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Classifications : Anticoagulants
2.Indandionic derivates
-phenyndione
-diphenandione
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HEPARIN:
*HEPARIN: Mechanism of action
AT-III plays a crucial role in natural endogenous anticoagulant mechanisms by blocking the activity
of activated clotting factors, XI, X, IX and II.
Heparin accelerates AT-III activity 1000 folds especially against clotting factors IIa and Xa
low molecular weight heparins accelerate AT-III activity only against clotting factors Xa (thrombin
is not).
*HEPARIN: INDICATIONS
1) Prevention and treatment of deep vein thrombosis and pulmonary embolism,
2) myocardial infarction, unstable angina,
3) during cardiac bypass surgery and in placing artificial heart valves to prevent formation of any
thrombus/emboli;
4) to prevent clotting in extracorporeal circulation (e.g. during haemodialysis);
5) for anticoagulation during pregnancy
*HEPARIN : ADR
1) Heparin-induced thrombocytopenia,
2) osteoporosis,
3) spontaneous fractures on prolong use,
4) transient alopecia,
5) hypersensitivity;
6) GIT bleeding,
7) Haematuria
*HEPARIN: CONTRAINDICATION
- hypersensitivity, hemorrhage, gastric ulcer, hemophilia, hypertension, cerebral trauma, sever liver
and kidney diseases , TB , leucosis , aneurysms , diabetes
ANTITHROMBIN III
*Antithrombin III concentrate is primarily used for the prophylaxis and treatment of patients with
congenital antithrombin III deficiency and disseminative intravascular coagulopathy.
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Trombolytics (fibrinolitics)
1. with direct action
- fibrinolysin
2. with indirect action
- streptokinase
- anistreplase
- alteplase
- Urokinase
M.O.A: - Rapidly lyse thrombi by catalyzing plasmin protease from its precursor plasminogen.
- Fibrin degradation
* Administered by intravenous infusion
Indications: pulmonary emboli, DVT, thrombosis of peripheral vessels, M.I (in the first 5 days)
ADRs: Hemorrhages, increase of temperature, allergy, livertoxicity, hypotension, dyspepsia
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Antifibrinolytics
M.O.A: decrease the formation of plasmin, the major fibrinolytic enzyme from plasminogen,
that degradate fibrin into fragments.
Indications:
Hemorrhage, tachycardia, prevention of hemorrhage in surgical interventions , myopathy ,
In over dosage with fibrinolytic.
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CLASSIFICATIONS
2) TXA2-receptor antagonists
- daltroban
a) Antagonists of glycoprotein-receptors
- Abciximab
- tirofiban
- Eptifibatide
- lamifiban
*Mechanism of action
irreversibly inhibits the enzyme COX which involved in the synthesis of TXA2 (prostaglandins)
resulting in the inhibition of platelet aggregation.
* INDICATIONS
1.prevention of ischemic attack
2.prevention of myocardial infarction
3.reduce the risk of heart attack and reduce the incidence of first incidence
4.reduce the risk of Venous Thromboembolism (VTE) after orthopedic surgery
5.Treatment of acute coronary syndromes
* ADR
1) Tinnitus
2) dyspepsia
3) bleeding
4) prolonged
5) time
6) bleeding
7) rash
8) renal insufficiency
9) thrombocytopenia
10) hepatitis
11) angioedema
12) asthma
13) Reye's syndrome
* CONTRAINDICATION
1) People with kidney disease, hyperuricemia, or gout
2) glucose-6-phosphate dehydrogenase deficiency
3) asthma
4) peptic ulcers
5) gastritis
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ticlopidine
Abciximab:
dipyridamole:
M.O.A: inhibits adenosindesaminase and increases quantity of adenosine, that are an antagonist of
ADP_endogenous. Also, it inhibits phosphodiesterase that increase the quantity of fixed Ca.
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CLASSIFICATIONS
b) animal origin
- aprotinin (contrical, trasilol)
a) platelet aggregants
- Calcium chlorite
- Calcium glyconate
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antihemorrhagics / haemostatics
With local drugs:
drugs that decrease platelet aggregation (antiaggregant)
*thromboplastin:
- activates prothrombin and other factors of coagulation
*indication: to stop bleeding of hemorrhages especially in otorhinolaryngologic - " ORL ".
*fibrin, gelatin
- can be applicated locally and they produce local vasoconstriction
*indication: epistaxis, uterus hemorrhages, intestinal hemorrhages, rectal hemorrhages
*vasoconstriction drugs
- (Ex: epinephrine) to stop bleeding that lasts 0.5-2h.
-indication: used topically in bleeding from superficial capillaries and veins, epistaxis,
tooth extraction, wounds
*thrombin
-indication: parenchymal hemorrhages from superficial capillaries, epistaxis, Hematemesis,
tonsillectomy, Werlhof's disease, hemoptysis, hypoplastic and aplastic anemia, neurosurgery, after
tooth extraction thromboplastin activates prothrombin and other factors of coagulation
*fibracel
- interacts with V, x factors and calcium produces one complex that activates the transformation
into thrombin from prothrombin.
-indication: used to prevent of hemorrhage in surgical interventions, dyspepsia, myopathy,
arrhythmias
Antifibrinolytics:
*aminocapronic acid
- activates physiologic fibrinolytic system, decreasing the formation of plasmin, the major
fibrinolytic enzyme from plasminogen, that degradate fibrin into fragments.
- stimulates thrombocytopoiesis, increases the thrombocyte receptor sensibility at the aggregation.
- also, it has an antiviral action and stimulates the detoxicant function of the liver.
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CLASSIFICATIONS
- Cobalt drugs
coamid
cobolamid
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CLASSIFICATIONS
sodium nucleinate
leucogen
methyluracil
pentoxyl
batilol
etaden
filgrastim
molgramostim
sargramostim
CLASSIFICATIONS
- glucocorticoids
- sodium cromoglicate
2.Drugs that inhibit interaction between histamine & its receptors
*glucocorticoids
* 4-aminoquinoline derivatives: chloroquine, hydroxichloroquine
*cytostatics: methotrexate, azathioprine, cyclosporine, mercaptopurine
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CLASSIFICATIONS
1. Ethanolamines:
a. diphenhydramine
b. clemastine (tavegyl)
2. Ethylendamines:
a. chlorophiramine (suprastine)
3. Alkylamines:
a. chlorphenamine
4. Phenothiasines:
a. promethasine
5. Imidasols:
a. antasoline
6. Hynuclidines:
a.quiphenamide (phencarol)
7. Piperidines:
a. astemisole
b. loratadine
c. terfenadine
8. Piperazines:
a. Cetirizine
II. according to the generations
*I generations
- diphenhydramine
- clemastine (tavegil)
- chlorophiramine (suprastine)
- chlorphenamine
- promethazine
- antasoline
- quiphenamide
*II generation
- astemisole
- loratadine
- terfenadine
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- cetirizinedipyridamole
H1- antihistamines : Mechanism of action
Contain a groupe ethanolamino as histamine has
inhibit competitively H1 receptors and the corresponding effects i. e. vasodilation and capillary
permeability increase.
do not inhibit antigen/antibodies reactions, nor histamine release, they inhibit H1 effects.
Effects : first-generation
1) Antiallergic (used in allergic rhinitis, conjunctivitis, allergic dermatitis etc.)
2) Sedative (inhibition of H1, muscarinic, serotoninic receptors from CNS) (ADRs - fatigue, dizziness, sedation)
3) Antivomiting (inhibit H1 HR from CNS)- used in kinetoses
4) Anticholinergic (peripheral effects atropine like effects) used in premedication
5) Antiparchinsonic (inhibit M ChR from CNS)
6) Anti serotoninic (antimigraine effect)
7) Antitussive (inhibit tussive center)- Control coughs due to colds or allergy
8) alpha1 adrenolytic activity (vasodilating effect)
9) Local anesthetic activity : used in urticaria
10) Tolerance (no more than 2-3 weeks)
Indications: first-generation
1. Allergic reactions (light & moderate).
2. Atopic dermatitis.
3. Kinetosis - difenhydramine & prometazine.
4. Itching - due to local anesthetics effect.
5. Orexigenic effect cyproheptadine
Diphenhydramine:
Side Effects: fatigue, dizziness, sedation.
Due to: the peripheral anticholinergic effects & the interactions with a number of
neurotransmitter systems in the CNS
has the ability to penetrate the blood brain barrier due to their relative lipophilicity.
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Second-generation / H1-antihistamines
- Selective action on H1 histaminoreceptors, no muscarinic and serotoninic action
- without sedating effect (do not cross blood-brain and thus their effects remain peripheral)
- No tolerance
- Favorable pharmacokinetics effects: onset (30-60 minutes)
- long duration of action (24-48 h).
3rd generation
Desloratadine & Levocetirizine: Active metabolites of II Generation
Characteristics: No sedative effects, less affect K channels from the heart
3rd generation
*Sodium cromoglicate
*Nedocromil
*Ketotifen
used to prevent or treat the symptoms of seasonal allergic rhinitis such as itching, sneezing, and
runny or stuffy nose
works by preventing the release of natural chemicals from cells in the body (mast cells) involved
in an allergic reaction
This medication may take up to one week before you begin to notice symptom relief.
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CLASSIFICATIONS
I. Endogenous origin:
drugs that decrease platelet aggregation (antiaggregant)
1 .Immunoregulatory peptides
a) drugs from thymus:
-natural: T-activin, Timalin, Timoptin, Timactid
-semisynthetic: Timogen, Imunofan.
b) From bone marrow: mielopid
2 .Cytokines:
a) recombined interleukins: Roncoleukin, Betaleukin.
b) Interferons :
-natural: Interferon, Leukinferon, Locferon.
-recombined: Chipferon, Reaferon, Viferon, Roferon A, Intron A
c) interferons inductors :
-natural: Aloxin , Megosin, Ridostin.
-semisynthetic: Amixin, Arbidol, Cycloferon,
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Immunomodulators
medicine, having immunotropic activity, which at therapeutic doses restore function
immune system (effective immune defense)
Immunosuppressant: these agents suppress the immune response and could be used for the
control of pathological immune response in autoimmune diseases, graft rejections etc
Interferons
- antiviral immunomodulatory activity
- bind to cell surface receptors initiate intracellular events
- enzyme induction
- inhibition of cell proliferation
- enhancement of immune activities
- increased phagocytosis
Immunosuppressant
A. Minor Immunosuppressants
4- aminoquininolinics derivates: cloroquine, hidroxicloroquine
B. Major Immunosuppressants:
1. Glucocorticoids
2. Cytostatics:
alchilants: cyclophosphamide, chlorambucil
Antimetabolites: mercaptopurine, azathioprine
Antibiotics: cyclosporine, tacrolimus, actinomycin
Antilymphocyte Serum
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Immunosuppressant
- work by suppressing the immune system and decreasing inflammation in the digestive tract in
people with inflammatory bowel disease, ulcerative colitis, and Crohn's disease.
- Tacrolimus can be used in Crohn's disease when corticosteroids prove ineffective.
- In children, immunomodulators are less likely to cause growth failure than corticosteroids.
- Topical immunomodulators such as tacrolimus and pimeocrolimus have been found to offer
benefits in patients with eczema, vitiligo and nickel allergy.
INDICATIONS:
- Organ transplantation
- Auto-immune diseases
- Life long use
- Infection
- Cancers
- Nephrotoxicity
- Diabetogenic problem
- natural immunomodulators are less potent than prescription immunomodulators and also less
likely to cause side effects.
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Azathioprine
- Purine antimetabolite
medication
- Incorporation
s of false nucleotide 6 Thio-IMP 6Thio-GMP 6Thio-GTP
-
Inhibition of cell proliferation
- Impairment of lymphocyte function
- Uses:
Prevention of organ transplant rejection, rheumatoid arthritis
- Toxicity:
Bone marrow suppression- leukopenia, thrombocytopenia, anemia
Increased susceptibility to infection, Hepatotoxicity, Alopecia, GI toxicity
Drug interaction: Allopurinol
Glucocorticoids
-
medications
-Induce redistribution of lymphocytes decrease in peripheral blood lymphocyte counts
- Intracellular receptors regulate gene transcription
- Down regulation of IL-1, IL-6
- Inhibition of T cell proliferation
- Neutrophils, Monocytes -display poor chemotaxis
- Broad anti-inflammatory effects on multiple components of cellular immunity
- Uses:
transplant rejection autoimmune diseases (RA, SLE), hematological conditions
psoriasis, inflammatory bowel disease, eye conditions
- Toxicity:
toxicity growth retardation, avascular necrosis of bone, risk of infection,
poor wound healing, cataract, hyperglycemia, hypertension
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- Uses:
Skin Conditions- Atopic dermatitis, Alopecia Areata, Pemphigus vulgaris, Lichen planus,
Pyoderma gangrenosum
Organ transplantation: Kidney, Liver, Heart
rheumatoid arthritis, Psoriasis, aplastic anemia
- Toxicity:
renal dysfunction, tremor, hirsutism, hypertension, hyperlipidemia
gum hyperplasia, hyperuricemia - worsens gout
Tacrolimu
s
- Inhibits T-cell activation by inhibiting calcineurin
- Uses:
Prophylaxis of solid-organ allograft rejection
- Toxicity:
nephrotoxicity, neurotoxicity-tremor, headache, motor disturbances, seizures
GI complaints, hypertension, hyperglycemia, risk of tumors, infections
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CLASSIFICATIONS
B) selective NSAIDs
- nimesulid
- meloxicam
- celecoxib
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Definition
Drugs that inhibit inflammation by preventing the synthesis of prostanoids.
-Prostanoid consisting of: the prostaglandins (mediators inflammatory and anaphylactic reactions)
-thromboxanes (mediators of vasoconstriction)
-prostacyclins (active in the resolution phase of inflammation).
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Indications
- Osteoarthritis, rheumatoid arthritis, dysmenorrhea, acute gouty attacks, musculoskeletal pain.
-
Rofecoxi
bs
- Higher
incidence of cardiovascular thrombotic events.
- Inhibits prostacyclin letting TXA2 act freely and promote platelet aggregation.
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Actions: Anti-inflammatory
- decrease recruitment of monocyte/macrophage into affected area
- decrease elaboration of chemotactic substances
- increase Lipocortin
- decrease TNF from phagocytic cells
- decrease IL1 from monocyte-macrophage
- decrease Formation of Plasminogen Activator
- decrease Action of MIF & fibroblastic activity
- decrease Expression of cyclooxygenase II
ADR's
1) Metabolic toxicity:
- Iatrogenic Cushings syndrome
- Hyperglycemia, glycosuria, diabetes
- Myopathy (negative nitrogen balance)
- Osteoporosis (vertebral compression fracture)
- Retardation of growth (children)
- Hypertension, edema, CCF
- Avascular necrosis of femur
2) Behavioral toxicity:
euphoria, psychomotor reactions, suicidal tendency
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Contraindications
- Infections
- Hypertension with CCF
- Psychosis
- Peptic ulcer
- Diabetes mellitus
- Osteoporosis
- Glaucoma
- Pregnancy: prednisolone preferred
therapeutical use
1. Arthritis
first choice
- Not the drug of
- Prednisolone5 or 7.5 mg
- Intra-articular injection
2. Rheumatic carditis
- Not responding to salicylates
- Severely ill pts.
- Prednisolone 40mg in divided doses
- Salicylates given concurrently to prevent reactivation
3. Collagen diseases
- pemphigus vulgaris, polyarteritis nodosa
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4-aminoquinoline derivatives
1. they stabilize lysosomal membranes and trap free radicals
2. they inhibit blastransformation of T lymphocytes.
3. inhibit collagen synthesis
D - penicillamide:
*Mechanism of action: it interacts with rheumatoid factor and inhibits its synthesis
- it inhibits collagen maturation
- cytostatic action (it binds with bivalent metals: Cu, Zn, Mg, I and inhibits protein synthesis)
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Hormones: biologically active substances, produced by the endocrine glands & special cell groups.
Hormones drugs:
- Natural (human, animal)
- Synthetic
Hormones antagonists: drugs that block the appropriate receptors or inhibit hormones synthesis
and and are used for the treatment of endocrine gland hyperfunctions
CLASSIFICATIONS
I. AGENTS OF PROTEIN OR PEPTIDE ORIGIN drugs that decrease platelet aggregation (antiaggregant)
CLASSIFICATIONS
I. Steroids and thyroid hormones: drugs that decrease platelet aggregation (antiaggregant)
- enter the cell and bind to cytosolic receptors that transport the steroid into the nucleus.
- the steroid-receptor complex alters gene expression.
- interact with the receptors on the cell surface, and activate various enzymes that
contribute to the formation of o lot of secondary mediators (cAMP, cGMP),
and increase the membranes permeability for Ca +2, and other metabolites.
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sermorelin
*M.O.A
- stimulates release of GH
*indication :
- diagnostic evaluation of decreased plasma GH.
- GH deficiency
- GH therapy in children with tertiary (hypothalamic deficient)
*side effect:
- transient flushing, injection site reactions, chest tightness, antibody development
*contraindications:
- not to use with other drugs which affect pituitary gland
*caution in children whose GH deficiency results from an intracranial lesion.
protirelin (TRH )
*M.O.A
- stimulates TSH release from pituitary gland.
*indication :
- diagnosis of thyroid function
*side effect:
- seizure , amaurosis fugax in patient with pituitary tumor
- anxiety, hyper and hypotension.
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somatostatin
*M.O.A
-inhibits GH release
*indication :
- VIPomas
- carcinoid tumors
- enterocutaneous and pancreatic fistula
- short bowel syndrome
*side effect:
- arrhythmias, erythroderma, life threatening water retention,
- glucose intolerance, rebound hormonal hypersecretion (seldom).
*contraindications:
- hypersensitivity to somatostatin
* reduces analgesic effects of morphine
octreotide
*M.O.A
-inhibits GH release
*indication :
- acromegaly
- flushing and diarrhea from carcinoid tumors
- carcinoid crisis
- diarrhea from vasoactive intestinal peptide secreting tumors
- to control GI bleeding and to reduce secretory diarrhea.
*side effect:
- arrhythmias, bradycardia, hypoglycemia, gallstones formation
- abdominal pain, constipation, diarrhea, nausea and vomiting.
*contraindications:
- hypersensitivity to octreotide
* octreotide also available in depot formulation
* decrease cyclosporine levels
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*M.O.A
- D2 receptor agonist inhibits spontaneous and TRH induce release of prolactin
- D1 receptor agonist (to a lesser extent)
*indication :
- amenorrhea and galactorrhea from hyperprolactenemia
- acromegaly
- Parkinson disease
- premenstrual syndrome
- cushing syndrome
- hepatic enhephalopathy
- neuroleptic malignant syndrome releated to neuroleptic drug therapy.
*side effect:
- Cerebrovascular accident (CVA), seizure, acute MI
- CNS effects such as psychosis, hallucination, insomnia, nightmares
- dizziness, hypotension, abdominal cramps, nausea and vomiting, headache
- nasal congestion, digital vasospasm
*contraindications:
- hypersensitivity to ergot derivates
- uncontrolled hypotension
- toxemia of pregnancy
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Prolactin Lactin
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octreotide
*M.O. A
*Exert their effects through G-protein coupled receptors
In women:
FSH direct ovarian follicle development
FSH and LH ovarian steroidogeneses
-Follicular stage:
LH androgen production
FSH- conversion of androgen to estrogen
- Luteal phase:
LH, estrogen and progesterone production
human chorionic gonadotropin (HCG) (if pregnancy) - estrogen and
progesterone production (nearly identical with LH) LH receptors)
In men:
FSH spermatogenesis, production of androgen binding protein and
conversion of testosterone to estrogen ( by sertoil cells )
LH production of testosterone by leyding cells.
*indication:
Diagnosis uses of gonadotropins
- pregnancy testing (urine HCG)
- ectopic pregnancy, hydatidiform mole, choriocarcinoma, malignancies (germ cells tumors)
(plasma hCG)
- localization if ovulation (urine LH levels)
-localization of endocrine diseases
Therapeutic uses of gonadotropins:
-male infertility -hypogonadotropic hypogonadism (hCG , menotropins
(FSH+LH) or recombinant FSH
- cryptorchidism(hCG)
- fertility induction in women
*side effect:
- Ovarian hyperstimulation syndrome (ovarian enlargement, ascites, hydrothorax,
and hypovolemia, sometimes shock)
- multiple pregnancies (15-20%)
- ovarian enlargement , hemoperitonium , fever
- arterial thromboembolism
- headache, depression, edema, precocious puberty, production of antibodies to hCG (rarely)
- ovarian cancer
- gynecomastia "in men "
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*M.O.A
- Its act via a specific GPCR (OXT) closely related to the v1a and v2 vasopressin receptors, in the
human myometrium, OXT couples to Gq-G11 activating the PLC IP3 calcium pathway and
enhancing activation of voltage sensitive calcium channels.
- Oxytocin also increase local prostaglandins production, which further stimulates uterine
contraction.
*Therapeutic use:
- Contraction of the uterus
- contracts the myoepithelial cells in the mammary glands "milk let-down"
- vasodilator action
- weak antidiuretic action
*indications:
- Induction of labor at term
- facilitation of threatened abortion
- postpartum control of bleeding after expuision of the placenta
*M.O.A
- Is an analogous of naturally vasopressin (ADH), primary action is enhanced reabsorption of
water in the kidneys.
*Therapeutic use:
- Prevention of nocturnal enuresis
- maintenance of appropriate body water content in in diabetes insipidus
- to control bleeding in certain types of hemophilia or von willebrand disease.
*indication:
- central Diabetes insipidus (caused by ADH deficiency) .
- to control bleeding in certain types of hemophilia and von willebrands"s disease.
- primary nocturnal enuresis.
*side effect:
- Seizures, drowsiness, headache, listlessness
- dyspnea, rhinitis, nasal congestion, flushing,
- hypertension, hypotension, tachycardia, mild abdominal cramps,
- nausea, vulval pain, water intoxication / hyponatremia, phlebitis at IV site,
*contraindications:
- hypersensitivity, hypersensitivity to chlorobutanol
- patient with type IIB or platelet type (pseudo) von willebrands disease
- hyponatremia
- use cautiously in: angina, hypertension, patients at risk of hyponatremia
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Thyroid hormones
1. monocomponent drugs
- Levothyroxine (T4, thyroxin, eutyrox, T4, etc)
- Liothyronine (T3 , triiodthyronin)
2. Combined drugs
- Thyreodin, thyireotom , (T3 + T4 = 1 : 4)
- Thyreotom forte , thyreocomb , (T3 + T4 +k1 = 1 : 7 : 15)
- Novothyral (T3 + T4 = 1 : 5 )
- Iodthyrox (T4 + KI)
*M.O. A
free hormones enter the cell by both passive diffusion and active transport and bind to
thyroid hormone receptors (TRs)
- nucleus and cytoplasm:
activation of gene transcription of down regulation gene expression
affect (increase) mitochondrial metabolism
- plasma membrane receptors:
stimulates intracellular signal transduction (Ex: increase cAMP)
*indications:
thyroid hormone replacement therapy (thyroid supplementation)
- hypothyroidism
- subclinical hypothyroidism
- myxedema coma (IV)
- thyroidectomy
Treatment or suppression of euthyroid goiters and thyroid cancer and suppression therapy of
thyroid cancer.
*ADRs:
usually seen when excessive doses cause iatrogenic hyperthyrodism :
CNS : nervousness , headache , insomnia , irritability
CVS : angina , arrythmias , hypotension , tachycardia
GIT : cramps , diarrhea , vomiting , choking , gagging , dysphagia
Derm : hair loss ( in children ) , sweating
Endo : hyperthyroidism , menstrual irregularities
Metabolism: heat intolerance, weight loss, accelerated bone maturation in children's
*contraindication:
- hyperthyroidism, recent MI, hypersensitivity
2) anti-thyroid drugs, which interfere with the synthesis of thyroid hormones (thioamines)
- carbimazole
- methimazole
- thiamazole
- propylthiouracil
- methylthiouracil
3) ionic inhibitors, which block the iodine transport mechanisms
- potassium perchlorate
- pertechnetate
- fluoborate
- thiocyanate
4) anti-thyroid drugs, which decrease release of thyroid hormones from the gland
(also may decrease hormone synthesis)
- potassium iodine
- sodium iodine
- lugol sol.
5) anti-thyroid drugs, which damages the thyroid gland with ionizing radiation
- radioiodine
- adrenoblckers
- ipodate
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*M.O. A/ thioamines
- thioamines compete with thyroglobulin for oxidized iodide in a process that is catalyzed by the
enzyme thyroid peroxidase.
- Propylthiouracil inhibits thyroid peroxidase as well as peripheral T4 and T3 conversion.
- iodinated thioamines may also be able to bind to thyroglobulin, further antagonizing any
coupling reactions.
*indications/thioamines
- palliative treatment of hyperthyroidism
- control hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy
- as definitive treatment, to control the disorders in anticipation of a spontaneous remission in
gravis disease
- in conjunction with radioactive iodine, to hasten recovery while awaiting the effects of radiation
*ADRs / thioamines
- goiter formation (goitrogens)
- pruritic rash
- arthralgia
- hypoprothrombinemia increase bleeding tendency
*contraindication / thioamines
- hypersensitivity
- lactation
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*excess transudation into the bronchial tree may lead to pulmonary edema,
*parotid and submaxillary glands may become enlarged and tender.
*inflammation of the pharynx, larynx, and tonsils.
*skin lesions usually are mildly acneform and distributed in the seborrheic areas. rarely severe
and sometimes fatal eruptions (iodemna)
*Diabetes mellitus
-Affects approx. 5-8%
-Mostly asymptomatic
-Tendency increase with obesity
-One of the leading cause of death by disease
-One of the leading cause of blindness
-One of the leading cause of renal failure
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CLASSIFICATIONS
-insulin
A. according to generation
a) I.generation
- tolbutamine
- chlorpopamide
- tolazamide
- carbutamide
b) II.generation
- glibenclamide (maninil)
- glipizide
- glyburide
- gliclazid
Meglitidine derivatives:
- Nateglind
- repaglind
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2.drugs that inhibits gluconeogenesis and promote glucose uptake in the tissues
Biguanides
a) short action (4-6 hours)
- metformin
- euformin
b) long duration (14-16 hours)
- buformin
- diformin
3. drugs that increase tissue sensibility to insulin
thiazolidinediones
- rosiglitazone
- pioglitazon
4. drugs that inhibits glucose absorption in the small intestine
(inhibitors of a- glucosidase)
-acarbose
5. inhibitors of aldoreductase
-tolrestat
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Oral Hypoglycemics
insulin
*M.O. A
-it binds to a specific receptor on the surface of cells that contains two alpha and beta subunits ,
the alpha subunit are entirely extracellular and binds with insulin , after it activates b subunits that
activates tyrosine kinase , tyrosine kinase is activator of a cascade of kinase and phosphates
*indication
-type I DM, retinopathy, uncontrolled type II DM, diabetic after pancreotomia, precoma and
coma, nephropathy , diabetic coma
*contraindication:
-allergy, hypoglycemia
*side effect:
-pain in the injected region, hypoglycemia, allergy, lipodystrophy, hypoglycemic coma
carbohydrate
- glucose uptake
- glycogen synthesis ( storage)
- gluconeogenesis(liver)
- glycolysis(muscle)
- conversion of carbohydrates to fat (lipogenesis)
FATS
- lipolysis
- lipogeneses
PROTENIS
- amino acid uptake (protein synthesis)
POTTASIUM
- potassium uptake into cells
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*M.O. A
- release of insulin from beta -cells
- reduction of serum glucagon concentration
- potentiation of insulin secretion action of target tissues
*ADRs
- nausea and vomiting, diarrhea, abdominal pain
- hypoglycemia, weight gain
- blood dyscrasias (agranulocytosis, pancytopenia, thrombocytopenia)
- hyponatremia and water intoxication
- Cholestatic obstructive jaundice (uncommon)
- dermatitis (mild)
- muscle weakness, headache, vertigo (no common)
- increased cardio-vascular mortality with long-term use
*contraindication
- type I DM (insulin dependent)
- parenchymal disease of the liver / kidneys
- pregnancy, lactation
- major stress
*M.O. A
- Bind to same k-ATP channel as do sulfonylureas, to cause insulin release from B-cells
*clinical use
- Approved as monotherapy and in combination with metformin in type 2 diabetes
Taken before each meal, 3 time /day
- Does not offer any advantage over sulfonylureas:
- Advantage pts. allergic to sulfer or sulfonylurea
*clinical use
- hypoglycemia, Wt gain (less than SUs), Caution in pts with renal & hepatic impairment.
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*pharmacokinetics
-given orally
-not bind to plasma proteins
-not metabolized
-excreted unchanged in urine
-t 2 hr
*M.O. A
1.increase peripheral glucose utilization
2.inhibits gluconeogenesis
3. impaired absorption of glucose from the gut.
*side effects
1. Metabolic taste in the mouth
2. Gastrointestinal (anorexia , nausea , vomiting , diarrhea , abdominal discomfort )
3. Vit B12 deficiency (prolonged use)
4. Lactic acidosis ( rare 01/30,000-exclusive in renal & hepatic failure)
*Contraindications
1.heaptic impairment
2.renal impairment
3.alcholism
4.herat failure
*indications
1.obese patients with type 11 diabetes
2.alone or in combination with sulfonylureas
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*M.O. A
-inhibits intestinal alpha glucosidases and delays carbohydrate absorption , reducing
postprandial increase in blood glucose
*side effects
-flatulence
-loose stool or diarrhea
-abdominal pain
-alone does not cause hypoglycemia
*indications
-Patients with type11 inadequately controlled by died with or without other agents (SU, metformin)
-Can be combined with insulin
-May be helpful in obese type 11 patients (similar to formation)
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-99% absorbed
-metabolized by liver
-99% of drug binds to plasma proteins
-half life 3-4h
-eliminated via the urine 64% and feces 23%
*M.O. A
*side effects
-mild to moderate edema
-wt gain
-headache
-myalgia
-hepatoxicity
*indications
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CLASSIFICATIONS
-Cortisone acetate
-Hydrocortisone acetate
-Prednisone
-Prednisolone
-Methylprednisolone
-Triamcinolone
-Dexamethasone
-Betamethasone
A. Intravenous B. Intramuscular
-Hydrocortisone hemisuccinat -Hydrocortisone acetate
-Prednisolone hemisuccinat -Prednisolone acetate
-Methylprednisolone hydrochloridone -methyl prednisolone acetate
-Dexamethason sodium phosphate -triamcenelone acetonide
-Betamethason sodium phosphate -plus, those for IV administration
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1) carbohydrate
2) protein
3) lipid
4) CND
5) blood
6) immunosuppressant
7) growth and cell division
8) electrolyte and H2O
9) CVS
10) skeletal muscle
11) stomach
12) anti-inflammatory
13) respiratory system
14) calcium metabolism
*Metabolic actions*
carbohydrate:
-decreased uptake and utilization of glucose accompanied by increased gluconeogenesis
-this causes a tendency to hyperglycemia
proteins:
Increased catabolism, reduced anabolism
lipids:
-a permissive effect on lipolytic hormones and a redistribution of fat, as observed in Cushing's
syndrome
increase gluconeogenesis
-peripheral actions (mobilize AAs, glucose and glycogen)
-hepatic action
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*Regulatory actions*
hypothalamus and anterior pituitary gland: a negative feedback action resulting
in reduced release of endogenous glucocorticoids
cardiovascular system: reduced vasodilation decreased fluid exudation
musculoskeletal: decreasing osteoblast and increasing osteoclast activity
mediators:
- decreased production and action of cytokines, including interleukins, tumor necrosis
factor a and granulocyte macrophage colony stimulating factor
-reduced generation of ecicosanoids
-decreased generation of IgG
-decreased in complement in the blood
-increased release of anti inflammatory factor such as interleukin -10and annexin 1.
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* Actions: CNS*
direct:
-mood
-behavior
-brain excitability
indirect:
- maintain glucose, circulation and electrolyte balance
* Actions: Stomach*
* Actions: Blood*
RBC:
-Increase HB and decrease content (erythrophagocytosis)
WBC:
-Decrease lymphocytes, eosinophils, monocytes, basophils
-Increase polymorphonucleocytes
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not bronchodilators
most potent and most effective anti -inflammatory .
effects not seen immediately (delay 6 or more Hrs.)
inhaled corticosteroids are used for long term control
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1.subestitution purposes :
-acute adrenocortical insufficiency (primary and /or secondary).
-chronic adrenocortical insufficiency ;
2.suppression purposes :
-congenital dysfunction (hyperplasia) of adrenal cortex.
3.diagnostic purposes :
-diagnosis and differental diagnosis of Cushing's syndrome .
4.with pharmacodynamic (palliative) purposes:
A. rheumatic diseases
1.systemic disease of conjunctive tissue (collagenosis):
-disseminated lupus erythematosus -polyarthritis nodosa
-lupus nephritis -polymyositis and so on ;
2.joint diseases
-rheumatoid arthritis -rheumatic fever;
-acute gouty arthritis -deformingosteoarthrosis;
-tendinitis -bursitis .
B. kidney disease
-glomerulonephritis (rapidly progressive , mezangiocapillary );
-nephrotic syndrome;
-focal glomerulosclerosis
C.liver and digestive diseases
-chronic active hepatitis , subacute hepatic necrosis;
-alcoholic hepatitis (severe form);
-nonspecific ulcerative colitis - crhon's diseases (ileitis);
D. ophthalmic diseases
-iridocyclitis
-oculomotor nerve neuritis;
-iritis,
- conjunctivitis;
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E. allergic diseases
-anaphylactic shock;
-status asthmaticus and severe forms of asthma;
-quincke edema -allergic reaction to drugs;
*dermatitis and allergic dermatitis (severe forms) ;
*allergic rhinitis (severe forms)
F. tumors
*acute lymphoblastic leucosis (acute leukemia in children)
*malignant lymphomas.
G. other conditions
-dermatitis of different origin cerebral edema , shock - collapsed state,
-thrombocytopenia (idiopathic thrombocytopenic purpura);
-immune hemolytic anemia spinal cord trauma;
- sarcoidosis, premature birth, organ transplant.
moon face , buffalo hump, trunk (love handles ), acne , hirsutism , wight gain.
impaired healing or brusing.
cns : neverousness , insomnia , depression , aggravation of pre_existing mental disorder
musculoskeletal: long term use can cause osteoporosis, muscle weakness and atrophy.
Git: peptic ulcer , increased appetite.
cardiovascular :fluid retention
ocular : increased intraocular pressure , glaumcoma , cataracts .
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*Sex organs:
-Vagina uterus and fallopian tubes
-Vaginal cornification
-Endometrium: proliferative and secretary phase menstruation
-Cervical secretion watery
*Metabolic effect
-Anabolic effect weak
-Fusion of epiphysis
-Salt and water retention
-Increase b.p
-Impaired glucose tolerance
-Increase coagulability
-Increase HDL and decrease LDL
-Increase cholesterol content of bile
-Increase thyroxine and cortisol binding globulins
-carcinogenic action
Use of estrogen
1. contraception
2. dysmenorrhea
3. hypogonadism
4. menopause hot flushes muscle cramp anexity over breathing
5. osteoporosis increase ca deposition in bone
6. prostatic cancer anti androgenic effect
*Adverse effect
1. nausea and breast tenderness
2. headache
3. increase skin pigmentation
4. impair glucose tolerance
5. increase incidence of breast vaginal and cervical cancer??
6. cardiovascular most concern:
A. thromboembolism
B. hypertension
7 increase frequency of gall bladder disease
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*Uterus:
Secretary change (with oestrogen)
If ovum is fertilized
Prepare endometrium : Decrease oxytocin and ergonovine actions
: Decrease FSH and LH ovulation decreased
Cervical secretion thick and viscid
*Vagina: wbc infiltration and cornified epithelium
*Breast: halts mitotic activity and stabilizes mammary cells; prepares breast for lactation
*Body temperature: Slight rise in body temperature
*Respiration: Stimulates respiration at higher doses
*Pituitary
Mifepristone
-19 nor steroid derivative
*M.O. A
- Blocks progesterone and glucocorticoid receptors
- During luteal phase: decrease pregest. ->PGs-> menstrual bleeding
- sensitize myocardium to PGs.
- HCG production falls
*ADME
- F:25%, CYP3A4 metabolism t1/2: 20h
*uses
- Termination of early pregnancy- along with prostaglandin.
- as a cervical ripening agent
- post coital contraceptive
- progesterone sensitive tumors
- Cushing's syndrome
*side effects
- vomiting, diarrhea, pelvic pain or abdominal pain ,
about 5% have severe vaginal bleeding
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CLASSIFICATIONS
1. female contraception
- containing estrogen and progestogen (combined)
drugs that decrease platelet aggregation (antiaggregant)
monophasic:
-minulen, femulen, microginon, rigevidon, minisiston, nonovion, lo-femenal
biphasic:
- anteovin , neo-eunormin
triphasic:
-trivilar, triregol, triziston, trinovum
- containing estrogen
ethinylestradiol, dirthylstilbestrol, conjugated estrogens.
containing progestogens
-peroral
linestrenol
norgestrel
-contraceptive Depo
medroxyprogesterone
-subcutaneous implants
levonorgestrel
norgestrel pointers
-intrauterine
levonorgestrel
Gine T 380S
Vaginal
-Nonoxynol
-benzalkonium chloride(farmatex)
2. male contraceptive:
-gossypol
-inhibin
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-Combination of estrogen and progestin are the most common (100% effective)
-The concentration of estrogen is very low to minimize its side effect.
-Contraceptive pills are taken for 21 days starting on 5 days of cycle.
-The tablets should be taken at approx. the same time each day.
-Phase formulation is more closely mimic normal endogenous hormonal activity
*M.O. A
Estrogen inhibits secretion of FSH via negative feedback on the anterior pituitary, and thus
suppresses development of the ovarian follicle.
Progestron inhibits secretion of LH and thus prevent ovulation, its makes the cervical mucus
less suitable for passage of sperm.
Estrogen and progesterone act in concert to alter the endometrium in such a way as to
discourage implantation.
Abnormal transport time through fallopian tube.
Abnormal contraction of fallopian tubes and uterine musculature.
Disadvantages
1.slightly higher failure rate (efficacy 97%)
2.irregular bleeding.
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*Side effects
Wight gain, owing to fluid retention or an anabolic effect, or both.
Mild nausea, flushing, dizziness, depression or imitability.
Skin changes (E.x acne and /or an increase in pigmentation).
Amenorrhea of variable duration on cessation of taking the pill.
*contraindications
thromboembolic disorders.
markedly impaired hepatic function.
suspected carcinoma of the breast.
Undiagnosed genital bleeding.
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*anabolic preparations*
1.steroidal
-nandronlone phenylpropionate (fenoboline )
-nandronlone decanoate (retabolil )
-methandienone (nerobol )
-oxandrolone
2.nonsteroidal
-potassium orotic
- inosine
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- these drugs may increase or decrease contractile activity and / or tone of myometrium & cervix
synthetic derivatives
- Cotarnine chloride
2) spondyloarthritis anchilozis
-phenylbutazone , dexamethasone , indomethacine
5) myositis
-phenylbutazone , dexamethasone , indomethacine
6) pollinosis
-sodium cromoglycate , ketotifen , dexamethasone
8) post-operatory vomiting
-diphenhydramine , clemastine , loratidine
18) AIDS
-imupurin , timalin , timogen , molgramostim
20) cancer
-interferon , imupurin , timogen , leukenferon
26) mixedema
-thiamasol , carbimazol , cibaclacin
27) hyperthyreosis
-propylthyouracil , thiamasol , carbimazole
30) metorrhagies
-ergotamine , oxytocin , metoxyprogesteron
34) alcoholism
-disulfiram , apomorphine , teturam ,
35) neuritis
-phenylbutazone , indomethacine , thiamine , pirodoxine
36) keratitis
-riboflavin , diphenhydramine , phenylbutazone , dexamethasone
3
37) pellagra
-nicotinic acid , nicotamide ,
38) leucopenia
-leucogen , batilol , inosine , ethaden
44) hemophilia
-tranexamin acid , desmopressin , concentration of factor VIII , IX , XII
48) Rachitis
-ergocalciferol , colecalciferol , calcidiol , calciterol
4
49) sterility
-neogest , regulon , ovulen , femulen , testosterone , androsterone
58) rheumatism
-dexamethasone , phenylbutazone , diclofenac
59) exema
-dexamethasone , diphenhydramine , pridnesolone
5
60) stimulation uterine contarcion
-oxytocin , ergotal , pituitrinum
64) bronchoectase
-bronhomunal , pyrogenal , ruzam
69) epilepsy
-phenobarbital , clonazepam , diazepam , sutiam , valporic acid
70) dysethalipoproteinemia
-nicotinic acid , clofibrat , bezafibrat , ciprofibrat
71) hypertrigliceridemia
-cholysteramine , bizafibrate , nicotinic acid , lovastatin
6
72) hypercholestrolemia
-cholysteramine , bizafibrate , nicotinic acid , lovastatin
76) premidication
-diphenhydramine , clemastine , chlorprophenamine ,
81) Eczema
-hydrocortisone , prednisolone , corticotropine