can be considered as monotherapy for acute migraine headache, particularly in the ED.

Back 72

anti-emetics

Front 73

Benzodiazepines, opioids and barbiturates are all options, but should not be used on a chronic basis since they are habit-forming and can contribute to the development of ________ headache

Back 73

migraines

rebound

Front 74

drugs valproate (Depakote, and others) and topiramate (Topamax) have been effective in decreasing migraine frequency; recent studies show have demonstrated that 30-50% of patients achieve a 50% reduction in headache frequency with these drugs. Topiramate was just recently approved for the indication of migraine prophylaxis by the FDA in August 2004.

Common side effects of valproate include nausea, fatigue, tremor and hair loss. Weight gain is also common in patients taking valproate, and has been associated with POS, hyperinsulinemia, lipid abnormalities, hirsutism, and menstrual disturbances.

Topiramate commonly causes paresthesia; other adverse effects include fatigue, language and cognitive impairment and weight loss, which some patients may prefer to the weight gain associated with valproate.

Back 74

anti-epileptics

Front 75

can prevent migraine in some patients and may be given concurrently with other prophylactic agents, but often cause sedation and weight gain. Amitriptyline has been shown to be effective. Nortriptyline (Aventyl, and others) is also frequently used for this purpose. They are not FDA-approved for migraine prevention.

Back 75

TCAs

Front 76

In small double-blind studies, the _________ lisinopril (Prinivil, Zestril) and the ____ candesartan (Atacand) were shown to reduce migraine frequency compared with placebo.

Back 76

ACEI
ARB

Front 77

riboflavin
feverfew
butterbur

Back 77

migraine