Pharmacology Flashcards
Define adverse drug reactions (ADRs)
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug.
What is the key difference between side effects and ADRs
Side effects can have unintended effects which are beneficial whereas ADRs are never beneficial
What is the Rawlins Thompson (RT) system for ADRs (ABCDEs)
Augmented
Bizarre
Chronic use
Delayed
End of use
RT: Explain a type A ADR and give an example
Common, predictable and dose dependent
e.g morphine and constipation
RT: Explain a type B ADR and give an example
Not predictable and not dose dependent
e.g. anaphylaxis ad penicillin
RT: Explain a type C ADR and give an example
Long term use
e.g. osteoporosis and steroids
RT: Explain a type D ADR and give an example
Uncommon, usually dose related, show itself some time after use of drug
e.g malignancies after immunosuppression
RT: Explain a type E ADR and give an example
Occurs after abrupt drug withdrawal
e.g opiate withdrawal syndrome
When is the local route of administration used
When you want to target a specific area of pathology without exposing the rest of the system to drugs
Give 3 examples of drugs used for local administration
Topical steroid creams
Eye drops
Intranasal
What are the 2 classifications of systemic routes of administration
Enteral (GI tract)
Parenteral (not GI tract)
When would systemic routes of administration be used
When whole system coverage is wanted
Give 3 examples of enteral administration
Oral (PO)
Rectal (PR)
Give 3 examples of parenteral administration
Intravenous (IV)
Intramuscular (IM)
Subcutaneous (SC)
Are inhalation and transdermal routes systemic or local
They can be either depending on the drug
Define pharmacodynamics
Action of the drug on the body
Define pharmacokinetics
Action of the body on the drug (how it’s broken down)
How can a paracetamol overdose be treated
If the patient presents to the emergency department within 1 hour of the overdose, they can be given activated charcoal
How is activated charcoal delivered in a paracetamol overdose
Nasogastric tube
How does activated charcoal treat a paracetamol overdose
A.C has a sticky texture
A.C sticks to the paracetamol (adsorption) that is in the stomach and prevents it from being absorbed
It will then be excreted
What are the 4 stages of pharmacokinetics (ADME)
Absorption (route)
Distribution (systemic spreading)
Metabolism (1st pass met)
Excretion (hepatically/ renally)
Define bioavailability
Rate and extent to which an administered drug reaches the systemic circulation
What is the assumed bioavailability of a drug given intravenously
100%
Why is IV quicker than oral administration
IV is injected directly into the bloodstream so it doesn’t cross any membranes or encounter first pass metabolism
What is first pass metabolism
This happens when the gut and liver metabolise drugs given orally before they reach the circulation
This results in a reduced concentration of the drug in the systemic circulation
What is the therapeutic range of a drug
upper and lower bounds of safe doses of a drug
Narrower range = more care dispensing
Pharmacokinetics: What does distribution describe
The journey of the drug through the bloodstream into target tissue
Name 4 types of drug target types
Give examples of each
- Cellular receptors (beta blockers)
- Enzymes (ACE-I)
- Membrane ion channels (Ca channel blockers)
- Membrane transporters (proton pump inihibitors)
Pharmacokinetics: What 5 factors can affect distribution
- Blood flow to area
- Permeability of capillaries
- Binding to proteins (albumin = slower)
- Lipophilicity - penetrate cell membrane easily
- Volume of distribution
What is the main route of elimination
The kidneys
What type of drug can the kidneys not eliminate
lipid soluble drugs
Where are lipid soluble drugs metabolised
Liver
Briefly describe how the liver converts lipid soluble drugs to water soluble drugs
Phase 1 - Make drug more hydrophilic (CYP450)
Phase 2 conjugation - If the drug is still too lipophilic, then add something to make it polar (acetylation)
How can an enzyme inducer and an inhibitor effect cytochrome p450
induction - other drugs are metabolised faster which can lead to sub-therapeutic overdose
Inhibition - other drugs are metabolised slowly and can reach toxic levels
What are the 2 main systems drugs are excreted by
Kidneys in urine
Liver in the bile and then faeces
State 4 types of receptors
Ligand-gated
G protein coupled
Kinase-linked
Cytosolic
Pharmacodynamics: describe signal transduction
Drug binds to extracellular or intracellular receptor
Leads to amplification or down-regulation of signals
What is an agonist
A compound that binds to a receptor and activates it ( full affinity and full efficacy)
What is an antagonist
A compound that binds to a receptor and prevents its activation (Full affinity and zero efficacy)
Define potency
concentration or amount of the drug required to produce a defined effect
i.e. lower dose needed for response = more potent
Define efficacy
How well the ligand (drug) successfully activates the receptor
What is EC50
the concentration that gives half the maximal response
Define affinity
How well a ligand binds to its receptor
Define tolerance in terms of drug response
Reduction in agonist effect over time
Repeated exposure to high concentrations
What is inverse agonism
A drug that binds to the same receptor as an agonist but induces an opposite pharmacological response
What is non-competitive inhibition
Inhibitor binds to an allosteric site on the receptor which alters the shape of the active site
* decreases efficacy irreversibly
* Affinity reduced
What is competitive inhibition
Inhibitor binds to the same site as the ligand
* reversible
* Less affinity and no affect on efficacy
Are ligands specific or selective to receptors
selective
Rawlins-Thompson system: Describe a type A drug reaction
Augmented
* Predictable
* Dose dependent
* Common
Rawlins-Thompson system: Describe a type B drug reaction
Bizarre
* Not predictable
* Not dose dependent
* e.g. anaphylaxis and penicillin
Rawlins-Thompson system: Describe a type C drug reaction
Chronic
* Occurs after long term therapy
Rawlins-Thompson system: Describe a type D drug reaction
Delayed
* Occurs many years after treatment
Rawlins-Thompson system: Describe a type E drug reaction
End of treatment
* Withdrawal reaction after long term use; complication of stopping meds
What is the yellow card scheme
ADR reporting scheme
Collects both spontaneous and suspected reactions
What are cholinergic receptors
Receptors on the surface of cells that bind the neurotransmitter Acetylcholine (Ach)
Name the 2 types of cholinergic receptors
Muscarinic (usually postsynaptic)
Nicotinic (usually presynaptic)
Where are M2 receptors mainly found
Heart
What happens when M2 receptors on hear SA and AV node are activated
SA node: decreases HR
AV node: decrease conduction velocity
Induces AV node block (increases PR interval)
What happens when M3 receptors are stimulated in the respiratory system
Produces mucus
Bronchoconstriction
What are adrenergic receptors
Receptors on the surface of cells that get activated when they bind a type of neurotransmitters called a catecholamine
Give 2 examples of catecholamines
Adrenaline (epinephrine)
Noradrenaline (norepinephrine)
Describe the length of pre and post ganglionic fibres in the parasympathetic NS
pre-ganglionic fibres are long
post-ganglionic fibres are long
This is opposite for the sympathetic NS
What receptor does Ach released from the preganglionic neurons act on
Nicotinic
In the sympathetic NS, what neurotransmitters are typically released by postganglionic neurons
adrenaline and noradrenaline
What are the 2 main types of adrenergic receptors
alpha and beta
In the PNS, postganglionic neurons release Ach. Name the receptor it binds to
muscarinic receptor
Symptoms of a cholinergic crisis (SLUDGE)
Salivation
Lacrimation
Urination
Defecation
GI upset
Emesis (vomiting)
What are cholinergic agonists
Mimic or enhance the action of ACh at the neuromuscular junction
What type of receptor is an adrenergic receptor
G-protein coupled receptor
Where is adrenaline released from
Adrenal glands
Where is noradrenaline released from
Sympathetic nerve fibre ends
Where are alpha 1 receptors mainly found
vascular smooth muscle and sphincters
Where are alpha 2 receptors mainly found
Brain and peripherally
Give 2 functions of alpha 1 receptors
Vasoconstriction
Increased bp
Name the drug that is used in benign prostatic hyperplasia
Tamsulosin
Block alpha 1 receptor in prostate
Give 2 functions of alpha 2 receptors
Inhibition of noradrenaline
Inhibition of Ach release
Where are B1 receptors mainly found
Heart
Kidneys
Fat cells
Give 2 functions of ß1 receptors
Increased myocardial contractility
Increased renin secretion
When are beta blockers contraindicated
In absolute asthma
Where are B2 receptors mainly found
lungs
Give 3 functions of ß2 receptors
Vasodilation
Bronchodilation
Increased release of glucagon
Give an example of a B2 agonist and which 2 conditions may they be prescribed
Salbutamol
COPD and Asthma
Give 2 functions of B3 receptors
Increased lipolysis
Relaxes bladder detrusor
What are NSAIDs
Non-steroidal anti-inflammatory drugs
Describe the difference between selective and non-selective NSAIDs
Non-selective: competitive reversible inhibitors of COX1 and 2
Selective: selectively inhibit COX 2
How do NSAIDs relieve inflammation
COX2 is needed for prostaglandin synthesis
Prostaglandins are responsible for pain and inflammation
NSAIDs reduce symptoms of pain and inflammation
Give 2 examples of non-selective NSAIDs
ibuprofen
naproxen
Give 2 examples of COX2-selective NSAIDs
celecoxib
Rofecoxib
Disadvantage of long term NSAID use
Can cause gastric bleeding
Prostaglandins are needed for gastric mucus production
Some NSAIDs inhibit COX 1 which is needed for prostaglandin synthesis
Define pro-drugs
Drugs that are not active until they are metabolised
What drug acts as an antagonist at the morphine receptor
Naloxone
What enzyme is needed to metabolise codeine
Codeine is a pro drug and is metabolised by CYP2D6
What is the bioavailability of morphine taken orally
50%
10mg of morphine is taken orally. What is the equivalent dose if given parenterally?
5mg
When are opioids used
Chronic severe pain relief - mostly cancer pain ana
Where might opioid receptors be found
Epidural space and CSF
physiological characteristics of diamorphine
More potent and faster acting as it crosses the blood brain barrier quickly
Give 5 side effect of opioids
Respiratory depression
Sedation
Nausea
Vomiting
Constipation (main)
What is released in the presence of pain
Endorphins
Describe the difference in potency between diamorphine and morphine
Morphine is half as potent as diamorphine so double the dose would be needed
5mg diamorphine = 10mg morphine = 100mg pethidine
Describe the dose-response curve for morphine
As dose increases, response increases. The association is initially rapid and the plateaus
4 classes of diuretics
- Thiazide - hydrochlorothiazide
- Loop diuretics - furosemide
- K-sparing diuretics - spironolactone
- Aldosterone antagonists
2 examples of
