Pharmacology and Therapeutics Flashcards
What is a prescription?:
- A legally binding document and must be written in indelible ink or sent electronically for printing
- By adding your signature, you take responsibility for the prescription
Factors driving increased medication use: (4)
- Ageing population
- Multimorbidity
- Guidelines
- EBM
Harmful effects of drugs: (5)
A
S
T
Tb
D
- Anaphylactic reactions
- Side effects
- Teratogenicity
- Treatment burden
- Dependency / addiction
Benefit versus risks: Number Needed to Treat
- The number of patients you need to treat to prevent one additional bad outcome (stroke, death, etc.)
Benefit versus risk: Number Needed to Harm (NNH)
- A derived statistic that tells us how many patients must receive a particular treatment for 1 additional patient to experience a particular adverse outcome
Relationship between NNT & NNH:
- Lower NNT and higher NNH values are associated with a more favourable treatment profile
Pharmacokinetics (PK): definition
- What the body does to the drug
Pharmacodynamics (PD):
- What the drug does to the body
Pharmacokinetics :
A
D
M
E
Absorption
Distribution
Metabolism
Elimination
Enteral routes of administration:
- Definition
- Examples (4)
- Routes in which the drug is absorbed from the GI tract
- Sublingual, buccal, oral and rectal routes
Oral route: Pros (4)
- Simple
- Cheap
- No equipment
- Acceptable to patients
Oral route: cons (5)
S
I
P
A
F
- Slow absorption
- Incomplete absorption (bioavailability)
- Preparation must be stable in gastric acid
- Affected by food, vomiting and GI motility
- First-pass metabolism via gut wall and liver
Injection route: Pros (4)
- Reliable
- Rapid absorption
- 100% bioavailability
- No first-pass metabolism
Injection route: cons (5)
- Inconvenient, invasive
- Requires training
- Infection control
- Equipment required
- Expense
Factors affecting drug distribution:
C
R
V
BC
F
D/L
- Cardiac output
- Regional blood flow
- Vascular permeability
- Fat/muscle body composition
- Fluid compartment volumes
- Drug solubility / lipophilicity (pKa)
Metabolism: phase 1 reactions (modification)
- Phase 1 reactions modify the chemical structure of the ingested drug. This can turn an inactive pro-drug (aspirin) into an active drug (Salicylic acid)
Metabolism: phase 2 reactions (conjugation) (2)
- Conjugation reactions often produce less active metabolites
- They also increase a metabolites polarity and water solubility, increasing renal excretion
Renal excretion: determined by (2)
- Plasma drug concentration
- Glomerular filtration rate
Digoxin:
- Effect
- Use
- Excretion
- Slows conduction at the cardiac AV node
- Used for arrhythmia management and heart failure
- It is renally excreted
Pharmacodynamics:
- Mechanism of action
- Dose response
- Molecular target (enzyme, receptor)
- Affinity, efficacy and potency
Molecular targets: (4)
- Enzymes
- Ion channels
- Transmembrane receptors
- Nuclear receptors
Transmembrane receptors: (3)
- Ligand-gated ion channels
- G protein-coupled receptors
- Hormones
B2-adrenoreceptors and asthma:
- Relation
- Salbutamol
- Propranolol
- B2 activation causes bronchial smooth muscle relaxation
- Salbutamol: short-acting B2 agonist asthma reliever
- Propranolol: Non-selective Beta antagonist
Anticholinergic effects:
- Smooth muscle
- Secretions
- Pupils
- CVS
- CNS
- Inhibits smooth muscle: constipation, urinary retention
- Reduced secretions: Dry mouth, eyes, skin
- Pupillary dilatation: blurred vision
- CVS: vasodilation, tachycardia
- CNS: Confusion, agitation
Clinical guidelines:
- What?
- Based on??
- Includes
- Recommend how clinicians should care for people with specific conditions
- Based on best available evidence
- May include recommendations on: prevention, diagnosis, treatment
NOT MANDATORY
What is a drug? (definition):
- Any synthetic or natural chemical substance that can alter biological function; it may be used in treatment, prevention, or diagnosis of disease
Attributes of a drug?: (2)
- Must be selective for a target
- Must give beneficial rather than adverse (side) effects
Drugs produce side effects when: (2)
- The target is too widespread in the body
- The drug hits other targets (lack of selectivity)
Molecular targets:
- R
- E
-T
- Receptors: transduce signal from drug
- Enzymes: activate or switch off
- Transporters: carry molecule across membrane
Molecular targets:
- I
- N
- M
- Ion channels: open or close
- Nucleic acids: affect gene transcription
- Miscellaneous: lipids, metal ions etc
Cyclooxygenase: enzyme inhibitors
- Inhibitors for pain relief, particularly due to arthritis
Angiotensin Converting Enzyme (ACE) inhibitors:
- For high blood pressure, heart failure, chronic renal insufficiency (captopril, ramipril)
Drugs as enzyme substrates:
- Inactive prodrugs are metabolized to active forms
Antimetabolite action of sulphonamides:
- Sulphonamides mimc the natural structure of a bacterial amino acid called PABA.
- This disrupts the bacterial DNA production by creating a false metabolite (lethal synthesis)
Receptor super families: Ionotropic
- Mechanism
- Time
- Receptor-operated channels
- Fast (msecs)
Receptor super families: Metabotropic
- Mechanism
- Time
- G-protein coupled
- Medium (secs to mins)
Receptor super families: TKR
- Mechanism
- Time
- tyrosine kinase receptors
- Medium (mins)
Receptor super families: DNA-linked
- Mechanism
- Time
- Intracellular
- Slow (hours)
receptor subtype importance:
- The existence of multiple receptor subtypes provides the opportunity to develop more specific drugs
Drug binding obeys the law of Mass Action:
Rate of association = K+1 [D][R]
Rate of dissociation = K-1 [DR]
Affinity equation:
- Quantified by the term …..
- Equation
- KD: dissociation equilibrium constant for binding
- KD = [D][R] / [DR]
What does the KD display about a drug:
- Relation to affinity
- The KD is the concentration of a drug that occupies 50% of the receptors, since at 50% occupancy [R] = [DR]
- THE LOWER THE KD, THE HIGHER THE AFFINITY
Total number of receptors (RT):
- equation
- How to use this to get P (fractional receptor occupancy)
[RT] = [DR] +[R] which means [R] = [RT] - [DR]
P = [D] / [D] + KD
Efficacy definition:
- A drugs ability to activate receptors and produce a response
Pharmacological response: relationship between response and occupancy
- Positional relation
- Curve separation
- Binding curve is always to the right of the functional response curve, you don’t need to occupy all receptors to get maximum response
- The higher the efficacy, the greater the separation of the two curves
Factors that determine the position of the concentration-response curve along the conc. axis (3)
- Affinity
- Efficacy
- Receptor number
Potency:
- How much drug is needed to produce a particular response
Partial agonism:
- Partial agonists occupy all receptors to evoke their maximum response, they leave no spare receptors
Efficacy and receptor number:
- Efficacy is a ….
- Description for low efficacy drugs
- Description for high efficacy drugs
- Efficacy is a spectrum
- drugs with low efficacy may appear to be full agonists in tissues with large receptor numbers but will mostly appear as partial agonists
- High efficacy drugs will primarily appear as full agonists as they do not require a large number of receptors to achieve full agonism
Therapeutic value of partial agonists: Why can’t adrenaline be used to treat asthma attacks?
- What needs to be achieved
- Adrenaline effects
- Need to relax smooth muscle of bronchi by activation of beta2 adrenergic receptors
- Adrenaline will achieve this but also activate heart B1 and the few B2 receptors, increasing HR and force of contraction. May cause heart attack
Therapeutic values of partial agonists: Salbutamol in asthma attacks
- Salbutamol characteristics
- Relevancy of this
- Salbutamol effects
- Salbutamol is a selective B2 adrenoceptor partial agonist
- The magnitude of its effect is determined by the receptor number. Bronchi smooth muscle is abundant in B2 receptors, while the heart has very few
- Salbutamol evokes significant bronchi relaxation with little or no effect on the heart
