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Clinical Pharmacology in Y3 Medicine
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Clinical pharmacology covering lectures on P450 system, inhibitors/inducers and other important interactions.
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[C2C]Clinical Pharmacology
Pharmacodynamics – what the drug does to the BODY.
Pharmacokinetics – what the body does to the DRUG.
Drugs work via enzymes or receptors (agonists/antagonists).
HTN drugs:
β-blockers – atenolol, bisoprolol.
CCBs – amlodipine, diltiazem.
ACEis – ramipril, lisinopril.
Thiazide diuretics – bendroflumethiazide,
indapamide.
Pharmacodynamic interactions – occur when 2 drugs work diff pathways to affect the same
outcome. E.g. digoxin + β-blockers.
When prescribing, don’t prescribe 2 drugs of the same class e.g. atenolol and bisoprolol in HTN.
Use 2 diff classes of drugs to treat.
Effective dose of paracetamol is 10mg.
The patient with AF and HTN should be treated with atenolol alone (↓ BP + HR) as opposed to
atenolol + digoxin (↓ HR). This prevents patient collapsing from excessive ↓ in HR.
Therapeutic index:
Effect that a drug has on body is dependent on dose.
Not all drugs have a linear relationship between dose and effect.
Some drugs have narrow TI – if dose low, no effect; if dose high, toxic.
Phenytoin at high levels can lead to ataxia.
Pharmacokinetics:
ABSORPTION:
o How drug gets into system.
o E.g. oral, IV, IM, SC, intra-articular, intra-ocular.
DISTRIBUTION:
o Some drugs lipophilic – distributed around whole body.
o Some drugs hydrophilic – stay in plasma.
METABOLISM:
o Takes place in liver via series of enzymatic processes.
o P450 system causes most pharmacokinetic drug interactions.
Warfarin, theophylline, carbamazepine, phenytoin, OCP affected by P450.
P450 inducers (↓ drug efficacy): P450 inhibitors (may lead to
toxicity):
Carbamazepine. Erythromycin/clarithromycin.
Phenytoin. Ciprofloxacin.
Rifampicin ( red body fluids). Miconazole.
Chronic alc intake. Sodium valproate.
Barbecued meat. Grapefruit juice.
St. John’s Wort. Cranberry juice.
ELIMINATION:
o Some lipophilic drugs are metabolised into active metabolites e.g. opioids.
May accumulate in renal F.
o Hydrophilic drugs are excreted unchanged e.g. digoxin.
Steady state – attained after ~ 4 half-lives. Time to steady state independent of dosage.
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