PHY Flashcards
Pharmacokinetics
Pharmacodynamics
Pharmacokinetics: what the body does to the drug
Pharmacodynamics: what the drug does to the body
Clearance
Volume of plasma cleared of a drug per unit time
Half-life
Time taken for drug concentration to decline to half its original value.
Depends on volume of distribution and clearance
Volume of Distribution
Volume into which a drug appears to distribute.
High for lipid-soluble drugs
Low for water soluble drugs
First Order Kinetics
Clearance of drug is always proportional to plasma concentration.
Most drugs are in this category
Zero Order Kinetics
Clearance of drug not always proportional to plasma concentration.
Saturation of metabolism → constant rate of elimination regardless of plasma levels.
E.g. phenytoin, salicylates, ethanol
Bioavailability
Percentage of the dose of a drug which reaches the systemic circulation.
100% for IV administration
Multiple Dosing
If a drug given at intervals the concentration will reach a steady state in ~ 5 half-lives.
Loading dose: ↓ time needed to reach a steady state.
Useful if long or short half life.
Phenytoin, digoxin, amiodarone, theophylline
Therapeutic Drug Monitoring
Indicated when lack of drug efficacy, possibility of poor compliance, suspected toxicity, or prevention of toxicity.
Aminoglycosides (essential) Vancomycin (essential) Li (essential) Phenytoin Carbamazepine Digoxin Ciclosporin Theophylline
First Pass Metabolism
Metabolism and inactivation of a drug before it reaches the systemic circulation.
i.e. pre-systemic elimination
Occurs in gut wall and liver
E.g. propranolol, verapamil, morphine, nitrates
Pathways of Drug Metabolism and Elimination
Excrete unchanged by the kidney (e.g. furosemide)
Phase 1 metabolism then renal excretion
Phase 2 metabolism then renal excretion
Phase 1 Metabolism
Creation of reactive, polar functional groups
- Oxidation: usually by CyP450 system
- Reduction and hydrolysis
Phase 2 Metabolism
Production of polar compounds for renal elimination
Either the drug or its phase 1 metabolite
- Conjugation reactions
- Glucuronidation, sulfonation, acetylation, methyl
Cytochrome P450 System
Most important system of phase 1 metabolism
> 11 subtypes
CyP3A4
- Most important subtype
- ≥ 30% of drugs: CCBs, β-B, statins, benzos
CyP2D6
- Second most important
- ≥20% of drugs: antidepressants, some β-B,
opiates
List of pro-drugs.
L-Dopa → dopamine
Enalapril → enalaprilat
Ezetimibe → ez-glucuronide
Methyldopa → α-methylnorepinephrine
Azathioprine → 6-mercaptopurine (by XO)
Carbimazole → methimazole
Cyclophosphamide
Adverse drug reactions (ADR)
Type A
- Common, predictable reactions
- Dose-related (but may occur @ therapeutic doses)
- Consequence of known pharmacology of the drug
Type B
- Rare, idiosyncratic reactions
- Usually not dose-related
- E.g. allergies and pharmacogenetic variations
Long-Term ADR
- Dependence, addiction
- Withdrawal phenomena
- Adaptive changes: e.g. tardive dyskinesia
Delayed ADR
- Carcinogenesis
- Teratogenesis
4 types of allergies
Type 1: anaphylaxis
- Penicillins, contrast media
Type 2: cytotoxic antibodies
- E.g. causing haemolysis
- Penicillins, cephalosporins, oral hypoglycemics
- Methyldopa
Type 3: immune complexes
- Serum sickness-like reaction
- Penicillins, sulphonamides
Type 4: cell-mediated
- Contact dermatitis
- Topical abx
- Antihistamine cream
ADR caused by the following?
- Carbamazepine
- Cyclophosphamide
- Chlorpropamide
- SSRIs
- TCAs
SIADH
ADR caused by the following?
- Spironolactone
- Digoxin
- Verapamil
- Cimetidine
- Metronidazole
Gynaecomastia
ADR caused by the following?
- Bleomycin
- Busulfan
- Amiodarone
- Nitrofurantoin
- Sulfasalazine
- Methotrexate
- Methysergide
Pulmonary Fibrosis
ADR caused by the following?
- Isonazid
- Vincristine
- Amiodarone
- Nitrofurantoin
- Penicillamine
Peripheral Neuropathy
Drugs that increase QTc
- Fluoroquinolones: cipro
- Venlafaxine
- Neuroleptics: phenothiazines, haldol
- Macrolides
- Anti-arrhythmics 1a/III: quinidine, amiodarone, sotalol
- TCAs
- Histamine antagonists
ADR caused by the following?
- Clavulanic acid: may be delayed
- Fluclox: may be delayed
- Erythromycin
- Sulfonylureas (glibenclamide)
- OCP
- Tricyclics
- Chlorpromazine, prochlorperazine
Cholestasis: decrease in bile flow
Which drugs cause hepatocellular damage?
- Paracetamol
- Valproate, phenytoin, carbamazepine
- Halothane
- Methotrexate
- Statins
- Rifampicin, isoniazid, pyrazinamide
Drugs that cause bone marrow toxicity
Pancytopenia /aplastic anaemia:
- Cytotoxics
- Phenytoin
- Chloramphenicol
- Penicillamine
- Phenothiazines
- Methyldopa
Neutropenia:
- Carbamazepine
- Carbimazole
- Clozapine
- Sulfasalazine
Thrombocytopenia:
- Valproate
- Salicylates
- Chloroquine
Extrapyramidal side effects are caused by?
Parkinsonism
Acute dystonia
Akathisia
Tardive dyskinesia
Typical antipsychotics
Rarely: metoclopramide, prochlorperazine
Esp. in young women
Dyskinesias and dystonias are common with anti-
parkinsonian drugs.
Mechanism:
- D2 block in the nigrostriatal pathway
- Excess AChM (hence effect of anti-AChM)
Parkinsonism
- Occurs w/i months
- Commoner in the elderly
- Bradykinesia tremor, rigidity
Treatment:
- Procyclidine (anti-AChM)
Acute Dystonia
- Occurs w/i hrs-days of starting drugs
- Commoner in young males
- Involuntary sustained muscle spasm
- E.g. lock jaw, spasmodic torticollis, oculogyric crisis
Treatment:
- Procyclidine
Akathisia
- Occurs w/i days-months
- Subjective feeling of inner restlessness
Treatment:
- Propranolol (crosses BBB)
Tardive dyskinesia
Rhythmic involuntary movements of head, limbs and trunk.
- Chewing, grimacing
- Protruding, darting tongue
- Occur in 20% of those on long-term neuroleptics (yrs)
Treatment:
- Switch → atypical neuroleptic
- Clozapine may help
- (procyclidine worsens symptoms)
Indirect drug interactions
Diuretics and steroids → Increase risk of digoxin toxicity via low K+
NSAIDs + warfarin → Increased risk of GI bleed
Abx + warfarin → Increase bleeding risk (Abx kill GI microflora that make vit K)
P450 Inducers
Mnemonic: CRAP GPS
- Carbamazepine
- Rifampicin
- Alcohol (chronic)
- Phenytoin
- Griseofulvin
- Phenobarbital
- St. John’s Wort
Important Drugs Metabolised by P450
- Ciclosporin
- Oral contraceptive pill
- Warfarin
- Epileptic drugs: phenytoin, CBZ
- Statins
- Theophylline
P450 Inhibitors
Google SICKFACE .COM
- Grapefruit juice
- Sodium valproate
- Isoniazid
- Cimetidine
- Ketoconazole
- Fluconazole
- Alcohol (binge)
- Ciprofloxacin
- Erythromycin/Clarithromycin
- Chloramphenicol
- Omeprazole
- Metronidazole
Extrapyramidal side effects list
Akinesia - finding it hard to start a movement
Akathisia - finding it hard to keep still, and with
‘an inner feeling of restlessness’
Dyskinesia – unusual movements or twitches
(usually of the face) that may keep on
repeating themselves
Oculogyric crisis – unusual eye movements,
most commonly with the eyes turning upwards
Parkinsonism – some of the symptoms look like
someone with Parkinson’s disease e.g. tremor
or stiffness
