Clinical pharmacology + toxicology Flashcards
Features of lithium toxicity?
coarse tremor (a fine tremor is seen in therapeutic levels)
hyperreflexia
acute confusion
polyuria
seizure
coma
Mx of lithium toxicity?
mild-moderate - fluid resus
(monitor Na levels if concern of nephrogenic DI)
severe - haemodialysis may be required
What are some side effects of metformin?
GI side effects
Lactic acidosis
What are some side effects associated with sulphonureas?
Hypoglycaemic episodes
Increased appetite and weight gain
Syndrome of inappropriate ADH secretion
Liver dysfunction (cholestatic)
What are some side effects associated with Glitazones?
Weight gain
Fluid retention + decompensation of HF
Liver dysfunction
Fractures
What are some side effects associated with Gliptins?
Pancreatitis
paraesthesia
visual field defects
hearing loss
irritability
renal tubular acidosis
Suggest what type of poisoning?
Mercury
Which drugs can cause urinary retention?
tricyclic antidepressants e.g. amitriptyline
anticholinergics e.g. antipsychotics, antihistamines
opioids
NSAIDs
disopyramide
Which drugs can cause lung fibrosis?
Amiodarone
Cytotoxic agents - busulphan, bleomycin
anti-rheumatoid drugs - methotrexate, sulfasalazine
Nitrofurantoin
Ergot derived dopamine agonists eg bromocriptine, cabergoline, pergolide
Octreotide MoA
Somatostatin analogue
Blood gas findings in ethylene glycol / methanol poisoning?
Mx?
Raised anion gap metabolic acidosis w high osmolar gap
Use Fomepizole / ethanol - act as competitive inhibitor of alcohol dehydrogenase
Which CCB can cause constipation?
Verapamil
Adverse effects associated with aminoglycoside use? examples? when to avoid?
Aminoglycosides like gentamicin can cause:
Irreversible ototoxicity - due to auditory / vestibular nerve damage
Nephrotoxicity secondary to ATN - using furosemide increases this risk
CI in myasthenia gravis
Examples of Quinolones? When are these CI?
Examples:
ciprofloxacin
levofloxacin
Contraindications:
Quinolones should generally be avoided in women who are pregnant or breastfeeding
avoid in G6PD - can percipitate haemolytic anaemia
Licenced indications of Botox
blepharospasm
hemifacial spasm
focal spasticity including cerebral palsy patients, hand and wrist disability associated with stroke
spasmodic torticollis
severe hyperhidrosis of the axillae
achalasia
Digoxin MoA?
Na/K ATPase pump inhibitor
Class II antiarrhytmic also BBs
Adrenaline doses in cardiac arrest and anaphylaxis?
anaphylaxis: 0.5mg - 0.5ml 1:1,000 IM
cardiac arrest: 1mg - 10ml 1:10,000 IV or 1ml of 1:1000 IV
Tamoxifen MoA?
Adverse effects?
SERM (Selective oEstrogen Receptor Modulator)
menstrual disturbance: vaginal bleeding, amenorrhoea
hot flushes - 3% of patients stop taking tamoxifen due to climacteric side-effects
venous thromboembolism
endometrial cancer (can use Raloxifene - pure oestrogen receptor antagonist - lower risk)
What are phase I and phase II reactions in drug metabolism?
phase I: oxidation, reduction, hydrolysis
phase II: conjugation
TB drug side effects?
Rifampicin = Red/orange body secretions
Isoniazid= Ice causes numbness on the skin = peripheral neuropathy
Pyrazinamide= P looks like a big toe = big painful toe bcz of hyperuricemia = Gout
Ethambutol = Eye = optic neuritis
Metformin MoA?
activation of the AMP-activated protein kinase (AMPK)
-> increased insulin sensitivity, decreased hepatic gluconeogenesis + ?reduced GI absorption of carbs
abciximab MoA? use case?
glycoprotein IIb/IIIa receptor antagonist
used in prevention of ischaemic events in patients undergoing percutaneous coronary interventions
Adverse effects associated with Quinolones? what are some examples?
Examples:
- Levofloxacin
- Ciprofloxacin
Adverse effects:
- Reduces seizure threshold
- Tendon damage inc. rupture
- Cartilage damage in animal models - hence generally avoided in children
- QT prolongation
Abdo pain / rectal bleeding following cocaine ingestion
Diagnosis?
Ischaemic colitis
Aspirin MoA?
Non-reversible COX 1 + 2 inhibitor
MoA of LMWH?
LMWH activates antithrombin III.
This forms a complex that inhibits factor Xa
MoA of Unfractionated heparin?
Unfractionated heparin forms a complex which inhibits thrombin, factors Xa, IXa, XIa and XIIa.
Rituximab MoA? Use?
MAb against CD20 used in R-CHOP regimen for non-hodgkins lymphoma
Also used in RA
Infliximab MoA? use?
Anti-TNFa used in RA and Crohns
Daratumumab MoA? Use?
Anti-CD38 used in multiple myeloma
Alemtuzumab MoA? Use?
Anti-CD52 used in CLL
Trastuzumab (Herceptin) MoA? Use?
Anti-HER2 used in HER2 +ve metastatic breast ca
Class 1a antiarrhytmics and some examples?
Mneumonic
“I am Ambivalent about the QUEEn PROofreading my DISsertation”: Class IA antiarrhythmic drugs are QUEEnidine, PROcainamide, DISopyramide.
These are Na channel blockers
Class 1b antiarrhytmics and some examples?
“LInDO MEXIco Is the Best”: LIDOcaine and MEXIletine are class IB antiarrhythmic drugs.
Also Na channel blockers
Class 1c antiarrhytmics and some examples?
Mneumonic
“I Can’t Fail, Please”: Class IC antiarrhythmics are Flecainide, Propafenone.
Class 3 antiarrhytmics and some examples?
Mneumonic
K channel blockers - prolonging cardiac AP and delays refractory period
“I Am Sober, Doctor, for III days”: Ibutilide, Amiodarone, Sotalol, and Dofetilide are class III antiarrhythmic drugs.
Features of organophosphate poisoning? Mneumonic
SLUDD
s=salivation
l=lacrimation, low BP, low pluse
u= urination
d=defecation
d=diarrhea, decrease pupil size.
Prognostic factors in Paracetamol Overdose
The arterial pH is the single most important prognostic factor ( <7.3 24h post-ingestion)
Others:
- Creatinine >300
- Increased PT time (>100s)
- Grade III or IV encephalopathy
NB these are the indications for liver transplantation (need all 3 others or JUST LOW PH)
MoA of allopurinol?
Allopurinol inhibits xanthine oxidase
(which oxidises 6-mercaptopurine into 6-thiouric acid)
TCA overdose with hypotension / widened QRS / VT
Mx?
IV bicarb
Which drugs commonly interact with CYP450 inhibitors / inducers?
Warfarin the Combined Contraceptive Pill, Theophylline, Corticosteroids, Tricyclics, Pethidine, and Statins.
Which drugs are common CYP450 inducers?
CRAP GPS - generally need prolonged exposure
Carbemazepines (+Phenytoin)
Rifampicin
Alcohol - chronic
Phenytoin
Griseofulvin
Phenobarbitone (Barbiturates)
Sulphonylureas + Smoking + St Johns Wort
Reduced drug concentration
Which drugs are common CYP450 inhibitors? effect?
SICK FACES.COM
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol & Grapefruit juice - acute (Also amiodarone + allopurinol)
Chloramphenicol
Erythromycin
Sulfonamides (SSRIs too)
Ciprofloxacin
Omeprazole
Metronidazole
Increased drug concentration
Drugs which are known to cause impaired glucose tolerance include:
‘STATIN’:
Steroids
Thiazides - Furosemide also but less
Antipsychotics
Tacrolimus/ciclosporin
Interferon-alpha
Nicotinic acid
Pilocarpine MoA?
Muscarinic agonist - M1-3 -> induction of parasympathetic action
Which drugs can cause cataracts?
steroids
Which drugs can cause corneal opacities?
amiodarone
indomethacin
Which drugs can cause optic neuritis?
ethambutol
amiodarone
metronidazole
Which drugs can cause retinopathy?
chloroquine, quinine
What can happen to the eyes with sildenafil?
Blue discolouration
Non-arteritic anterior ischaemic neuropathy
Why can Sodium Bicab be considered in lithium toxicity?
Increases urine alkalinity thus promoting lithium excretion
HTN in Lithium patients?
ACE-i and ARBs can cause toxicity
CCBs - Diltiazem / Verapamil - increase risk of neurotoxicity
Amlodipine is fine
When to give sodium bicarb in mx of TCA overdose?
pH <7.1
widened QRS esp >160 ms
Arrhythmias
Hypotension
Example of a1 antagonist?
doxasosin
Example of a1a agonist?
tamsulosin acts mainly on urogenital tract
Example of a2 antagonist?
yohimbine
example of non-selective a antagonist
phenoxybenzamine - used be used in peripheral arterial disease
Example of b1 antagonist?
Atenolol
Example of non-selective b antagonist?
Propanolol
example of a + b mixed antagonists?
Carvedilol
Labetalol
confusion, headache, and characteristically cherry-pink mucous membranes
Suggestive of what condition?
CO poisoning
How does aspirin achieve antiplatelet effect?
Inhibits the production of thromboxane A2 secondary to irreversible inhibition of COX1
How do ciclosporin and tacrolimus work?
Inhibit calcineurin in T cells thus decreasing IL-2
Mx of organophosphate poisoning?
Atropine
Which drugs commonly cause urticaria?
aspirin
penicillins
NSAIDs
opiates
Which medications are best for motion sickness?
Motion sickness - hyoscine > cyclizine > promethazine
Ketamine MoA?
NMDA receptor antagonist
MoA of finasteride and adverse effects?
Finasteride = 5a reductase inhibitor
Adverse:
>impotence
>decrease libido
>ejaculation disorders
>gynaecomastia and breast tenderness
Disadvantages of POP contraceptive?
irregular periods: some users may not have periods whilst others may have irregular or light periods. This is the most common adverse effect
increased incidence of functional ovarian cysts
common side-effects include breast tenderness, weight gain, acne and headaches. These symptoms generally subside after the first few months
Licensed indications for Botox?
blepharospasm
hemifacial spasm
focal spasticity including cerebral palsy patients, hand and wrist disability associated with stroke
spasmodic torticollis
severe hyperhidrosis of the axillae
achalasia
Management of accidental injection of adrenaline? e.g. resulting in digital ischaemia
Local infiltration of phentolamine
Drugs that most commonly cause urticaria?
aspirin
penicillins
NSAIDs
opiates
Blood gas in mercury poisoning + why?
Hyperchloraemic metabolic acidosis consistent with renal tubular acidosis i
Which abx inhibit protein synthesis by acting on 30s subunit of ribosome?
Aminoglycosides - Gentamicin
Tetracyclines - demeclocycline
Which abx inhibits DNA synthesis?
quinolones (e.g. ciprofloxacin)
MoA of Metronidazole?
Damage DNA
Which abx inhibit folic acid formation
Sulphonamides
trimethoprim
Which endocrine med can cause gallstones secondary to biliary stasis?
Octreotide - somatostatin analogue