ICS 2 Flashcards
Definition of ‘pharmacodynamics’
The drug’s effect on the body (mechanism of action)
4 examples of pharmacodynamic interactions
Sometimes drugs don’t have an effect - summation (1 + 1 = 2)
Sometimes drugs will enhance each other’s effects - synergistic (1 + 1 > 2)
Sometimes drugs will inhibit each other’s effects - antagonists (1 + 1 = 0)
Drug A has the same effect, but drug B gets affected - potentiation (1 + 1 = 1 + 1.5)
Definition of ‘pharmacokinetics’ - 4 parts
The body’s effect on the drug - Absorption, Distribution, Metabolism, Excretion
What is ‘bioavailability’?
What is the bioavailability of oral compared to IV?
The proportion of a drug which enters the circulation into the body.
Oral: lower (eg, 0.7)
IV: absolute (1.0)
What is the (apparent) volume of distribution?
High means…
Low means…
The distribution of a medication between plasma and the rest of the body (how much of the drug is lost to other organs/tissues, or bound to proteins)
High: moves to no effect tissues, bound to proteins
Low: stays is blood, only moves to effect tissue
Definition of ‘potency’
What is EC50?
The amount of a given drug that is required to produce a given effect
The concentration that gives half the maximal response
Definition of ‘efficacy’
The maximum effect that a given drug will produce - irregardless of the dose
EFFICACY vs POTENCY on a graph
Drug Conc - x axis
Response - y axis
Difference in height = efficacy
Difference in width = potency
AFFINITY vs EFFICACY
Affinity: how well a ligand binds to a receptor
Efficacy: how strong is the signal after binding (maximal effect)
2 natural opioids?
Chemical modified opioids? (3)
Synthetic opioids? (2)
Opioid antagonist?
NATURAL: Morphine, Codeine MODIFIED: Diamorphine, Oxycodone, Dihydrocodeine SYNTHETIC: Fentanyl, Tramadol ANTAGONIST: Naloxone
List the types of opioid receptors?
How do the receptors work?
What receptor do the drugs target?
MOP, KOP, DOP, (mu, delta, kappa), NOP
G-protein that inhibit neurotransmitter release
All the drugs are MOP agolnists
Why is morphine dangerous with renal failure?
Morphine is metabolised into morphine 6 glucuronide - which is more potent than morphine.
Will build up in those with renal failure and cause opioid-induced respiratory depression.
What is prodrug?
Two opioid examples?
Significance?
A medication that is metabolised by the body to become active.
Codeine & Tramadol
Response will be different to each person - effects could be exaggerated or inhibited
Catecholamine production order (5)
Tyrosine L-DOPA Dopamine Noradernaline Adrenaline
Alpha 1 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gq-protein, increasing calcium
Contracts smooth muscle
Vascular smooth muscle, GI sphincters, pupil
Alpha 2 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gi-protein (inhibitory to Adenyl Cyclase)
Inhibits neurotransmitter release
Pre-synaptic terminals, pancreas, platelets, salivary glands etc
Beta 1 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gs-protein (activates Adenyl Cyclase)
Heart and Kidney
Increases heart rate and renin secretion
Beta 2 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gs-protein (activates Adenyl Cyclase)
Vasodilation, Bronchodilation, Stimulates insulin release
Vascular smooth muscle, Bronchioles, Liver, Proprioceptors
Beta 3 adrenergic receptor:
Mechanism?
Effects?
Where is it found?
Gs-protein (activates Adenyl Cyclase)
Lipolysis, Bladder relaxation
Adipose tissue, Bladder
What is the structure of cholinergic nicotinic receptors?
Two types and where they are found?
Ligand-gated ion channels
NN - autonomic ganglia and CNS (cognitive function)
NM - neuromuscular junction (skeletal muscle)
What is the structure of cholinergic muscarinic receptors?
5 types and where they are found, which G protein?
M1 (Gq): brain, parietal cells
M2 (Gi): heart (activation slows the heart, eg atropine = blocks slowing of heart)
M3 (Gq): glandular and smooth muscle (bronchoconstriction, sweating, salivary
glands)
M4 (Gi): CNS
M5 (Gq): CNS
Drug development process:
Discovery/Preclinical:
Proof of concepts, animal studies, safety data
Clinical Phase 1: Healthy volunteers (safe?)
Clinical Phase 2: Limited patients (safe and effective?)
Clinical Phase 3: Larger sample of patients (safe and effective?)
Licensing from MHRA/ERA, NICE/NHS,
What is ATOPY?
What makes up the ATOPIC TRIAD?
Inherited tendency for overproduction of IgE antibodies to common environmental antigens
Asthma
Eczema (atopic dermatitis)
Hay Fever (allergic rhinitis)
Gell and Coombs
Mechanism, Examples
TYPE 1 (allergy)
Sensitisation. IgE of mast cells is activated, release of histamine and chemokines
Atopic triad, Anaphylaxis, Hives
TYPE 2 (cellular)
IgG and IgM bind to cell-surface antigens
Haemolytic disease of newborn (Rhesus), Blood transfusions, Goodpasture’s syndrome
TYPE 3 (immune complexes)
IgG binds to soluble antigens forming circulatory immune complex, cause local inflammation
System lupus erythematosus, Farmer’s lung
TYPE 4 (delayed Delayed t-helper cells activated leading to inflammation and granulomatous diseases Contact, dermatitis, Sarcoidosis?, TB?
Define “adverse drug reactions”
How are they different from side effects?
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
Side effects can be beneficial
Name of classification system with adverse drug reactions?
Name the groups with an example
Rawlins Thompson Classification
• Augmented: extension of primary effect (bronchospasm in beta-blockers)
• Bizzare/Idiosyncratic: unpredictable, not dose dependant (allergy, idiosyncrasy)
• Chronic: steroids leading to iatrogenic Cushing’s syndrome
• Delayed: carcinogenesis, cyclophosphamide (chemotherapy) damages bladder
• End of treatment: glucocorticoid withdrawn leading to adrenocortical insufficiency
Failure of therapy: OCP failure
