Pharmacokinetics Flashcards
What is pharmacokinetics?
What the BODY does to the drug
What is pharmacodynamics?
What DRUGS do to the body. How drugs work
4 stages for how a drug targets pain for pain relief
- Take drug
- Enters GI system
- Absorbed into blood stream
- Goes around body into all tissues
How does lignocaine work in regards to providing local anaesthesia?
It blocks voltage gated Na+ channels on nerve cell axons.
Sodium & potassium channels are responsible for A.P & muscle potentials. Therefore by giving small amount into local tissue, AP can’t occur so the area becomes paralysed = causes local anaesthesia
What is the effect of giving large doses of lignocaine?
It stops AP in many tissues, e.g. in heart muscle cell membranes = stops propagation of heart. CARDIAC TOXIC
Why can lignocaine be used to treat some tachyarrhymias?
Lidocaine preferentially Indus to depolarised membranes.
Ischemic myocardium tends to be partially depolarised & excitable = causing eptopic beats
Why is lignocaine concentration dependent?
A high plasma concentration of lignocaine will cause electrical activity to cease everywhere
What does this mean?
[lignocaine]plasma
Plasma concentration of lignocaine
What’s the difference between a drug & poison?
Dose
Pharmacology is based on WHAT equation?
D+R=DR
Drug (ligand) + receptor = ligand-receptor complex
What affects the effect of a drug?
- the plasma concentration
- the concentration of the drug
- number of receptors which are bound to the drug
- the interaction of the drug with the receptor
What is an agonist?
A drug which binds to a receptor & switches it on
Define therapeutic index
Therapeutic index = toxic dose (mg)/therapeutic dose
Name 2 drugs that have a NARROW therapeutic range
Warfarin digoxin Lithium Phenytoin Carbamazepine
What does ED50 mean?
Effective dose in 50% of population
What does LD50 mean?
Lethal dose in 50% of population
What does Emax mean?
Dose that produces the maximal response of a drug
What happens if a drug is given to someone in shock?
E.g. if adrenaline or morphine is given to someone in shock, then the drug can sit in the tissue & not be flushed away if their peripherals are shut down
What are the 4 areas of pharmacokinetics that determines what happens to a drug in vivo?
Absorption, distribution, metabolism & excretion
Factors affecting tissue drug concentrations
Dose- amount & rate
Absorption - route of administration, solubility, physical form
Elimination- renal &hepatic clearance, interactions
Which enzyme in the liver chemically changes drugs?
Cytochrome oxidase P450
Define enzyme inhibition
When a drug inhibits an enzyme to prevent the breakdown of another drug
Define enzyme induction
When one drug potentates the clearance of another
E.g. ethanol enhances the enzyme which metabolises warfarin
Define equation for clearance
Rate of elimination (mgmin-1) = clearance (Ctotal) . [D]plasma
C total = C renal + C hepatic
Define plasma half-life
The time taken for plasma concentration to drop by half
What’s an important thing to note with half life in regards to agonists & antagonists
Have DIFFERENT half life’s
E.g. opiate = 2-4h
Narcan = 30min
What does F stand for? Define it
Bioavailability. It’s the amount of a substance that enters the circulation that has an active effect
F = amount administered / amount absorbed
What a pro drug. Give 2 examples
Drug which is taken into the body in an inactive form & metabolised into an active form.
E.g. diamorphine & diazepam
What’s the effect of a drug being highly protein bound?
Takes a long time to break down (long half life)
E.g. diazepam & Amiodarone
What is the elimination rate constant (Kel)
The fraction of a drug present at any time that would be eliminated in unit of time.
Kel = 0.69 / t
E.g. if Kel = 0.02min -1 (means 2% of drug present is eliminated in 1 min)
Volume of distribution equation
VD (volume of distribution) = dose / Co (initial plasma concentration)
How does drug metabolism effect drug solubility
It makes the drug more hydrophilic. This speeds up excretion rate of kidneys, as less soluble metabolite is not readily reabsorbed in the renal tubes.
What are the 5 factors affecting drug metabolism?
Enzyme inhibition Enzyme induction Age Genetic polymorphisms Metabolism & drug toxicity (e.g paracetamol at high doses becomes saturated & conjugated with glutathione. If the glutathione depletes, a reactive & lethal hepatotoxic metabolite accumulates)
What is first mass metabolism
Involves how much of the drug is metabolised by the liver, the first time the drug molecules pass through, before it enters the circulation.
E.g. aspirin, GTN, levodopa, morphine, metoprolol, salbutamol & verapamil
What’s the plasma volume in body for adults
70ml per kg
What’s the plasma volume in body for paediatrics <12
80ml per kg
What are the 3 factors affecting absorption?
- Physiochemical factors
- chemical properties (lipid solubility of drug)
- physical form - Metabolism
- some drugs are activated by metabolism or have active metabolites
- total surface area for absorption - Compartments
- solubility
- ionic property’s- strong alkaline drugs poorly absorbed in stomach, BBB
What does parental admission mean?
Non GI route
What administration routes avoid the portal circulation?
SL, PR
What angle does IM & SC injections go into skin at?
IM = 90 o SC = 45 o
Where does most of the absorbtion take place & why?
In the small intestine. This is because it has a larger surface area compared to stomach
If a drug is weakly acidic where will it ionise? Give an example
A weakly acidic drug will ionise in a basic environment e.g. small intestine & NOT in an acid environment such as stomach.
E.g. aspirin, won’t ionise in stomach -so will be absorbed through stomach mucosa
Where will a basic drug ionise? Give an example.
A basic drug will ionise in the stomach, but become uncharged in the small intestine.
E.g. morphine is a basic drug. It will ionise in stomach & so will not be readily absorbed there. In morphine will then become un-ionised in the small intestine so can be absorbed more rapidly.
Is absorption faster or slower in the small intestine compared to the stomach?
Slower
Give an example of 2 drugs that require a carrier system within there body because they are very similar to biological molecules?
Levodopa (Parkinson’s) & levothyroxine (hormone produced in thyroid gland)
The drug concentration in the intestine depends on?
- amount of drug ingested
- rate in which drug is released from the formulation
- volume of GI contents with which its mixed
Why is it recommended to take antibiotics an hour before food?
Because drugs are absorbed more quickly if the stomach & small intestine are empty.
Other factors affecting drug absorption?
- interactions with other drugs that inhibit gastric emptying e.g. atropine, morphine - may reduce absorption of other drugs
- diseases of Gi system e.g. ulcerative colitis
- the longer the medication is in the gut the more of it that will be absorbed. If there is excessive peristalsis i.e. diarrhoea, the drug won’t have time to be absorbed
- ileostomy effects absorbtion especially if the drug has an enteric coating
What is the bioavailability of amoxicillin?
90%
What is the bioavailability of digoxin?
70%
Some drugs bind to plasma proteins in the blood. What do acidic and basic drugs bind to?
Acidic drugs usually bind to albumin. Plasma proteins don’t usually leave bloodstream. So drug won’t reach the tissues
Basic drugs bind to some globulins
What happens when free drug leaves the bloodstream?
More bound drug will be released from plasma protein to maintain equilibrium. The stronger a drug binds to plasma protein, the less free drug will be available = drug remains in plasma longer.
What happens if aspirin & warfarin are administered together?
Both drugs bind to same site on the plasma protein. Aspirin can displace some of warfarin from its binding sites = raise the free concentration of warfarin. Warfarin is highly toxic = dangerous
Why would there be a deficiency of plasma proteins, and what would it’s affect be?
Severe malnutrition , burns or liver disease can cause a deficiency of plasma proteins. As a result this may raise concentration of free drug available = enhance its effects.
When a drug is administered orally, where does it go before it reaches the target tissue?
Enters GI tract, leaves GI tract via hepatic portal vein, enters liver (most drugs are heavily metabolised here) & then reaches target tissue
Why can’t GTN be given orally?
96% of drug is destroyed the first time it passes through the liver
Why is part of the vomiting centre NOT protected by brain?
Protective mechanism. It enables toxic substances to cause vomiting before they reach the brain
The volume distribution is LARGER if the drug is more widely distributed in the body. Where does digoxin concentrate?
Digoxin concentrates is muscle tissue. This means the dose to produce the correct therapeutic level in the plasma varies according to the patients muscle mass.
What are the 2 phases of drug metabolism?
Phase 1 reactions- oxidation, reduction or hydrolysis reactions that usually increase water solubility.
Phase 2 reactions- involve the attachment of a chemical group to the molecule & facilitate excretion from body usually by increasing water solubility.
Give an example of an enzyme inducer?
Omeprazole
Why is drink driving tested using a breathalyser?
Alcohol is excreted by the lungs
What is first order kinetics?
When the rate of elimination depends on how much drug is present, higher when there is more drug in plasma.
What is zero order kinetics?
When the rate of elimination of the drug is constant and is independent of the drug concentration
How can a person be over the limit of blood alcohol concentration the morning after a heavy night of drinking in relation to order kinetics?
Alcohol follows first order kinetics at low concentrations.
If the concentration of alcohol increases, the liver enzyme that metabolised alcohol is saturated & elimination of drug follows zero-order kinetics.
