DRUG INTERACTIONS

WHAT IS AN INTERACTION?

An interaction occurs when the effects of one drug are changed by the presence of another drug,
food, drink or chemical agent.

PHARMACOKINETIC

These interactions affect the processes of absorption, distribution, metabolism and excretion (ADME)
throughout the body.

PHARMACODYNAMIC

These are interactions where the effect of one drug is changes by the presence of another drug at
the site of action. They may include direct competition (ie, beta-2 agonists and beta- antagonists) or
indirect competition (affecting mechanisms).

10 INTERACTIONS WE SHOULD ALL KNOW!!

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Tetracyclines and antacids (Al3+, Ca2+, Mg2+, milk and Fe2+)

The antacid causes the formation of poorly soluble chelates, which reduce the absorption of
tetracycline may result in loss of therapeutic effect.
Need to leave at least 2 hours apart (ideally longer)
Oral contraceptives and anti-epileptics (carbamazepine / phenytoin / etc)
The contraceptive effect is reduced due to the enzyme inducing effect of the anti-epileptic,
causing contraceptive failure.
May also result in intermediate break-through bleeding.
Effect of anti-epileptic may also be affected, causing a disturbance in seizure control.
Sodium valproate and lamotrigine are safer!
Metronidazole and alcohol
A disulfiram-like interaction occurs, due to the metronidazole inhibiting acetaldehyde
dehydrogenase, so causing a build-up of acetaldehyde in the blood.
Lithium and thiazide (& related) diuretics
Serum lithium levels can increase with thiazides, leading to lithium toxicity.
Avoid all thiazide diuretics unless lithium levels can be monitored closely.
Beta blockers and sympathomimetics
B.P. & heart rate
- Stimulation of alpha and beta receptors by the
sympathomimetic (causing vasoconstriction) is enhanced by beta
receptor blockade (usually vasodilatation).
- Causes severe hypertensive reaction &/or bradycardia (ie,
withpropranolol and phenylephrine).

Bronchi

Anaphylaxis

- Beta receptors are blocked in the bronchi, so the normal

bronchodilation is reduced = may cause bronchoconstriction in
asthmatics (esp. non selective propranolol)
- Increased risk with beta blockers
- Patients may also be resistant to sympathomimetics, ie adrenaline.

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Tyramine and MAOIs

Life threatening hypertensive crisis can develop, especially with the older MAOIs (phenelzine/
tranylcypramine).
Tyramine has been found in foods such as; cheese, yeast extracts, salami, chicken and beef.
It has been found in several drinks also; chianti, beer, and other various wines.
Newer MAOIs (moclobemide / selegiline) interact minimally or not at all!

Macrolides (erythromycin) and anticonvulsants

If taken concurrently, erythromycin causes carbamazepine levels to rise to toxic
concentrations.
Phenytoin is not affected.

SSRIs and MAOIs

MAOIs increase the CNS effects of SSRIs.
SSRIs should not be started until 2 weeks after stopping the MAOI.
MAOIs should not be started until at least 2 weeks after stopping paroxetine / sertraline
MAOIs should not be started until at least 1 week after stopping citalopram
MAOIs should not be started until at least 5 weeks after stopping fluoxetine

Cardiac glycosides and K+ depleting diuretics

Results in an increased risk of cardiac toxicity if hypokalaemia occurs.
Occurs with diuretics such as; acetazolomide, loop, thiazides and related diuretics.

Nitrates and sildenafil / tadalafil / vardenafil

Causes increased hypotensive effects of the nitrate
Avoid concomitant use!

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15 DRUGS WE SHOULD KNOW!!

1.

DIGOXIN

- Uses

- Heart failure
-Supraventricular tachycardia
- Side effects- n & v / anorexia
- diarrhoea
- headache/ dizziness
- confusion
- abdominal pain
- depression

2.

DIURETICS

- Uses

- Oedema
- Hypertension
- Oliguria due to renal failure
- Side effects- hyponatraemia
- postural hypotension
- hypercalcaemia
- hypo/hyperkalaemia
- GI problems

hypokalaemia
gout
impotence
confusion
Dry mouth
Heart failure
M.I.
Thyrotoxicosis
hypotension
fatigue
GI problems

3.

BETA BLOCKERS

- Uses

- Hypertension
- Angina
- Arrythmias
- Side effects- cold extremities
- sleep problems
- conduction problems

4.

ACEIs

- Uses

- M.I.

- Hypertension
- Coronary heart failure
- Side effects- renal impairment
- angioedema
- dizziness/ headache

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ALPHA BLOCKERS

- Uses

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NITRATES

- Uses

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CA2+ BLOCKERS

AMIODARONE

- dry cough
- URTIs
-n&v

- Hypertension
- Benign prostatic hypertrophy
- Side effects- postural hypotension
- dizziness
- headache
-n&v
- Prophylaxis of angina
- Tx of angina
- Side effects- headache
- postural hypotension

- flushing
- dizziness

- Uses

- Arrythmias

- Hypertension
- Prophylaxis of angina
- Side effects- headache
- flushing
- nausea
- Uses
- Arrythmias
- Side effects- night glare
- phototoxicity
- thyroid problems
- metallic taste

- fatigue
- oedema
- dizziness

bradycardia
n&v
hot flushes
nightmares

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LITHIUM

- Uses

- Tx & prophylaxis of mania

- Tx & prophylaxis of bipolar disorders
- Side effects- GI problems
- oedema
- tremor
- polydipsia
- renal impairment
- blurred vision
- muscle weakness
- CNS problems
- convulsions
- hyper-reflexia
- syncope

Normal

Toxicity

Overdosage

10.

T.C.A.s

- Uses
- Depression where sedation required
- Side effects- arrhythmias
- convulsions
- drowsiness
- sweating
- urinary retention
- blurred vision
- constipation
- dry mouth

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S.S.R.I.s

- Uses

- Depression
- Panic disorders
- Side effects- less sedating
- less anti muscarinic
- less cardiotoxic

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PHENYTOIN

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STEROIDS & IMMUNOSUPPRESANTS

- Uses
- Transplants
- Rheumatoid arthritis
- Side effects- hypersensitivity
- liver impairment
- hypotension
- diarrhoea

- GI problems
- anorexia
- rash

- Uses
- All epilepsy except absence seizures
- Side effects- n & v
- dizziness
- mental confusion
- confusion
- headache
- tremor
- insomnia
- nervousness

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THEOPHYLLINE

- Uses

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WARFARIN

- Uses

hair loss
infections
n&v
abdominal pain

- Reversible airways obstruction

- Acute severe asthma
- Side effects- tachycardia
- palpitations
-n&v
- headache
- CNS stimulation
- insomnia
- Embolisation prophylaxis in heart disease
- Prophylaxis after prosthetic heart valve
- Prophylaxis & tx of venous thrombosis
- Transient ischaemic attack
- Side effects- haemorrhage
- rash
- hypersensitivity
- diarrhoea
- purple toes
-n&v