CYP450 Inhibitors And Inducers Flashcards
What are CYP450 enzymes?
These are enzymes that metabolise most drug molecules.
What is polymorphism in the context of CYP450 metabolism?
This relates to the mutations in the CYP450 enzymes that will affect how CYP450 substrates are metabolised.
What are the 4 types of CYP450 polymorphism and what are the implications?
- 🦥 slow metaboliser - increased risk of toxicity
- 🟡 intermediate metabolisers - increased risk of side effects and tox compared to extensive metabolisers
- 👍 extensive metaboliser - normal metabolism
- 🐆 ultra rapid metaboliser - reduce therapeutic efficacy of the drug
Give some examples of CYP450 substrates - ie drugs that get metabolised by CYP450 enzymes.
Amlodipine, warfarin, citalopram, CCBs, losartan, sertraline, statins, lidocaine, Clopidogrel
What are CYP450 enzyme INDUCERS and what is their effect on therapeutics of the drug?
These are drugs or substances that bind to the CYP450 enzyme and enhance its action as a metaboliser.
As a result the drug is metabolised and cleared much faster - reduction in therapeutic action + benefit for the patient
Which pneumonic can we use to remember the CYP inducer drugs?
CRAP GPS
List the CYP Inducers
💩 🗺️
Carbamazepine
Rifampicin
Alcohol
Phenobarbital
Griseofulvin
Phenytoin
St John’s wort
Carbamazepine
- drug class
- main indications
- side effects and tox
- notable side effects
- monitoring
😵💫 anti epileptic
Typically used for epilepsy as 2nd line monotherapy treatment after lamotrigine and levetiracetam
🇨🇳 🇹🇭 Px with the HLA-B1502 alleles (Han Chinese or Thai) - strong association with SJS - pre screening is needed.
🇯🇵 🇷🇴 The presence of HLA-A3101 allele, particularly in individuals of European or Japanese origin, is associated with an increased risk of cutaneous adverse reactions but there are insufficient data to support pre-treatment screening.
Common side effects - dizziness, drowsiness, dry mouth, fatigue, headache, skin rx, vomiting, increased weight - excluding increased weigh, these SE are dose related and more common at start/elderly
⚠️ px being treated for epilepsy should not be switched to another formulation or brand - different BV!
📊 Monitor plasma conc after 1 -2 weeks, blood counts and hepatic and renal function tests
Rifampicin
- drug class
- main indications
- side effects and tox
- notable side effects
- monitoring
Drug class - Rifamycins
🫁 It is used in conjunction with isoniazid (with pyridoxine) for the 3 month treatment of TB
It is also used to treat legionnaires disease 🦠, endocarditis 🫀, staph infections.
Common side effects
- nausea, vomiting, thrombocytopenia
It is taken daily - if px take it intermittently - may have influenza like symptoms as SE (ie fever, chills, dizziness), resp (SOB), collapse shock. Etc - discontinue if srs SE occur
⚠️ Rifampicin reduces the effect of hormonal contraceptives (leveo
Phenobarbital
- drug class
- main indications
- side effects and tox
- notable side effects
- monitoring
Barbiturates
Not commonly used anymore but used for
- all forms it epilepsy except typical absence seizures
- status epilipticus
It has a risk of suicidal thoughts and behaviour as with all anti epileptics
General side effects
- confusion, depression, drowsiness, movement disorders, resp depression
High risk of NTD and major congenital deformations in pregnancy
Avoid in breastfeeding
Avoid abrupt withdrawal
Griseofulvin
- drug class
- main indications
- side effects and tox
- notable side effects
- monitoring
🍄 Antifungal
Used to treat times pedis, dermatophyte infections of the skin, scalp, hair and nails when topical therapy has failed
👀 AVOID CONTACT WITH EYES +MUCOUS MEMBRANES
Common side effects
- diarrhoea, epigastric discomfort, headache , nausea+ vomiting
🚘 May impair performance of skilled tasks - ie driving,
🍷 increases effects of alcohol
Phenytoin
- drug class
- main indications
- side effects and tox
- notable side effects
- monitoring
Antiepileptics
Typically used for tonic - clonic seizures, and focal seizure
Can be given in status epilepticus - medical emergency - rx IV phenytoin (after giving dextrose, thiamine and lorazepam IV)
🛌 Has a longer half life thus can be given OD at bed time
Risk of NTDS in women
Side effects include
Vitamin D deficiency, electrolyte imbalance , arrhythmias with parenteral use
If the px presents with a rash - discontinue, if the px presents with bradycardia and hypotension - with IV use - reduce the rate of admin.
Oversee sympotms - nystagmus 👀, diplopia 👯♀️, slurred speech, confusion 😵💫, hyperglycaemia 🍫
Monitoring
Plasma phenytoin concentration , blood counts, when used IV - monitor ECG and blood pressure
- vitamin D
St John’s wort
- drug class
- main indications
- side effects and tox
- notable side effects
- monitoring
Herbal medicine 🌱
It may improve subthreshold or mild depression however bc it interacts with so many drugs - its not really recommended
What are CYP enzyme inhibitors ❌
These are drugs that bind to the CYP450 enzyme and inhibit its action, preventing metabolism of the substrate drugs. As a result we get accumulation and toxicity and increased side effects experienced by the px.
What is the pneumonic that we use to remember CYP450 inhibitors ?
SICK FACES. COM G
List all the CYP450 enzyme inhibitor drugs?
Sodium Valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol
Chloramphenicol
Erythromycin and Clarithromycin
Sulfonamide
Ciprofloxacn
Omeprazole
Metronidazole
Grapefruit Juice
Sodium Valproate
- drug class
- main indications
- notable side effects
- contraindication
Antiepileptic
Generally used as an antiepileptics however some brands can be used for mania and migraine prophylaxis.
⚠️ contraindicated in women and girls of childbearing potential unless they have a pregnancy prevention plan - bc it is teratogenic - congenital malformation and neurodevelopemental disorders
Side effects include :
- anaemia, alopecia, confusion, diarrhoea, drowsiness, headache, nausea, vomiting
❌ avoid abrupt withdrawal - reduce dose gradually over at least 4 weeks
Isoniazid
- drug class
- main indications
- notable side effects
Antimycobacterials
Typically used to treat TB in combination with rifampicin ( a CYP inducer!)
Side effects include :
- hepatic disorders, anemia , nerve disorder, gyneacomastia
Px should be told how to recognise liver disorder + should be advised to discontinue treatment if symptoms such as persistent nausea, vomiting, malaise, or jaundice develope
Cimetidine
- drug class
- main indications
- notable side effects
H2 receptor antagonist (like ranitidine :)
Used for a plethora of GIT ulcerations (ie NSAIDs associated, gastric , duodenal)
Common side effects
- constipation, diarrhoea, dizziness, fatigue, headache, myalgia and skin rx
‼️ cimetidine can be sold to the public for adults and kids 16+ provided the packs dont contain >14 days supply , for the symptomatic relief of heartburn, dyspepsia and hyperacidity
Ketoconazole
- drug class
- main indications
- notable side effects
Imidazole antifungal
- can be used for tines pedis, fungal skin infections, and treatment of seborrhoea dermatitis and dandruff , vaginal and vulva candidiasis, prophylaxis of pityriasis versicolor
- can also be used by specialists for endogenous Cushing syndrome
Common side effects - skin reactions,
With oral use - adrenal insufficiency, diarrhoea, gastrointestinal discomfort, nausea and vomiting
Erythromycin and clarithromycin
- drug class
- main indications
- notable side effects
- macrolides
Typically used for infections as 2nd line if px have allergy or are pregnant
Common side effects
- reduced appetite, diarrhoea, dizziness, headache, nausea, vomiting, vision disorders, insomnia
Sulfonamide
- drug class
- example
Bactrin
Ciprofloxacin
- drug class
- main indications
- notable side effects
Fluroquinolone
Antibacterial
Px have reported tendon damage with this drug , essp in px over 60 , those have hx of tendon damage and px on concomitant steroids - avoid
Common or very common side effects
- When used by eye (topical) -> Corneal deposits (reversible after completion of treatment)
- With intravenous use -> Arthropathy (in children)
- With oral use-> Arthropathy (in children)
Omeprazole
- drug class
- main indications
- notable side effects
PPI
Used to treat H pylori in combination with other drugs, and a plethora of GI ulcers , oesophagi tips, dyspepsia, acid reflux
SE
- common ones include abdominal pain, constipation, diarrhoea, dizziness, dry mouth, nausea vomiting, headache and skin rx
Cautions
- risk of osteoporosis and gastric cancer
