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All main topics / Medicine / Pharmacology

PharmaSkills (60 Cards)

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Which hypertensive patients do I prescribe antihypertensive drugs to?
● Antihypertensives are obligatory for Grade 2 or 3 patients and for Grade 1 patients with hypertension-related organ damage, cardiovascular co-morbidities, diabetes, or chronic kidney disease. Also for Grade 1 patients solely at high or very high cardiovascular risk estimated using the SCORE calculator.
● Antihypertensives are not obligatory but may be considered for Grade 1 patients at low or moderate cardiovascular risk, especially when blood pressure remains elevated despite prior implementation of lifestyle measures.
● There is no evidence supporting antihypertensive treatment of patients with high-normal blood pressure.
● Note that via the determination of the cardiovascular risk you will frequently identify treatment-obligatory dislipidemia.
Section 4.2    
Which non-pharmacological measures should I recommend to a patient with hypertension?
● Obese patients should reduce weight to a BMI of 25 and inactive ones should commence regular physical activities such as running, cycling, swimming, or walking; smokers should quit and alcohol users restrict the amount to <20 g/d for women and <30 g/d for men. Dietary changes should involve reduction of meat consumption in favor of fruits, vegetables, and low-fat dairy foods as well as restricting salt consumption to 5 g/d.
● Smoking cessation reduces the cardiovascular risk via blood pressure-independent mechanisms. All other "life-style changes" reduce blood pressure and - if implemented and adhered to - could obviate or at least reduce the use of antihypertensives in a majority of patients. Therefore they are tried without drugs in the first months or weeks in newly diagnosed patients with low or moderate cardiovascular risk, respectively. But patients should be regularly encouraged to implement blood pressure-lowering life-style changes even if they turn out to require pharmacotherapy!
Section 5.1
How do I decide which antihypertensive drug to start with?
● If available, use drugs with proven clinical benefits, i.e. angiotensin converting enzyme inhibitors (if not tolerated replace with an angiotensin receptor blocker), calcium channel blockers (usually dihydropyridine type), beta blockers, and thiazide diuretics.
● The reduction of blood pressure and of cardiovascular morbidity and mortality is similar for these so called 1st line antihypertensives. Therefore in most cases you decide based on the patient's preference in conjunction with his/her co-morbidities.
Angiotensin converting enzyme inhibitors are drugs of choice in patients with diabetes mellitus, with diabetic nephropaty, post-myocardial infarction patients, and in those with a congestive heart failure. On the other hand, they are contra-indicated in cases of renal failure, renal artery stenosis, and pregnancy. Due to a diabetogenic effect, thiazide diuretics and beta blockers should be avoided in obese, pre- or manifest diabetic patients. Such "pros" Table 15 and "contras" Table 14 exist for all other 1st line antihypertensives and they are sometimes substance-specific.
Do I need to consider differences among the different members of a given class of antihypertensives?
● Yes. Prescribe drugs which are sufficiently effective if given once daily, as this improves therapy adherence. For example, prescribe the long-acting angiotensin converting enzyme inhibitor ramipril rather than the short-acting captopril. Likewise, among calcium channel blockers amlodipine is favored over nifedipine. Due to the slower effect onset, amlodipine causes less reflex tachycardia and is safer in patients with latent or manifest coronary heart disease.
● If applicable and possible, choose a drug effective against co-morbidities frequently associated with or resulting from hypertension. For example, ramipril is prescribed so frequently for hypertension due to its proven effects against diabetic nephropathy, myocardial infarction, and congestive heart failure. The only calcium channel blockers considered safe for hypertensive patients with congestive heart failure are amlodipine and felodipine. The effectiveness against congestive heart failure favors using metoprolol succinate, bisoprolol, and carvedilol over other beta blockers.
● Antihypertensives differ in efficacy and side-effects. Atenolol is inferior to the aforementioned beta blockers, probably due to the absence of CNS effects caused by its poor lipophilicity. Propranolol causes more bronchospasms due to its non-selectivity towards towards ß1 receptors and is considered obsolete against hypertension if other drugs are at your disposal.
Which potential side-effects of antihypertensive drugs do I need to inform the patient about?
● Informing the patient will increase the therapy adherence and, via earlier feedback and intervention, reduce the associated morbidity.
● All antihypertensives may result in hypotensive episodes. Examples of frequent drug class-specific side-effects are arrhythmia due to hyperkalemia with angiotensin converting enzyme inhibitors and angiotensin receptor blockers, persistent cough with ACE inhibitors (switch to an angiotensin receptor blocker), headache and ankle edema with calcium channel blockers, and bradycardic arrhythmias with beta blockers. Beta blockers and thiazide diuretics are diabetogenic and should be avoided in obese patients and those with pre-diabetes or diabetes.
Which target blood pressure do I want to achieve with an antihypertensive therapy?
● <140/90 mm Hg. The exceptions are patients with diabetes (<140/85 mm Hg) and less fit elderly (>65 years) patients (140-150/<90 mm Hg).
● Most likely there is a limit to the beneficial effects of a therapeutic blood pressure lowering ("J curve concept"), so do not overdo! Especially in the elderly too strong or rapid lowering of blood pressure may be deleterious. Starting therapy with a fraction of the target dose ("start low, go slow") in these patients is especially critical.
Section 4.3
What do I do if the target blood pressure has not been reached by the primary antihypertensive therapy?
● If your initial treatment was a monotherapy and had no effect at all despite escalation to the maximal approved dose, switch to an antihypertensive drug with a different pharmacological mechanism.
● If lowered blood pressure was detected but was insufficient, include a second drug with a different pharmacological mechanism.
● In a high-risk patient your initial treatment most likely was a two-drug combination. If no effect at all, switch to a different two-drug combination. If the lowering of the blood pressure was insufficient, include a third appropriate drug.
● Above-the-target blood pressure in spite of concurrent use of three antihypertensive agents belonging to different antihypertensive drug classes is defined as resistant hypertension. It can be treated by including a 2nd line antihypertensive drug such as urapidil or - if available - interventionally by renal sympathetic denervation.
Fig. 3
Which combinations of antihypertensive drugs do I prefer, which do I avoid?
● Never combine angiotensin converting enzyme inhibitors with angiotensin receptor blockers (more hypotensive episodes, hyperkalemia, renal failure), or cardio-prevalent calcium channel blockers such as verapamil with beta blockers (two cardiodepressive drug classes). Do not combine thiazide diuretics with potassium-sparing drugs such as triamterene or amiloride in normokalemic patients co-treated with (likewise potassium-sparing) angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Avoid combining beta blockers with thiazide diuretics, especially in obese, pre- and diabetic patients (two diabetogenic drug classes).
● Beta blockers can be combined with vaso-prevalent calcium channel blockers such as amlodipine to control vasodilation-induced and baroreflex-mediated tachycardia. Other useful combinations are: angiotensin converting enzyme inhibitors or angiotensin receptor blockers with calcium channel blockers, as these drugs are non-diabetogenic and angiotensin converting enzyme inhibitors and angiotensin receptor blockers ameliorate peripheral (usually ankle) edema caused by vaso-prevalent calcium channel blockers. A similar amelioration can be achieved by supplementing calcium channel blockers with thiazide diuretics.
Fig. 4

How do I treat hypertension in sub-Saharan Africa?
● Based on evidence of higher propensity to vascular damage, target blood pressure values for Blacks have been lowered  by The International Society on Hypertension in Blacks: <130/80 mm Hg for patients with either target organ damage or cardiovascular disease and 135/85 for the remaining patients.
● When blood pressure is >15/10 mm Hg above target, two-drug therapy is recommended, with either a calcium channel blocker (typically amlodipine) plus a renin-angiotensin system blocker or, alternatively, in edematous and/or volume-overload states, with a thiazide diuretic plus a renin-angiotensin system blocker. Monotherapy with a diuretic or calcium channel blocker is preferred if blood pressure is ≤10 mm Hg above target levels. However, do not neglect to consider drug choice-relevant comorbidities and to establish antihypertensive effectiveness!
● Using the Framingham cardiovascular risk score, validated in Blacks, is recommended.
● Note that these recommendations may apply only to populations along the West African coast as they are based on studies mostly on US African-Americans.

How do I treat a pregnancy-associated hypertension?
● Alpha-methyldopa or a beta blocker such as metoprolol are suitable for long-term treatment, which is indicated at blood pressure values >160/100.
● Hypertensive emergencies (>170 diastolic or 110 systolic) can be treated with urapidil i.v.
● Seizures during eclampsia can be treated or prevented with magnesium sulphate or diazepam.
How do I treat a hypertensive urgency/emergency?
● The primary goal is to determine the presence of end-organ damage which is indicative of a hypertensive emergency and necessitates immediate i.v. therapy.
● The goal is to reduce the mean arterial pressure within 60 minutes, but not more than by 25%, or the diastolic pressure to 100-110 mm Hg.
● Among the many drugs recommended, glyceryl trinitrate and urapidil appear to have the least contra-indications. Vaso-prevalent calcium channel blockers are problematic due to the vasodilation-induced reflex tachycardia which may make a pre-existing coronary heart disease symptomatic. Further drugs may be needed depending on the organ damage, e.g. furosemide in cases of lung edema.
● In contrast, blood pressure in patients without symptoms (hypertensive urgency) should be normalized with oral drugs within 24 hours.
Which non-pharmacological measures should I recommend to a patient with a coronary artery disease?
● The life-style changes to be recommended to patients with a coronary artery disease are almost identical to those recommended to hypertensive patients.
● Obese patients should reduce weight, smokers should quit and alcohol users moderate the amount. Dietary changes should involve reduction of meat consumption in favor of fruits and vegetables as well as salt reduction.
● An important difference is that the regular physical activity, which is beneficial and important, should be undertaken only in the absence of coronary symptoms.
Which patients with a stable coronary artery disease would I recommend an interventional therapy in addition to pharmacotherapy?
● Generally, patients in higher classes of coronary artery disease opt more frequently for interventional procedures such as coronary artery bypass graft or percutaneous intervention (PCI, "stenting") due to reduced life quality.
● Which patients profit from an elective (scheduled) percutaneous intervention followed by pharmacotherapy in comparison to pharmacotherapy alone is controversial. Currently, PCI seems to be beneficial to patients with ischaemia encompassing more than 10% of the myocardium or with "functional" (i.e. advanced) stenoses with functional flow reserve values <0.80.
Which drugs do I prescribe in a patient with a stable coronary artery disease?
● The drug of choice for acute pain relief is the short-acting nitrate glyceryl trinitrate.
● Prognostically, the most important are aspirin and statin treatments. Aspirin in LOW DOSE (75-100 mg/d), because higher doses are not only more toxic (gastro-intestinal bleedings!), but also less effective as the resulting endothelial COX2 inhibition causes vasoconstriction. If contraindicated or not tolerated, aspirin should be replaced with clopidogrel. If causing gastro-intestinal side-effects, aspirin can be combined with omeprazole.
● Statins are given irrespective of the initial lipid profile (fixed-dose approach). In case of side-effects, such as myalgia, reduce the dose then try another statin or switch to another class of lipid-lowering drugs such as fibrates (fenofibrate). Simvastatin is the most investigated statin but it may be replaced with fluvastatin in case of interactions with other CYP3A4 substrates.
● Beta blockers and angiotensin converting enzyme inhibitors are prescribed to most patients, but the benefits are most clear for those which already had a post-myocardial infarction or developed a congestive heart failure.
● Whether calcium channel blockers, used in instances of contra-indications or intolerance of beta blockers, are beneficial is controversial and these drugs should be discontinued in cases of unstable angina and in the first weeks post myocardial infarction.
Which potential side-effects do I need to inform a patient appropriately treated for a stable coronary artery disease?
● Most important are the gastro-intestinal side-effects of aspirin, which unattended may result in ulcers, gastro-intestinal bleeding, and sometimes even in death.
● Statins can evoke myalgia and, very infrequently, rhabdomyolysis, in extreme cases leading to renal failure.
● Angiotensin converting enzyme inhibitors may trigger persistent cough (switch to angiotensin receptor blockers) and arrhythmia due to potassium accumulation.
● Beta blockers may evoke bradycardic arrhythmia, worsen symptoms of a peripheral artery disease or of asthma. Asthma symptoms may be also evoked by aspirin.
● Glyceryl trinitrate can induce headache and hypotensive episodes.
How do I treat an unstable angina pectoris?
● By default patients with chest pain of >20 min duration are considered as suffering from an Acute Coronary Syndrome until this syndrome has been excluded.
● A minority of such patients will immediately display an ST elevation in ECG, which is pathognomonic for transmural myocardial infarctions (STEMI).
● Patients with no ST elevation should be monitored over several hours for changes in the concentration of troponin, which is released from an ischaemic myocardium. You diagnose NSTEMI if troponin is elevated in the absence of ST elevation.
● The remaining patients (those with neither ST elevation nor troponin accumulation) are classified as having an Unstable Angina Pectoris. Once the symptoms have subsided, these patients are usually discharged but make sure that they are prescribed and take drugs against coronary artery disease, most importantly low-dose aspirin and a statin, and that they have at their disposal the symptom reliever glyceryl trinitrate.
● Scoring systems such as TIMI or GRACE can be used to determine the need and urgency for a diagnostic percutaneous intervention, which usually results in stent insertion. For a limited time period "stented" patients receive an ADP receptor blocker in addition to statin and low-dose aspirin.
How do I treat a myocardial infarction?
● To reverse thrombus formation aspirin is given in the recently lowered dosage of 150-300 mg p.o. or 80-150 mg i.v. The oral route is preferred, to achieve a preferential inhibition of the thrombocytic COX1 over endothelial COX2. Furthermore, low molecular weight heparin is given at a brand-specific dosage or, if not available, unfractionated heparin. The third antithrombotic drug is determined by the subsequent treatment: if percutaneous intervention is available, patients receive an ADP receptor antagonist. Currently, the prodrug clopidogrel (2 activation steps) is being replaced by prasugrel (1 activation step; approved for STEMI) and ticagrelor (active substance; approved for NSTEMI).
● If percutaneous intervention is not available, you treat with fibrinolytics instead of ADP antagonists. The drug of choice is tenecteplase, as it can be given as an i.v. bolus owing to a longer half-life. Fibrinolysis is less efficient and more toxic (bleedings!) than percutaneous intervention, but it is independent from high-cost infrastructure. "Lysed" patients still profit and should undergo percutaneous intervention, if available.
● Besides resting, reduce ischaemia by applying oxygen (only to hypoxic patients, to minimize the risk of oxidative myocardial damage), beta blockers, and glyceryl trinitrate. The latter two drugs are given in the absence of hypotension and (beta blockers only) bradycardia. Morphine alleviates pain and metoclopramide nausea and vomiting.
Which drugs do I prescribe to a survivor of a myocardial infarction?
● Treatment is similar to that of patients with stable coronary artery disease and no history of myocardial infarction. The most important difference is that patients treated for myocardial infarction with percutaneous intervention receive an ADP receptor antagonist for up to 12 months.
● The drug of choice for acute pain relief is the short-acting nitrate glyceryl trinitrate.
● Prognostically, the most important are aspirin and statin treatments. Aspirin in LOW DOSE (75-100 mg/d), because higher dosing is not only more toxic (gastro-intestinal bleedings!), but also less effective as the resulting endothelial COX2 inhibition causes vasoconstriction. Statins are given irrespective of the initial lipid profile (fixed-dose approach).
● Beta blockers and angiotensin converting enzyme inhibitors are recommended and prescribed to most patients, but they are obligatory only in patients with additional problems, e.g. congestive heart failure.
Which lifestyle changes should I recommend to a patient with a chronic heart failure?
Compensated patients benefit from moderate physical activities and all patients from weight normalization as well as from are smoking cessation and alcohol abstinence. The importance of salt (<3 g/d) and fluid (<2L/d; 1-1.5L/d in decompensated patients) is controversial.
How do I treat patients with chronic heart failure?
● Diuretics should be given only at symptoms of fluid retention (edema, weight increase), with loop diuretics prescribed only if thiazide diuretics are insufficient.
● In contrast, all patients should be treated continuously with an angiotensin converting enzyme inhibitor (if not tolerated replace with an angiotensin receptor blocker) in combination with one of the clinically-proven beta blockers (bisoprolol, metoprolol succinate, carvedilol, or nebivolol).
● Patients remaining symptomatic despite this treatment should additionally receive a mineralocorticoid receptor antagonist.
● If this triple therapy is insufficient, you should consider ivabradine in patients in sinus rhythm with heart rate >70 b.p.m. and EF <35%. (Note that ivabradine may be also considered for patients in sinus rhythm with an EF <35% and a heart rate >70 b.p.m. intolerant of beta-blockers.)
● Low-dose digitalis glycosides may be considered for patients with EF <45% who remain symptomatic despite treatment with an angiotensin converting enzyme inhibitor, beta blocker, and a mineralocorticoid receptor antagonist.
● Note that pharmacotherapy of chronic heart failure is increasingly supplemented by interventional approaches such as cardiac resynchronisation therapy and biventricular pacing.
Guidelines of cardiovascular disease  Addenda 2012           
How do I start therapy of a chronic heart failure?
● As usual you should exclude the most critical contraindications for the drugs to be used. Prospectively, especially important are the prokalemic and adverse renal effects of angiotensin converting enzyme inhibitors and of angiotensin and mineralocorticoid receptor antagonists. Therefore measure the plasma potassium concentration and estimate renal function. e.g. using the Cockroft-Gault formula.
● Start with a fraction (~25%) of the target dose and double at intervals of at least 2 weeks. Angiotensin converting enzyme inhibitors and angiotensin and mineralocorticoid receptor antagonists should be discontinued (or not administered in the first place) at values in the range of plasma potassium >5.5 mM, plasma creatinine >3.5 mg/dL, or eGFR<20 ml/min. Less critical but abnormal values of these parameters may necessitate dosage reductions to be conducted in a substance-specific manner.
● In addition to bradycardia and bradyarrhythmia, beta blockers, starting at ~10% of the target dosage, may initially depress cardiac function so watch out for weight gain and other symptoms of an acute cardiac decompensation.
Which potential side-effects do I need to inform a patient appropriately treated for a chronic heart failure?
● Patients should be sensitized to side-effects of the applied drugs which require therapy adjustment, such as cough, hypotensive episodes, dyspnea, arrhythmias, edema, and weight gain.
● On the other hand, you should make clear that the worsening of the kidney function in response to angiotensin converting enzyme inhibitors and to angiotensin and mineralocorticoid receptor blockers as well as cardiac decompensation in response to beta blockers are usually transient. Explaining this will improve the therapy adherence and thereby achieve the intended clinical benefits resulting from reduced cardiac remodelling and improved contractility after several months.
Which therapy-related patient parameters should I check regularly in chronic heart failure patients?
● Angiotensin converting enzyme inhibitors as well as angiotensin and mineralocorticoid receptor antagonists are prokalemic and they also speed up the progression of renal failure. Therefore, renal function should be estimated and potassium measured every 6 months, and more frequently at decompensation, onset of new co-morbidities, or at therapy adjustment. The aforementioned drugs need to be dose-reduced or even discontinued at advanced renal failure.
● Blood pressure and pulse (if needed, the latter one supplemented by ECG) will help to detect other common treatment-related side-effects such as hypotension, bradycardia, or bradyarrhythmia. These side-effects may also require such dose reduction or even drug discontinuation.
● Patients should be encouraged to record weight and report short-term increases (e.g. >2.5 kg/week) which frequently indicate cardiac decompensation.
How do I start and manage stroke propylaxis at atrial fibrillation?
● Oral anticoagulants are deployed in patients with atrial fibrillation based on a risk factor score, the simplest of which is CHADS2 (chronic heart failure, hypertension, age >75 years, diabetes, stroke).
● Give a loading dose (usually 3 average daily doses) of warfarin/phenprocoumon simultaneously with a standard s.c. dose of a low molecular weight heparin. Reduce and further adjust warfarin/phenprocoumon upon daily INR measurements until similar INR values within the target range of 2.0-3.0 have been measured on two consecutive days. Discontinue heparin at INR>2.0.
● Thereafter determine INR every 3 weeks in every warfarin/phenprocoumon-treated patient and more frequently upon any co-medication changes or after INR value derangements.
● Make sure that warfarin/phenprocoumon-treated patients understand why they must not commence, interrupt, or dose-adjust any concomitant treatment without consulting a physician.
● New oral anticoagulants such as rivaroxaban are similarly effective, cause less bleedings, and require no monitoring. Due to the high cost they are currently prescribed mostly to patients with frequent INR derangements.
When and how do I assess the risk for venous thromboembolism (VTE)?
● The VTE risk is usually estimated in the context of hospitalisation. But note that the deployed VTE pharmacoprophylaxis is continued after hospital discharge following certain procedures and in patients with risk factors or with leg fractures.
● Most common patient-specific risk factors are chronic pulmonary disease, chronic heart failure, and obesity, in addition to VTE history, varicose veins or venous insufficiency, thrombophilia, post-menopausal hormone replacement therapy, long term immobility, pregnancy, contraceptives, hemiplegia, acute infection, and shock.
● Patient-specific risk factors are aggravated by treatment-related ones such as ICU treatment, central venous catheter, mechanical ventilation, and the type and length of the planned surgical intervention and of the resulting patient's immobility (partial or total).
● In consequence of the multitude of potential risk factors, VTE risk is increased in approximately 40% of conservatively and 60% of interventionally-treated hospitalized patients.
● There is no universally accepted risk assessment score but pharmacoprophylaxis is indicated in all but "low-risk" patients.
In which patients and how do I implement a short-term prophylaxis of venous thromboembolism (VTE)?
● Pharmacoprophylaxis is indicated in patients with medium or high VTE risk and normal bleeding risk.
● Due to good controllability (short half-life, antagonisation with protamine) and therapy adherence (injections) low molecular weight heparins are drugs of choice. Products with larger molecules such as dalteparin are safer due to lower risk of accumulation during renal impairment. Patients with heparin-induced thrombocytopenia (HIT) history should receive argatroban.
● The intensity of anticoagulation depends on the individual VTE risk and - in interventional patients - also on the bleeding risk.
● In interventional patients the therapy is interrupted for a peri-operative period of 12-24 h and then resumed and continued until full mobilization and up to 5 weeks after certain, mostly orthopedic, procedures.
● In discharged patients with expected high therapy adherence VTE prophylaxis can be continued with one of the new oral anticoagulants (NOAC, e.g. rivaroxaban). Older oral anticoagulants such as warfarin and phenprocoumon are not economical for short post-discharge treatments due to the laborious dosage determination.

How do I monitor the safety of a heparin treatment?
● Monitoring platelet number twice per week is indicated in all patients in the first 3 weeks.
● Monitoring factor Xa activity is indicated only during pregnancy, in cases of obesity, kidney or liver failure, and in children.
How and in which patients do I perform the so-called "bridging"?
● Bridging is a peri-interventional thrombosis prophylaxis in patients chronically treated with oral anticoagulants warfarin or phenprocoumon, or with the thrombocyte aggregation inhibitors aspirin or clopidogrel. These long-acting and poorly controllable drugs are replaced ("bridged") by shorter-acting low molecular weight heparins, which can be antagonized during bleeding emergencies with protamine.
● Warfarin and phenprocoumon are replaced with heparin at least 5 days and aspirin 7 days prior to the scheduled intervention.
● The heparin "bridge" is interrupted for a peri-operative period of 12-24 h.
● Heparin replacement with the original long-acting antithrombotic drug begins within 1-2 days at normal post-interventional recovery and hemostasis. In warfarin/phenprocoumon patients heparin injections are discontinued at INR=2.0.
● Note that the implementation and intensity of bridging are determined by weighing the prothrombotic against bleeding risk factors contributed both by the patient and the procedure. For example bridging is not indicated during minor dermatological interventions or minor dental procedures whereas interrupting aspirin in patients with a coronary heart disease should be avoided.
● Bridging with heparin is unnecessary for new oral anticoagulants which are discontinued for 24 h on the eve of the intervention.
How do I treat a deep vein thrombosis (DVT)?
● DVT and pulmonary embolism (PE) are the two forms of venous thromboembolism (VTE). Treatment is commenced with a low molecular weight heparin s.c. at a weight- and kidney function-adjusted dosage. The alternative fondaparinux induces no type II heparin-induced thrombocytopenia (HIT II) but it cannot be antagonized in case of bleeding.
● Heparin or fondaparinux treatment is commenced in most patients together with warfarin/phenprocoumon and discontinued once a stable INR of >2.0 has been reached. In early post-surgery patients the warfarin/phenprocoumon treatment is delayed until the bleeding risk has normalized.
● The acute treatment of at least 5 days is followed by a secondary DVT thromboprophylaxis of variable length with warfarin/phenprocoumon. Three months suffice after a first thrombosis with a known provoking factor (e.g. trauma or post-surgery). Recurrent idiopathic DVT requires life-long anticoagulation.
● Both treatment and the secondary prophylaxis can be alternatively conducted with new oral anticoagulants such as rivaroxaban. This eliminates the need for thrombocyte and (in some patients) factor Xa activity monitoring during heparin treatments as well as the laborious warfarin/phenprocoumon dosage finding and follow-up INR measurements.
How do I treat a pulmonary embolism (PE)?
● PE is responsible for 10% of hospitalization-related mortality! Treatment with a low molecular weight heparin s.c. or with fondaparinux s.c. should be started based on clinical symptoms i.e. without delay for confirmatory diagnostics.
● Due to the absence of comparative study data, unfractionated heparin continues to be used in patients with the highest risk of mortality. It is also preferred in cases of high bleeding risk (best response to the antidote protamine) and during renal failure.
● Patients with a high risk of mortality are sometimes treated with thrombolytics or thrombectomy.
● Heparin or fondaparinux are commenced together with warfarin/phenprocoumon and may be discontinued once a stable INR of >2.0 has been reached, but not earlier than after 5 days. Warfarin/phenprocoumon is continued during the obligatory secondary thromboprophylaxis of variable length. Three months suffice after a first event with a known provoking factor (e.g. immobilization or post-surgery). A second or more pulmonary embolism requires life-long anticoagulation.
● Both treatment (3 weeks) and the lower-dose secondary prophylaxis can be conducted with a new oral anticoagulant such as rivaroxaban which, in addition to reducing bleedings eliminates the need for thrombocyte and (in some patients) factor Xa activity monitoring as well as warfarin/phenprocoumon dosage finding and INR measurements.
How do I minimize and react to the side-effects of an anticoagulant therapy?
● To reduce bleedings avoid fondaparinux and dabigatran during renal impairment and generally use low molecular weight heparins (LMWH) with larger molecules.
● Adjust dosage of LMWH and new oral anticoagulants as recommended for a given drug at low estimated GFR values.
● Monitor the effect of LMWH using factor Xa activity during renal or hepatic impairment, pregnancy, in cases of obesity, and in children.
● Determine INR every 3 weeks in every warfarin/phenprocoumon-treated patient and more frequently upon any co-medication changes or after INR value derangements. Make sure that warfarin/phenprocoumon-treated patients understand why they must not commence, interrupt, or dose-adjust any concomitant treatment without consulting a physician.
● Use protamine in cases of serious LMWH-related bleedings, but do not overdose (anticoagulant effect). Temporarily interrupt treatment and give vitamin K during mild warfarin/phenprocoumon-related bleedings and fresh frozen plasma in life-threatening cases.
● To reduce the complications of type II heparin-induced thrombocytopenia (HIT II) measure the platelet number twice per week in all heparin-treated patients (both unfractionated and LMWH) in the first 3 weeks. At HIT II diagnosis replace heparin with argatroban (replacement with fondaparinux is off-label). HIT I resolves spontaneously and requires no drug replacement.

Which anticoagulants can I use in pregnancy?
● The risk of venous thromboembolism (VTE) is increased during pregnancy and it is highest during puerperium.
● Therapeutic anticoagulation, preferentially with low molecular weight heparins, is indicated at VTE and prophylactically pre- and/or post-partum in women with known persisting prothrombotic factors or with unexplained VTE history. Although they lack formal approval for pregnancy, heparins do not cross placenta and are considered safe based on clinical experience. Monitor factor Xa for the preferred low molecular weight heparins and aPTT for unfractionated ones.
● Heparin therapy should be discontinued 24 hours prior to elective induction of labor but it should be resumed and continued, usually for 6 weeks.
● A longer post-partum thrombopropylaxis can be conducted with vitamin K antagonists, which are compatible with breast feeding. But note that vitamin K antagonists are absolutely contraindicated pre-partum due to early teratogenicity and later due to bleedings reflecting the immaturity of the fetal liver.
● New oral anticoagulants are contraindicated both during pregnancy and breast-feeding due to the lack of clinical experience.
Which lifestyle changes should I recommend to a type2 pre- or diabetic patient?
● Weight reduction through dietary adjustments (surgically only in patients with BMI >40) reduce glycemia and other cardiovascular risk factors. In addition to caloric restriction, foods high in fiber (such as vegetables, fruits, whole grains, and legumes), low-fat dairy products, and fresh fish should be recommended, while those rich in saturated fats, and sweet desserts and snacks discouraged.
● Patients reduce glycemia (in addition to weight) also through physical activity, ideally at least 150 min/week of moderate activities such as fast walking, cycling, swimming, aerobic, resistance, or flexibility training.
● Implementing these changes critically depends on personalized training conducted according to an approved curriculum. Patient training should be periodically repeated, especially in patients who fail to achieve the set goals and in cases of pharmacotherapy adjustments or new comorbidities.
Slices 8 to 10
How do I set the therapeutic goals for a patient with type 2 diabetes?
● The ultimate goals are to avoid acute osmotic symptoms of hyperglycemia and to prevent/delay the development of diabetes complications.
● Glycemia and HbA1c are useful control parameters, with target values determined by the patient's profile.
● In older adults (>65-70) you focus on therapy safety, as the risk for hypoglycemia and the resulting injuries is high and the lifetime remaining to develop cardiovascular complications short. But encourage safe lifestyle changes, as even modest weight loss (5-10%) and any physical activity improve glycemia. Both weight reduction and HbA1c target values goals should be numerically defined and clearly communicated. HbA1c values of 7.5-8.0% or even higher are acceptable in the elderly as well as in patients with severe hypoglycemic episodes, with multiple, especially cardiovascular, comorbidities ("point of no return" concept), and in those in who miss the set HbA1c values despite repeated training and polytherapy, including insulin.
● Conversely, most stringent HbA1c target values (<6.5-7.0%) should be set for newly or recently diagnosed, motivated patients with long life expectancy and no cardiovascular complications or comorbidities.

Slide 3 to 4
How do I select and start the primary medication of type 2 diabetes?
● Highly motivated patients with near-target HbA1c values should initially try lifestyle changes for 3-6 months before commencing with pharmacotherapy.
Metformin is the drug of choice in the absence of contraindications, most importantly of risk factors for lactate acidosis. Titrate metfomin gradually to reduce gastro-intestinal side-effects.
● The most affordable and clinically validated metformin alternatives are glibenclamide and insulin. The much more costly pioglitazone, DPP-4 inhibitors, and GLP-1 receptor agonists are the best metformin alternatives if the primary goal is to avoid hypoglycemia and the latter two if the goal is to reduce weight.
● In the aged, the choice of antihyperglycemic agent should primarily focus on drug safety, trying to avoid hypoglycemia (sulfonylurea, insulins), heart failure (pioglitazone), renal dysfunction (metformin), bone fractures (pioglitazone), and drug-drug interactions resulting from treatments of comorbidities.
● Combining two antidiabetic drugs at diagnosis may be justified in patients with HbA1c values of 9.0%, with long-acting insulin (insulin glargine) recommended at HbA1c >10.0%.
Which important side-effects do I need to prepare a patient with type 2 diabetes for?
Metformin-, GLP1 receptor agonist-, and acarbose-treated patients develop gastro-intestinal symptoms such as diarrhea and flatulence. Unlike with the former two drugs, these symptoms persist and practically preclude the utilization of acarbose.
● Gastro-intestinal symptoms of metformin should be reported as they may indicate a beginning lactate acidosis.
● Sulfonylurea and insulins evoke hypoglycemic episodes manifesting as tremor, sweating, tachycardia, and various neurological (neuroglycopenic) manifestations.
● Sulfonylurea, insulins, and  pioglitazone may increase body weight, which should be self-monitored by all patients with diabetes.
● Pioglitazone may precipitate heart failure symptoms such as dyspnea and edema, but also edema alone, due to fluid retention.
When and how do I intensify the therapy of type 2 diabetes?
● If the HbA1c value remains above the target longer than 3 months, you add an additional (i.e. second or third) hypoglycemic agent. The higher the HbA1c value, the more likely insulin (initially a long-acting one) will be required.
● Low costs and clinical data explain and justify the predominance of combinations involving metformin, sulfonylurea, and insulin. But uniform recommendations on combinations cannot be made due to paucity of long-term comparative-effectiveness trials. Rather, the combination suitable for a particular patient is the result of safety considerations, effectiveness, and tolerability. The latter two usually need to be established by trying different drugs.
How do I deploy insulin in a patient with type 2 diabetes?
● You typically start with basal (e.g. NPH) insulin given at a low dose (e.g., 0.1-0.2 U/kg) as a single daily injection. The timing of administration depends on the patient's schedule and the overall glucose profile.
● Up titrate at increments of 5-10% until the fasting glucose levels remain above the target (typically <130 mg/dL). Reduce at persisting hypoglycemic episodes.
● Add prandial (normal) insulin at significant postprandial hyperglycemia (>180 mg/dL), when the fasting glucose is at target but the HbA1c remains above goal after 3-6 months of basal insulin titration, or if large drops in glucose occur during overnight hours or in between meals. In the last case reduce the basal insulin dose as you initiate prandial insulin.
● Note that sulfonylurea should be discontinued at the latest upon intensification of insulin therapy with normal (prandial) insulin, reflecting the termination of secretion. Metformin should be continued, as it reduces the insulin-driven weight gain.
How do I calculate the insulin dose for a 70 kg patient with type 1 diabetes?
● To best mimic the physiological insulin excretion, the hormone is usually given as a basal, long-acting insulin, combined with several meal-matched (prandial) injections of a normal insulin.
● The average dose of basal insulin is 0.35 IU/kg/d, corresponding to some 24 IU for a 70 kg individual per day. The cost-effective basal NPH insulin would be typically given as 2 injections of 14 IU in the morning and 10 IU in the evening.
● The typical energy intake of 1800 kcal/d subdivided into 3 equal meals of 600 kcal would require 12 IU of normal insulin in the morning, 6 IU at lunch time, and 9 IU in the evening. These differences reflect the varying efficacy of insulin depending on the time of the day.
● Prandial injections are also used to correct any hyperglycemia, which should be verified by glucose measurement prior to every meal. On average, 1 IU is needed to reduce glycemia by 30 mg/dL.
Slide 32
How do I treat a hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA)?
● HHS (DM type 2-typical) and the more common DKA (DM type 1-typical) are life-threatening emergencies most frequently caused by therapy non-adherence or infections and characterized by hyperglycemia, glycosuria, severe dehydration, and acidosis. DKA is additionally accompanied by ketonemia and the pH and bicarbonate are lower (pH<7.2, HCO3<5 mmol/L) than in HHS, reflecting the totality of insulin loss.
● Treat in an ICU, immediately injecting heparin to prevent thrombosis. Correct the substantial (several liters!) fluid loss i.v. with isotonic solutions. The infusion rate (0.1-1.0 L/h) should ideally be guided by central venous pressure. Add potassium chloride under ECG monitoring unless hyperkalemia. Administer 10 mmol/h at potassium level of 4.5-6 mmol/L and 20 mmol/h at 3-4.5 mmol/L.
● Treat hyperglycemia with normal insulin i.v. Start with a bolus of 2-10 IU, depending on the initial glycemia. Follow by an infusion of 2-6 IU/h, adjusting to achieve a rate of glycemia decrease not exceeding 50 mg/dL/h. Reduce to 2-6 IU/h at glycemia of 250 mg/dL, to avoid hypoglycemic undershoot.
● Identify and treat the factor that triggered the emergency.
HSS Slides 14 to 19
How do I assess the Therapy Step of an asthma patient referred to my office?
● Step1 consists of a short-acting beta2 agonist, typically salbutamol inhaled on demand for relief of asthma symptoms.
● Step 2 ADDITIONALLY comprises a low-dose of an inhaled glucocorticoid, typically budesonid.
● Step 3 is reached either by DOUBLING budesonid OR by ADDING a long-acting B2 agonist, typically formoterol.
● Step 4 obligatorily comprises formoterol and a medium (i.e. doubled original) or high (i.e. quadrupled original) dose of budesonid.
● Step 5 ADDITIONALLY comprises a minimal effective dose of a systemic glucocorticoid, typically prednisolone or methylprednisolone. The anti-IgE antibody omalizumab may be deployed in patients with severe allergic asthma who are sensitive to perennial allergens.
● In Steps 2-4 the leukotriene receptor antagonist montelukast is sometimes used instead of formoterol or, in the absence of long-acting B2 agonist treatment, instead of budenosid.


When and how do I de-escalate an asthma treatment?
● You de-escalate as your goal is to control asthma with the lowest sufficient of the 5 standard Therapy Steps. Controlled asthma is defined by daytime symptoms and reliever use ≤2x/week and by the absence of other asthma features.
● Attempt de-escalation  if asthma has been controlled for >3 months.
● De-escalating measures depend on the patient's current Therapy Step. Typical examples are the reduction of glucocorticosteroids or discontinuation of long-acting B2 agonists. Inhaled glucocorticoids should be initially halved and then phased out, but never upon continuing treatment with a long-acting B2 agonist.
● While de-escalating therapy, confirm asthma control every 4 weeks. Attempt further de-escalating steps at intervals of >3 months.
When and how do I escalate an asthma treatment?
● You should consider therapy escalation If asthma is no longer controlled and the patient's medication technique, therapy adherence, and avoidance of risk factors have been verified.
● Consider escalation in partly-controlled but implement it immediately in uncontrolled patients. Escalate stepwise until asthma control has been reinstated. Escalating measures depends on the patient's current Therapy Step. Typical examples are doubling of inhaled glucocorticosteroids and deployment of long-acting B2 agonists (never without inhaled glucocorticoids!), of oral glucocorticoids, or of omalizumab (in severe allergic asthma).
● Assess the escalation effect every 4 weeks. Escalate further if no control has been achieved. Maintain the Therapy Step at which asthma control has been achieved for several months, then attempt de-escalation.
● Note that limited therapy escalation can be implemented autonomously by the patient, based on self-assessment and a pre-agreed action plan.
How do treat a newly diagnosed asthma case?
● A new case may present itself either as a partly controlled or an uncontrolled asthma.
Partly controlled asthma is defined by any of the following: daytime symptoms such as wheezing, breathlessness, chest tightness, and coughing >2x/week, limitation of activities, nocturnal symptoms/awaking, need for reliever >2x/week, lung function (PEF or FEV1) <80%. Deploy Treatment Step 2. Upon clinical assessment at intervals of ≤4 weeks stepwise escalate the therapy if needed until controlled asthma has been achieved.
Uncontrolled asthma is defined by three or more features of partly controlled asthma. Deploy Treatment Step 3. Assess clinicals and, if needed, stepwise escalate therapy as above.
● Confirm asthma, control every 3 months. An online self-assessment test can be helpful in resource-limited settings. Attempt de-escalatation after >3 months of asthma control.
How do I treat asthma in children?
● Treatment steps are similar to those for adults.
● Ipratroprium bromide is used as reliever instead of or in addition to a rapid-acting beta2 agonist such as salbutamol.
● Long-acting B2 agonists are more frequently substituted with the leukotriene modifier montelukast.
● Theophyllin can be used only in Treatment Step 5.
How do I treat an acute asthma exacerbation?
● Treat mild and moderate exacerbations (e.g. pulse <120 bpm, patient talks in sentences) with oxygen (2-4l/min) plus the short-acting B2 agonist salbutamol administered every 20 min via an inhaler. Give p.o. or. i.v. 0.4-0.8 mg/kg of methylprednisolon or another glucocorticosteroid in a dose equivalent to 0.5-1.0 mg/kg prednisolone to patients with no immediate response to salbutamol.
● Treat severe exacerbations (e.g. > pulse 120 bpm, patient talks in words or phrases) as above plus with ipratropium bromide (0.5 mg) via an inhaler.
● In therapy-refractory patients ("status asthmaticus") you may try terbutaline (0.25-0.5 mg s.c.)
● Theophyllin can be used ONLY if no inhaled B2 agonist is available!
Do not overhydrate! Do not administer sedatives, mucolytics, antibiotics!
Component 4

How do I treat a first-time seizure in children and adolescents?
● Seizures persisting longer than 5 min are treated as status epilepticus. Rectal Diazepam (5 mg at <20 kg, 10 mg at >20 kg body weight) is a convenient first-line option for small children.
● In children up to 5 years most first-time seizures are accompanied by fever >38°C and require no further treatment in the absence of CNS infection, trauma, tumor, or malformation.
● Recurrent febrile seizures (30% of cases) can be prevented with diazepam given for up to 3 days at the onset of a subsequent febrile event. The otherwise reasonable antipyretic therapy has no preventative effect.
● Afebrile first-time seizures require further diagnostics. Treatment usually starts after the occurrence of at least two unprovoked epileptic seizures or a single episode of status epilepticus. Drug choice depends on the diagnosed epilepsy form.
How do I treat status epilepticus?
● Generalized convulsive cases are defined as one or more seizures of >5 min duration without recovery between attacks. 
● Midazolam (10 mg i.m.), Lorazepam (4 mg i.v.), or Diazepam (10 mg i.v.) should be administered as early as possible. If available, midazolam can be administered nasally or buccally and diazepam rectally by laypersons.
● If there is no improvement after 10 min, hospitalize. Apply phenytoin (20 mg/kg i.v., <50 mg/min, under ECG monitoring) as 2nd line treatment. Alternatives are valproic acid, phenobarbital, and levetiracetam. Monitor and - if necessary - correct ventilation, blood gases, body temperature, glucose, and electrolytes.
● If no improvement after 30 (max. 60) min, induce general anaesthesia using thiopental or propofol.
● Focally convulsive and non-convulsive forms are treated similarly, but general anaesthesia is implemented more conservatively, usually after the failure of 2nd line treatments tried sequentially.
● Determine and treat precipitating causes to prevent recurrence.
How do I treat epilepsy in a woman of childbearing age?
● For efficient contraception, women treated with the Phase I-inducing anticonvulsants phenytoin, phenobarbital, and carbamazepine need up to double the usual dose of hormonal contraceptives. Weaker inducers of contraceptive metabolism are felbamate, topiramate, and oxcarbazepine.
● Conversely, Lamotrigin may need to be increased due to Phase II-induction by ethinyl estradiol.
● Despite the absence of supporting epidemiological evidence, folic acid (5 mg/d) may be offered to women considering pregnancy, especially to those treated with valproic acid.
● If valproic acid is indispensable in a pregnancy-planning patient, its dosage should remain below 1000 mg/d as both associated side-effects, i.e. developmental defects and IQ reduction are dose-dependent.
Monitor carefully but do not switch anti-convulsives during pregnancy.
What do I do upon suspicion of a new case of rheumatoid arthritis?
● Formally you suspect early rheumatoid arthritis in patients with more than 2, usually symmetrically distributed, usually small joints which have been painful and swollen for >6 weeks irrespective of physical activity and remain stiff in the morning for >60 min.
● As the above symptoms vary in scope and persistence, confirm the tenttative diagnosis using the 2010 ACR/EULAR Rheumatoid Arthritis Classification scoring system or refer the patient to a rheumatologist.
Do not hesitate with confirming diagnostics or referring your patient, as you may miss the most significant therapeutic window of opportunity! The first months are characterized not only by the fastest disease progression but also by the best treatment response! The therapy should commence within 3 months since symptom onset, yet this is achieved in <25% of patients!
Ibuprofen (not glucocorticoids - interference with further diagnostics!) can be prescribed immediately for symptoms relief.  
How do I start treating a confirmed new case of rheumathoid arthritis?
● An immediate monotherapy with a Disease-Modifying Anti-Rheumatic Drug (DMARD) constitutes the treatment basis. Methotrexate given weekly (not daily!) is the first-line DMARD based on clinical experience and tolerance. Folic acid can be given to reduce its side-effects.
● In patients with poor prognostic factors such as functional limitation, extra-articular disease, positive rheumatoid factor, anti-cyclic citrullinated peptide antibodies, or bony erosion, methotrexate is started in combination with 1 or 2 other DMARDs such as sulfasalazine or hydroxychloroquine, or with an anti-TNF alpha drug.
● Glucocorticoids (preferably prednisolone) are usually given as a step-down therapy to bridge the time until the immunosuppressive effects of DMARDs have set in. Delayed-release prednisone taken in the evening is particularly effective against morning stiffness.
● Use NSAID drugs or opioids against pain as needed.
When and how would I intensify an initial therapy of rheumatoid arthritis?
● Treatment goal is remission (DAS28 score <2.6) or low disease activity (<3.2) under continuing low-intensity therapy.
● In the absence of any major improvement after 4-6 weeks, first increase the first-line DMARD (if using methotrexate, first switch from oral to subcutaneous). If still insufficient after another 4-6 weeks, add one or more further DMARDs such as leflunomide, sulfasalazine, or hydroxychloroquine.
● If still insufficient after another 3 months, switch to methotrexate combined with an inhibitor of the TNF alpha, IL-6, or the CTLA-4 signaling. Second line option is the antibody against the B cell CD20 receptor rituximab.
How do I minimize side-effects of antirheumatoid treatments?
● Complete blood count, serum creatinine, and liver transaminases should be determined every 3 months and more frequently while starting, resuming, or intensifying therapy. Yearly influenza vaccination is indicated in all patients, whereas pneumococcus and hepatitis vaccinations only for certain drugs in combination with additional risk factors. Yearly ophtalomologic testing is indicated for hydroxychloroquine. Inhibitors of TNF alpha, IL-6, CTLA-4, and CD20 signaling should be given with isoniazid to patients with latent tuberculosis.
● Most antirheumatic drugs cause gastrointestinal side-effects, cutaneous allergies, and predispose patients to infections due to myelosuppression. During physical examination, watch out for symptoms of mucositis, skin allergy, and - in methotrexate-treated patients - dyspnea.
● Urge the patient to report immediately in case of fever, shortness of breath, cough, and allergic reactions.
Tables 4-6
How do I treat lupus erythematosus and minimize the associated drug toxicity?
● The treatment is determined by the disease activity and by organ involvement. 
● In the absence of major-organ involvement, the cornerstone drug hydroxychloroquine is supplemented as-needed with an NSAID such as naproxen and with prednisolone in low to moderate doses. Mycophenolate mofetil, azathioprine, and methotrexate are reserved for refractory cases.
● In lupus with major-organ (kidney, CNS) involvement, these treatment options extend onto low-dose cyclophosphamide and belimumab, an antibody against the B-lymphocyte stimulator. The induction therapy is more intensive than the subsequent maintenance therapy.
● Prevention and monitoring of drug toxicities are similar to those recommended for rheumatoid arthritis. Give vitamin D to offset the effects of glucocorticoids and the recommended sunlight avoidance.

In which patients and how do I implement goiter prophylaxis?
● The drug of choice is potassium iodide.
● Primary prophylaxis is recommended for breast-feeding and for pregnant women beginning with week 12. It is especially critical in regions with iodine defficiency. Other at-risk groups are children during puberty, vegans, and vegetarians.
● Secondary prophylaxis is indicated after goiter-reduction therapy, but only in the absence of autonomous nodules. Start with a fraction of the target potassium iodide dosage and increase stepwise to account for the possibility of a disseminated (non-nodular) autonomy. Patients treated with thyreidoectomy or with radioiodine therapy may remain hypothyreotic despite potassium iodide supplementation, in which case they additionally require thryoxine substitution. 

How do I treat an eutyhyreotic goiter?
● Euthyreotic goiter results predominantly from endemic iodide defficiency.
Diffuse goiter is treated for 12-18 months with potassium iodide in children and in combination with levothryoxine in adults. Treatment is adjusted to maintain low-normal TSH level (0.3-1.2 µIU/ml) and it is followed by life-long secondary prophylaxis with potassium iodide.
● Pharmacotherapy is less effective in nodular goiter due to fibrotic remodelling of the gland and it is contraindicated in the presence of autonomous ("hot") nodules. Thyreidectomy is best for rapid relief of mechanical symptoms and obligatory in the presence of malignant nodules. Radioiodine works better in patients without fibrotic remodelling and it is preferred in multimorbid elderly patients. It is contraindicated in the presence of malignant nodules, in children, and during pregnancy. Either therapy may result in treatment-obligatory hypothyroidism. Post-treatment thyroid function should be monitored annually.

How do I treat hyperthyroidism?
● Most cases result from Graves' (Basedow's) disease and thyroid gland autonomy, with the latter one predominating in areas of endemic goiter and frequently manifesting upon commencement with amiodarone therapy.
● Beta blockers are indicated in patients with heart rates >90 or with cardiovascular comorbidities. Following the determination of the complete blood count, bilirubin, and liver transaminanses, methimazole (propylthiouracil in pregnancy) is given for several weeks to achieve euthyreosis prior to causative treatment. Due to the risk of allergy, agranulocytosis, and hepatotoxicity, thyreostatic-treated patients should report any skin rash, fever, sore throat, and jaundice.
● Causative treatments comprise surgery and radioiodine therapy, depending on iodine uptake, comorbidities and patient's preferences. Thyreostatics can be used curatively for 12-18 months in Graves' disease upon complete blood count, and transaminase monitoring. All causative treatments may result in hypothyreosis.
● Subclinical hyperthyreoidism (normal free thyroxine) should be treated if TSH <0.1 mIU/L is accompanied by hyperthyroidism symptoms, age >65 years, cardiac disease, or osteoporosis.
How do I treat hypothyroidism?
Levotyroxine is the drug of choice for most patients irrespective of the underlying etiology (iodine defficiency, Hashimoto and other forms of threoiditis, thyroidectomy and radioiodine treatments, thyreostatic drugs such as thionamides and lithium). 
● Treatment is indicated in cases with symptoms and/or with TSH>10 mIU/L. TSH levels between 4.5 and 10 mIU/L require levothyroxine treatment only in conjunction with pregnancy, presence of anti-TPO antibodies, coronary artery disease, or heart failure. The benefit of levothyroxine treatment of other patients in this TSH range is unclear.
● Start with one-quarter of the average daily maintenance dose of 2 µg/kg and with one-eighth in patients with cardiac disease. Double the dose every 4-6 weeks until TSH has returned to the reference range of 0.5-4.5 mIU/L. Thereafter control TSH level every 6-12 months together with symptoms of hyperthyreosis such as tachycardia and -arrhythmia, tremor, and sleeplessness. Avoid switching levothyroxine preparations due to differences in bioequivalence.

In which patients and how do I implement thyrotoxicosis prophylaxis prior to the administration of iodine-based contrast media?
● Formally, prophylaxis is unnecessary in patients with negative history of thyroid disease, no thyroid gland enlargement, and no clinical symptoms of hyperthyroidism. However, in regions of endemic goiter such as Germany, latent hyperthyroidism (TSH<0.5 mIU/L) due to thyroid autonomy is found in 7% of patients scheduled for iodine contrast media administration. The additional determination of TSH  is therefore particularly sensible in all patients in such regions, most importantly in older ones with cardiac disease.
● Patients with latent hyperthyroidism (6% in South Germany) should be given sodium perchlorate 2 hours prior and 7-10 days after the procedure. Beta blockers should be considered in patients with cardiac disease.
● Patients with manifest hyperthyroidism (1% in South Germany) should be given iodine contrast media only if absolutely necessary (life-saving emergencies, no alternative diagnostic procedures) in consultation with an endocrinologist. If possible, sodium perchlorate should be started 2 days prior to the procedure and it should be supplemented with a beta blocker and with methimazole. Chapter 1.3.1
How do I treat thyroid emergencies?
● During a thyroid storm, reduce the hormone production with propylthiouracil (loading dose 1000 mg, therafter 250 mg every 4 hours) and methimazole (80 mg/d), inhibit hormone release with lithium carbonate (initially 300 mg every 6 hours) and the tyroxine to triiodothyronine conversion with prednisolone and propranolol. Reduce fever with paracetamol and tachycardia/-arrhythmia with propranolol. Replace fluid lost via fever and sweating. Prevent desiccation-induced thrombosis with heparin. If insufficient and plasmapheresis is unavailable, consider early thyreidectomy. Otherwise treat the underlying cause (usually Graves disease or thyroid autonomy, frequently accompanied by a precipitating factor such as excessive iodide exposure, surgery, labor, or infection).
● Patients in myxedema coma require mechanical ventilation and blankets to treat hypothermia. Correct hyponatremia and hypotension with appropriate fluids and glucocorticoids. Under ECG monitoring give i.v. levotyroxine (300 µg/d1, 100 µg/d2, 50 µg on day 3 and following), in combination with triiodothyronine (10 µg every 12 hours), as peripheral conversion may be impaired. Identify and treat the precipitating factor (typically infection, congestive heart failure, cerebrovascular injury). 

Flashcard set info:
Author: LWojnowski
Main topic: Medicine
Topic: Pharmacology
School / Univ.: University Clinical Center
City: Mainz
Published: 24.05.2013
Tags: Professor Leszek Wojnowski
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