11. Drug Interactions 1 Flashcards
What is a drug interaction?
Drug Interactions - Occur when one drug modifies the effect of another drug
What is the difference between Pharmacodynamics and Pharmacokinetics?
Pharmacodynamics → relates to what the drug does to the body (drug acts on receptors, enzymes, transport mechanisms, modifies processes etc to produce its pharmacological effects)
Pharmacokinetics → relates to what the body does to the drug (absorption, distribution, metabolism and excretion of the drug)
What are the 2 types of Drug Interactions?
Drug Interactions
- Pharmacodynamic Interactions → occur when the pharmacodynamic effects of one drug are modified (enhanced or reduced response) by the co-administration of another drug
- Pharmacokinetic Interactions → occur when the co-administration of a drug enhances or reduces the response to another drug by altering the way in which the body handles the other drug (absorption, distribution, metabolism or excretion)
What are 5 examples Pharmacodynamic Interactions?
Pharmacodynamic Interactions
- Opioid analgesics + benzodiazepines → sedation, mental clouding
- e.g. morphine + diazepam
- Beta2 agonists and beta competitive antagonists (beta blockers) → reduce/block the bronchodilator effect
- e.g. salbutamol + propranolol
- Antiplatelet drugs + anticoagulants → ↑ tendency to bleed
- e.g. aspirin + warfarin
- ACE inhibitors (or angiotensin 2 receptor antagonists) + an NSAID + Diuretic → renal impairment
- (Triple Whammy)
- Drugs which ↑ the concentration of serotonin when used together → Serotonin Syndrome
- e.g. sertraline and tramadol
What is the effect of using both opioid analgesics and benzodiazepines?
Pharmacodynamic Interactions - Examples
- Opioid analgesics and benzodiazepines
- Opioid analgesics e.g. morphine may produce sedation, drowsiness, mental clouding etc
- Benzodiazepines e.g. diazepam may produce sedation, drowsiness and mental clouding
- Using the two products together may produce profound sedation, impaired performance, and possible respiratory depression and coma
What is the issue with taking Beta adrenergic receptor agonists with competitive beta adrenergic receptor antagonists?
Pharmacodynamic Interactions - Examples
2) Beta adrenergic receptor agonists and competitive beta adrenergic receptor antagonists
- an agonist has affinity and intrinsic activity (efficacy)
- a competitive antagonist has affinity but no intrinsic activity (efficacy)
- Stimulation of beta2 adrenergic G-protein coupled receptors on bronchiole smooth muscle produces bronchodilation
- Beta2 receptor agonists such as salbutamol are used in the treatment of asthma
- They produce bronchodilation and are useful in the treatment of symptoms such as wheezing, breathlessness etc
- Beta adrenergic receptor agonists and competitive beta adrenergic receptor antagonists
- beta adrenergic receptor agonists e.g. salbutamol stimulate beta2 receptors on bronchiole smooth muscle and produce bronchodilation
- competitive beta adrenergic receptor antagonists e.g. propranolol competitively inhibit beta2 receptors
- Using the two products together may inhibit the bronchodilation produced by beta2 agonists
- Beta adrenergic receptor antagonists (beta blockers) are contraindicated in asthma
- Ie. Ventolin won’t work as it competes with the same receptors
What is the issue with taking low dose aspirin inhibits platelet aggregation and anticoagulants?
Pharmacodynamic Interactions - Examples
-
Low dose aspirin inhibits platelet aggregation + anticoagulants e.g. warfarin inhibit clot formation
* Using the two products together may lead to an increased risk of bleeding
Which 3 drugs produce the Triple Whammy?
Give examples of each
Pharmacodynamic Interactions
-
ACE inhibitor + NSAIS + Diuretic → Renal Impairment (Triple Whammy)
* The following combination of medications in susceptible patients may produce renal impairment: - angiotensin converting enzyme (ACE) inhibitor (or an angiotensin II receptor antagonist)
- e.g. enalapril, perindopril, ramipril
- e.g. candesartan, irbesartan
- NSAID including COX 2 inhibitors
- e.g. celecoxib, ibuprofen, naproxen
- Diuretic
- e.g. hydrochlorothiazide, frusemide
What do Angiotensin converting enzyme (ACE) inhibitors do?
Renin-Angiotensin-Aldosterone System
Angiotensin converting enzyme (ACE) inhibitors reduce the formation of angiotensin II
What do Angiotensin II receptor antagonists do?
Renin-Angiotensin-Aldosterone System
Angiotensin II receptor antagonists act as competitive antagonists of angiotensin II at angiotensin II type I receptors
What do NSAIDs do?
How can a Triple Whammy lead to renal failure?
Triple Whammy
In elderly patients, and those patients with heart failure, hypertension, renal impairment or dehydration, maintenance of renal perfusion is often regulated by
- A vasodilator effect of prostaglandins on afferent renal vessels (so more blood can get in)
- A vasoconstrictor effect of angiotensin II on efferent renal vessels (harder for blood to get out = increased glomerular pressure to maintain filtration)
- An NSAID may inhibit the vasodilator effect of prostaglandins on afferent vessels, reduce renal blood flow and reduce renal function
- An ACE inhibitor (or A II receptor antagonist) may inhibit the vasoconstrictor effect of angiotensin II on efferent vessels, reduce glomerular perfusion pressure and reduce renal function
- A diuretic may produce dehydration
- The combination of all three may cause significant renal impairment -Triple Whammy
How does the Triple Whammy usually come about?
Triple Whammy
Usually occurs when:
- a susceptible patient is taking an ACE inhibitor (or an A II receptor antagonist) and a diuretic
- the patient then requires an analgesic and takes an NSAID
- Does not occur with paracetamol or opioids
What is Serotonin Syndrome?
Serotonin Syndrome
- May be caused by drugs which increase the concentration of serotonin (5-hydroxytryptamine, 5HT) in the brain
- Possibly caused by an overstimulation of 5HT1A and 5HT2A receptors in the central grey nuclei and medulla
- Involves a triad of mental, autonomic and neurological effects
- Condition may deteriorate rapidly and may cause death
Which symptoms are associated with Serotonin Syndrome?
Serotonin Syndrome - Symptoms
- Abdominal cramps, diarrhoea
- Agitation, tremor, myoclonus (skeletal muscle spasms)
- Confusion, disorientation, manic activity
- Tachycardia, hypertension
- Profuse sweating, hyperpyrexia, shivering
- Coma and possible death
What is an example of a drug that causes the:
- release of serotonin?
- blocks the reuptake of serotonin?
- stimulate serotonin receptors?
Serotonin Nerve
- Some drugs can cause the release of serotonin e.g. ecstasy
- Some drugs can block the reuptake of serotonin e.g. sertraline (SSRI)
- Some drugs can stimulate serotonin receptors e.g. sumatriptan
- Many drug combinations may produce the Serotonin Syndrome e.g. sertraline and tramadol
- Both sertraline and tramadol block the reuptake of serotonin and increase the concentration of serotonin (5HT) in the synapse
- Serotonin reuptake is inhibited by drugs such as sertraline and tramadol
