Pharmacologycal

Aspects in Anaemia

Eti Nurwening Sholikhah

Department of Pharmacology and Therapy
Faculty of Medicine
Universitas Gadjah Mada

What are vitamins?

Complex substances that regulate

body processes
Coenzymes (partners) with
enzymes in reactions
No calories, thus no energy

Categories
Fat-soluble
Dissolve in fat
Can be stored

Water-soluble
Dissolve in water
Carried in
bloodstream, not
stored

A, D, E, K

C and B-complex
vitamins

A and D excess can

be harmful
E and K usually not

Excess amounts
may cause extra
work on kidneys

Vitamin A (and carotenoids)

Functions:
Normal vision
Protects from
infections
Regulates
immune system
Antioxidant
(carotenoids)

Food sources:

Liver
Fish oil
Eggs
Fortified milk or
other foods
Red, yellow,
orange, and dark
green veggies
(carotenoids)

Vitamin D (the
sunshine vitamin)

Functions:
Promotes
absorption of
calcium and
phosphorus
Helps deposit those
in bones/teeth
Regulates cell
growth
Plays role in
immunity

Sources:
Sunlight (10 15
mins 2x a week)
Salmon with
bones
Milk
Orange juice
(fortified)
Fortified cereals

Vitamin E

Functions:
Antioxidant, may
lower risk for
heart disease and
stroke, some
types of cancers
Protects fatty
acids and vitamin
A

Sources:
Vegetable oils
Foods made from
oil (salad dressing,
margarine)
Nuts
Seeds
Wheat germ
Green, leafy
veggies

Vitamin K

Functions:
Helps blood clot
Helps body make
some other
proteins

Sources:
Body can produce
on its own (from
bacteria in
intestines)
Green, leafy
veggies
Some fruits, other
veggies, and nuts

Thiamin (B1)

Functions:
Helps produce
energy from
carbs

Sources:
Whole-grain and
enriched grain
products
Pork
Liver

Riboflavin (B2)

Functions:
Produce energy
Changes
tryptophan
(amino acid) into
niacin

Sources:

Liver
Yogurt and milk
Enriched grains
Eggs
Green, leafy
veggies

Niacin

Functions:
Helps body use
sugars/fatty acids
Helps enzymes
function normally
Produces energy

Sources:
Foods high in
protein typically
(poultry, fish,
beef, peanut
butter, legumes)
Enriched and
fortified grains

Pyridoxine (B6)

Functions:
Helps body make
non-essential
amino acids
Helps turn
tryptophan into
niacin and
serotonin
Help produce body
chemicals (insulin,
hemoglobin, etc)

Sources:

Chicken
Fish
Pork
Liver
Whole grains
Nuts
Legumes

Folate (folic acid)

Functions:
Produces DNA and
RNA, making new
body cells
Works with vitamin
B12 to form
hemoglobin
May protect against
heart disease
Lowers risk of neural
tube defects in babies

Controls plasma
homocystine levels
(related to heart
disease)
Sources:
Fortified and
enriched grains and
breakfast cereals
Orange juice
Legumes
Green, leafy veggies
Peanuts
Avocados

Vitamin B12
(cobalamin)

Functions:
Works with folate
to make RBCs
In many body
chemicals and
cells
Helps body use
fatty acids/amino
acids

Sources:

Animal products
Meat
Fish
Poultry
Eggs
Milk, other dairy

Biotin

Functions:
Produces energy
Helps body use
proteins, carbs,
and fats from
foods

Sources:
Wide variety of
foods
Eggs
Liver
Wheat germ
Peanuts
Cottage cheese
Whole grain bread

Pantothenic Acid

Helps produce
energy
Helps the body
use proteins, fat,
and carbs from
food

Sources:
Found in almost
all foods
Meat, poultry, fish
Whole grain
cereals
Legumes
Milk
Fruits, veggies

Vitamin C

Heals cuts and

wounds
Protects from
infection, boosts
immunity
Antioxidant

Functions:
Helps produce
collagen (connective
tissue in bones,
muscles, etc)
Keeps capillary
walls, blood vessels
firm
Helps body absorb
iron and folate
Healthy gums

Sources
Citrus fruits
Other fruits,
veggies

Deficiencies

Rickets (children and vitamin D)

Osteoporosis/osteomalacia
(vitamin D)
Scurvy (vitamin C)
Night blindness (vitamin A)
Beriberi (thiamin)

What are minerals?

Regulate body processes

Give structure to things in the
body
No calories (energy)
Cannot be destroyed by heat

Categories of minerals

Major minerals

Calcium
Phosphorus
Magnesium
Electrolytes
(sodium, chloride,
potassium)

Trace minerals

Chromium
Copper
Flouride
Iodine
Iron
Manganese
Selenium
Zinc

Calcium

Bone building
Muscle contraction
Heart rate
Nerve function
Helps blood clot

Phosphorus

Generates energy
Regulate energy metabolism
Component of bones, teeth
Part of DNA, RNA (cell growth,
repair)
Almost all foods, especially proteinrich foods, contain phosphorus

Magnesium

Part of 300 enzymes (regulates

body functions)
Maintains cells in nerves, muscles
Component of bones
Best sources are legumes, nuts,
and whole grains

Electrolytes

Chloride:
Fluid balance
Digestion of food, transmits nerve impulses

Potassium
Maintains blood pressure
Nerve impulses and muscle contraction

Sodium

Fluid balance
Muscles relax, transmit nerve impulses
Regulates blood pressure

Sources:
Salt (sodium chloride)
Fruits, veggies, milk, beans, fish,
chicken, nuts (potassium)

Iron

Part of hemoglobin, carries oxygen

Brain development
Healthy immune system
Sources:

Animals (heme) vs. plants (non-heme)

Better absorbed from heme
Consume vitamin C with non-heme
Fortified cereals, beans, eggs, etc.

Antioxidants

Slow or prevent damage to body cells

May improve immune function and lower
risk for infection and cancer
Carotenoids beta carotene (familiar)
Vitamin C
Vitamin E
Found in colorful fruits/veggies and grains

Phytonutrients

Phyto plant
Spark body processes that may fight, or
reduce risk for some diseases
Fruits/veggies
Examples:

Carotenoids
Lutein
Lycopene
Flavanols
Prebiotics/probiotics
Soybeans

Functional Foods

Foods that provide benefits beyond

basic nutrition
Phytonutrients
Prebiotics/probiotics
Fatty fish/omega 3s
Soy protein
Oats (heart-healthy)
Flaxseed

Water

Water

Involved in every process of the body

Represents large portion of bodys mass

Men: 57-65%
Women: 46-53%
Due to differences in Body Composition.
Muscle has higher hydration level than fat
tissue.

Water
Two

main Water
Compartments
Intracellular fluid (ICF)
Extracellular fluid (ECF)
Plasma

/ interstitial fluid
Lymph / CSF / Urine / etc

Functions of Body Water

Serves as Bodys transport medium

Gas diffusion / nutrient transport /
waste disposal
Heat dissipation
Joint lubrication
Provides turgor for cell structure

Water Balance
Normally

about 2.5 L of fluid

intake required
Water obtained from three
sources: Liquid, food, &
metabolism.

Water Intake

Normal = 1200 ml/day

( 6X w/ exercise)

Food = 1000 ml /day

Metabolism = 350 ml / day
Up to 25% of water requirement
Combination of H- and O2+ as end result
of metabolism.

Water Output

Urine: (95% H2O) 1500 ml/day

w/ high protein diets

Skin: Evaporative cooling; 700 ml /

day ( drastically w/ ex.)
Water Vapor: Exhaled air; 350 ml/day
(Varies w/ climate & ex.)
Feces: 200 ml/day (may significantly
w/ illness)

Water and Exercise

Humidity greatly H2O loss

Ingest 600 ml before exercise

Drink OFTEN during exercise!

Gastric Emptying
Temperature: Cold fluids empty
faster
Volume: volume = faster
Osmolarity: Emptying is slowed
when liquid is concentrated with
simple sugars.

Energy

Requirement:
Growth and maintenance of body
tissue
Maintenance of body temp.
involuntary muscle movement
Voluntary muscle movement

Sources: from oxidation, 1gm

CAH 16kJ (4kcal)

Fat 37kJ (9kcal)
Protein 17kJ (4kcal)

Energy

4.2 J = 1cal
Measurements
Direct calorimetry
Indirect calorimetry

Basal metabolism
Amount of energy required to
carry out the basic processes
such as cellular activity, heart
beat & respiration

BMR:
Man 65kg
woman 55kg

1.14k cal/min
0.91k cal/min

Total energy requirement:

time X number of unit /min
Factors affecting energy
requirement

Age
Environmental temp.
Disease
Pregnancy
Energy intake

Specific dynamic
action of food
The increased of energy
expenditure due to food metabolism
equals 10% of expenditure
Excess energy intake is stored as
fat in the body

Fiber

Definition: plant material that

cant be digested by enzymes
of GIT
Found in the cell wall and
within cell of seed, roots,
leaves, fruits

 Composition:

Cellulose: glucose polysaccharide,

tough fibrous strand, leafy veg.
Pectin, plant gum, mucilages: non
cellulose polysaccharide
Pectin

combine with water to form

gel
Plant gum to cover site of injury
Mucilages hold water in seed to
prevent drying

Lignin: gives the wood its

strength and shape

Analysis of fiber:
Crude fiber content
Roughage

Effects of dietary fibers:

Mouth:keeps teeth, gum healthy
Stomach: slow emptying of stomach &
digestion
Small bowel: viscosity & transit time,
complete absorption
Large bowel: bacteria in stool, H2O, stool
bulk, defecation, intracolonic pressure,
colonic transit time

Fiber in diet: depends on type of

diet
Fiber hypothesis: 1970
( degenerative disorder in UK)
Low intake of fiber related to the
following disease:
Colonic

disorder (con., d.d,c.c,app)

Disorder which are 2dry to colonic
disorder (h.h, dvt, pe)
Metabolic disorder (ob, dm, ac, gs)

Disadvantage of fiber in
diet:
Mineral deficiency
Flatulence

Antioxidants

Slow or prevent damage to body cells

May improve immune function and lower
risk for infection and cancer
Carotenoids beta carotene (familiar)
Vitamin C
Vitamin E
Found in colorful fruits/veggies and grains

Phytonutrients

Phyto plant
Spark body processes that may fight, or
reduce risk for some diseases
Fruits/veggies
Examples:

Carotenoids
Lutein
Lycopene
Flavanols
Prebiotics/probiotics
Soybeans

Functional Foods

Foods that provide benefits beyond

basic nutrition
Phytonutrients
Prebiotics/probiotics
Fatty fish/omega 3s
Soy protein
Oats (heart-healthy)
Flaxseed

Micronutrient
supplementation in
pregnancy

Micronutrient needs in
pregnancy

Iron
Folate
Vit A
Zinc
Other?

Infection
Malaria; Intestinal helminths;
other common infections

Decreased nutrient intake

Increased nutrient use
Infection-specific insult

OBAT-OBAT HEMATINIK

Eritropoesis normal
memerlukan:
Zat besi (Fe)
Vitamin B12
Asam folat

Defisiensi
diatur oleh: eritopoetin

anemia

Defisiensi besi
anemia
mikrositik hipokromik
Sebab:
perdarahan
kehamilan
various abnormalities of the gut
bayi prematur (dengan status besi rendah)

BESI
Absorbsi:
di duodenum dan jejunum proksimal
5-10% dari yang dikonsumsi (+ 0,5-1 mg/hr),
bertambah bila persediaan kurang
diabsorbsi dalam bentuk ferro, dengan transport
aktif
ditingkatkan oleh: kobal, inosin, etionin, vitamin C,
HCl, suksinat, senyawa asam lain
menurun bila terdapat fosfat atau antasida

Transport
- setelah diabsorbsi, diikat oleh transferin
- kalau tidak untuk eritropoesis, disimpan
sebagai feritin
Ekskresi
- 0,5 - 1 mg/hari
- melalui sel epitel kulit & saluran cerna yang
terkelupas, keringat, urin, feses, kuku,
rambut

Kebutuhan
laki-laki dewasa
: 10 mg/hari
wanita dewasa
: 12 mg/hari
wanita hamil & menyusui : + 5 mg/hari
Sediaan
garam ferro
absorbsinya paling efisien:
25%
defisiensi, perlu 50-100mg/hr (intake 200400mg)
Preparat parenteral diberikan hanya bila tidak
bisa diberikan per-oral

Efek nonterapi:
Iritasi saluran cerna:
nausea
- diare
nyeri epigastrik - konstipasi
Toksisitas
- terutama pada anak-anak
- necrotizing gastroenteritis : nyeri perut, muntah,
diare bercampur darah, syok.
- Asidosis, koma, meninggal
- setelah konsumsi 1 g
- antidotum: deferoksamin

Riboflavin (B2)

Koenzim dalam metabolisme flavoprotein dalam respirasi sel

dapat mengatasi anemia normositiknormokromik
anemia terjadi pada malnutrisi proteinkalori
10 mg/hari peroral atau im

Piridoksin (B6)

Koenzim yang merangsang pertumbuhan heme

Defisiensi

an. mikrositik hipokromik,

an. megaloblastik

absorbsi Fe meningkat
Fe-binding protein jenuh, hiperferemia
regenerasi darah menurun
hemosiderosis

Kobal

Biasanya terdapat sebagai campuran dalam

sediaan Fe
Meningkatkan absorbsi Fe melalui usus
Efek toksik: erupsi kulit, struma, angina,
tinnitus, tuli, payah jantung, sianosis, koma
malaise, anoreksia, mual, muntah

Vitamin B12 & Asam folat

Penting pada beberapa reaksi untuk sintesis
DNA
defisiensi

anemia megaloblastik

Sianokobalamin (vitamin
B12)
sianokobalamin
hidroksokobalamin
kobalamin

deoksiadenasil kobalamin &

metil kobalamin
(aktif dalam tubuh)

Defisiensi Vitamin B12

Tanda-tanda:
- gangguan hematopoesis
- gangguan neurologi
- kerusakan sel epitel

degenerasi SSP

biasanya karena malabsorbsi

karena kekurangan faktor intrinsik (anemia
pernisiosa)
post gastrectomi
beberapa gangguan yang mengakibatkan
gangguan absorbsi

Kebutuhan
- 1 g/hari
- pada defisiensi tanpa komplikasi, 1 g/hari
sudah mencukupi
- bila faktor intrinsik berkurang, kebutuhan
meningkat
Sumber alami:
makanan hewani (hati, ginjal, jantung), kerang
kuning telur, makanan laut
Efek samping:
transient hipokalemia pada terapi defisiensi berat

Absorbsi
- diabsorbsi baik dan cepat pada pemberian
secara im & sk
- absorbsi pada pemberian peroral lambat di
ileum
- faktor intrinsik eksogen hanya berguna bila
defisiensi faktor intrinsik
- setelah diabsorbsi, hampir semua
Vit
B12 dalam darah terikat dengan protein
plasma

Sediaan

tablet peroral, suntikan

sianokobalamin 10 -1000 g/ml
hidroksokobalamin 100 g
pemberian peroral pada anemia pernisiosa
tidak bermanfaat
cara pemberian terbaik: im, sk
dosis pada anemia pernisiosa tergantung
berat anemia, ada tidaknya komplikasi,
respon terhadap pengobatan

Defisiensi asam folat

pada kehamilan
syndroma malabsorbsi
alkoholisme
anemia hemolitik
penggunaan obat-obat yng menghambat enzim
dihidrofolat reduktase (trimetoprim, metotreksat)
obat yang berinteraksi pada absorbsi &
penyimpanan

anemia megaloblastik

Kebutuhan: 50 g/hari
meningkat pada: peningkatan metabolisme
karena infeksi, anemia hemolitik, tumor
ganas
Gejala defisiensi:
hematopoesis megaloblastik
glositis
diare
penurunan berat badan
tidak ada gangguan neurologik

Absorbsi baik pada pemberian peroral

Ekskresi melalui ginjal
Sediaan:
tablet
injeksi
dalam multivitamin
dalam tablet antianemia lain
Efek samping: sangat jarang
dosis tinggi: berinteraksi dengan antikonvulsan

Hidroksiurea

untuk terapi sickle cell anemia

efek samping:
depresi sistem hemopoetik
netropenia

Imunosuppressants

Siklosporin
antithymocyte globulin

terapi anemia aplastik

prednison
untuk anemia hemolitik: mensupresi antibodi IgG
yang melapisi eritrosit pada anemia hemolitik
autoimun
siklofosfamid dosis tinggi dan radiasi
untuk anemia aplastik berat yang gagal dengan
terapi lain

Eritropoetin

Untuk terapi:
anemia pada penderita infeksi HIV
anemia yang berhubungan dengan multiple
myeloma
transplantasi sumsum tulang
monitor hematokrit seminggu sekali sampai
tercapai hematokrit normal
dapat menyebabkan hipertensi