Common
Disease Warfarin
Management management
• Asthma Indications
• COPD
DVT (last 3mth)
• Diabetes
Pul. Embolus (last 3mth)
• Cardiovascular disease
Recurrent DVT or PE
o H/T
AF with valve Dz
o Angina
AF no valve prob but >50yo
o AF
Stroke
o Stroke
o HF Major risk factor = bleed
• Depression
• Infection (UTI, chest)
• OA
Pt education
1. Report bleeds
2. Keep diary (dosage, INR)
3. Don’t change brands (not equiv)
Starting Tx
No loading dose (risk bleed)
o Start dose = 5mg d (adjust with INR)
o Maint = 1‐10mg d
o Tabs: 1,2,3,5mg
If event, start with heparin/LMWH while warfarin
works (min. 48hr after INR at target‐eTG)
Monitor = PT or INR (=stdised PT)
o Before Tx
o Daily or 2nd day until stable (eTG)
o Then every 4wks
o Target INR = 2‐3
o When add/remove other drug, monitor
until other drug clears from system (4‐5
t1/2)
Other monitoring (not mentioned in AMH!)
Genetic issues
S‐warfarin metabolised by CYP2C9
o S‐warfarin more active than R
VKOR enzyme is major target of warfarin
FRUSEMIDE
OSTEOARTHRITIS
Indications
Inflammatory condition
Oedema from HF, renal fail, liver cirrhosis
Tx
Dosing
Start = 20‐40mg OD‐BD Use paracetamol, not NSAID (bleed)
Maint = 20‐400mg daily o Slow release ‘OSTEO’: 665mg tab
Max 1g daily o Dose SR = 2 q6‐8h
T1/2 = 2hr (varies with renal f’n) o Max 6 tabs/day
Onset = 30‐60min after oral dose, peak 1‐2hr Avoid NSAID (↑ BP, ↑ bleeds)
Dosing usu early am + noon (after 6pm = pee Glucosamine can stop progression
no sleep!) o 1.5g gluc. Sulphate daily
Non‐drug
Monitoring o Exercise
o Wt loss
1. ↓K+ = monitor K+ o Topical: capsaicin, rebefaciant, NSAID
2. ↓Na+ = monitor Na+
3. ++fluid loss = monitor wt daily (+/‐1kg tell Dr)
Interactions
1. Frusemide = hypotension + lose K+ +
oto/nephrotoxic
2. ACEI = hypotension + K+ retention
a. ↑ 1st dose hypotension (stop
frusemide 24hr or split dose)
b. ↑ risk renal impair =monitor renal
3. SARTANS (ARBS) = hypotension + K+ retention
a. As above
4. NSAIDs: AVOID COMBO (low dose aspirin OK)
a. ↓ renal f’n (monitor)
b. ↓ diure c effect (monitor BP, wt)
c. ↑ risk nephrotoxic
5. Thiazide (AVOID COMBO)
a. ↑ diuresis
b. ↓ K+
6. Lithium = ↑ Li [ ]
a. Monitor Li, ↓ dose if needed
DIABE
ETES II
Tx a
aims
1. Control bld gluc
2. Prevent microvasc d damage (CVDD, eye,
kidney,n
nerve)
3. Relieve SSx (thirst, urination)
Drug Tx: start n
non‐drug first (3mth w
wt loss,
exercise,diet)
1. Metform
min first for aall
• =diabex, meetformin, glucovance
• =biguanide ((↓glucose prod’n)
• sulfonylureaa first OK if not fat
2. Add Sulffonylurea (glliclazide=diamicron)
• ↑insulin seccre on
3. Other m
meds
• Low dose asspirin if high CVD risk
• ACEI to slow w renal Dz prrogression
• Sartan if can n’t do ACEI
Mon
nitoring
1. Bld gluc
• Fasting: 3.3‐‐5.6mmol/L
2. HbA1C
• Looks at long‐term gluc control
DMII: METFORMIN DMII: SULFONYLUREAS (Gliclazide)
• ↓gluc prod’n by liver ↑ insulin secre on
• ↑gluc use in periphery ↓ insulin resistance
Trade: diabex, metformin, glucovance Trade: Diamicron, Nidem, Gliclazide, Glyade
CN:
• Ketoacidosis
• Dehydration
• EtOH excessive
• Trauma/infection
Probs with metformin Probs with sulfonylureas
1. Lactic acidosis risk (↑risk with renal impair) 1. ↑ insulin secre on ‐> hypoglycaemia risk
• Watch out for N, V, wt loss, anorexia ‐> take with food
• Metformin cleared 100% renal Recognise hypo Sx
• Renal impair =↓H+ excr/↑HCO3 reabs.
2. Wt gain
2. Lower risk of hypos cf. sulfonylurea
Dosage
Dosage
Start = 40‐320mg daily in 1‐2 doses
• Start = 500mg OD‐tds
Max 160mg OD
• Maint = 850mg bd‐tds
• Max = 3g daily CR:
o Start = 30mg OD
Interactions o 2wk +30mg OD
o Max 120mg OD
1. EtOH
• ↑ risk lac c acidosis (liver can’t get Interactions
rid of lactic acid ‐> accumulation)
• ↑ risk hypos (mask Sx) 1. Rifamipicin = ↑ metab of gliclazide
=↓hypoglycaemic effect
2. Cimetidine (use other H2 antag eg ranitidine) ‐> monitor bld gluc + ↑ glic. if nec.
• ↑ [ ] me ormin (↓ renal excre on)
3. Other antiDMs = ↑risk hypos
4. Metformin = 100% renal clear
Induced renal fail = lactic acidosis
• ↓H+ excre on, ↓HCO3 reabsorp on
• Eg. contrast media ‐> stop metformin
48hr before/after
• Cyclosporin
• aminoglycosides
HEART FAILURE ACEI for HF
Block conversion ATI ‐> ATII
Tx Aims First drug choice for HF
Also used in H/T, post‐MI
Sx
↓worsening
Category I ACEIs
↓death and hospitalisa on
Captopril = Capoten, Captopril
Perindopril arginine = Coversyl (2.5.5,10mg)
Perindopril erbumine = Perindopril, (2,4,8mg)
Before Tx HF: Tx cause if possible
Usu. HF b/c of sth else: AF, H/T, valve Dz, angina, Probs with ACEI
infections, etc.. drugs:
1. 1st dose hypotension
↓force contractn (‐ve inotrope)= verapamil, Esp. if already on frusemide
diltiazem ‐> stop frusemide 24‐48hr before ACEI or
salt‐retaining drugs = corticosteroids, NSAIDs separate dose
2. Bradykinin cough (↓b‐down of bradykinin)
If prob, refer (change class; ARB may ↓)
Non‐Drug Tx
3. Angioedema ‐> use different class
↓ salt, EtOH, H2O Can come on after years!
↓wt, ↑exercise
4. ↑[K+ ] ‐> monitor, esp. if taking spiro (K+ sparing)
No K+ supplemts
Drug Choice: must have ACEI+BB+diuretic 5. ↓[Na+ ] SIADH?
Life savers (↑ survival) Dosage: all ACEI same, start low+titrate. All OD
1. Start with ACEI/ARB
dosing except captopril
+ frusemide if needed for Sx only
Captopril HF H/T
2. BB (esp. if AF) –stabilise on diuretic first
3. Spironolactone (severe HF) Start 6.25mg BD 12.5mg BD
↑ each 2wk ↑each 2‐4 wks
Other drug:
Maint. 25‐75mg BD 25‐50mg BD
1. Digoxin (severe HF‐last resort; or HF+AF)
2. Warfarin DVT prophylaxis if bed‐ridden or +AF Max 150mg daily
Perindopril arg HF H/T
Start 2.5mg OD 5mg OD
↑each 1‐2wk
Maint. Max 5mg OD Max 10mg OD
Monitor: before start + 2wk, then if needed
1. Renal f’n (SeCr)
2. [K+ ], [Na+ ]
ACEI Interactions FRUSEMIDE for HF
ACEI = 1st dose hypotension+↑K+ +renal impair
Indications
+↓Na+ (SIADH)
Oedema from HF, renal fail, liver cirrhosis
1. Frusemide/thiazide diuretics Dosing
↑1st dose hypotension
o Start low dose ACEI or separate Start = 20‐40mg OD‐BD
dose (frusemide am, ACEI pm) Maint = 20‐400mg daily
↑Renal impair Max 1g daily
o Monitor renal (SeCr, T1/2 = 2hr (varies with renal f’n)
electrolytes) Onset = 30‐60min after oral dose, peak 1‐2hr
Dosing usu early am + noon (after 6pm = pee
2. NSAIDs = AVOID USE (low dose aspirin OK) no sleep!)
Renal impair (monitor SeCr, K+ ,wt)
↑BP (monitor) Monitoring
1. ↓K+ = monitor K+
3. Drugs that ↑K+ ‐> avoid combo or monitor K+ 2. ↓Na+ = monitor Na+
Eg. spironolactone (monitor) 3. ++fluid loss = monitor wt daily (+/‐1kg tell Dr)
4. Drugs that react badly to ↑K+
• Digoxin = ↑bradycardia
(x0.5 digoxin + monitor [ ], A/E, renal)
Interactions
Frusemide = hypotension +↓K+ + oto/nephrotoxic
+↑ risk renal fail
1. ACEI = hypotension + ↑K+
↑ 1st dose hypotension (stop
frusemide 24hr or split dose)
↑ risk renal impair =monitor renal
2. SARTANS (ARBS) = hypotension + K+ retention
As above
3. NSAIDs: AVOID COMBO (low dose aspirin OK)
↓ renal f’n (monitor)
↓ diure c effect (monitor BP, wt)
↑ risk nephrotoxic
4. Thiazide (AVOID COMBO)
↑ diuresis = ↓↓ K+
5. Lithium = ↑ Li [ ]
Monitor Li, ↓ dose if needed
6. Renal CL drugs = ↑[ ] = toxicity
Digoxin = monitor digoxin [ ], A/E
BETA BLOCKERS (BB) FOR HF Monitoring:
1. daily wt, Sx: BP, HR, heart f’n
Also for H/T, AF, angina, MI
Interactions
Avoid combo with:
1. Asthma (contraindicated) BB = hypotension + ↓contrac lity + ↑K+ (in overdose)
2. DM (mask hypos) 1. not with drugs that cause hypotension
3. AV block (full block) vasodilators
4. Some BB renal elim, some liver o CCB (heart selective:
Breastfeed: use metoprolol or propranolol (protein verapamil, diltiazem)
bound, not excreted in milk)
2. Metoprolol + amiodarone = ↑metop
Category I BB Start low dose metop, monitor
Atenolol: Noten, Tenormin, Tensig 3. Metoprolol+cimetidine = ↑metop
Metoprolol: Betaloc, Minax, Lopresor Use different H2 antag
or use atenolol (renal CL)
B1 selective: atenolol, metoprolol (good for DM, 4. NSAIDs (AVOID USE. Low dose aspirin OK)
asthma) ↑BP
Most lipid sol (BBB!) + hepatic cleared
5. Beta2 agonists = ↓asthma control
Except atenolol
o Renal CL
6. Ergot alkaloids (migraine) = AVOID COMBO
o ↓lipid sol = no nightmares (no BBB)
↑vasoconstrict
Dosage:
7. Digoxin + ↑K+ = digoxin toxicity
Atenolol (H/T, angina): ↑bradycardia
o 25‐100mg OD
Metoprolol :
o HF =CR dosage form
Start 23.75mg OD x2wk
Dose x2 each 2wk
Maint. 190mg OD
o H/T
Start = 50‐100mg OD x 1wk
Maint = 10‐100mg OD or BD
Start when stabilised on ACEI/frusemide
Start dose v. low, increase v. slow.
Stop slow
o HF: x 0.5 each wk
o Others: over 2wks
o Yrs Tx: over 4‐6wk
↑ACEI/frusemide if BB =↑HF
SPIRONOLACTONE FOR HF
Aldosterone antagonist (K+ sparing diuretic)
For severe HF (Tx oedema)
Trade: Aldactone
Dosage:
Start = 25mg OD x8wk before ↑
Max = 50mg OD (if progress of HF + no ↑K+ )
o If ↑K+ then 25mg each 2nd day
Use with ACEI + frusemide +/‐ digoxin
Monitoring: K+ sparing = ↑ K+ (esp. with renal fail)
b/c use with ACEI (↑K+ ) monitor K+
o weekly x 1mth
o then mthly x 2mth
o then 3mth and when needed
monitor renal
o SeCr, Na+ /Cl‐ (↑ Na+ /Cl‐ excretion)
Interactions
Spiro = ↑K+
1. Drugs that cause ↑K+ = AVOID COMBO
ACEI, sartan: needed, so monitor K+
K+ supplemts (AVOID)
2. Digoxin = ↑ digoxin
Toxicity ‐> monitor digoxin [ ] and A/E
3. NSAIDs (AVOID USE. Low dose aspirin OK)
↑BP, ↑K+
DIGOXIN FOR HF Digoxin Interactions: MANY! List only significant
Digoxin =↓conductn+↓HR + Δ electrolytes+ renal CL
Only with HF + AF or severe HF (last resort)
1. Drugs that cause Δ electrolytes = ↑ toxicity
Cardiac glycoside: ↑ force of contrac on, ↓ HR a. ↓K+ drugs ‐> arrhythmia
Eg. thiazides, loop diuretics,
corticosteroids, amphotericin B, beta
Trade: Lanoxin
agonists (salbutamol),aminoglycoside
AB (gentamicin), hi‐dose penicillin
Probs with Digoxin
b. ↑ K+ drugs ‐> bradycardia
1. Low TxI = toxicity! –> Tx Drug Monitoring Eg. spiro, ACEI ‐> monitor
2. ↓HR NSAID = AVOID USE
↑bradycardia if ↑K+ Heparin, trimethoprim,
Eg. spiro, ACEI ‐> monitor BB (in overdose)
NSAID = AVOID USE
Arrhythmia if ↓K+ (see Interactions) 2. ↑digoxin drugs = toxicity
‐> monitor [ ], ↓dig if nec
Dosage a. Quinidine (antimalarial)
b. Amiodarone (x1/2 digoxin, monitor)
Start = 250‐500mcg q4‐6h, max 1.5mg c. CCB eg. diltiazem, verapamil (↓dig
Elderly start half dose, max 500mcg dose, monitor)
Monitor [ ] and adjust to response/toxicity d. Spironolactone
T1/2 = 24hr min (no renal fail) e. Macrolides:
o 5 days to steady state (5 x t1/2) NB long t1/2 ‐> monitor 5t1/2
o Drug redistribution delays effect f. Itraconazole
3. ↓digoxin drugs = ↑ dig if necessary
a. Penicillamine
Monitoring b. Rifampicin
1. Trough bld [ ] immed. before dose or 6hr after c. St John’s wort (AVOID COMBO)
(drug redistributes) d. Sulfasalazine (Crohn’s UC, RhA)
2. Renal f’n + electrolytes before start
SeCr
K+
Na+
HYPERTENSION
COMBOS:
Good BAD
Tx Aims ACEI /ARB + CCB ACEI/ARB + spiro =↑K+
ACEI/ARB + thiazide ACEI + ARB = ↑K+
Long term (prevention):
o ↓death
Other:
o ↓complica ons eg. stroke, athero,
microvascular BB + ACEI/ARB Verapamil + BB
BB+CCB =↓↓ HR + heart block
Before start Tx H/T:
From AMH:
make sure in mod‐high risk grp (∴ benefit)
o different risk grp = diff target BP
↓other lifestyle risk factors Coexisting condition Drugs with favourable effect
o Smoking, wt loss, exercise
Consider low‐dose aspirin (anti‐platelet)
DM + proteinuria or ACEI / ARB = ↓ Dz progress
microalbuminuria
Drug choice: All classes same efficacy.
HF ACEI /ARB,
Start 1 drug, review 4‐6wk, ↑ dose, review. No
BB (carvedilol, metoprolol CR,
good = try different drug. Still no good = add 2nd
bisoprolol),
drug.
thiazide diuretics
1. ACEI or ARB (usu. first choice)
a. Categ I drugs: captopril, perindopril
post MI BB (except oxprenolol, pindolol),
2. CCB ACEI (or sartans)
a. Dihydropyridines OK (periph select)
Categ I: amlodipine angina BB (except oxprenolol, pindolol),
Others: felodipine, nifedipine CCB, ACEI
b. Others: cardioselective (not with HF)
Categ I: verapamil, diltiazem AF ACEI /ARB, (verapamil, diltiazem, BB
may help rate control)
3. Thiazide diuretic: 1st line >65yo (↑DM in
young) Coexisting condition Drugs with unfavourable effect
4. Betablockers (BB): not 1st line (no stroke asthma, COPD BB1
prevent, ↑DM). Only 1st if other probs:
NB: cardioselective BB (eg atenolol,
MI: use heart selective metop., atenolol
metoprolol) may be used cautiously
Coronary Dz + angina
in mild‐to‐moderate reactive
Post‐MI airways diseases
HF
o Categ I drugs: metop., atenolol
bradycardia, 2nd BB, diltiazem, verapamil ‐>block
or 3rd degree AV
SEE UNDER HF INDICATIONS block
ACEI heart failure CCB (especially verapamil, diltiazem)
BB
gout thiazide diuretics (compete for
excretion of uric acid ‐> worse
THIAZIDES FOR H/T Interactions of Thiazides
Low dose thiazide for H/T = vasodilator Thiazide = ↓BP + ↓K+ +↑bld gluc (hi‐dose)+renal CL
1. ACEI or ARB
Indications ↑1st dose hypotension
H/T (mild‐moderate) o take 1st ACEI pm
o 1st choice if > 65yo (↑DM risk) ↑renal impair (monitor, ↓ACEI if
o Not for gout needed)
Oedema from HF
2. NSAID (low dose aspirin OK)
Renal impair (AVOID COMBO)
Categ I drugs listed only: Or monitor BP, renal, wt
Hydrochlorothiazide = Dithiazide Adjust diuretic dose
3. Loop diuretics
↑↑ effect (monitor BP, renal,
Combo prods: elctrolytes, ↓ thiazide if needed)
+ ACEI (enalapril) = Renitec Plus
+ Sartan (irbesartan) = Avapro HCT, Karvezide
+K+ sparing diuretic (not categ I)
Probs with thiazides
1. ↑bld glucose, ↑ lipids
no prob if low –dose
1st choice not young people (>65 only)
+
2. ↓K
OK if used with ACEI/ARB (↑K+ )
3. Orthostatic hypotension
4. Not for preg (ADEC C)
Not for Br‐feed (↓ milk)
Dosage:
12.5‐25mg mane (after 6pm= pee, no sleep)
CCB for H/T Interactions of CCB
Block Ca ch into smth muscle (bv, heart, cardiac CCB = hypotension
conduction) ‐>↓contrac on Amlodipine interactions:
1. Cyclosporin = ↑ cyclo ‐> toxicity
Indications: Monitor cyclo [ ] + A/E
2. Ritonavir = ↑amlodipine ‐>↑A/E
o H/T
Monitor A/E, ↓amlo if needed
o Angina
o Also for Verapamil : AF (vent. rate control)
Verapamil = antiarrhythmic + bradycardia +
CN: ↓conduc on + hypotension +CYP3A4
H/T + HF = don’t use heart selective 1. CYP3A4 inhib+substrate
(verapamil. Diltiazem) CYP1A2: weak inhib, good substrate
Verapamil, diltiazem not with BB in HF i. Carbamazepine = ↑CBZ ‐> A/E
Monitor CBZ [ ] + A/E
↓CBZ if needed
Categ I CCB:
ii. Erythromycin (AVOID COMBO,
Verapamil = Isoptin, Anpec unpredictable, else monitor heart f’n)
o +ACEI (not in Categ I) Can ↑erythro = ↑QT
Amlodipine = Norvasc Can ↑verap = cardiotoxic
o +statin (atorvastatin) = Caduet iii. Midazolam = ↑midaz ‐>longer
sedation + respir depression
↓midazolam + monitor
Problems with CCB: depend on site of action clinical effect
1. Peripheral selective = didhydropyridines 2. Other arrhythmics = ↑HF, bradycardia,
o periph oedema, flushing, palpitations, proarrhythmia (AVOID COMBO)
hypotension i. Digoxin = ↑dig + ↓conduct + ↓HR
2. heart selective = verapamil, (diltiazem =both) Monitor dig [ ]+A/E
o bradycardia ↓dig if needed
o verapamil = constipation
Dosage
Verapamil (H/T or angina)
o Start = 80mg BD‐TDS
o Maint. = 160mg BD‐TDS
Verapamil CR
o H/T: Start = 120‐180mg OD
o Angina: Start = 180‐240mg OD
o Max = 240mg OD – BD
Verapamil (Arrhythmia) = IV only
Amlodipine (H/T or angina)
o Start = 2.5‐5mg OD
o ↑ over 1‐2wk
o Max = 10mg OD
