General principles Flashcards
(20 cards)
Describe the ideal drug? (Induction agent etc.)
When considering the ideal agent we can categories factors into physical or pharmaceutical properties.
Physical:
- cheap and easy to produce.
- long shelf life and easy storage as doesn’t degrade when subjected to changes in light or temperature.
- Water soluble and stable in solution, therefore making it easier to handle as does not require reconstitution
Pharmaceutical can be broken down into PK or PD
PK describes how the body handles a substance I.e. the ADME
- rapid onset and offset
- no accumulation with infusion or repeated boluses
- completely metabolised to inactive substances therefore safe in liver and renal impairment
PD: how a drug effects the body
- painless injection and safe in extravasation/arterial injection
- have no physiological effects except the intended use of the drug e.g. anti hypertensives
- no allergy or histamine release causing bronchospasm etc.
- no unpleasant emergence phenomena
+/- other helpful e.g. analgesia, anxiolysis
What are drug interactions and how are they classified?
A drug interaction is when one drug modifies the action of another, usually increasing or decreasing the effect.
Classified as Physiochemical, pharmacokinetic and pharmacodynamic.
Physiochemical are due to the physical properties of the drugs themselves.
Examples are:
- precipitation e.g. thio (WA) and sux (WB)
- Adsorption e.g. halothane and rubber
- neutralisation e.g. heparin and protamine
- chelation e.g. sugammadex and rocuronium
PK:
A: adrenaline and LA’s
D: aspirin and warfarin (increased)
M: phenytoin, carbamazepine, rifampicin are inducers = accelerate breakdown of others. Omeprazole, metronidazole and ciprofloxacin are inhibitors.
E: alkalinization of urine increases aspirin excretion
PD:
Potentiation: one drug which has no independent action of its own can increase the action of another e.g. probenicid increasing penicillin (compete for the same receptor)
Antagonism: morphine and naloxone
Synergism: combined action more than sum e.g. propofol and remi
Summation: additive effect e.g. nitrous and volatiles
What is ED 50?
ED50 is the dose of a drug required to produce 50% of its maximal effect, or the dose of a drug that will produce a specified effect in 50% of the
sample population.
What is EC50?
EC50 is the serum concentration of a drug required to produce 50% of its maximal effect, or the concentration of a drug that will produce a specified effect in 50% of the sample population.
What is LD50?
LD50 is the dose of a drug required to produce a lethal effect in 50% of the sample population.
How do we calculate the therapeutic ratio of a drug?
Therapeutic Ratio = LD50/ED50
What is drug potency?
Potency describes the dose of drug required to produce a response of a given magnitude. A drug with a high potency requires a smaller dose than one of low potency to produce the same effect. Usually, the more lipid soluble a drug, the greater is its potency.
Potency’s are compared using ED50
How can drug manufacturers alter the rate of absorption of a drug?
Change its particle size - bigger absorb more slowly
Enteric coating - to stop it being absorbed in the stomach
Use different compounds e.g. MR
What are some basic drugs?
Some acidic?
Basic: opiates, LA’s, BDZ’s, ketamine and etomidate
Acidic: aspirin, atropine, furosemide, paracetamol and propofol
Give examples of drugs that go through phase one metabolism (HOR)?
Hydrolysis = usually esters of amines and done by enzymes throughout the body e.g. plasma cholinesterases.
- drugs = remifentanil, suxamethonium
O: most common phase 1 e.g. paracetamol and BDZ
R: prednisolone
What are some common drugs that undergo phase 2 metabolism?
Gluc = propofol and morphine
Glutathione conjugation e.g. paracetamol
Acetylation: hydralazine and isoniazid
What drugs can damage the liver?
Most common in UK = ethanol = direct and metabolic damage through production of free radicals. Hepatitis then stimulates the immune system to create autoantibodies which can cause cirrhosis.
Halothane = reversible transmainitis, but in susceptible = the TFA’s produced during metabolism (which bind to cells) cause autoantibodies which can cause centrilobar necrosis and hepatitis.
Paracetamol =
How can liver disease affect the drugs we use in anaesthesia?
Cirrhosis can reduce hepatic flow, altering metabolism of flow dependent drugs increase BA
Impaired albumin alters protein binding
Ascites increases VD
Reduced metabolic function
Impaired coagulation me and neuroaxial might be contraindicated
What are the two main plasma proteins that drugs bind to?
Albumin binds acidic as is a weak base
Alpha-1-acid glycoprotein binds bases
What drugs have protein binding over 90%?
BDZ, NSAIDS, warfarin and phenytoin
How are hepatic metabolism and renal excretion coupled and what drugs may accumulate and why?
Hepatic phase 2 metabolism generally makes drugs more water soluble and therefore ready for excretion.
In the kidney, phase 1 metabolites and parent drugs are actively reabsorbed in the tubules, whereas phase are excreted.
Some parent drugs are excreted prior to detoxification so can be toxic in accumulation e.g. gentamicin, furosemide and sotalol.
Describe the three main stages of how drugs are handled by the kidney?
Glomerular filtration: of low molecular weight drugs (under 60k Da, not heparin) that are not PB (not propofol etc.).
Active proximal tubule excretion: carrier mediated (ones for acid/base) and dictated by RBF (80% escapes GF e.g. penicillin and ACE). Can be secreted against there concentration gradient.
Passive distal tubule reabsorption: concentration increases as water reabsorbed along tubule. Lipid soluble reabsorbed, so changed in pH can alter this.
How does age affect renal drug metabolism?
What drugs does this affect?
Old:
- decreased GFR and kidney tissue (less glomeruli) and reduction an arteriolar tone.
- decreases yearly after age 40.
- cr normal stays the same as muscle mass falls.
- blood flow declines about 10% per decade over 40
Systemic in old:
- reduced CO and increased BP
- reduced vasodilation and increased vasoconstriction
Opiates, NMB’s, diuretics and the cin antibiotics
What is a receptor and a ligand?
Receptors are proteins, usually found in cell membranes that have ligand binding sites.
Ligand = any substance that can bind to receptor and bring about an effect
What are the main mechanisms of receptor action, with examples?
Altered ion permeability e.g. ACH receptor allowing Na influx
Activation of intermediate secondary messengers e.g.cAMP, cGMP and DAG. This causes signal transduction and amplification
Regulation of gene transcription: e.g. steroid or thyroid hormones
