AntiHelminthics drugs.pptx

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

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

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.

Anthelmintic Drugs.
Anticestodes-(tapeworms) effective against
cestodes
niclosamide,
albendazole,
 mebendazole,
praziquantel.
ANTIHELMINTIC DRUGS

ANTIHELMINTIC DRUGS
Antitrematodes(flukes)- effective against
trematodes. e.g.
 praziquantel,
 bithionol,
metrifonate,
 oxamniquine.

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

Mechanisms of action of anthelminths.
1)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

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

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

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

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

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

 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

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

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

 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

 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

 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.
 T½ for the parent compound is 60-90 minutes.
18

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

Piperazine:
 Used to treat infections with the common round
worm (Ascaris lumbricoids) and threadworm
(Enterobius vermicularis) which is called pin worm.
 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

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

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

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

Clinical uses.
Treatment of:
a)Enterobius vermicularis
b)A lumbricoides
c)Hookworm &
d)T orientalis
24

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

 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

Oxamniquine:
 This drug is active against schistosoma mansoni.
 It affects both immature and mature forms
 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

 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.
 T½ 1-2 hrs and is eliminated in the plasma by 10-12 hours.
28

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.

Metrifonate:
 This is an organophosphate and anticholinesterase that was
originally used as an insecticide.
 It was subsequently found to be effective against schistosoma
haematobium.
 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

 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

 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

 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

 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

 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

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

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

 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

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

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 B1a &
Avermectin B1b.
 It is used in the treatment of onchocerciasis.It is
given orally and it has a T½ of 11 hrs.
 Doxycycline 200 mg daily for 4 weeks greatly
enhances the action of ivermectine.

 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

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

END
BY
DR NDAYISABA CORNEILLE
MBChB,DCM,BCSIT,CCNA,Cyber Security
contact: amentalhealths@gmail.com ,
ndayicoll@gmail.com
whatsaps :+256772497591 /+250788958241
THANKS FOR LISTENING

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