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Flashcards in TDM DRUGS COPY Deck (53)
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1
Q

What is the difference between HYPERglyceamia and HYPOglyceamia symptoms?

A

HYOGLYCEAMIA-

Think how you feel if you have not eaten sugar for a while:

Dizzy, head hurts, shaky, hungry, cannot see or think straight, sweaty

HYPERGLYCEAMIA:

Just think how you feel if you’re BUZZING:

Dry mouth, need water, lots of weeing, wetting bed, stomach pain

blood glucose concentration is high so fluid moves out of cells into circulation due to osmosis so you get dehydration

2
Q

What is an ionotrope? What is a positive and what is a negative ionotrope?

A

A drug that alters the force or energy of heart contractions

So positive ionotrope (e.g. Digoxin, Amiodarone): increases force of contractions of heart, used in conditions such as decompensate Heart Failure, shock (severe hypotension) and Myocardial Infarction as they get blood pumping again!

NB: these do not increase rate, digoxin actually decreases the rate, just increase force of contraction. Digoxin used as rate control in AF, Amiodarone used as Rhythm.

Negative ionotropes: decrease force of contractions of the heart, used in conditions such as Hypertension to bring blood pressure down and Angina. Examples: Rate limiting CCB’s, cardio-selective beta blockers e.g. bisoprolol, carvedilol, metoprolol, some anti-arrhythmics such as flecainide

3
Q

What is the desired serum concentration of Digoxin?

A

1 - 2 mcg / L

4
Q

What is the difference between bradycardia and tachycardia? What is the the classified pulse rate for these?

A

Bradycardia: slow heart rate: pulse under 60 bpm

Tachycardia: fast heart rate: pulse over 100 bpm

5
Q

What are the symptoms of DIGOXIN toxicity? (i.e. levels over 2 mcg/ L)

A

Gastro:

Nausea and vomitting

Abdominal pain

Anorexia (weight loss)

Cardiac:

Bradycardia- (HR under 60 bpm) heart slowed down too much by digoxin

Arrythmias (irregular heart beat)

Mental:

Delirium (confusion)

Visual disturbance- blurred, seeing yellow, blind spots

6
Q

Digoxin needs close monitoring. It slows the heart rate, but increases the force of contraction. We need to monitor the heart rate: When should we be worried?

A

If it falls below 60 BPM (i.e. becomes bradycardic)

7
Q

We need to monitor the plasma concentration of Digoxin closely. When should levels be taken?

A

at least 6 HOURS after a dose given

8
Q

Digoxin toxicity can be fatal. What electrolyte imbalance can precipitate digoxin toxicity?

A

HYPOKALEAMIA is a big one. We manage this by giving K+ sparing diuretics (e.g. spironolactone) and K+ supplements.

Hypomagnesaemia

Hypocalcaemia

9
Q

How is digoxin excreted? Therefore what do we need to monitor and decrease dose if impaired?

A

Renally

decrease dose if patient has renal impairment

10
Q

What is digoxin used in?

A

Most use in persistent & permanent Atrial Fibrilation as RATE control

Has a role in Heart Failure

Role in Atrial flutters

11
Q

Amiodarone is used in the rhythm control of AF.

Digoxin is used as rate control.

interaction between these 2 drugs?

A

Amiodarone INCREASES plasma concentration of digoxin

It is an ENZYME inhibitor but not one of the P450’s (so not part of SICKFACES)

Digoxin dose needs to be decreased by 50% if given with Amiodarone

12
Q

Digoxin is metabolised by the CYP450 enzyme system, primarily 2C19. It therefore has many interactions. Can you think of any drugs that increase its concentration?

A

Macrolides: Erythromycin

Clarythromycin, Azithromycin

Ciclosporin

Itraconazole

Amiodarone (but not through CYP)

13
Q

Rifampicin and St Johns Wort are both CYP450 enzyme inhibitors. What TDM drug do they reduce the concentration of?

A

Digoxin

14
Q

Why does Digoxin interact with Diuretics?

A

Diuretics (Loop and thiazide/ thiazide- like) may cause HYPOKALEAMIA

Digoxin toxicity is precipitated by HYPOkaleamia

Therefore be careful with:

Furosemide, Bumetanide

Bendroflumethiazide, indapamide, chlortolidone

Potassium sparing diuretics are Okay:

Amiloride Triamterene

Spironolactone (this can increase [Digoxin]), Eplerenone

15
Q

What drugs other than diuretics can interact with digoxin due to their Hypokaleamic effects?

A

Amphotericin (Antifungal!)

16
Q

Can you think why ACE inhibitors and NSAID’s interact with digoxin?

A

Remember digoxin is excreted renally and caution in kidney impairment

ACE inhibitors and NSAID’s can both decrease kidney function and precipitate digoxin toxicity

17
Q

What happens if a CCB is administered to someone on Digoxin?

A

Plasma conc of digoxin increased by:

Diltiazem

Nicardepine

Nifedipine

Verapamil (also increases risk of AV BLOCK & bradycardia [slows rate])

18
Q

What are the signs of Lithium toxicity?

A

GI disturbance warning signs:

Vomitting, Diarrohea

Then Mostly CNS effects:

Fine Tremor to start then coarse tremor

Involuntary movement (ataxia)

Involuntary eye movement (Nystagmus)

Blurred vision

Thirst- due to hypernatreamia?

Severe toxicity (level over 2 mmol/L):

Convulsions

Coma

Renal failuire

19
Q

Lithium can cause problems in some of our organs. What are these, what would be the signs if their function had altered?

A

Kidney- monitor renal function

Sign of decline: Polyuria, Polydipsia

Thyroid- usually hypothyroidism

Signs: unexplained fatigue

Benign intracranial hypertension (high BP in brain)

Signs: persistent headache, visual disturbance

20
Q

You know the target range for lithium is 0.4 - 1.0 mmol/L.

What is the target in acute episodes of mania?

A

0.8 - 1.0 mmol/ L- upper end of the range!

21
Q

What three drugs do you legally have to provide a patient alert card with?

A

Lithium

Steroids

Anticoagulant

22
Q

Lithium interacts with

ACE inhibitors/ ARB’s

NSAIDS

What is this interaction?

A

Ace inhibitors / ARB’s and NSAIDs can decrease renal perfusion

Lithium excreted by Kidneys

Lithium levels risk= lithium toxicity

23
Q

Why does Lithium interact with the Diuretics (loop, thiazide AND potassium-sparing)?

A

Diuretics can cause electrolyte disturbance

Hyponatreamia may be a result

Lithium levels influenced by sodium levels- lithium toxicity

24
Q

Which antibiotic could possibly cause Lithium toxcity/ levels to rise?

A

Metronidazole

25
Q

Please note there is increased risk of neurotoxicity when Lithium is given with things like methyldopa, phenytoin, carbamazepine

& the rate limiting CCB’s diltiazem and verapamil

A

There is increased risk of EPSE’s when Lithium is given with antipsychotics

26
Q

What type of seizures can phenytoin be used in?

A

Focal

Tonic- clonic

Myoclonic

But not first/ 2nd line in any. Its use is fizzling out.

All types of seizure but Absent!

27
Q

Desired therapeutic range for Phenytoin?

Why is it so important to monitor phenytoin levels?

A

10 - 20 mg/ L

= 40- 80 micromol/L

Non-linear relationship between dose and plasma conc: small change in dose= big change in conc

28
Q

What are the symptoms of Phenytoin toxicity?

A

CNS:

Nystagmus (involuntary eye movement)

Ataxia (involuntary body movement)

Slurry speech

Confusion

suicidal thoughts

HYPERGLYCEAMIA

Double vision (diplopia), blurred vision

NB: Similar to Lithium toxicity: remember the differentials (hyperglyceamia, no convulsions)

29
Q

Phenytoin is related to SKIN & BLOOD disorders

What does the patient need to look out for?

A

Skin- look out for RASH

Phenytoin also causes:

HIRSUTISM (excess hair growth)

gingival hypertrophy (enlarged gums)

acne

Blood disorder:

Fever, sore throat, mouth ulcers, bruising, bleeding

30
Q

With phenytoin, we should monitor ECG & BP with IV use.

Should also monitor _____ function, especially in elderly

A

LIVER

Phenytoin hepatically metabolised: Caution in Hepatic impairment

31
Q

What is the desired range of Theophylline levels?

A

10 - 20 mg/ L

55 - 110 micromol/ L

(mg/ L= same as phenyotin! and digoxin is 1 - 2 mcg/ L so similar! and you know Lithium!)

32
Q

Phenytoin is an interesting drug when it comes to interactions as it itself is an enzyme inducer, but its levels are effected by other enzyme inducers/ inhibitors. It can (effectively) induce its own metabolism.

This weird effect is displayed by its varied interactions with the anti-fungals. Ketoconazole and Fluconazole are both Part of SICKFACES and are enzyme inhibitors…

A

However,

Phenytoins own levels are INCREASED by fluconazole and miconazole= phenytoin TOXICTY

Phenytoin itself INCREASES the levels of Ketoconazole and itraconazole

33
Q

What is the interaction between PHENYTOIN and AMIODARONE?

A

Amiodarone inhibits the metabolism of Phenytoin:

Phenytoin concentration increases

34
Q

Phenytoin is metabolised by CYP450 enzymes. Some of the enzyme inhibitors can therefore increase [Phenytoin]. Which ones?

A

I soniazid

C imetidine

F luconazole

C hloramphenicol

E rythromycin

S ulfamethoxazole

C iprofloxaxin

O meprazole

M etronidazole

35
Q

What electrolyte disturbance can Theophylline cause?

A

Hypokaleamia

Patients may also be on salbutamol (/ beta 2 agonists) for their asthma- can also cause hypokaleamia

Severe asthma patients- monitor K+ as may also be on corticosteroids- can cause hypokaleamia

Diuretics- hypokaleamia

Monitor plasma Potassium in severe asthma/ with theophylline therapy

36
Q

What is Theophylline? How does it work?

A

It is a xanthine

Same family as Caffeine

It is a broncho dilator

37
Q

Theophylline is used in Chronic Asthma Therapy only, usually orally as an MR prep.

When is Theophylline used in Asthma therapy?

A

Can be used at step 3 or 4 of the asthma pathway

Step 3: as an add-on therapy to ICS/ LABA

Step 4: As a regular bronchodilator (6 week trial)

38
Q

Signs of Theophylline toxicity?

Hint: same family as caffeine

A
  • Vomiting
  • Restlessness
  • Agitation
  • Dilated Pupils
  • Sinus tachycardia (palpitations)
  • Hyperglyceamia
  • Severe HYPOKALEAMIA
  • Hallucinations

Severe toxicity: convulsions, arrhythmias, throwing up blood

39
Q

How do we treat theophylline toxicity?

A

Treatment: Repeated activated charcoal, odansetron for vomitting, potassium chloride

Short acting beta-blocker (e.g. Esmolol) may reverse severe tachycardia, hypokalemaia and hyperglyceamia.

40
Q

The plasma concentration of theophylline is increased in ….3…. conditions?

A

Heart Failure

Hepatic impairment

Respiratory Viral infections

So watch out for signs of toxicity (plasma conc rising above 20mg/ L)

41
Q

What two social activities can DECREASE theophylline levels?

A

SMOKING

Alcohol consumption

42
Q

Why is it important to ensure the same BRAND of theophylline is maintained?

A

Rate of absorption from different modified release preparations can change between brands

The brands have different dosing regimes

Brands: Uniphyllin Continus®, Slo-phyllin ®, Nuelin SA®

43
Q

How can Slo-phyllin (theophylline) capsules be taken?

A

Swallow whole with water OR granules can be sprinkled onto yoghurt/ soft food and swallowed without chewing

44
Q

How is theophylline metabolised?

A

HEPATICALLY

therefore reduce dose in liver impairment!

45
Q

What are the three E’s that Theophylline should be used in caution with?

A

Epilepsy- reduced seizure threshold (Hence interaction with Quinolones!)

Elderly- Increased plasma theophylline conc- maybe due to reduced Liver function?

Elevated BP- Hypertension, also hyperthyroidism

46
Q

Theraputic range of Carbamazepine?

A

4 - 12 mg / L

47
Q

Gentamicin- multiple daily dose regimen- one hour peak serum concentration?

And for endocarditis?

NB: For once-daily: consult local guidelines

A

5 - 10 mg / L

Endocarditis: 3 - 5 mg/ L

48
Q

Gentamicin- pre-dose trough concentration?

And for endocarditis?

A

< 2 mg/ L

Endocarditis: < 1 mg/ L

49
Q

For Vancomycin monitoring, we just take Pre-dose Trough levels.

What should this be?

Different for endocarditis?

When should this be taken?

A

Trough level: 10 - 15 mg/ L

Endocarditis: Aim higher for Vancomycin (its lower for Gentamicin): 15- 20 mg/L

Take this after 3rd or 4th dose if renal function normal, 30 MINUTES before next dose is due

50
Q

When should plasma theophylline concentration be measured after starting oral treatment?

How many hours after a dose should a blood sample be taken?

A

5 days after starting

Take blood sample 4 - 6 hours after an oral dose of a Modified release preparation

51
Q

Why is it important for prescribers to specify the brand of aminophyllin or theophylline MR tablets?

What can be done for smokers on aminophylline?

A

The rate of absorption from MR preparations can differ between brands

Specific brand of aminophylline (phyllocontin continus) forte tablets are for smokers (smoking induces metabolism of aminophylline/ theophylline)

52
Q

What are the side effects of Theophylline?

A

Diarrhoea

Convulsions- lowers seizure threshold

Arrythmias

Headache

Insomnia

Vomitting

53
Q

We know that sodium effects Lithium levels. How does it effect lithium levels?!

A

Lithium will follow sodiums movement:

So if plasma sodium is low, renal reabsorption of sodium occurs (as the sodium ions move from high to low concentration) and lithium follows, so lithium levels RISE- lithium toxicity

If plasma sodium is high: more sodium excreted/ less reabsorption- lithium follows and lithium level decreases- subtherapeutic

This is why we say keep your salt intake stable- dont increase or decrease it!

Decks in Pharmacy Pre-Registration 20/21 Class (82):