4. Drug effects and interactions Flashcards
What is an unwanted drug effect?
Any noxious or unintended reaction when a drug has been given correctly (dose, route, person etc).
What are the three categories we can divide ADR’s into?
- Can happen to anyone: OD (excess dose or impaired secretion), side effects, interactions.
- Susceptible people: intolerance and idiosyncrasy e.g. genetically determined such as sux apnoea.
- Allergies.
What is a pseudo allergy?
One that manifest similarly clinically due to histamine release, but not immune mediated e.g. morphine.
What are the A to F classifications of ADR’s,with examples?
Augmented: dose related e.g. propofol hypotension = dose related
Bizarre: not dose related e.g. Anaphylaxis = dose unrelated
Chronic: dose and time e.g. propofol infusion syndrome = dose and time
Delayed: time related e.g. fluoride nephrotoxicity = time related
End of use: withdrawal e.g. clonidine rebound hypertension = withdrawal
Failure: unexpected failure e.g. the pill = unexpected failure.
What is the DOTS classification of ADR’s?
Dose related: sub therapeutic doses, therapeutic doses and sub in susceptible
Time related: rapid (administered too quickly), first dose (e.g. hypotension with ACEi- may not recur), early (gets better e.g. nitrate headache), intermediate (Coombs 2 to 4), late (e.g. withdrawal) and delayed (e.g. post exposure)
Susceptibility
What are the three different broad categories of drug interactions?
Pharmacodynamic
Pharmacokinetic
Pharmaceutical incompatibility
What are the different types of pharmaceutical incompatibility with examples?
Neutralisation e.g. heparin and protamine
Precipitation: thio and sux
Chelation: sugammadex and roc
Absorption: halothane into rubber. Paraldehyde and plastic (needs glass syringe)
What are the different pharmacokinetic interactions with examples?
Absorption: charcoal and poisoning or prokinetics
Distribution: anything that alters cardiac function e.g. beta blockers make it longer for sux to work
Metabolism: e.g. enzyme inducers
Elimination: e.g. doxapram makes volatiles be eliminated more quickly
What are pharmacodynamic interactions?
What are the different categories with examples?
When drugs have an agonist or antagonist effect on other drugs. Can be direct or indirect.
Summation: additive e.g. nitrous and volatiles
Synergism: paracetamol and opiates
Potentiation: non depolarising NMB and Mg
Antagonism: flumazenil and benzo’s (direct)
What can hyponatraemia do to a commonly used anaesthetic drug?
Potentiate LA’s
What does echinacea do and what interactions does it have?
Modulates cytokines, and stimulates macrophages and NK’s
Avoid with hepatotoxic
What does ephedra do and what interactions does it have?
CNS stimulant, weight loss and asthma treatment as is a sympathomimetic
Caution with others. Log term use can deplete catecholamine stores causing tachyphylaxis. Arrhythmia with halothane
What does garlic do and what interactions does it have?
HTN, hyperlipidaemia and atherosclerosis
Increased bleeding risk
What does ginger do and what interactions does it have?
Anti inflammatory and anti emetic through inhibiting serotonergic pathways and stimulating the GI tract
Risk of bleeding
What does ginko biloba do and what interactions does it have?
Neuroprotective and increased blood flow as is a free radical scavenger with antiplatelet effects
Increased risk of bleeding
What does ginseng do and what interactions does it have?
Mood enhancer / aphrodisiac - sympathomimetic
Risk of bleeding, hypoglycaemia and interactions with other sympathomimetics
What does St John’s wart do and what interactions does it have?
Antidepressant - inhibits MAO and induces CYP3A4 and 2C9
Serotonergic crisis, sedative, reduces effect of: midazolam, alfi, lidocaine, warfarin and NSAIDs
What does valerian do and what interactions does it have?
Anxiolysis by potentiating GABA
Reduced anaesthetic requirement
What is a drug?
An exogenous substance that alters a physiological system.
What are the 6 kinds of non-specific Physiochemical reactions of a drug?
Examples of each
Adsorption = charcoal and paracetamol
Bonding = covalent etc.
Chelation = O, N or S make coordinate bonds with heavy metals
Neutralisation = sodium citrate or protamine and heparin
Osmotic = mannitol
Radio opacity = contrast
What is a ligand?
Chemical messenger with the ability to bind to a receptor
What is a receptor?
An area of a tissue, molecule or membrane which responds specifically to the binding of a ligand
What are the two main categories of drug receptors?
Membrane and nuclear
What are the three main types of membrane drug receptors?
GCPR’s
Enzyme linked
Channels
What is a g coupled protein receptor?
How are they activated?
How many drugs use these? Examples?
Membrane receptor with an intracellular and extracellular binding domain, with 7 transmembrane proteins.
G protein = alpha, beta and gamma subunits
Activated via association of alpha subunit triggering a secondary messenger.
50% of drugs use them e.g. atropine, or phone and salbutamol.
What is the basic make up of enzyme linked membrane receptors?
Extracellular ligand binding domain
Transmembrane amino acids
Intracellular active enzyme domain - usually kinases.
What type of receptors do anaesthetic agents predominantly target?
Channels
What are the the main types of membrane channels and examples of some others?
Voltage gated or ligand gated e.g. nicotinic.
Aquaporin and CFTR etc.
What are the two different types of nuclear receptor?
Type 1 =ligand binds to cytosol receptor
Type 2 = ligand binds directly to DNA
What is drug tolerance?
Reduced response to a drug after repeated or prolonged exposure (reduced potency)
- reversed with a holiday
- toxic dose can stay the same
What are the different types of drug tolerance?
Innate e.g. in high BMI or genetics
Acquired:
- pharmacodynamic = e.g. receptor down regulation
- kinetic e.g. alcohol enzyme induction
- behavioural e.g. opiates
Cross tolerance: resistance to one drug, reduces effect of another e.g. heroin and methadone.
What is tachyphylaxis?
Hyper acute drug tolerance e.g. hydralazine or ephedrine.
- can happen after first dose.
What happens in nitrate tolerance?
Lack of vasodilation due to tolerance to NO.
What is inversely drug tolerance?
Sensitisation, where taking the drug heightens the effect over time
