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