Module One: Clinical Pharmacology Flashcards
Therapeutics
Right drug and dose for the right patient
Clinical toxicology
Identifying poisons in clinical and forensic cases (via clinical manifestations, measurable indices)
Clinical drug trials
Testing drugs in man
Drug regulation
Drug choices for nation, hospitals and practitioner
The link between drug dose and drug level is dependent on:
Patient: age, sex, size, history of drug response Genetics: Pk and response Disease: elimination and target organs Other therapies: interactions Therapeutic drug monitoring Drug effect Pk and PD
Rationale for TDM
Pk variability
Narrow therapeutic range
Response itself is difficult to quantify
What’s the definition for therapeutic range?
Concentration range where efficacy without toxicity maybe expected in most patients
Drugs with narrow therapeutic range, where response is difficult to quantify clinically
Digoxin Cyclosporine, sirolimus, tacrolimus Anticonvulsant drugs Lithium Amino glycoside antibiotics Methotrexate
What does the AUC estimate?
Target organ exposure - steady state
What are drugs that follow non-linear pharmacokinetics?
Perhexiline, phenytoin, alcohol
How to calculate drug dose for renal impairment?
Dose = clearance x AUC
How is clearance measured?
Measure the amount of creatinine in the blood plasma and urine
CLcr (L/hr)= amount excreted (uMol/hr) / serum concentration (uMol/L)
Examples of phase one reactions
Oxidation, hydroxylation, deamination, dealkylation, hydrolysis
Examples of phase II reactions
Conjugation- mainly glucuronidation or sulphate
Excess 6-thioGTP causes what
Neutropaenia
Warfarin is a competitive antagonist for
Vitamin K for VKORC1
VKORC1 is polymorphic. What are the consequences of different sensitisation to warfarin?
Too little anticoagulation: blood clots forms in circulation, embolism and lethal
Too much: bleeding, may be lethal in brain or other critical area
What are the three VKORC1 polymorphisms?
Changes number of VKORC1 transcribed
1639GG: less sensitive needs larger dose
1639GA: intermediate sensitivity
1639AA: more sensitive, smaller dose
What is the second warfarin metabolism polymorphism?
CYP2C9:
1/1: rapid metaboliser
1/(2/3): intermediate metaboliser
2/3* / 2/3: poor metaboliser
Symptoms of stimulant (amphetamine, cocaine etc.) toxicity
Tachycardia, hypertension, agitation, dilated pupils, seizures
Symptoms of opioids (heroin, morphine etc.) overdose?
Drowsy => coma, hypo ventilation, miosis (tiny pupils)
Symptoms of sedative (benzodiazepines, ethanol etc.) overdose?
Drowsy: coma, staggering, slurred speech, hypo ventilation
Symptoms of cholinesterase inhibitor (organophosphate insecticide) poisoning?
Bradycardia, bronchconstriction, small pupils, sweating
Symptoms of antimuscarinic (TCA, deadly nightshade) poisoning
Tachycardia, vasodilation, pyrexia, dilated pupils (e.g. Atropine)
