CHAPTER 11
W hat are the adve rse e ffe cts of phe nte rmine and sibutramine ? T achycardia; hypertension; headache; insomnia; dry mouth; constipation W hat drugs should be avoide d in patie nts taking sibutramine ?
Monoamine oxidase inhibitors (MAOIs); selective serotonin reuptake inhibitors (SSRIs); dextromethorphan
W hat popular name was give n to the combination re gime n fe nfluramine and phe nte rmine and why was it e ve ntually pulle d off of the marke t?
Fen-phen (combination of fenfluramine and phentermine); pulmonary hypertension and heart valve abnormalities. Fenfluramine was removed from the markets in 1997 in the United States because of these side effects.
W hat antiobe sity age nt inhibits gastric and pancre atic lipase , the re by inhibiting bre akdown of die tary fat?
Orlistat
W hat are the adve rse e ffe cts of orlistat?
Oily spotting; abdominal discomfort; flatus with discharge; fatty stools; fecal urgency; increased defecation W hat vitamin supple me ntation is re comme nde d in patie nts taking orlistat?
Fat-soluble vitamins
W hat are the fat-soluble vitamins?
A; D; E; K
AGENTS FOR OS TEOPOROS IS
Give e xample s of me dications that be long to the bisphosphonate drug class:
Alendronate; risedronate; etidronate; pamidronate; ibandronate W hat is the me chanism of action of the bisphosphonate s?
Inhibition of osteoclast-mediated bone resorption
W hich bisphosphonate can only be administe re d intrave nously?
Pamidronate
W hat must patie nts be counse le d on re garding oral bisphosphonate the rapy?
T ake medication with a full glass of water and stay in a sitting or standing position for 30 minutes following administration to prevent esophageal irritation.
Intrave nous pamidronate can also be use d to tre at what conditions?
Hypercalcemia of malignancy; osteolytic bone lesions associated with multiple myeloma or metastatic breast cancer
W hat se le ctive e stroge n re ce ptor modulator can incre ase bone de nsity in wome n without incre asing the risk for e ndome trial cance r?
Raloxifene
How is calcitonin administe re d?
Intranasally
W hat is the source of me dically use d intranasal calcitonin?
Salmon
How much calcium should a postme nopausal woman take daily?
C alcium should be take n with what othe r supple me nt to e nhance its absorption?
Vitamin D
W hat re combinant N-te rminal 34-amino-acid se que nce of parathyroid hormone stimulate s oste oblast function, incre ase s gastrointe stinal (GI) calcium absorption, and incre ase s re nal tubular re absorption of calcium?
T eriparatide
AGENTS FOR ERECTILE DYS FUNCTION
W hat prostaglandin ET(PGE1) analog is inje cte d into the corpus cave rnosum and cause s incre ase d arte rial inflow and de cre ase d ve nous outflow to and from the pe nis, re spe ctive ly?
Alprostadil
W hat is the me chanism of action of silde nafil?
Enhances the vasodilatory effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE-5) which allows for increased cyclic guanosine monophosphate (cGMP) levels (cGMP causes smooth muscle relaxation in the corpus cavernosum)
Name two othe r PDE-5 inhibitors use d in the tre atme nt of e re ctile dysfunction:
1. T adalafil 2. Vardenafil 3. Udenafil 4. Avanafil
W hat are the adve rse e ffe cts of silde nafil?
Headache; dizziness; color vision disturbances; hypotension
Silde nafil is contraindicate d in patie nts taking what type of me dications?
Nitrates (potentiates hypotension) AGENTS FOR RHEUMATOID ARTHRITIS
For the following dise ase -modifying antirhe umatic drugs (DMARDs), give the me chanism of action:
Glucocorticoids
Decrease production of inflammatory mediators; suppression of neutrophil migration Etane rce pt
Recombinant tumor necrosis factor (T NF) receptor linked to the Fc portion of human IgG1; binds T NF and inhibits its interaction with cell surface receptors Infliximab
Chimeric monoclonal antibody that binds to human T NF-α, thereby interfering with its activity Le flunomide
Inhibits dihydro-orotic acid dehydrogenase, thereby inhibiting pyrimidine synthesis Anakinra
IL-1 receptor antagonist Gold salts
Inhibit phagocytosis and lysosomal enzyme activity of macrophages Me thotre xate
Inhibits dihydrofolate reductase; increases adenosine levels (this is methotrexate’s anti-inflammatory mechanism of action)
Hydroxychloroquine
Interferes with lysosomal function; inhibits chemotaxis of neutrophils and eosinophils Pe nicillamine
Depresses circulating rheumatoid factor (RF); depresses T -lymphocyte activity W hat is RF?
IgM directed against IgG
W hat othe r dise ase is pe nicillamine use d to tre at?
Wilson disease
W hat are the adve rse re actions for the following DMARDs?
Glucocorticoids
Acne; insomnia; edema; hypertension; osteoporosis; cataracts; glaucoma; psychosis; increased appetite; hirsutism; hyperglycemia; muscle wasting; pancreatitis;
striae; redistribution of body fat to abdomen, back, and face Etane rce pt
Hypersensitivity; headache; local injection site reactions; respiratory tract infection; positive antinuclear antibody (ANA); activation of latent tuberculosis Infliximab
Headache; rash; nausea; diarrhea; urinary tract infection; infusion reactions; arthralgia; upper respiratory infection; activation of latent tuberculosis Le flunomide
Pregnancy category X; hepatotoxicity; rash; alopecia Anakinra
Local injection site reactions; headache; infection Gold salts
Nephrotoxicity; dermatitis; alopecia; eosinophilia; leukopenia; thrombocytopenia; hematuria; nausea; vomiting Me thotre xate
Mucositis; nausea; vomiting; diarrhea; nephrotoxicity; leukopenia; thrombocytopenia; hepatotoxicity; pneumonitis; crystalluria Hydroxychloroquine
Cardiomyopathy; alopecia; visual disturbances; anorexia; nausea; vomiting; diarrhea; aplastic anemia; agranulocytosis; hemolysis in G6PD deficiency;
cinchonism; exacerbation of porphyria Pe nicillamine
Vasculitis; alopecia; hypoglycemia; thyroiditis; eosinophilia; hemolytic anemia; thrombotic thrombocytopenic purpura (T T P); hepatotoxicity; proteinuria AGENTS FOR GOUT
W hat two cate gorie s do gout patie nts fall into pathophysiologically?
1. Overproducers 2. Underexcretors
W hich drug is a xanthine oxidase inhibitor?
Allopurinol
W hat bioche mical proce ss is the e nz yme xanthine oxidase involve d in?
Purine metabolism
W hich two drugs re quire dosage re ductions whe n give n concomitantly with allopurinol (be cause the y are me taboliz e d by xanthine oxidase )?
1. 6-Mercaptopurine
2. Azathioprine (reduce to 25% of normal dose)
W hat is the most common side e ffe ct of allopurinol?
Skin rash
Name othe r pote ntial side e ffe cts of allopurinol:
Nausea; vomiting; renal impairment; acute tubular necrosis; agranulocytosis; Stevens-Johnson syndrome Name thre e uricosuric age nts:
1. Probenecid 2. Sulfinpyrazone 3. High-dose aspirin
De fine uricosuric:
Enhancing renal excretion of uric acid
W hat is the me chanism of action of probe ne cid?
Inhibits proximal tubular resorption of uric acid
Probe ne cid inhibits the tubular se cre tion of what antibiotic and is some time s give n in combination to prolong its half-life ? Penicillin
How is acute gout tre ate d?
Colchicine; nonsteroidal anti-inflammatory drugs (NSAIDs)
W hy is allopurinol not use d in the tre atme nt of an acute gout attack?
May actually precipitate acute gouty arthritis and therefore perpetuate the acute gout attack (used for prevention and not treatment of gout attacks) W hat is the me chanism of action of colchicine ?
Increases depolymerization of microtubules; decreases leukocyte motility; decreases phagocytosis in joints and lactic acid production, thereby reducing deposition of urate crystals
W hat are the adve rse e ffe cts of colchicine ?
Nausea; vomiting; diarrhea; abdominal pain; agranulocytosis; aplastic anemia; bone marrow suppression; alopecia; myopathy; arrhythmia; hepatotoxicity RETINOIDS
Re tinoic acid share s a similar structure and function with what fat-soluble vitamin?
Vitamin A
13-cis-Re tinoic acid is also known as what drug?
Isotretinoin (Accutane)
W hat is the major the rape utic indication of isotre tinoin?
Acne
Isotre tinoin be longs in what pre gnancy risk factor cate gory?
Pregnancy category X. T his drug should not be used in pregnant patients under any circumstances. Fetal isotretinoin syndrome involves fetal craniofacial, cardiac, and CNS defects.
W hat is the me chanism of action of isotre tinoin?
Decreases sebaceous gland size and reduces sebum production; regulates cell proliferation and differentiation; decreases hyperkeratinization; decreases androgen levels; decreases Propionibacterium acnes levels (bacterium associated with acne)
Hype rvitaminosis A can damage what major organ?
Liver
All-trans-re tinoic acid (ATRA) is also known as what drug?
T retinoin
W hat is the major the rape utic indication of ATRA?
Induction of remission in patients with acute promyelocytic leukemia (APL) W hat is the me chanism of action of tre tinoin (whe n use d for acne )?
Binds to nuclear receptors and inhibits clonal proliferation and granulocyte differentiation HERBAL MEDICATIONS
Doe s the Unite d State s Food and Drug Administration (FDA) re gulate he rbal me dications?
No
Are he rbal me dications conside re d “drugs” by FDA standards?
No, considered “ nutritional supplements”
W hat he rbal me dication is use d for migraine and fe ve r?
Feverfew
W hat he rbal me dication is use d for “je t lag”?
Melatonin
W hat he rbal me dication is use d for de pre ssion?
St. John’s wort
W hat he rbal me dication is use d for be nign prostate hype rplasia (BPH)?
Saw palmetto
W hat he rbal me dication is use d for anxie ty?
Kava kava
W hat he rbal me dication is use d for Alz he ime r dise ase ? Gingko biloba
W hat he rbal me dication is use d for hype rchole ste role mia?
Garlic
W hat he rbal me dication is use d for the common cold?
Echinacea
W hat he rbal me dication is use d for he patitis?
Milk thistle
W hat he rbal me dication is use d to tre at hot flushe s in me nopause ? Black cohosh
Is St. John’s wort a me tabolic e nz yme induce r or inhibitor?
Inducer
W hat he rbal supple me nts should one use with caution whe n using warfarin concomitantly?
T he G4 supplements: garlic, ginger, gingko, and ginseng. T hese substances may interact with warfarin, and some, especially gingko which has antiplatelet effects, may increase bleeding risk. Ginseng may decrease warfarin’s effects.
S UBS TANCE ABUS E AND TOLERANCE
W hat are the physiologic e ffe cts of he roin?
Euphoria; decreased motor function; respiratory depression; miosis W hat are some of the signs/symptoms of he roin withdrawal?
Nausea; vomiting; muscle aches; yawning; lacrimation; rhinorrhea; diarrhea; sweating; fever; mydriasis; piloerection; insomnia W hat is anothe r name for piloe re ction?
Goose bumps
How can he roin ove rdose le ad to de ath?
Acute respiratory depression
W hat drug is use d for the tre atme nt of he roin abuse ? Methadone (jo,-receptor agonist)
W hat drug is use d to tre at re spiratory de pre ssion during an opioid ove rdose ? Naloxone
W hat drug is use d to counte ract the sympathe tic e ffe cts of he roin withdrawal?
Clonidine
W hat is the me chanism of action of cocaine ?
Blocks reuptake of dopamine, serotonin, and norepinephrine W hat is the me chanism of action of amphe tamine s?
Ultimately, they increase the release of catecholamines from presynaptic nerve endings.
W hat are the physiologic e ffe cts of cocaine and amphe tamine s?
Euphoria; reduced inhibitions; reduced sleep; reduced appetite; tachycardia; sweating; increased alertness; pupillary dilation W hat are the withdrawal signs/symptoms of cocaine and amphe tamine s?
Depression; increased sleep; increased drug cravings; bradycardia; dysphoria W hat are the physiologic e ffe cts of marijuana?
Analgesia; increased appetite; impairment of short-term memory; antiemetic; altered perception of time and space; change in motor and postural control W hat is the active psychotropic compone nt of marijuana?
Delta-9-tetrahydrocannabinol (Δ9-T HC)
W hat me dication is a synthe tic form of THC formulate d in se same oil and is use d as an appe tite stimulant in AIDS patie nts and as an antie me tic during che mothe rapy in cance r patie nts?
Dronabinol
W hat are the signs/symptoms of marijuana withdrawal?
Restlessness; irritability; agitation; insomnia; nausea Is ove rdose of marijuana fatal?
No
Give e xample s of hallucinoge nic drugs:
Methylenedioxymethamphetamine (MDMA; has hallucinogenic properties, yet is usually classified as a stimulant); mescaline; psilocybin; lysergic acid diethylamide (LSD); phencyclidine (PCP)
MDMA is also known as?
Ecstasy
Ecstasy can be ne urotoxic to which type of ne urons?
Serotonergic neurons
W hat is a major side e ffe ct of LSD?
Flashbacks
Is ove rdose of LSD fatal?
No
Doe s LSD have re inforcing e ffe cts?
No
W hat drug class doe s PC P and ke tamine be long to?
Dissociative anesthetics Is ove rdose of PC P fatal?
Yes, it is potentially fatal.
Doe s PC P have re inforcing e ffe cts?
Yes
W hat type s of ocular disturbance s are se e n in PC P intoxication?
Vertical and horizontal nystagmus TOXICOLOGY
Name the antidote for e ach type of poisoning:
Atropine
Acetylcholinesterase inhibitors Arse nic, gold
Dimercaprol Le ad, me rcury
Dimercaprol; succimer; penicillamine Ace tylcholine ste rase inhibitors Atropine with pralidoxime Ace taminophe n N-acetylcysteine Be nz odiaz e pine s Flumazenil β-Blocke rs Glucagon C oppe r Penicillamine C arbon monoxide Oxygen (hyperbaric) Digoxin
Digoxin immune Fab He parin
Protamine Iron
Deferoxamine; deferasirox The ophylline
β-Blockers W arfarin
Vitamin K; fresh frozen plasma (FFP) Thrombolytics
Aminocaproic acid; tranexamic acid O pioids
Naloxone
W hat are the signs and symptoms of arse nic poisoning?
“ Rice water” stools; GI discomfort; seizures; pallor; skin pigmentation; alopecia; bone marrow suppression; stocking glove neuropathy W hat are the signs and symptoms of iron poisoning?
Bloody diarrhea; shock; coma; dyspnea; necrotizing gastroenteritis; hematemesis W hat are the signs and symptoms of le ad poisoning?
Nausea; vomiting; diarrhea; tinnitus; encephalopathy; anemia; neuropathy; nephropathy; infertility; hepatitis W hat are the signs and symptoms of me rcury poisoning?
Ataxia; auditory loss; visual loss; chest pain; pneumonitis; nausea; vomiting; renal failure; shock W hat are the signs and symptoms of tricyclic antide pre ssant (TC A) poisoning?
Hyperthermia; coma; convulsions; cardiotoxicity; mydriasis; constipation; prolonged QT interval
W hat are the signs and symptoms of SSRI poisoning (must be whe n use d concomitantly with othe r se rotone rgic age nts such as MAO Is or TC As)?
T achycardia; hypertension; seizures; hyperthermia; agitation; muscle rigidity; hallucinations CLINICAL VIGNETTES
A 66-ye ar-old man with a past me dical history of stable angina we ll controlle d with oral nitroglyce rin come s in for a re gular che ck up to his primary care physician’s office . Afte r you polite ly ask about his wife he re plie s, “We ll, she ’s not too happy with me late ly.” Afte r some ge ntle prodding you e licit a history of e re ctile dysfunction. He asks you about a me dication he saw on TV, Viagra (silde nafil). You inform him that be cause he take s nitrate s he cannot also take this me dication due to pote ntially fatal inte ractions. W hat alte rnative me dication might you sugge st for this patie nt?
T he phosphodiesterase inhibiting properties of sildenafil cause vasodilation, allowing increased blood flow to maintain an erection. However, when used concomitantly with another vasodilating drug such as nitroglycerin, blood pressures may fall to levels insufficient to perfuse vital organs, especially in someone with preexisting heart disease. T herefore, an alternative agent must be used to treat this man’s erectile dysfunction. Alprostadil is a less popular medication than sildenafil since it must be injected directly into the corpus cavernosa, but it does not have the systemic effects seen with sildenafil, making it a viable alternative to treat this patient’s condition.
A 74-ye ar-old woman unde rgoe s a bone scan to e valuate he r bone de nsity. He r T-score come s back at –2.7. W hat is the me chanism of the class of me dications that are first-line the rapy for this woman’s me dical condition?
T his patient has osteoporosis, defined as a T-score of less than -2.5. Studies have found the most benefit in early preventative treatment in women with the highest risk for fracture, that is, those with lower (more negative) T-scores. Bisphosphonates are generally first-line therapy for osteoporosis. Bisphosphonates work by binding to hydroxyapatite crystal in bone and inhibiting osteoclast-mediated bone resorption.
A 53-ye ar-old man pre se nts to your office with a warm, swolle n right me tacarpal phalange al joint. He note s that this pain be gan sudde nly, and is e xquisite ly painful. W hat are your options for imme diate tre atme nt for this man’s pain, as we ll as long-te rm manage me nt for his condition?
T his is a classic presentation of gout, seen most commonly in older men. It is caused by an accumulation of uric acid crystals in a joint or tendon. Acute management involves NSAIDs, colchicine, or steroids (local or systemic). Long-term management includes life-style modifications to decrease purine breakdown such as decreased intake of red meat and alcohol. Allopurinol, a xanthine oxidase inhibitor, may be helpful as well.