ANTIMIKOTIK

Classification
1. Antibiotic : Griseofulvin and antibiotic polyen (amfoterisin
B, nistatin, natamisin)
2. Derivat Imidazole : Mikonazole, Ketokonazole, Klotrimazole,
Bifonazole, Ekonazole, Isokonazole, Tiokonazole.
3. Derivat Triazole : Flukonazole, Itrakonazole, Terkonazole
4. Organic Acid : Benzoat acid, Salisilat, Propionat, Kaprilat,
Undesilinat
5. Ect, Terbinafin,Tolnaftat, Haloprogin,Naftifin,
Sikopiroks,Selensulfida, Pirition
 Mechanism of action
Antibiotik
(Griseofulvin,amfoterisin B,
Nistatin, Natamisin

The drugs are Bound to Ergosterol (a cell

membran sterol is found in the cell
membrane of fungi)  Permeability of the
Cell membrane of fungi ↑  destroy of
cell O
 
 Mechanism of action
Griseofulvin,amfoterisin B,
Nistatin,natamisin
▌
▼
Ergosterol

Permeabilitas Cell ↑↑
Fungi ↓
destroyed

O
 
 Mechanism of action
Derivat Imidazol
(Mikonazole,Ketokonazole,Klotrimazole
,Bifonazole,Ekonazole,Isokonazole,Tio
konazol)

The drugs results from the reduction of

ergosterol synthesis by inhibition of fungal
cytochrome P450 enzymes

O
 
Antibiot Griseofulvin Amfoterisin B Nistatin Natamisin
ic
Source Penicillium Streptomyces Streptomyc Streptomyce
griseofulvum nodosus es noursei s nataliensis
Used Oral Oral & IV Oral,Vagin Vaginal &
al & Topical
Topical
Reabsorpt Better with Nothing Nothing Nothing
ion in Lipid
Usus
Distributi Keratin, Not diffution to Not Not
on Stratum Skin, and diffution to diffution to
(Diffution corneum mucous Skin, and skin,
) (skin),nail, membran mucous mucous
root of hair membran membran
 Griseofulvin Amfoterisin Nistatin Natamisin
B
Side Efect Fotosensitisasi, Nefrotoksik Unpleasent taste Irritation on the
urtikaria,liver (vomiting) skin and
destroyed mucous

Pregnance Don’t give it Not have enough Can Give Can Give
(destroy mitosis data
of cromosom)

Drug of Dermatofit (not Candida Candidiasis The same with

Choise efective for usus,stomatitis,s Nistatin but
Candida,Pityriasis ariawan,vaginiti natamissin
Versikolor,Ragi, s, therapi with lesser degree of
Bacteria) tetrasiklin and specivity than
kortikosteroid nistatin
 Griseofulvin Amfoterisin B Nistatin Natamisin

Dose and Oral : 4 dd 125 mg or Oral : 2-4 dd 100 mg Oral : 3 dd Vaginal : 2 dd

Preparatio 1 dd 500 mg p.c Talsuin vaginal tab : 0,5-1 MU 25 mg for 10
n amfoterisin B 50 mg (1 million days ; topical 5
+ tetrasiklin 100 mg Unit) ; % opthalmic
vaginal ; 1 suspension
tab
(100.000 U
for 14 days,
zalp & Talk
100.000
U/g 2-3 dd
Nistatin 1
mg = 3.000
U
Imidazol Mikonazole Ketokonazol Klotrimaz
ole
Side Efect Irritation,Allergic, skin Hepatotoksik if we use Urtikaria,Burn
burn taste more than 14 days, inhibit taste
testosteron hormon if we
give more than 600
mg/day

Pregnance Can Give Don’t give it. Can Give

Teratogenic ???

Drug of Choise Dermatofit and Candida Systemic antifungal Candidiasis

( not efective for infection kronic, eczeme usus,stomatitis,
Aspergillus) seboroik (ketombe) and sariawan,vagini
(not efective for tis, therapi with
Aspergillus) tetrasiklin and
kortikosteroid
 Mikonazol Ketokonazol Klotrimaz
ol

Dose / Skin infection 1-2 dd Oral : 1 dd 200 mg until 7 Vaginitis

Preparation Zalp 2 % for 3-5 days the symtomp has Candida, 200
weeks, nail infection gone, if important we cab mg tab for 3
1-2 dd tingtur 2 % for give 400 mg/day ; child 3 days or single
8 months, cream mg/kgBB dose 500 mg
vaginal 2 % at night Vaginitis candida : oral 2 Skin infection
for 2 weeks and dd 200 mg for 5 days (Panu) ; cream
100,200 mg vaginal / lotion 1 %
suppositories
Triazole Itrakonazol Flukonazol

Side Efect Interaction with hepatic The Least effect of All the azoles
microsomal enzym (but
lesser degree than
ketokonazol)

Drug interaction Inhibit metabolism of Drug interaction are also less

antihistaminika long common
acting terfenadin,
astemizol

Pregnance Don’t give it. Unknown

Mamalian can destroy
fetus

Drug of Choise Dermatofit,Ragi Oral candidiasis, candidiasis

patogen,and Aspergillus vaginal, treatment and secondary
prophilaxis of cryptococcal
meningitis
FLUCONAZOL

• Fluconazole displays a high degree of water

solubility and good cerebrospinal fluid
penetration
• Oral bioavaibility is high
• Fluconazole has the widest therapeutic index of
the azole
 Itrakonazol Flukonazol
Dose / Preparation Vaginitis Candida 1 dd Oral candidiasis ; 1 dd 50-
200 mg for 3 days 100 mg for 1-2 weeks,
Oral : 100 mg capsule ; Vaginal candidiasis : 150
10 mg/ml solution mg single dose, Sistemic
Parenteral : 10 mg/ml Candidiasis the first dose
for IV infusion 400mg and than 1 dd 200-
400 mg
Organic Salisilat Acid Benzoat Acid Undesillen
Acid at Acid
Dose / Fungisid  The same with Fungistatis for
Preparation consentration 3- Salisilat Acid dermatofit,
especially for
6% zalp Tinea Pedis
Keratolitis  (kutu Air) 
consentration 5- consentration
10% 5-10%

Mild fungal
infection
Whitefield(salisilat
5% + benzoat 5%
Ec Tolnaftat Haloprogin Naftitin Siklopiroks Terbinafi
t n
Efective  Efective Efective Efective Terbinafin
dermatofit Epidermofito Nail Candida Mallass
 n, infection albicans and ezia furfur
Zalp + Pitirosporum, & Trichopyton (panu),
tolnaftat 2 Trichopiton.C Mallassezi rubrum candida 
%+ andida  a furfur dose : 2 dd dose : oral
heksaklorof Cream 1 % (panu)C cream 1% for 1-2 dd 250
en 0,5% ream 1 % 2-4 weeks mg and
topical 1-2
dd cream
10 mg
 Autacoids
Autacoids are endogenous substances
with complex physiologic and
pathophysiologic functions
HISTAMIN
 Released from mast cells in response to IgE-
mediated allergic reactions (rhinitis seasonal/hay
fever, urticaria, and angioneuritic edema.
 Plays an important physiologic role in the control
of acid secretion in the stomach and as a
neurotransmitter
 Histamin has no clinical application
 Receptors anf Effects
• H1 receptor– important in smooth muscle
effects, especially those caused by IgE-
mediated responses. Effects :
bronchoconstriction, and vasodilation
• H2 receptor – mediates gastric acid secretion
by parietal cells in the stomach and also has
cardiac stimulation effects
• H3 receptor – involved mainly in presynaptic
modulation of histaminergic
neurotransmission in the CNS
 Histamine H1 Antagonists
Classification and prototype :
1. First generation H1 blockers
(dyphendramine, doxylamine,
chlorphenyramine, cyclizine)  highly
sedating agents with significant autonomic
receptor-blocking effects
2. Second generation H1 blockers
(fexofenadine, loratadine, cetirizine) free
of sedating and autonimic effects
 Mechanism and Effects
• Competitive pharmacologic antagonists at the H1
receptor, no effect on histamine release from storage
sites. More effective if given before histamine release
occurs
• Antagonists at autonomic receptor (muscarinic
blockers and  adrenoceptor blockers
• A few also blocks serotonin receptor
• No effects at H2 receptors
• Effects : sedating, antimotion sickness, potent local
anesthetics
Clinical use
• Allergies (hay fever, urticaria)
• Antimotion sickness (diphenhydramine,
dimenhydrinate, promethazine)
• Management of chemotherapy-induced
vomiting (diphenhydramine)
Toxicities
• Sedation (especially with first generation H1
blockers)
• Antimuscarinic effects (dry mouth, and
blurred vision) occur with first generation
• Alpha blocking drugs may cause orthostatic
hypotension
 Histamine H2 Antagonists
• Prototype : cimetidine, ranitidine, famotidine, and nizatidine
• Mechanism of action : pharmacologic antagonists at H2
receptors
• Effects : reduction of gastric acid secretion
• Clinical use :
- acid peptic disease
- prevent recurrences of gastric peptic ulcers
- Zolinger-Ellison syndrome (acid hypersecretion, severe
recurrent peptic ulcer, GI bleeding, diarrhea)
- gastroesophageal reflux disease (GERD)
• Toxicities
- Inhibitor of hepatic drug-metabolizing enzymes and reduce
hepatic blood flow
- Antiandrogen effects
 Serotonin
Serotonin plays a physiologic role as a neurotransmitter in both
the CNS and enteric nervous system
Receptor and Effects
1. 5-HT1 receptor – mediate both excitatory and
inhibitory effects in various smooth muscle
tissues
2. 5-HT2 -- mediate synaptic excitation in the
CNS and smooth muscle contraction (gut,
bronchi, vessels) or dilation (vessels)
3. 5-HT3 – found in the chemoreceptive are and
vomiting center & in peripheral sensory and
enteric nerves
Clinical use : Serotonin has no clinical application
 Other Serotonin Agonists
1. 5-HT1D agonists – (sumatriptan, naratriptan).
Effective in the treatment of acute migrain and
cluster headache attacks
2. Serotonin reuptake inhibitors – Fluoxetine,
fluvoxamine, sertraline are antidepressant drugs.
Dexfenfluramine reducing appetite
Serotonin Antagonists
• Prototype :
- 5-HT2 blockers (ketanserin, phenoxybenzamine,
cyproheptadine)
- 5-HT3 blockers (ondansteron, granisetron, dolasetron,
alosetron)
 Mechanism of action
• Ketanserin, cyproheptadine, and
phenoxybenzamine are poorly selective
antagonists
• Ondansetron, granisetron, and dolasetron are
selective 5-HT3 receptor and have a central
antiemetic action
Toxicities
• Ketanserin :  blockade, h1 blockade
• Ondansetron : diarrhea and headache
• Dolasetron : QRS and QT prolongation ECG
• Alosetron : constipation
 Clinical use
 Antihypertensive (ketanserin)
 Treatment carcinoid tumor (a neoplasma that
secretes large amounts of serotonin 
Ketanserin, cyproheptadine, and
phenoxybenzamine
 Control of vomiting associated with cancer
chemotherapy and postoperative vomiting
 Irritable bowel syndrome with diarrhea
(alosetron)