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Flashcards in 2 - Antimalarial Agents Deck (79):

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



Antimalarials bind avidly to tissue proteins, therefore the concentrations are highest in liver, spleen, and kidney tissues, especially in nuclei and mitochondria



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



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



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



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



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



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



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)



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)


Hypersensitivity is the only absolute contraindication to Antimalarial therapy



Further use of Antimalarial therapy is contraindicated In a patient with documented retinopathy whilst on Antimalarial therapy



Pregnancy and lactation is a relative contraindication to the use of Antimalarial therapy because the drugs can cross the placenta and secreted in breast milk

True (although several reports suggest that the risk of discontinuing Antimalarial therapy in pregnant SLE patients outweighs the risk of toxicity to the fetus + several long term follow up of children exposed to CQ or HCQ during the antenatal period experienced no ocular toxicity or ototoxicity) - although in small doses Antimalarials are safe in children, mothers of infants should refrain from breastfeeding while on Antimalarials or the Antimalarials should be discontinued as it is not clear how great the concentration of these drugs would be in breast milk


With the exception of 'true retinopathy', most of the adverse effects of Antimalarial therapy are reversible on discontinuation of the Antimalarial agent



Yellow pigmentation of the skin is limited to quinacrine therapy

True (may not be suitable for fairer skin types as this pigmentation is more noticeable)


Haematologic adverse effects are more common with quinacrine than CQ or HCQ



Ocular toxicity is not seen with quinacrine

True (associated with CQ and HCQ, with CQ > HCQ)


Both CQ and HCQ have been associated with retinopathy, although CQ is more toxic than HCQ at therapeutically equivalent doses



Ophthalmoscopic toxicity is the issue of most concern to physicians who prescribe Antimalarials

True (corneal deposits, neuromuscular eye toxicity, retinopathy)


The 3 types of ocular adverse effect caused by Antimalarials are
(1) corneal deposits
(2) neuromuscular eye toxicity
(3) retinopathy

True (only retinopathy is potentially irreversible)


Retinopathy from Antimalarial therapy is divided into 2 forms: (1) 'true' retinopathy
(2) 'premaculopathy' - defined as changes on visual field or fundoscopic examination that are not associated with visual loss

True ('true' retinopathy is irreversible, but premaculopathy would progress if the Antimalarial agent was continued but it is potentially reversible with drug discontinuation)


The American Academy of Ophthalmology recommends that patients be evaluated for retinopathy at baseline within the first year of CQ or HCQ therapy, and then the first annual evaluation should take place after 5 years of continuous therapy (the frequency is altered in patients at higher risk, primarily elderly patients)

True (when HCQ is used at a dose of 400mg/day and CQ used at 250mg/day, the risk of retinopathy is the first 5 years of therapy is negligible; at 5 years the risk begins to rise to roughly 1%) - complete ophthalmologist examination including visual acuity, dilated examination of the cornea and retina with slit-lamp and fundoscopic exam, and baseline visual field testing by static and kinetic techniques; Amsler grid testing is no longer recommended


In patients with possible early retinopathy to CQ or HCQ, the drug should be stopped if possible, or more frequent examinations might be used to observe progression

True (CQ > HCQ)


Once present, there is no effective therapy for Antimalarial-induced retinopathy

True (irreversible)


Reversible Corneal deposits from CQ or HCQ (CQ > HCQ) are usually asymptomatic, but patients may experience halos around lights

True (not a contraindication for continued therapy, but will progress with continued therapy) - reversible upon cessation


Reversible Corneal deposits from CQ or HCQ (CQ > HCQ) does not reduce visual acuity



Reversible Corneal deposits from CQ or HCQ (CQ > HCQ) does not correlate with retinopathy

True (and so not a contraindication for continued therapy but will progress with continued therapy) - reversible upon cessation


Corneal deposits from CQ or HCQ (CQ > HCQ) are generally reversible over a period of 2-6 months with cessation of CQ or HCQ therapy



Reversible Neuromuscular eye toxicity (reduction in the accommodative power of the eye and a change in the extra ocular muscle balance) may occur soon after the initiation of CQ

True (specific to CQ, has not been reported in HCQ)


Antimalarials can be safely and successfully used in the treatment of children with LE, dermatomyositis, panniculitis, morphea and PCT



Risk of 'true' retinopathy is greatest with CQ

True (some risk with HCQ, no risk with quinacrine)


GI side effects such as nausea, vomiting and diarrhoea are the most common reasons for early reductions in dosage or discontinuation of CQ and HCQ (CQ > HCQ)

True (10% of CQ patients have intolerable GI side effects)


CQ is more toxic than HCQ

True (retinopathy, corneal deposition, neuromuscular toxicity, GI side effects, agranulocytosis, progressive bleaching of the hair roots of the scalp face and body, psoriasis flare-ups, fatal irreversible cardiac arrest)


Quinacrine may cause aplastic anaemia (pancytopenia)



CQ may cause agranulocytosis

True (WCC)


CQ and HCQ has been associated with haemolytic anaemia in patients with G6PD deficiency

True (though not in the usual dose range, and risk is more likely with the combination of CQ and primaquine for malaria prophylaxis)


Antimalarials may rarely cause neuromuscular side effects in uniquely susceptible patients or with higher than recommended dosages I.e. Restlessness, excitement, confusion, headache, seizures, myasthenia and toxic psychosis



A bluish-grey to black hyperpigmentation typically affecting the shins (resembling ecchymoses), face, palate (sharp line demarcating hard and soft palates), nailbeds (as transverse bands) may occur in 10-30% of patients treated with Antimalarials for 4 months or longer

True (biopsies show haemosiderin around capillaries and dermal melanin) - pigmentation may take months to fade after discontinuation of therapy


10% of CQ patients may experience reversible progressive bleaching of the hair roots of the scalp, face and body



Pruritus and various cutaneous eruptions have been associated with Antimalarials

True (urticaria, exanthematous, eczematous, lichenoid, exfoliative dermatitis, erythema annulare centrifugum patterns)


Quinacrine is responsible for greatest frequency of exfoliative erythroderma

True (CQ most commonly responsible for significant psoriasis flare-ups, and a markedly low incidence for both types of reaction was noted for HCQ than CQ or quinacrine)


CQ is most commonly responsible for significant psoriasis flare-ups

True (Quinacrine is responsible for greatest frequency of exfoliative erythroderma, and a markedly low incidence for both types of reaction was noted for HCQ than CQ or quinacrine)


Fatal reactions with irreversible cardiac arrest have been reported after accidental or intentional overdosage with CQ

True (particular sensitivity in young children aged 1-3 years to a dose as low as 1g only)


CQ or HCQ treatment should be discontinued if bilateral field defects are confirmed on follow up



Higher dosages of Antimalarials may increase the risk of GI side effects and retinal toxicity



If GI side effects (esp in CQ) such as nausea, vomiting, diarrhoea becomes problematic, stopping the Antimalarial drug and then restarting at a lower dosage may circumvent the problem



Patients who develop an Antimalarial drug-related eruption must discontinue the Antimalarial

True (however patients who are intolerant of or allergic to HCQ may tolerate CQ, and vice versa + if a relatively low risk cutaneous drug reaction such as morbiliform or lichenoid reactions developed then rechallenge with the alternative Antimalarial agent is quite reasonable)


CQ and HCQ should not be used concurrently due to the additive retinotoxic potential



Antacids such as Aluminium, Magnesium, H2 antihistamines, and PPIs reduce the GI absorption of Antimalarials and this reduces Antimalarial serum levels and efficacy

True (Antimalarials are crystalline water soluble agents)


Cimetidine (H2 antihistamine) may decrease the clearance rate and metabolism of CQ and thereby increase the serum levels of CQ



CQ and HCQ may increase the serum levels and potential toxicity of digoxin



CQ may increase the serum levels and potential toxicity of CsA

True (and result in CsA adverse effects such as renal toxicity, hyperlipidaemia, hypertension)


CQ and HCQ may increase the serum levels and potential toxicity of penicillamine

True (result in adverse effects such as severe haematologic and renal toxicity)


CQ may decrease the serum levels of penicillins and result in loss of efficacy

True (separate administration of at least 2 hours advisable)


Concomitant CQ and macrolide antibiotics I.e. Clarithromycin, erythromycin may induce QT prolongation and arrhythmias



Concomitant CQ with tramadol may increase risk of seizures



Local anaesthetics I.e. Benzocaine (ester), prilocaine with lidocaine (amide) may increase the risk of methaemoglobinaemia when used concurrently with CQ

True (due to oxidative stress - similar to when local anaesthetics used with dapsone)


Combination of CQ and nitroprusside (nitrates) increases the risk of methaemoglobinaemia

True (due to oxidative stress)