AntiHelminthics drugs.pptx

Helminths - are multicellular organisms that affect a large number humans and cause broad range of diseases
Include:
Roundworms (nematodes)
Flukes (trematodes)
Tapeworms (cestodes)
Antitrematodes(flukes)- effective against trematodes. e.g.
praziquantel,
bithionol,
metrifonate,
oxamniquine.

1. Dr. NDAYISABA CORNEILLE CEO of CHG MBChB,DCM,BCSIT,CCNA Supported BY NEMATODES,TREMATODES AND CESTODES

2. Introduction Helminths - are multicellular organisms that affect a large number humans and cause broad range of diseases Include: Roundworms (nematodes) Flukes (trematodes) Tapeworms (cestodes) Dr Ndayisaba Corneille

3. Anthelmintic Drugs. Defined as used in controlling the parasitic worms or that inhabit in the GIT, other tissues & organs of the body. Antihelmintic drugs includes : Antinematodes – effective against nematodes( roundworms ).e.g. albendazole, vermectin, mebendazole, pyrantel pamoate, diethylcarbamazine. Dr Ndayisaba Corneille

4. Anthelmintic Drugs. Anticestodes-( tapeworms ) effective against cestodes niclosamide, albendazole, mebendazole, praziquantel. ANTIHELMINTIC DRUGS Dr Ndayisaba Corneille

5. ANTIHELMINTIC DRUGS Antitrematodes( flukes )- effective against trematodes. e.g. praziquantel, bithionol, metrifonate, oxamniquine. Dr Ndayisaba Corneille

6. Why control helminths ? They suck blood and cause anemia e.g. hook worms. Some destroy GIT mucosa –interfering with absorption of nutrients.e.g. strongyloids. Some block GIT e.g. Ascarides, Tape worms. Some damage internal organs.e.g. flukes damage the liver. Some block blood vessels Some block air way & destroy lung tissue 6 Dr Ndayisaba Corneille

7. Mechanisms of action of anthelminths . Those that affect energy production in the worm. These could be inhibitors of polymerization of tubulin. Polymerization is necessary for synthesis of microtubules in ER of worm. Such drugs include: Benzimidazoles & probenzimedazoles. Inhibitors of oxidative phosphorylation in mitochondria e.g.Niclosamide. c) Inhibitors of glycolysis .e.g.clorsulan. 7 Dr Ndayisaba Corneille

8. 2) Those that act by causing paralysis. Cholinergic agents. These are neuromuscular blockers.e.g. imidazoles, tetrahydropyrimidines(e.g.pyrantel). GABA agonists. e.g.Avermectins. Muscle hyperpolyrisers. e.g.piperazines. Acetylcholinesterase inhibitors.e.g.dichlorvos. These have narrow safety margin since they affect the host. 8 Dr Ndayisaba Corneille

9. 3) Drugs that affect the permeability of the integument & also causing vacuolation of the integument . These include:-praziquantel. 9 Dr Ndayisaba Corneille

10. ANTIHELMINTHIC DRUGS Benzimidazoles : Mebendazole , Thiabendazole and Albendazole These compounds are broad spectrum agents and constitute one of the main groups of antihelminthics used clinically. 10 Dr Ndayisaba Corneille

11. Mechanism of action : The drugs bind to free β -tubulin,inhibiting its polymerisation and thus interfering with microtubule-dependent glucose uptake. They have a selective inhibitory action on helminth microtubular function,being 250-400 times more potent in helminths than in mammalian tissue. The effect takes time to develop and worms may not be expelled for several days. 11 Dr Ndayisaba Corneille

12. Pharmacokinetics : Only 10% of mebendazole is absorbed after oral administration. A fatty meal increases absorption. It is rapidly metabolized, the products being excreted in urine and bile within 24-48 hrs. Single dose for threadworm,but twice daily for three days for hookworm and roundworms. 12 Dr Ndayisaba Corneille

13. Thiabendazole is rapidly absorbed from the gut. It is rapidly metabolised and excreted in urine in the conjugated form. Given twice daily for 3 days for guinea worm and strongyloides and for up to 5 days for trichnosis and cutaneous larva migrans. 13 Dr Ndayisaba Corneille

14. Adverse effects : These are few with mebendazole – git symptoms occasionaly. Thiabendazole causes transient GIT dist.,headache,dizziness and drowsiness,allergic reactions (fever,rashes) can occur. Liver damage in a few cases. 14 Dr Ndayisaba Corneille

15. Albendazole : Most recently introduced benzimidazole. It is broad-spectrum. Pharmacokinetics : Rapidly absorbed from the gut. It is metabolised to the sulphoxide and sulphone which may be responsible for the antihelmintic actions. The plasma concentration of its active metabolite is 100 times greater than that of mebendazole. 15 Dr Ndayisaba Corneille

16. Unwanted effects : GIT disturbances but not common. Praziquantel : Broad-spectrum antihelmithic drug. It is the drug of choice for all species of schistosomes(haematobium,mansoni, japonicum ) and is effective in cysticercosis, for which there was previously no effective therapy. 16 Dr Ndayisaba Corneille

17. Mechanism of action : It acts by increasing membrane permeability to calcium. This causes marked contraction of the musculature and eventually results in paralysis and death of the worm. It has been suggested that praziquantel modifies the parasite so that it becomes susceptible to hosts normal immune responses. 17 Dr Ndayisaba Corneille

18. The drug affects not only the adult schistosomes but also the immature forms and cercaria – the forms of the parasite that infect humans by penetrating the skin. Praziquantel has no pharmacological effects in humans in therapeutic dosage Pharmacokinetics : Rapidly absorbed and is rapidly metabolised on first passage through the liver. Inactive metabolites are excreted in the urine. T ½ for the parent compound is 60-90 minutes. 18 Dr Ndayisaba Corneille

19. Adverse effects : Mild and transient git disturbances,dizziness,aching in muscles and joints,skin eruptions and low grade fever. Some effects are more marked in patients with a heavy worm load and may be due to products released from the dead worms. 19 Dr Ndayisaba Corneille

20. Piperazine : Used to treat infections with the common round worm ( Ascaris lumbricoids ) and threadworm ( Enterobius vermicularis ) which is called pin worm. Mechanism of action : Piperazine inhibits neuromuscular transmission in the worm, probably by acting like GABA the inhibitory neurotransmitter on GABA gated chloride channels in the nematode muscle. The paralyzed worms are expelled live. 20 Dr Ndayisaba Corneille

21. Pharmacokinetics : Partly absorbed from the gut. The absorbed drug is partly metabolised and the remainder is eliminated unchanged. The drug has significantly little pharmacological actions in the host. Adverse effects : Uncommon but include: Git disturbances,urticaria and bronchospasm. Some patients experience dizziness, paraesthesia,vertigo,incoordination . 21 Dr Ndayisaba Corneille

22. Clinical uses : Piperazine is used to treat round worms (in single dose). For threadworm a longer course (7 days) at lower dosage is necessary. The drug has largely been superseded by the benzimidazoles. 22 Dr Ndayisaba Corneille

23. Pyrantel pamoate : A derivative of tetrahydropyrimidine. Mechanjsm of action : it stimulates nicotinic receptors present at neuromuscular junction of nematodes. Pyrental causes spasm and paralysis of nematode muscles. It also has some anticholinesterase activity Pharmacokinetics : Poorly absorbed from the gut. More than 50% of the drug is eliminated in faeces. Adverse effects: Mild and transient git upsets,dizziness and fever have been reported. The drug has been largely superseded by the benzimidazoles. 23 Dr Ndayisaba Corneille

24. Clinical uses . Treatment of: Enterobius vermicularis A lumbricoides Hookworm & T orientalis 24 Dr Ndayisaba Corneille

25. Niclosamide : This was the drug of choice for tapeworm infections but has now largely been superseded by praziquantel. It’s a salicylamide derivative. Mechanism of action: The scolex and a proximal segment are irreversibly damaged due to the drug’s inhibition of oxidative phosphorylation or to its ATPase stimulating property. The worm separates from the intestinal wall and is expelled. Neither the larvae nor the ova are affected. 25 Dr Ndayisaba Corneille

26. For T. solium the drug is given in a single dose after a light meal, the tablets are chewed followed by a purgative 2 hrs later. A purgative is necessary because the damaged tapeworm segments may release ova which are not affected by the drug, so there is a theoretical possibility that cysticercosis may develop. For other tape worms it is not necessary to give a purgative after administration of niclosamide. Pharmacokinetics :Negligible absorption of the drug from the git. Adverse effects :Few,infrequent and transient. They include nausea and vomiting. 26 Dr Ndayisaba Corneille

27. Oxamniquine : This drug is active against schistosoma mansoni. It affects both immature and mature forms Mechanism of action : The drug may act by DNA binding, it causes contraction and paralysis of the worms resulting in detachment from terminal venues in mesentery and shift to liver. The parasite concentrates the drug . Resistance has developed in some geographical areas. 27 Dr Ndayisaba Corneille

28. Pharmacokinetics : It is given orally and it is well absorbed. It is metabolised in the gut wall and in the liver (first pass effect) to inactive metabolites that are exreted in the urine. T ½ 1-2 hrs and is eliminated in the plasma by 10-12 hours. 28 Dr Ndayisaba Corneille

29. Unwanted effects : Transient dizziness and headache. Gastrointestinal disturbances. CNS stimulation (hallucinations,convulsive episodes). Allergic manifestations and other symptoms that appear several days after treatment has stopped,may be related to the release of products from dead flukes. Dr Ndayisaba Corneille

30. Metrifonate : This is an organophosphate and anticholinesterase that was originally used as an insecticide. It was subsequently found to be effective against schistosoma haematobium. Pharmacokinetics : The drug is given orally and it is rapidly absorbed. The parent compound is cleared from the blood within 8 hrs. The plasma concentration of active metabolite constitutes about 1% of that of the parent compound. Both are cleared from the tissues within 1-2 days. 30 Dr Ndayisaba Corneille

31. Mechanism of action : Metrifonate is a prodrug giving spontaneously to the active drug dichlorvos in vivo. Its action is thought to be due to an inhibitory effect on cholinesterases in the helminth causing paralysis. 31 Dr Ndayisaba Corneille

32. Pharmacological actions : Effects of the drug on the enzymes occur but do not usually result in serious physiological changes. Plasma cholinesterase activity is inhibited and there is a marked decrease in red cell acetylcholinesterase activity. Recovery from these effects takes 4-15 weeks,the plasma enzymes recovering more rapidly. 32 Dr Ndayisaba Corneille

33. Adverse effects : Gastrointestinal disturbances,bronchospasm,dizziness, but usually last less than a day. Foetal damage has been reported. Diethylcarbamazine citrate : This is a piperazine derivative that is active in filarial infections caused by W.bancrofti and Loa loa. 33 Dr Ndayisaba Corneille

34. Mechanism of action : The drug immobilizes the microfilariae & alters their surface structure, making them more susceptible to destruction by host defense mechanisms. It may also interfere with the parasites arachidonate metabolim. Diethylcarbamazine rapidly removes the microfilariae from the blood circulation and has a limited action on adult worms in lymphatics but has little action on microfilariae in vitro. 34 Dr Ndayisaba Corneille

35. Pharmacokinetics : The drug is given orally and is absorbed from the gut. It is distributed throught the cells and tissues of the body,excepting adipose tissue. It is partly metabolised and both the parent drug and its metabolite are excreted within about 48 hrs. 35 Dr Ndayisaba Corneille

36. Adverse effects : Common but transient:- Git disturbances,arthralgia,headache and a general feeling of weakness. Allergic reactions due to products of the filaria. These start from 1 st day of treatment and last for 3-7 days. 36 Dr Ndayisaba Corneille

37. They include:- skin eruptions,enlargement of lymph nodes,dizziness and respiratory disturbances. When they disappear even larger doses of the drug can be used without any further problems. Diethylcarbamazine is not used in the treatment of onchocerciasis where serious unwanted effects can occur. . 37 Dr Ndayisaba Corneille

38. Pharmacokinetics : The drug is given orally. It is rapidly absorbed and widely distributed. It crosses the blood brain barrier. It is metabolised in the liver to inactive metabolites,which are excreted via the kidneys. 38 Dr Ndayisaba Corneille

39. Adverse efcets : Few and soon subside: GIT disturbances,dizziness and skin eruptions. High conentrations can have nicotinic actions on autonomic ganglia in the mammalia host. 39 Dr Ndayisaba Corneille

40. Ivermectin : A semisynthetic macrocyclic lactone derived from a group of natural substances,the ivermectines obtained from the soil actinomycete sreptomyces avermitilis. It’s a mixture of avermectin B 1a & Avermectin B 1b . It is used in the treatment of onchocerciasis.It is given orally and it has a T ½ of 11 hrs. Doxycycline 200 mg daily for 4 weeks greatly enhances the action of ivermectine. Dr Ndayisaba Corneille

41. Mechanism of action : Ivermectine is thought to kill the worm either by opening glutamate gated chloride channels (found only in invertebrates) and increasing chloride conductance or by binding to a novel allosteric site on the acetylcholine nicotinic receptor to cause an increase in transmission leading to motor paralysis. 41 Dr Ndayisaba Corneille

42. This binding site is diferrent from that in mammalian species and distinct from all other effector molecules of the chloride channel. Adverse effects : Skin rashes,fever,giddiness,headaches and pains in muscles,joints and lymph glands. 42 Dr Ndayisaba Corneille

43. END BY DR NDAYISABA CORNEILLE MBChB,DCM,BCSIT,CCNA,Cyber Security contact: [email protected] , [email protected] whatsaps :[phone] / [phone] THANKS FOR LISTENING Dr Ndayisaba Corneille