rangkuman obat penting

7/27/2019 rangkuman obat penting

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DRUG EXAMPLES USES MECHANISM SIDE EFFECTSACE inhibitors Ramipril,

Lisinopril Hypertension Heart Failure Post MI

Block ATIATII by binding tothe site on the enzyme thatnormally accommodates theterminal leucine of ATI.Inhibits vasoconstriction.

Hypotension Dry cough

(increasedbradykinin)

Renal failure in ptswith bilateral renalstenosis

Beta-Blockers Atenolol,

Propanolol Hypertension Angina Arrhythmias Stable heart failure

block -adrenergic receptors inhibitingtheeffects of adrenaline and nonadrenaline.

1 (heart) blockage decreases HRand

contractility, 2 (bronchial andvascularsmooth muscle) blockage causesvasodilation.

Provocation ofasthma, heartfailure.

Cold hands Bradycardia -

fatigue

CalciumChannel

Blockers

Dihydropines Amlodipine,

Phenyalkylamines -Verapamil,Benzthiazepines -Diltiazem

Hypertension Angina

Supraventriculararrhythmia (Phenylalkylaminesonly)

Vasodilationblock cellular entry of Ca+ by

preventing opening ofvoltage-gated L-type and T-type calcium channels

Flushing, headache, P.oedema

Phenyalkylamines can worsen heartfailure

Gynaecomastia Impotence

ThiazideDiuretics

Bendrofluazide,hydrochlorothiazide

Hypertension Combined with loop

for Heart Failure

increase water excretion bydecreasing reabsorption ofNa+ and Cl- in the distaltubule by binding to the Cl-

site of the electroneutralNa+/Cl- co-transport system

and inhibiting its actioncausing a decrease in bloodvolume, venous return andCO

Hypokalaemia Hyponatraemia Hypotension Gout Type II DM

Loop Diuretics Frusemide,Bumetanide

Hypertension (butless effective thanthiazides usedwhen renalimpairment orresistant to multipledrug Tx)

Heart Failure

Block Na+ resorption inascending loop of Henle diuretic effect.

Hypokalaemia Hyponatraemia Hypotension Gout

Potassium-sparingdiuretics

Spironolactone,Amiloride

SecondaryHypertension

Severe heart Failure

Blocks action of aldosteronein distal convoluted tubule diuretic effect

Hypokalaemia Hyponatraemia Abdominal

discomfort


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Angiotensin IIreceptorantagonists

Losarten,Valsarten

Hypertension Alternative to ACE

inhibitor in heartfailure

Vasodilation by inhibitionat the angiotensin II receptor

Usually mild No cough like in

ACE inhibitors

Alpha-adrenoreceptor antagonists

Doxazosin,Prazosin

Hypertension (inaddition to otherhypertensives)

Reduces peripheral

resistance by inhibiting 1-adrenoreceptor-mediatedvasoconstriction.

PosturalHypotension

Dizziness


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Fibrinolytics Streptokinase Thrombolysis Acute MI, stroke, PE

Forms a complex with, andactivates, plasminogen intoplasmin.

Nausea/vomiting Bleeding

Antiplatelet agentsAsprin Prevention and

treatment of MI andstroke.

Irreversibly inhibits COX andso stops synthesis ofThromboxane A2 fromArachidonic Acid which leads

to platelet aggregation.

Haemorrhage

Clopidogrel Prevention andtreatment of MI andstroke.

Inhibits activation of theglycoprotein IIb/IIIa receptoron the surface of plateletswhich is required foraggregation to occur.

Haemorrhage

AnticoagulantsWarfarin Prophylaxis+treatme

nt DVT, PEProphylaxis ofembolization in AF,Rheumatic disease +

prosthetic valves.

Blocks reduction of Vit. K

epoxide necessary forsynthesis of factors II, VII, IXand X.

Haemorrhage

Heparin Treatment of DVT,PE. Prophylaxis ofDVT/PE post op.

MI.

Activates antithrombin III,which limits blood clotting byinactivating thrombin andfactor X.

Haemorrhage

Statins Atorvastatin,Simvastatin,Pravastatin

Prevention ofcardiovasculardisease

Reversibly inhibit enzymeHMG CoA reductase whichcatalyses the rate-limitingstep in the synthesis ofcholesterol:

HMG CoAmevalonic

acidcholesterol.This in synthesis LDLreceptors so LDL levels.

Myopathy (muscleache)

Disturbed LFTs Abdominal pain

Nitrates Glyceral trinitrate(GTN), Isosorbidemononitrate

Prophylaxis andTreatment of angina.

LVF

Prodrugs they decomposeto form NO which activates

guanylyl cyclase, thereby cyclic guanosinemonophosphate (cGMP).Protein kinase G is activatedand contractile proteins arephosphorylated. This allleads to Dilation of vessels.

Posturalhypotension

Tachycardia Headache Flushing Dizziness

Potassiumchannelactivators

Nicorandil (onlylicensed one)

Prophylaxis ofangina

Relaxation of smooth muscleand vasodilation.Activates K+ channels ofvascular smooth muscle

Headache


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causing K+ to flow out of cellscausing hyperpolarization.This therefore inhibits influxof Ca2+ and so inhibitscontraction.

AntiarrythmicsClass Ia Quinidine,

Disopyramide,Procainamide

VT WPW

Block Na2+ channels whichincreases refractory periodand in addition there is a

blockade of K+ channelswhich delays repolarisation.

GI disturbances Hypotension

Class Ib Lignocaine,Mexiletine,Phenytoin

Ventricular arrythmi,especially VT

Block Na2+ channels but littleeffect on refractory period as

K+ channels not blocked. duration of the actionpotential.

Nausea andVomiting

CNS toxicity Hypotension Bradycardia

Class Ic Flecainide Pre-excitation AF cardioversion of

paroxsms,AVNRT,AVRT, WPW, AF ,

AT , NSVT (non-sustained VT)

Marked Na2+ channel

blockage refractory period,no effect on the duration ofthe action potential.

CNS toxicity Hypotension Proarrythmogenic

after recent MI

may increasemortality

Class II Beta blockers(see above also)

Junctionaltachyarrhythmias,Paroxysmalevents,AF, Flutter,NSVT, SVTs.

rate of spontaneousdepolarisation of SA and AVnodal tissue

conduction through AVnode

Provocation ofasthma, heartfailure.

Cold hands

Class III Amiodarone,Bretylium, Sotalol(Beta blocker with

class IIIproperties)

AF, AT, AVRT,AVNRT, WPW, NSVT

Block K+ channels so prolongthe duration of the actionpotential.

Amiodarone : GIdisturbances.Corneal

microdeposits,throtoxicosis,photosensitivity

Class IV Calcium channel

blockers (seeabove also)

AVRT, AVNRT,Paroxysms

Block Ca2+ channels actspredominantly on the AVNand affect the plateau phaseof the action potential.

Flushing, headache P.oedema Phenyalkylamines

can worsen heartfailure

Gynaecomastia Impotence

Digoxin AF Atrial Flutter Not strictly antiarrythmic indirect actions on the Actionpotential through stimulationof the vagus nerve:

Intracellular Ca2+

overload junctional escapebeats, junctional


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automaticity of the SAnode which slows sinus rate

refractory period of the AVNwhich AV conduction

tachycardia,ventricular ectopicbeats, VT.

Increased vagalactivity can causeAT with 2:1 AVNblock

GI disturbances Neurological

disturbances Gynaecomastia

Adenosine Supraventriculararrythmias

Potent effect on SA nodeproducing sinus bradycardia.Slows impulse conductionthrough the AVN but has noeffect on conduction in theventricles.

Bradycardia and AVblock

Malaise, flushing,headache chestpain, bronchospasm

Atropine Sinus bradycardia AV block Cardiopulmonary

resuscitation

Inhibits effect of the vagusnerve on the heart which

rate of firing of SA node

conduction through theAVN via blockade ofmuscarinic M2 receptors.

Rhythmdisturbances

Constipation

Reduced Bronchialsecretions

Endocrinology-DiabetesInsulin: Is a polypeptide containing 51 amino acids arranged in two chains (A and B) linked by Disulphide bridges. A precursorcalled proinsulin, is hyrdolysed inside storage granules to form insulin and a residual C-peptide. The granules store insulin ascrystals containing zinc and insulin.Insulin Release: Glucose is the most potent stimulus for insulin with surges at meal times. The B cells possess K+ channelsthat are regulated by intra cellular adenosine triphosphate (ATP) (Katp channels). When the blood glucose increases, moreglucose enters the B-cells and its metabolism results in an increase in intracellular ATP, which closes the Katp channels. Theresulting depolorization of the B-cell initiates an influx of Ca2+ ions through you voltage sensitive Ca+ channels and thistriggers insulin release.

Insulin is destroyed the GI tract so must be given subcutaneously and IV or IM in some circumstances. Injections should berotated within the same region to avoid lipid hypertrophy. Absorption is fastest from the abdomen and slower from the thigh.

Insulin Regimes1) Short acting insulin mixed with intermediate acting insulin injected subcutaneous twice daily, before breakfast and

before the evening meal/2) Injection of intermediate acting insulin to provide background level of insulin and soluble insulin three times a day.

Short Acting Insulin

Soluble Insulin Actrapid IV forhyperglycaemicemergencies.

Subcutaneousinjection

Simple solution of insulin(onset 30 mins, peakactivities 2-4hrs, subsides by8hrs)

If IV effects only last 30minutes.

Insulin lisproand Insulin

Humalog andNovorapid

Blood glucosecontrol

Insulin analogues have afaster onset and shorter

Hypoglycaemia


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aspart (RapidActing)

action than soluble insulin.This is because they do notself associate to formdimmers.Onset 20-30 minutes Peakaction 1-2 hrs Duration 3-4hrs

Insulin autoantibodies

Lipohypertrophy

Intermediate and Long Acting Insulin(duration of action between 16-35 hours)

Semilente(amorphousinsulin zinc)

Blood glucosecontrol

Suspension of amorphousinsulin zinc.

Hypoglycaemia

Lente Humulin L orMonotard

Blood glucose conrol Mixture of amorphous insulinzinc (30%) and insulin zinccrystals (70%), the latterprolonging the duration ofthe preparation Onset ofaction (2-4 hours). Peakaction (6-12hrs) (Duration 20hrs)

Hypoglycaemia

Isophane

Insulin (NPH)

Insulatard A complex of protamine and

insulin. The mixture is suchthat no free binding sitesremain on the proatmine.After injection, proteolyticenzymes degrade theprotamine and the insulin isabsorbed. The duration ofNPH is similar to that ofLenteOnset of action (30-90mins) Peak action (4-6 hrs)Duration action (8-16 hrs)

Hypoglycaemia

Biphasic fixedmixtures

Human mixed(short- andintermediate-acting) insulins:These includeHumulin 20/80,Humulin 30/70,Humulin 50/50,Mixtard 20/80,Mixtard 30/70,and Mixtard50/50.

Human mixedinsulin analogues(with ultra-

Contain various proportionsof soluble isophane insulin(e.g. 30% soluble and 70%isophane) The solublecomponent gives rapid onsetand the isophane insulinprolongs the action.A pre-mixed short andintermediate-acting insulinwill start to work half an hourafter being injected, peak at1-12 hours and last for 16-24

hours.The ultra-short actinginsulins lispro and aspart arealso available in a biphasic

Hypglycaemia


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short andintermediate-actingproperties):These includeHumalog Mix25(insulin lispro)and NovoMix 30(insulin aspart).

form which retains the rapidonset of action (about 15minutes) but has a durationof action similar to that ofintermediate-acting isophaneinsulins.

Ultralente Humulin ULUltratard

A suspension of poorlysoluble insulin zinc crystalsthat has a duration of up to35 hours. The long durationof ultra lente can lead toinsulin accumulation anddangerous hypoglycaemia.Onset of action (2-4 hrs)Peak (6-23 hours)

Hypoglycaemia

Insulinglargine

Lantus Is soluble at acid pH. It has along peakless activity (11-12hrs) and is given once a day.

Hyoglycaemia

Oral Anti Diabetic DrugsTablets are introduced when metabolic control cannot be obtained by diet and lifestyle changes alone. Choice depends onindividuals characteristics. Patients with baseline Hb1A1c 9% are les likely to achieve target HbA1c with monotherapy. Drug ofchoice started at low dose, dose is increased, additional drugs are introduces in combination therapy to maximum of 2-3 drugs.Insulin is usually introduced in combination with metformin.

Bigunides MetforminOnly diabeticdrug that reducescardiovascular

risks.It reduces weight.

Type 2 diabetes PCOS Non Alcoholic fatty

liver disease

The exact mechanism ofaction of metformin isuncertain. It appears to actmainly by reducing hepatic

gluconeogenesis, it alsodecreases absorption ofglucose from thegastrointestinal tract andincreases insulin sensitivityby increasing peripheralutilization of glucose.]

Evidence suggests thatincreased peripheralutilization of glucose may bedue to improved insulinbinding to insulin receptors

since metformin is noteffective in patients who nolonger have any residualinsulin production.The

Lactic acidosis rareand limited to thosewith impaired liverof kidney function.

GI upset diarrhoea,vomiting cramps.
http://en.wikipedia.org/wiki/Mechanism_of_actionhttp://en.wikipedia.org/wiki/Mechanism_of_actionhttp://en.wikipedia.org/wiki/Gluconeogenesishttp://en.wikipedia.org/wiki/Gastrointestinal_tracthttp://en.wikipedia.org/wiki/Metformin#cite_note-21http://en.wikipedia.org/wiki/Metformin#cite_note-21http://en.wikipedia.org/wiki/Gluconeogenesishttp://en.wikipedia.org/wiki/Gastrointestinal_tracthttp://en.wikipedia.org/wiki/Metformin#cite_note-21http://en.wikipedia.org/wiki/Mechanism_of_actionhttp://en.wikipedia.org/wiki/Mechanism_of_action


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'average' person with type 2diabetes has three times thenormal rate ofgluconeogenesis; metformintreatment reduces this byover one third.Metformin stimulates thehepatic enzyme AMP-activated protein kinase

(AMPK), which plays animportant role in themetabolism offats andglucose. Causing weight loss.The molecular targets withwhich metformin directlyinteracts remain elusive.Metformin is notmetabolized, rather it isprimarily excreted in theurine with an eliminationhalf-life of 6.2 hours

Sulphonyreas Glipizide (shorthalf life)Glicazide (shorthalf life)Glibenclamide(longer durationof action)Tolbutamide.

Type II diabetes(people with idealweight)

These drugs are indicated inpatients (especially thosenear their ideal weight) inwhom diet fails to control thehyperglycaemia. In about30% control is not achievedby these drugs. Theystimulate insulin releasefrom the pancreatic isletsand so patient must havepartially functional B-cells for

these drugs to be of use.

GI disturbance Rashes Hypoglycaemia Hypoglycaemic

coma

Contraindicated inseverehyperglycaemia,surgery and majorillness

Glitazones Rosiglitazone andPioglitazone

Type II diabetesgiven alone or incombination withmetofrmin orsulphonyreas inpatients who cannottolerate metforminor sulphonyreascombinations.

Slow onset maximum effect1-2 months of treatment.Reduce hepatic glucoseoutput and increaseabsorption into theperipheral tissues.Triglycerides decline and LDLis also reduced.Drugs increase sensitivity toinsulin by binding to thenuclear peroxisome

proliferator activatedreceptor gamma (PPAR-y)and by derepression,increase transcription of

Weight gain Fluid retention Contraindicated in

pregnancy
http://en.wikipedia.org/wiki/AMP-activated_protein_kinasehttp://en.wikipedia.org/wiki/AMP-activated_protein_kinasehttp://en.wikipedia.org/wiki/Lipidhttp://en.wikipedia.org/wiki/AMP-activated_protein_kinasehttp://en.wikipedia.org/wiki/AMP-activated_protein_kinasehttp://en.wikipedia.org/wiki/Lipid


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insulin sensitive genes.

a- Glucosidaseinhibitors

Acarbose Type II diabetes Inhibits intestinal a-glycosidases, delaying thedigestion of starch andsucrose. It is taken withmeals and lowers the postprandial increase of bloodgluocose.

Flautlence Diarrhoea Abdominal Pain

Prolactinomas- oligomenorrhoea, amenoffhoea, galactorrhea, infertility, loss of libido, erectile dysfunction, osteoporosis. TRHstimulates prolactin, Dopamine inhibits it.Dopamineagonist drugs

Bromocriptine(ergot derivative)Cabergoline

Prolactinoma Acromegaly Hypogandism Galactorrhea

Stimulates dopaminereceptors in the brain.

Nausea Psyhchiatric

Symptoms

PosturalHypotension

Fibrotic changeswhich can lead tovalvular heartdisease.

Acromegaly Over secretion of GH =gigantism before puberty, acromegaly after puberty. (growth of hands feet, tightening ofrings)Somatostatinanalogues

SomatulineAutogelSandostatin LAROcreotide

Acromegaly Somatostatin analogue.Inhibits the production of GH.

Gallstones Conratindicated in

liver and kidneyfailure, diabetesmellitus,Insulinoma.

Diabetes Insipidus (no ADH produced so leads to excretion of large volumes of isotonic water)

ADH analogue Desmopressin(nasal spray,tablets, or

subcutaneousinjection)

Diabetes Insipidus Desmopressin is preferred tovasopressin because it is alonger acting analogue. Make

sure to reduce fluid intake.

Water retention Hyponatremia Contraindicated in

heart failure, peopleusing diuretics forother conditions.Alcoholics

Hypothyroidism tiredness and lethargy are the most common symptoms. Depression of basal metabolic rate, appetite andcardiac output. Low output heart failure might occur. Skin is dry. Thyroid deprivation in early life leads to dwarfism andcretinism.

Thyroxine Levothyroxine Hypothyroidism Administered orally is thetreatment of choice.Synthetic T4 is the sodiumsalt of levothyroxine (L-thryoxine). Its effects are

delayed until the plasmaprotein and tissue bindingsites are occupied.Treatment is assessed by

Concomitantconditionsworsened bythyroxine therapy.Heart disease, heart

failure, infarction,angina, chronic lungdisease,breathlessness,


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monitoring TSH levels, whichfall to normal when optimumdose is achieved. Daily dose100 and 150ug best take onwaking.

adrenal disease.Due to increase inoxygen demand ofmost tissues as wellas myocardium

Liothyronine Hypothyrioidism Is the sodium salt of T3 andbecause it is less proteinbound, it acts more quicklythan T4. The main use of T3

is in hypothyroid coma, whenit is given withhydrocortisone by IVinjection.

See above

Hyperthyroidism basal metabolic rate is increased, causing heat intolerance, arrthymias and increased appetite with weightloss. Skin is warm and moist. Tachycardia sweating and tremor. Angina and high output failure may occure. Upper eyelids areretracted. Treatment also includeds beta blockers discussed above (Propranalol or atenolol)Antithyroids Carbimazole Hyperthyroidism Rapidly converted to

methimazole in vivoOnce daily doses, 40mg for 1month, then 30mg for 1month, 20mg for 1 month

and then 10 mg daily untilreassessed.. Onset of action3-4 weeks

Rashes Agranulocytosis Patients should

report a sorethroat!

Thionamides Hyperthyroidism Possess a thiocarbamidegroup that is essential fortheir activity. They preventthe synthesis of thyroidhormones by competitivelyinhibiting the peroxidisecatalysed reactionsnecessary for iodineorganification. They also

block the coupling ofiodotyrosine especiallydiiodothyronine formation.Onset of action 3-4 weeks

?immunosuppressive

Propylthiouracil Hyperthyroidism Reserved for patientsintolerant of carbimazole.Also inhibits the peripheraldeiodination of t4

?immunosupressive

Iodides Hyperthyroidism Have poorly understoodactions on the thyroid. Theyinhibit organification and andhormone release. In addition

iodide decreases the sizeand vascularity of thehyperplastic gland, effectswhich are useful in

Skin rashes Nausea Vomiting

Allergic reaction.


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preparation of patients forthyroidectomy. They inhibithormone release quickly (2-7days) is a valuabe treatmentfor thyrotoxic crisis. Cannotbe used in long termbecause its antithyroidaction tends to diminish.

Primary Hypoadrenalism: Addisons disease Normally! Glucocorticoids mainly cortisol are produced in the cells of the zona

fasiculata and zona reticularis. The release of cortisol is controlled by negative feedback mechanism involving the hypothalamusand anterior pituitary. Low plasma cortisol levels results in the release of ACTH. Which stimulates coritsol synthesis and releaseby activiating adenlyl cyclise. Cyclic adenosine monophosphate (cAMP) then activates protein kinase A, which phoshoporylatesand increases the activity of cholesterylester hydrolase, the rate limiting step in steroid synthesis. Alodosterone release iseffected by ACTH, but Renin release is more important influence. The steroids are examples of gene active hormones. Thesteroid diffuses into the cells. In the absence of cortisol the receptor is inactivated by a heat shot protein (hsp 90). Cortisoltriggers the release of hsp90 and the activated receptor SR enters the nucleus where it stimulates or inhibits the production orproteins, which then produce the characteristic actions of the hormone.Coritcothrophin releasing hormone (CRH) is a 41 amino acid polypeptide whose action is enhanced by arginine avasopressin(ADH). It is produced in the hypothalamus and reaches the adenopophysis in the hypothalamus-hypophsyial portal systemwhere it stimulates the production of corticotrophin.ACTH is process from large molecular weight precursor, pro-opiomelanocortin (POMC) present in corticotroph cells of the

adenohypophosis, its main action is to stimulate the synthesis and release of cortisol.Cortisol Hydrocortisone Addisons Immediate management.

If acutely sick!Take blood cortisol glucoseurea and electrolytes. Givehydrocortisone 100mg as IVbolus. Give saline infusionlitre initially over 4-6 hours.Correct hypoglycaemia iwthIV bolus of 20% glucose.Continue with with IMhydrocortisone 100mg 6

hourly.Long termHydrocortisone orally10mg on waking, 5mg atlunch and evening (dosevaries)Fludrocortisone 0.1-0.2mgper day.

Moon face Striae Fat redistribution Hirsutsim Infection Proximal muscle

wasting

Bruising

SyntheticAldosterone

Fludrocortisone Addisons Synthetic mineralcorticoidderivative of aldosterone.Plasme rennin acitivityshould be measured 2 hours

after the flurdrocortisonedose and maintained in thenormal range.

Hypertension Oedema Peptic ulcers Mood changes GI upset Glaucoma

Cushings Syndrome Excess production of cortisol


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Ketoconazole Cushings Anti fungal

Well absorbed orally, widespectrum anti fungal drugwhich has adrenalsuppression effects

Hepatic necrosis Adrenal suppression

Metirapone Cushings Metyrapone blocks cortisolsynthesis by inhibitingsteroid 11-hydroxylase.

Nausea vomiting,abdominalcramping pain.

Mitotane Cushings Adrenal adenoma

Unknown mechanism ofaction but inhibits adrenal

steroidal action

Dizzyness,drowsyness nausea

and vomiting.Hyperparathyroidism and Malignancy account for 90% of Hypercalcaemia

Rehydration IV Saline Hypercalcaemia Hydration must bemaintained with IVintravenous saline. Thiswill prevent severehypercalcaemia. Oncevolume status is normal usebisphosphonates

Hypernaetremia

Bisphosphonates

AlendronateEtidronate

Hypercalcaemia Bind to hyrdoxyapatitecrystals and reduce boneresorption.

GI upset, Erosion ofOesophagus

Hypocalaemia Commonest cause is Vit D deficiencyCalciumSupplements

CalcicaOsteocare

Hypocalaemia Hypercalcaemia Stomach pain Diarrhoea

Vitamin Danalogue

Ergocalciferol VitD2Cholecalciferol VitD3Alfacalcidol 1-hydroxyvitamin DCalcitriol 1,25

Dihydroxy D

Hypocalcaemia Vit D deficiency

Vitamin D analogues allowabsorption of calcium fromthe gut.

Hypercalcaemia

RecombinantPTH analogue

Teriparatide Hypocalcaemia Hypoparathyriodism

Stimulates bones resorption,Kindey to re absorb calcium,stimulates production of 1.25Dehydroxyvit D at kidney.

Dizzyness Leg Cramps Nausea

Phaeochromocytoma Neoplasm of the adrenal medulla. 10% are malignant, 10% are extra-adrenal, 10% are bilateral, 10%are familial. Blockage of adreno receptors must be started first.

a-adrenoreceptor antagonist

PhenoxybenzamineLabetalolDoxazosin

Phentolamine

PrazosinTamsulosin

Terazosin

Tumours of adrenalmedulla

An irreversible antagonist isused to block the a-effects ofthe large amounts ofcatecholamines fromtumours of the adrenal

medulla.

Reflex tachycardia
http://en.wikipedia.org/wiki/Cortisolhttp://en.wikipedia.org/wiki/Steroid_11-beta-hydroxylasehttp://en.wikipedia.org/wiki/Doxazosinhttp://en.wikipedia.org/wiki/Phentolaminehttp://en.wikipedia.org/wiki/Prazosinhttp://en.wikipedia.org/wiki/Prazosinhttp://en.wikipedia.org/wiki/Tamsulosinhttp://en.wikipedia.org/wiki/Tamsulosinhttp://en.wikipedia.org/wiki/Terazosinhttp://en.wikipedia.org/wiki/Cortisolhttp://en.wikipedia.org/wiki/Steroid_11-beta-hydroxylasehttp://en.wikipedia.org/wiki/Doxazosinhttp://en.wikipedia.org/wiki/Phentolaminehttp://en.wikipedia.org/wiki/Prazosinhttp://en.wikipedia.org/wiki/Tamsulosinhttp://en.wikipedia.org/wiki/Terazosin


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b-blockers Atenolol (seeabove)

Conns excess production of aldesterone

Aldosteronereceptorblockers

Spironolactone(see above)Eplernone

Conns Liver disease with

ascites

Blocks the binding ofaldosterone to its receptorand increases the excretionof Na+ and decreases theelectrically coupled K+secretion.

SevereHyperkaleamia

PainfulGyanocamastia

PostassiumSparingDiuretic

AmilorideTriamterene

Potassium sparingdiuretic

Conns

Decrease the luminalmembrane Na+ permeabilityin the distal nephron bycombining with Na+channels and blocking them1:1 basis. This increases Na+(Cl- and H2O) excretion anddecreases K+ excretion.

SevereHyperkalaemia

Zero OrderKinetics

Common drugsPhenytoin,Aspirin, Ethanol,Theophylline,

Thiopentone

Anti-Epileptics Epilepsy is a chronic disease in which seizures result from abnormal discharge of cerebral neurones. Epilepsyis defined as a tendency to recurrent seizures i.e. two or more seizures. Partial seizures (seizures begin focally) Simple(consciousness not impaired) Complex (with impairment of consciousness) Beginning as a simple partial seizure andprogressing to a complex partial seizure. Impairment of consciousness at onset. Partial seizure becoming secondarygeneralised. Generalised Seizures Absence Seizure Typical (petit mal) Atypical. Others Myoclonic seizure, Clonic seizure,Tonic seizure, Tonic-clonic seizure (grand mal) Atonic seizure.Treatment should be considered when two or more unprovoked seizures have occurred within a short period. Wheneverpossible, treatment should involve only one drug.GeneralisedEpilepsy

LamatrogineSodium Valproate

Lamatrogine andValpraote have similarmech of action as

Phenytoins discussedbelow. Valproate alsoseems to in increaseGABAergi central inhibitionmechanisms that mayinvolve stimulation ofglutamic acid decarboxylaseactivity and/ or inhibition ofGABA-T activity.

Lamatrogine Blurred visiondizziness and

drowsyness. Seriousskin reactions canoccur especially inchildren.

Valproate - Nausea,weight gain,bleeding tendenciesand transient hairloss). The maindisadvantage is thatoccasionalidiosyncracticreactions causesever or fatalhepatic failiure.


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Focal Epilepsy CarbamazepinePhenytoin

Phenytoins anticonvulsantaction is probably a result ofits ability to prevent highfrequency repetitive activity.Phenytoin binds prerentiallyto inactivated (closed) Na+channels stabilizing them inthe inactivated state andpreventing them from

returning to the restingclosed state which they mustdo before they can openagain. High freuquencyrepetitive depolarisationincreases the proportion ofNa+ channels in theinactivated state and,because these aresusceptible to blockade byphenytoin, the Na+ isprogressively reduced until it

is eventually insufficient toevoke and action potential.Neruonal transmission atnormal frequencies isrelatively unaffected byphenytoin because a smallerportion of the Na+ channelsare in the inactivated state.Carbamazepine, lamotrigine,valproate, and topiramate.Have similar actions onneuronal Na+ channels.

Carbamazepine ismetabolised in theliver tocarbamzepine-10,11- epoxide, anactive metabolitethat partlycontributes to bothits anti-convulsant

action andneurotoxicity. Incontrast tophenytion there is alinear increase inserumconcentration withdosage. Mildneurotoxic effectsare common(nausea dizzinessdrowsyness, blurred

vision and ataxia)Agranulocytosis is ararer idyiosyncraticreaction.

Phenytoin ishyroxylated in theliver by a saturableenzyme system.The rate ofmetabolism variesgreatly in patients.And up to 20 days

maybe required forthe serum level tostabilize afterchanging the dose.Dose is increasedgradually until fitsare prevented , oruntil signs ofcerebellardisturbance occur(nystagmus, ataxia,involuntary

movements) Onethe metabolizingenxymes aresaturated , a small


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increase in dosemay produce toxicside blood levels ofthe drug. Othereffects Gumhypertrophy, acne,greasy skin,coarsening of thefacial features and

hirsutism.AbsenceEpilepsy inChildren

EthosuximideSodium Valproate

Absence seizures involveoscillatory neuronal activitybetween the thalamus andthe cerebral cortex. Thisoscillation involves (T-type)Ca2+ channels in thethalamic neurones, whichproduce low threshold spikesand allow the cells to fie inbursts. Drugs (Ethosuximideand Valproate) that control

absences reduced this Ca2+current dampening thethalmacortical osciallationsthat are critical in thegeneration of abseceseizures.

Ethosuximide-Nausea vomiting.

Parkinsons Main pathology is the extensive degeneration of the dopiminergic nigrostriatal tract, but the cause of thedegeneration is usually unknown. Replacement therapy alone is not possible in parkinsons because the dopamine does not passthe blood brain barrier. However its precursor levodopa (L-dopa), does penetrate the brain where it is decarboxylated todopamine. Orally administered, levodopa is largely metabolized outside the brain and so it is given with a selectiveextracerebral decarboxylase inhibitor (carbidopa or benserazide). Some of the peripheral side effects of dopaminergic drugscan be reduced with domperidone, a dopamine antagonist that does not penetrate the brain. Inhibition of the drug monoamine

oxidase B (MAOb) with selegilene potentiates the actions of levodopa. Anti-muscarincs are used for the tremor that occurs withparkinsons.

Levodopa SinematMadoparBoth these drugscome withextracerebraldecarboxylaseinhibitors)

Parkinsons Levodopa is the immediateprecursos of dopamine and isable to penetrate the brainwhere it is converted todopamine. The site of thedecarboyxlation is uncertain,but as dopa decarboxylase isno rate limiting there maybesufficient enzyme in theremaining dopaminergic

nerve terminals. Anotherpossibility is that theconversion occurs in noradrenergic or seratonergic

Nausea andvomiting caused bystimulation of theCTZ.

Psych effects vividdreams,hallucinations,psychotic statesand confusion.

Posturalhypotension iscommon.

Dyskinesias (jerky


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terminals. Because the de-carboxylase activity in theseneurones is not specific.

or dance likemovement) are animportant adverseeffect.

Long term after fiveyears treatmentabout 50% ofpatients will havelost ground. In some

there is a gradualrecurrence ofparkinsionianakinesia. A secondform ofdeterioration is theshortening ofduration of action ofeach dose. Variousdyskinesias mayappear and, withtime rapid

oscillations inmobility anddyskinesias.

DopamineReceptorAgonists

Bromocriptine(ergot derivative)Ropinirole (nonergot derivative)Apomorphine(very powerfulgiven byparenteraladministration)

Parkinsons Prolactinomas

Dopamine agonists have noadvantage over levopdopaand the adverse effects aresimilar.Used with young patients, inparticular who are given adopamine agonist as initialtherapy (sometimes togetherwith selegeline). This

strategy may slow thedevelopment of dyskinesiasbut only 50% of patientsshow any beneficial responseto monotherapy withdopamine agonists.When patients on levodopatherapy start to showdeterioiration dopamineagonists are often added totry and reduce the offperiods.

Nausea, psychiatricsymptoms, posturalhypotension.

Pulmonary fibrosisand retroperitonealfibrosis.

Apomorphine(highly emetogenic)domperidone should

be given beforetreatment started.

Pre SynapticRe-Uptakeinhibitor

Amantadine Parkinsons Potentiates dopamine bypreventing re-uptake in thepre-synaptic terminals.Moderate effect but toleranc

Dizzyness, Loss ofco-ordindation,inability to sleep,nausea,


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soon develops nervousness

Monamineoxidaseinhibitor typeB (MAO-B)

Selegiline Parkinsons Inhibits monoamine oxidasetype B (MAO-B) there byincreasing dopamine. This isdone by reducing themetabolism of the dopaminein the brain potentiating thelevdopa which can bereduced by up to one 1/3. It

is used to reduce end of doseakinesia.

Nausea Heartburn Dry mouth

COMTinhibitors

EntacaponeBenzarazide

Parkinsons Inhibbits catechol-O-methltransferase (COMT) andprevents peripheralconversion of Levodopa to(inactive) 3-O-methyldopa. Itincreases the plasma half lifeof levodopa and increases itsaction.

Drowsyness Dizzyness Stomach upset Diarrhoea

Antimuscarinics

BenzetropineProcyclidine

OrphenadrineBenzhexol

Parkinsons Produce a modestiimprovement in the early

stages of parkisons disease,but the akinesia responsiblefor most of the functionaldisability responds least well.

Dry mouth Urinary retention

and constipation. Effect memory and

concentration.

Myaesthenia Gravis An acquired organ specific autoimmune disorder in which antibodies are directed at the post synapticacetycholine receptor. This results in weakness and fatiguability of skeletal muscle groups. The most commonly effectedmuscles are the proximal limbs and the ocular an bulbar muscles.

Oralacetycholinesterase

Prydostigmine Myaesthenia gravis Most widely used drug; it hasa duration of about 3-5hours. Patients response willdetermine the dose required.Great symptomatic drug but

does not alter the naturalhistory of the disease.

Overdose causes acholinergic crisiswith severeweakness. Colic anddiarrhoea may

occur.

Motor neurone diseaseRiluzole Rilutek MND Used to treat amyoptrophic

lateral sclerosis. Delays theonset of ventilatordependence or tracheostomyby 2 months.

Nausea Fatigue Hepatitis

Guillain- Barres syndrome (post-infective polyneuropathy) Inflammtory demyelinating polyradiculoneuropathy.Often followsone to two weeks after infection or diarrhoea, which may have been mild. Campylobacter jejuni has been particularly implicatedas a cause of the diarrhoea and is associated with the most severe form. Classic presentation distal paraesthesie, often withlittle sensory loss, and weakness can occure proximally, distally spreading or generalised. The symptoms ascend up lower limbs

and body over days to weeks. Facial weakness present in 50% cases. In sevre cases respiratory and bulbar involvement occurs.IF VC drops to 1 litre of below: artificial ventilation is needed.

High dose (IVIg) Guillen Barres Either high-dose intravenous Hepatitis


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immunoglobulins

immunoglobulins (IVIg) at400mg/kg for 5 days orplasmapheresis can beadministered, as they areequally effective and acombination of the two is notsignificantly better thaneither alone. Therapy is nolonger effective after 2

weeks after the first motorsymptoms appear, sotreatment should beinstituted as soon aspossible. IVIg is usually usedfirst because of its ease ofadministration and safetyprofile, with a total of fivedaily infusions for a totaldose of 2 g/kg body weight(.4kg each day).

Renal failure

Glaucomas- Mixed group of disorders that have some common features: Optic disc cupping, visual field loss and usually, raised

intraocular pressure (IOP).Beta-Blockers Timolol, carteolol,

betaxolol,levobunolol

Glaucoma Reduce aqueous secretion byinhibitory action on betaadrenoreceptors in thecilliary body.

Ocular irritation Bronchospasm Bradycardia Nightmares Exacerbation of

hear failureMuscarinic(parasympathetic)simulates .

Pilocarpine (alsoa differential forbilateralconstrictedpupils!)

Glaucoma Increase aqueous outflow viatrabecular meshwork byciliary muscle contraction

Ocular: Misosis(reduced vision inthe presence of acataract) spasm ofaccommodation,brow ache

Systemic: Swaeting,bradycardia, GIdisturbance

Alpha2-stimulantsTopical

Brimonidine,Apraclonidine

Glaucoma Reduces aqueos secretion byselective stimulation ofalpha2 and adrenocrecptorsin the ciliary body increaseoutflow by the uveoscleralroute

Ocular: Irisdarkening,conjunctivalhyperaemia,eyelash growth.

Systemic: bittertaste, asthma.

CarbonicAnhydraseInhibitors

Acetazolamide(systemic)Dorzolamide,Brinzolamide

Glaucoma Reduce aqueous secretion bythe cilliary body Ocular route:irritation and allergy

Systemic route:Malaise,
http://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Plasmapheresishttp://en.wikipedia.org/wiki/Immunoglobulinhttp://en.wikipedia.org/wiki/Plasmapheresis


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paraesthesia, ureaand electrolyedisturbance,aplastic anaemia

Mydriatics and cycloplegics ( Used for retinal examination and objective refraction (retinoscopy)Antimuscarinics

Tropicanamide,cyclopentolate,atropine.

Eye dilation for exam Inhibit muscarinic receptorsof parasympathetic nervoussystem to paralyse papillarysphincter and ciliary muscle.

Ocular: Blurredvision, glare, angleclosure glaucoma.

Systemic:

Tachycardia, drymouth, confusion,tremor.

Alpha-stimulant

Phenylephrine Eye dilation for exam Stimulates dilator muscle ofthe pupil no cycloplegiceffect.

Ocular: Blurredvision, glare, angleclosure, glaucoma,conjunctivalblanching.

Systemichypertension

Lubricants There are a wide rangeCarbomers,

hyrpmellose,polyvinyl alcohol,liquid paraffin

Dry eye Exact mechanism dependson the agent

Ocular: Allergy,blurred vision

Ant-Inflammatory Agents. Most important drugs are corticosteroids, a Variety of other drugs are available including systemicimmnosuppressantsCorticosteroids

Prednisolone,betamethasone,dexamethasone

SuppressInflammation

Suppresion of broadspectrum of inflammatoryprocesses (seecorticosteroids)

Ocular: Glaucoma(especially withlocaladministration),cataract (especiallyprolonged systemic

use) exacerbationof someinfections !!! e.g.herpes simplex.

Systemic: Negligiblewith topical use,common and variedwith systemicadministration.

Mast cellstabilisers

Cromoglicate,nedocromil,lodoxamide.

Allergy Stabilise mast cells Occular: Irritation

Anti-histamines Topical:Antazoline,azelastine,levocabastine.

Allergy Block histamine receptor Occular route:Irritation Sytemic route:

Drowsiness


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Systemic(chlorphenamine,terfendaine,cetirisine)

NSAIDS Topical:(ketorolac,diclofenac,fluribiprofen)

Eye inflammation Modulate prostaglandinproduction.

Systemic: Pepticulceration, asthma.

Anti-Infective agents:Topically applied antibacterial and antiviral drugs are very commonly prescribed. The use of antifungal

and antiparastic agents is much less frequent.Antibacterials Topical:

Chloramphenicol,gentamicin,ciprofloxacin,Neomycin, fusidicacid.Occassionallyintra-ocular,systemic

Bacterial Infection Range of activities andspecificities

Vary with agent Ocular: allergy;

corneal toxicitycommon withintensive use.

Systemic: generallyonly with systemicuse.

Antivirals Aciclovir, topicalor systemic

Herpes simplex,zoster

Inhibits herpes virus DNAsynthesis

Ocular: blurredvision, cornealtoxicity

Systemic: Rashes:kidney, liver andother effects mayoccur with systemicuse.

Local Anaesthetics: Major uses are to relieve pain and thereby assist with clinical examination and the facilitation of surgicalanaesthesia

Localanaesthesia

Topical or peri-ocular injection.Oxyburprocaine,proxymetacaine.Tetracaine,lidocaine.

Clinical exam Block conduction along thenerve fibres

Ocular: Irritation,corneal toxicicty.

Systemic: generallyaccidentalintravascular orintrathecal(cerebrospinal fluid)injection. Duringsurgicalanaesthesia,cardiacarrythmmias,respiratory

depressionBotulinum toxin: Used in the management of certain ocular motility disorders amd blepharospasm, and to induce ptosis forcorneal protection

Botulinum Injection at site of Motility disorder Prevents release of the Dependant on


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toxin action neuro-transmitteracetycholine atneuromuscular junctions

treatment sitee.e.gunwanted ptosis ordouble vision

MigrainePizotifen Serotonin

Antagonist5HT

Migraine

SumatriptanAcute

Migraine

SerotoninAntagonist

5HT

Migraine

MethysergideLong termmigraine

SerotoninAntagonist5HT

Migraine

Urinary TractInfection

E.coli, proteus,saprophiticus.

Trimethoprim UTI NOT used inpregnancy

Use nitrofurentoininstead oramoxicillin

Amoxicillin UTI Used in pregnancy

Diazoxide Insulinoma Blocks insulin release Teriparatide Hypocalaemia PTH analogue Corticosteroids Release of cortisol is controlled by negative feedback mechanism involving the hypothalamus and anteriorpitruitary. Low plasms cortisol levels result in release of ACTH which stimulates cortisol synthesis and release by activatingAdenylate cyclise. cAMP then activates protein kinase A which phosphorylates and inceases the activity of cholesterylesterhydrolase, the rate limiting step in steroid synthesis. Aldosterone release is affected by ACTH but other factors (reninangiotensin are more important.Steroids are examples of gene active hormones. Steroid diffuses into cells where it binds to cytoplasmic glucocorticoid

receptors. IN the absence of cortisol the receptor is inactivated by a heat shock protein. Cortisol triggers the release of hsp90and the activated receptor enteres the nucleus where it stimulates the synthesis of proteins, which then produce thecharacteristic actions of the hormone.Corticotrophin is prcessed from a large molecular weight precursor pro opiomelanocortin (POMC) precent in the corticotrophcells of the adenohypophysis; its main action is tto stimulate the synthesis an release of cortisol. POMC also contains thesequences for B lipoprotein (B-LPH) and B-endorphin, which are co comittantly release into the blood. Corticotrophin is alsobelieved to sensitize the zone glomerulosa to other stimuli which cause aldosterone release.Glucocorticoids:- Mechanism of action-Cortisol and synthetic glucocorticoids diffuse into target cells and binds to a cytoplasmic glucocorticoid receptor that belongs tothe superfamily of steroid thyroid and retinoid receptors. The activated receptor-glucocorticoid complex enters the nucleus andbinds to the steroid respsones elements on target DNA molecules. This either induces the synthesis of mRNA or represses thegenes inhibiting transcription factors e,g, NFkB for most clinical purposes, synthetic glucocoritcoids are used because they have

a higher affinity for the receptor are less rapidly inactivated and have little or no salt retaining properties.Effects Glucorticosteroids are essential for life their most important function being facilitating the conversion of protein toglycogen. They inhibit protein synthesis and stimulate protein catabolism to amino acids. Gluconeogenesis glycogen depositionand glucose release from the liver are stimulated, but peripheral glucose uptake is inhibited. During fasting they are essential


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for keeping blood sugars level.Anti Inflammtory Effects and Immunosuppresive effects. Cotricosteroids have profound anti-inflamm effects. Theysuppress all phases of inflammatory response, include the early swelling , redness pain and the later proliferative changes seenin chronic inflammtation. Inflammation is suppressed by several mechanismsCirculating immunocompetent cells and macrophages are reduced and the formation of pro inflammatory mediators, asprostaglandins leukatrienes and platelet activating factor is inhibited. Done by stimulating the synthesis in leucocytes of aprotein (lipocortin) that inhibits phospholipase A2. This enzyme in cell membrane is activated in damaged cells adn isresponsible for the formation of arachdonic acid. The precursor of many inflammatory mediators. Corticosteroids suppress thegenes coding for phospholipase A2, (COX2) and the interleukin-2 (IL-2) receptor. These genes are normally switched on by NFkB

but steroids induce the synthesis of IkB that binds to the NFkB and inhibits it by preventing its entry into the nucleus. They alsodepress monocytemacrophages fintion and decrease T-Cells, IL1 and IL2 is inhibited.

Hydrocortisone

Coritcosteroid Anti Inflamm (iI)s used orally forreplacement (ii) intravenously in shock and statusasthmaticus and (iii) topically(e.g. ointments in eczemaenemas in ulcerative colitis

Moon face, fat totrunk and face,purple striae,hirsutism,acne,infections

Osteoporosis, bruiseskin, diabetes,hypercalaemia,

Fluid retention,hypokalaemia.

Prednisolone Corticosteroid Anti Inflamm Is the most widely used drugdriven orally in inflammatoryand allergic diseases.

A s above

Betamethasone andDexamethasone

Corticosteroid Anti Imflamm Are very potent and have sosalt-retaining actions. Thismakes them especiallyuseful for high dose therapyin conditions, such ascerebral oedema wherewater retention would be adisadvantage.

As above

Beclometason

e andBudesonide

Corticosteroid Anti Inflamm Pass membranes poorly andare more active topicallythan when given orally. Theyare used in asthma andtopically in sever eczema toprovide a local antiinflammatory action withminimal systemic effects.

As above

Triamcinolone Corticosteroid Anti Inflamm Used in sever asthma and byintra articular injection forlocal inflammation of thejoints.

As above

NSAIDS inhibit COX and inihibit prostaglandin synthesis. COX exists in tissue as constitiutive isoform (COX-1) but at sites ofinflammation cytokines stimulate the induction of a second isoform (COX-2) Inhibition of of COX-2 is thought to be responsible


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for the anti-flamm effects of NSIADS. Inhibition of COX 1 is responsible for GI problems. Most current NSAIDS are COX 1inhibitors, but selective COX 2 are on the market (Celecoxib, eterocoxib, valdecoxib) are selective COX 2 inhibitors incidence ofgastric perforation obstruction and bleeding is reduced by at least 50%.Aspirin is long standing NSAID and anti analgesicParacetamol is just analgesic

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