Drug metabolism Flashcards
What is the best way for lipid soluble drugs to be taken?
Better absorbed when taken orally
What affects absorption?
Route
Lipid solubility
Gastric acidity
What is distribution affected by?
Lipid solubility: Rapidly move out of blood into fat/lipids (e.g propofol)
Protein binding: Many drugs bind to albumin and become inactive
What is the equation for volume of distribution?
Vd = total amount of drugs in body/ drug plasma conc
What are the phases of metabolism?
Phase 1: Add polar group (-OH), makes drug more reactive
Phase 2: Additional molecules added to make drug more soluble to kidneys
What important enzyme is used in phase 1 metabolism?
Cytochrome P450
What is a pro drug? Give an example
Drug given is inactive but becomes active substance when it undergoes metabolism
Codeine metabolised to morphine in phase 1 metabolism
Give examples of enzyme inducers
Phenytoin
Carbamazepine
Rifampicin
ETOH
Barbituates
Sulphonylureas
Give examples of enzyme inhibitors
Cimetidine
Amiodarone
Allopurinol
Ketoconazole
Erythromycin
Valproate
What is first pass metabolism?
Oral drugs are absorbed in the gut and all pass through the liver
If >60% is removed then drug has high 1st pass metabolism
E.g: Morphine, propranolol, Diazepam, lidocaine, nitroglycerin
How are drugs eliminated?
Hepatic - in faeces but usually in bile
Renal
What is First order kinetics?
Most drugs
However much of the drug is in the body a fixed amount is metabolised over a fixed period of time
E.g 1/2 life is the same regardless of the amount in the body
What is zero order kinetics?
Limited amount of enzyme, when that enzyme is saturated no more metabolism can happen
E.g ETOH is metabolised at 1 unit per hour if you have 3 units they will still only be metabolised at 1unit per hour
E.g ETOH, phenytoin
When is a steady state of a drug reached?
Usually 5 1/2 lives of the drug with regular dosing
E.g paracetamol 1/2 life = 2hours so steady state will be reached 2x5=10hours
When is a loading dose given?
Drugs who’s steady state time will take too long to reach
E.g Digoxin 1/2 life is 40hours so steady state would take 1 week
What determines the loading dose quantity?
- Desired peak conc (conc)
- Vol of distribution (Vol)
Dose = Conc x Vol
How do alginates work?
Float on top of the stomach acid so the drug is refluxed not the acid
How do the different types of laxatives work?
Bulking: Fibre (Fybogel)
Stimulant: Senna, bisacodyl
Osmotic: Lactulose
What does infliximab work on?
TNF
What drugs are used to treat malaria?
Quinine: 1st line for Falciparum
Chloroquine: 1st line for Vivax
Malarone: Alt for Falciparum
Primaquine: Vivid/Ovale (needed to be check for G6PD levels)
What are the SE of COX-2 inhibitors?
Inc thrombotic risk in COX-2 selective agents (Naproxen) = double risk of MI
General: Peptic ulcer, HF, asthma exacerbation, interstitial nephritis
What are the SE of Thiopental?
Rapid recovery from small doses but prolonged in large doses
Cardioresp depression
What are the SE of Etomidate?
Suppresses adrenal function- may need steroids afterwards
Avoid in sepsis
Minimal HypoT
What are the effects of Propofol?
Loss of airway
Hypotension
Bradycardia
Allergic reaction
Pain on injection
What are the effects of Ketamine?
Dissociative anaesthetic - higher function maintained e.g BP & airway
Bronchodilation (useful in asthma)
Inc Salivation which can cause laryngospasm
Emergence phenomena in adults
How do induction agents act on BP?
Prop: Big drop
Thio: Drop
Ket: Inc
Etom: Normal
How do induction agents act on CO?
Prop: Big drop
Thio: Drop
Ket: Inc
Etom: Normal/drop
How do induction agents act on HR?
Prop: Drop/norm
Thio: Inc
Ket: Inc
Etom: Normal
How do induction agents act on SVR?
Prop: Drop
Thio: Drop
Ket: Inc
Etom: Normal/drop
How do induction agents act on ICP?
Prop: Drop
Thio: Drop
Ket: Inc
Etom: Normal
How do neuromuscular blocking agents work?
Antagonises acetylcholine receptors
Non-depolarising: Atracurium.
Depolarising: Suxamethonium
Who should Suxamethonium be avoided in?
Fhx of malignant hyperthermia
Hyperkalaemia
Recent major trauma/burns
Causes painful fasciculations so should be given after anaesthetic
What are the max doses of the different LAs?
Lidocaine: 3mg/kg
Lidocaine w/adrenaline: 7mg/kg
Bupiv: 2mg/kg
Prilocaine: 7mg/kg
What are the max doses of the different LAs?
Lidocaine: 3mg/kg
Lidocaine w/adrenaline: 7mg/kg
Bupiv: 2mg/kg
Prilocaine: 7mg/kg
