2 - Antimalarial Agents Flashcards
Hydroxychloroquine (HCQ), chloroquine (CQ) and quinacrine are the Antimalarial drugs used for the treatment of dermatologic disorders
True (HCQ and CQ are most commonly used)
HCQ and CQ are 4-aminoquinolines and derivatives of quinine, a naturally occurring alkaloid substance from the bark of the South American cinchona tree
True (this bark is used initially for its antipyretic effects)
Antimalarials are bitter, water soluble crystalline powders that are absorbed rapidly and completely from the GI tract
True
Antimalarials bind avidly to tissue proteins, therefore the concentrations are highest in liver, spleen, and kidney tissues, especially in nuclei and mitochondria
True
HCQ has a higher bioavailability than CQ but CQ is more toxic than HCQ
True (although distributions of the 2 drugs in tissue are qualitatively similar)
The lowest concentrations of HCQ and CQ are found in bone, skin, fat and brain tissues
True
Greater concentrations of HCQ and CQ are found in muscle, eye, heart, kidney, liver, lung spleen and adrenal glands
True (visceral organs)
The terminal half-lives of HCQ and CQ are similar at 40-50 days and is attributed to extensive tissue uptake and slow release into circulation
True (despite extensive tissue uptake, the attainment of steady-state concentrations is in 3-4 months and this may account for the slow appearance of therapeutic benefit)
The metabolism of HCQ and CQ differs in that HCQ breaks down into first and second-stage metabolites (desethylhydroxychloroquine and desethylchloroquine) whereas CQ breaks down into first-stage metabolite (desethylchloroquine)
True (the first-stage desethylchloroquine breaks down into a primary amine metabolite)
There is a difference in the relative amounts of HCQ and CQ excreted in urine and faeces in that approximately 3X more CQ than HCQ can be accounted for in urine and 3X more HCQ than CQ can be accounted for in the faeces
True
3X more CQ than HCQ is excreted in the urine (42-47%)
True (CQ has first-stage metabolism where as HCQ has 2-stage metabolism)
3X more HCQ than CQ is excreted in the faeces
True (HCQ breaks down into metabolites over 2-stages where CQ is broken down via 1-stage; HCQ also forms an ether glucuronide that is excreted in bile)
As a low proportion of unchanged HCQ (approx 20%) is excreted/eliminated unchanged in the kidneys/urine, this indicates that no dosage adjustment of HCQ is necessary for patients with mild to moderate renal impairment
True
One of the mechanism of action of Antimalarials is an effect on light filtration
True (therefore may inhibit UV-induced cutaneous reactions in lupus erythematosus and polymorphous light eruption)
One of the mechanism of action of Antimalarials is an immunosuppressive effect
True (useful in inflammatory immunomodulated dermatoses)
One of the mechanism of action of Antimalarials is an anti-inflammatory effect
True (impair chemotaxis of various inflammatory cells)
Antimalarials inhibit platlet aggregation and adhesion, thereby inhibiting thrombus formation
True (fewer thromboembolic events in patients with LE and antiphospholid antibody syndrome when treated with Antimalarial therapy)
There are reports of lower lipid levels with Antimalarials
True (studies have suggested a decrease in cholesterol and possible protection from coronary artery disease in patients with SLE on prednisone)
One of the mechanism of action of Antimalarials is an antiviral effect
True (a study noted a modest decrease in HIV load)
One of the mechanism of action of Antimalarials is an antiproliferative effect through inhibition of DNA/RNA biosynthesis
True
Antimalarials are FDA approved for LE
True (although certain subsets of LE respond less well: patients with widespread involvement, those with hypertrophic or verrucous lesions, and those who have SLE with prominent discoid LE lesions)
Anectodal reports suggests that when HCQ is not effective, a switch to CQ may result in control of the process
True (HCQ and CQ should not be used simultaneously because of the potential for additive retinal toxicity)
The onset of action for Antimalarials used for cutaneous LE is between 4 and 12 weeks
True
The use of HCQ significantly delayed the time to fulfill criteria for SLE
True (many of the patients were treated with HCQ because of the existence of LE-specific skin lesions)
Significant scalp involvement with alopecia (scarring alopecia) in addition to disseminated discoid, annular, or papulosquamous subacute cutaneous LE skin lesions also warrant Antimalarials
True
There is conflicting and controversial data that Antimalarial therapy in cutaneous LE is less effective in patients who are smokers
True (the mechanisms by which smoking lessens the effects of Antimalarials is not known, but it has been postulated that smoking increases disease activity in LE patients and that smoking might reduce the efficacy of Antimalarials by blocking their accumulation within lysosomes) - regardless of whether smoking is associated with more active LE or lessens the effect of Antimalarials, smoking cessation should be advised for improved general health outcome
Antimalarials are not the first choice of therapy for porphyria cutanea tarda
True (after exogenous hepatotoxins/exacerbating factors such as alcohol, Oestrogens, and iron supplements are removed/discontinued, and possible viral infections such as HIV or hepatitis C have been assessed for and treated, phlebotomy remains the primary therapy, including patients with hepatitis C infection) - for patients who are anaemic where removing whole blood is not ideal or who fail to respond to phlebotomy, Antimalarial therapy may be attempted
The mechanism of Antimalarials for porphyria cutanea tarda (PCT) is the effect on hepatocytes, with release of porphyrins into the circulation and eventual excretion
True (recovery from the toxic reaction resulted in remission of the PCT) - This therapy should not be used in patients with renal failure on haemodialysis because the porphyrins released from the liver would not be cleared effectively
Despite HCQ being a treatment option for patients with dermatomyositis and difficult to treat cutaneous disease, the potential for a drug eruption from HCQ in patients with dermatomyositis appears to be greater than for other patients with other diseases who are treated
True (as high as 20% higher risk than other diseases treated with HCQ) - Pruritus and various cutaneous eruptions have been associated with Antimalarials
Antimalarial therapy may be of benefit for patients with benign lymphocytic infiltrates of the skin (pseudolymphoma/lymphocytoma cutis, Jessner lymphocytic infiltrate)
True
The use of Antimalarials in patients with psoriasis has been reported to increase the severity of psoriasis, and in some this may lead to an exfoliative erythroderma
True (quinacrine responsible for greatest frequency of exfoliative erythroderma, CQ most commonly responsible for significant psoriasis flare-ups, and a markedly low incidence for both types of reaction was noted for HCQ than for the other 2 Antimalarials)