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Principles of Pharmacology > Unit 5 > Flashcards

Unit 5 Flashcards

1
Q

What is the summary of drug development?

A
  1. Discovery
    - Screening
    - Design
  2. Laboratory testing (pre-clinical)
    - Safety
    - Quality
    - Efficacy
  3. Clinical trials
    - Confirmation
  4. Marketing authorisation (MA)
  5. Post authorisation surveillance

Increase in cost
Decrease in number of candidates

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2
Q

What is the importance of dose selection?

A

“Need to provide rapid access to the patient outweighs the need to optimise dose (breakthrough treatments for cancer)”

Temptation to speed up return on investment

Risky and short-sighted strategy as poor dose selection is one of the main reasons for FDA denial of MA approval
- Soaring cost of drug development
- Increased risk for patient and prescribers

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3
Q

What are the three main parts of dosage design?

A

SAFETY:
- Target animal, consumer, handler, environment

QUALITY:
- Strength, purity, stability, sterility, long shelf-life
- Cost

EFFICACY:
- Optimal or sufficient?
- Without compromising future use (emergence of resistances)

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4
Q

What do you want to achieve in dosage design in Veterinary medicine?

A

ADMINISTRATION:
- Systemic effect (Oral, S/C, I/V…)
- Local effect (Topical: Gut, mammary gland, eye, airways)

EFFECT:
- Prophylaxis (Prevention)
- Cure

TARGET:
- Individual
- Population (herd, flock)

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5
Q

What are the 3 parts of dosage design regarding PK/PD?

A
  1. Dose response (D-R) characterisation: Why do we need PK?
  2. PK/PD integration for the average scenario
  3. PK/PD modelling and stimulation for tailored population medicine approach
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6
Q

What is dose titration?

A

Where the optimal effective concentration at the site of action is not known (e.g. anthelminthic drugs) dose titration studies must be carried out

These are normally carried out in three phases:
- Dose finding study
- Dose titration study
- Dose confirmation study

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7
Q

What is Dose finding study?

A

Administration over a wide range of doses to a small number of target or model animals

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8
Q

What is Dose titration study?

A

Four groups of sufficient number to which 0, 0.5, 1 and 2 times the anticipated recommended dose are administered (each group uniformly infected, for example)

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9
Q

What is Dose confirmation study?

A

Two studies in infected animals*
Using the recommended dose

  • Experimental disease model or field study
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10
Q

What are some advantages and disadvantages of traditional dose titration studies: Parallel design

A

Advantages:
- Easy to perform
- Statistical pairwise comparison between a finite number of doses

Disadvantages:
- Major disadvantage: CAN NOT interpolate between or extrapolate out of doses tested

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11
Q

Is dose the best predictor for effect?

A

Variability in bioavailability (formulation, individual intake) and in clearance (age, disease) –> Product or animal related

Where the target plasma concentration is known and pharmacokinetics have been determined in the target species, dosage can be calculated.

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12
Q

What is PK-PD integration?

A

Link between concentration, effect and time.

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13
Q

What are some examples of antimicrobial drugs?

A

Studies with clinical endpoints
Vs
Studies with microbiological endpoints (minimum inhibitory concentration: MIC)

Dose-response studies (no knowledge of target tissue concentration)
Vs
PK-PD studies (the target tissue concentration is measured)

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14
Q

What happens to antimicrobials if efficacy is measured by clinical response?

A

Antimicrobials with poor bactericidal activity appear more efficacious than they really are

Antimicrobials with excellent bactericidal activity appear less efficacious than they really are.

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15
Q

What are the microbiological endpoints of antimicrobial design?

A

Spectrum of activity (gram +, gram -)

Minimum inhibitory concentration (MIC) in relevant target population

Bacteriostatic vs bactericidal

Mode of killing (time, concentration or co-dependency)

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16
Q

What are surrogate markers to predict efficacy?

A

T% > MIC (I.e. time dependent)

Cmax/MIC ratio (i.e. concentration dependent)

AUC24h/MIC ratio (i.e. co-dependent)

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17
Q

What is Cmax?

A

Maximum plasma concentration

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18
Q

What is AUC?

A

Area under plasma concentration time curve

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19
Q

What is the relationship between Time above MIC and Efficacy for Cefotaxime against Klebsiella pneumoniae in a murine pneumonia model?

A

Neutrapaenic mice infected by Klebsiella aerosol

Cefotaxime (=ß-lactam) given 14hrs later

24 different dosage regimen (dose and frequency)

Correlation between surrogate and bactericidal effect

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20
Q

What is the Monte Carlo simulation for population approach?

A

“One dose fits all” possibly leads to over-exposure of some individuals, under exposure of others

Monte-Carlo method: Random sampling procedure

Statistical tool to calculate probability of adequate exposure (and cure) of a percentage of the population knowing

  • Variability in MIC: Distribution 1
  • Variability in individual clearances: Distribution 2
  • Variability in bioavailability + food intake: Distribution 3
  • Variability in target of PK/PD index: Tailor to bug/drug association
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21
Q

What do we know about PK/PD target refinement: Static in vitro bacterial kill curves?

A

Specific to bacteria/drug/host

Choice of inoculum size and matrix (serum vs artificial media)

Incubate with multiples of MIC concentrations for 24hrs

Plot bacterial count versus AUC/MIC ratio

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22
Q

What is the formula for the computation of the dose using Monte Carlo simulation?

A

Dose = clearance x 90 x MIC / F%

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23
Q

What is a drug?

A

A chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which when administered to a living organism, produces a biological effect

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24
Q

What is pharmacology?

A

The study of the effects of drugs on the function of living systems

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25
Q

What is clinical pharmacology?

A

A translational discipline in terms of the basic tools of human pharmacology (e.g. receptor pharmacology) and applied pharmacology (e.g. pharmacokinetics) and how they are used in drug discovery and development and in solving practical therapeutic problems in individuals and populations

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26
Q

What is ADME in clinical pharmacokinetics?

A

Absorption
Distribution
Metabolism
Elimination

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27
Q

What do we know about (broncho-)pneumonia in dogs?

A

Aspiration
Infectious
Foreign body
Nosocomial/Hospital acquired
Secondary to immunodeficiency/congenital defects

Treatment options for bacterial (infectious/ aspiration) bronchopneumonia
- Empirical antibiotic therapy
- Targeted-antibiotic therapy
- Supportive therapies
–> Pain relief/anti-inflammatory medications
–> Inhaled therapies
—-> Nebulisation
—-> Mucolytics (can also be given orally)

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28
Q

What is empirical antibiotic selection?

A

What bacteria are likely to be present? Which antibiotics have a spectrum of activity that match?

Which antibiotics reach therapeutic levels in the target tissue (the lungs)?

Existence/production of a suitable formulation….

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29
Q

What are the common causative agents of infectious bronchopneumonia and aspiration pneumonia?

A

Infectious pneumonia:
- Many viral!
- Bacteria: Mycoplasma spp. (stains as gram -Ve [lacks cell wall]), Bortadella bronchiseptical (gram -ve)

Aspiration pneumonia:
- Secondary causative bacteria
- Usually mixed!!
- E.coli (gram -ve), pasteurella spp. (gram +ve), Staphylococcus spp. (gram +ve), Klebsiella spp. (gram -ve), Enterococcus spp. (gram +ve)

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30
Q

What is targeted-antibiotic therapy? Enrofloxacin and marbofloxcacin

A

Enrofloxacin and marbofloxcacin:
- Fluroquinolones
- Typical target organisms: broad (gram -ve and +ve spp.)
- Oral and injectable formulations readily available
- Arthropathy/cartilage lesions in immature animals (humans, foals, dogs)..

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31
Q

What is targeted-antibiotic therapy? Gentamycin

A

Gentamycin
- Aminoglycoside
- Typical target organisms: Many gram -ve, some grams +ve spp.
- Commonly used topically for bacterial skin/ear infections, available as injectable
–> Low oral availability (polarised, water-soluble compounds, poor intestinal membrane permeability)
- Nephrotoxicity possible

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32
Q

What is targeted-antibiotic therapy? Co-amoxiclav

A

Amoxicillin-clavulanate (beta-lactam) IV
- Broad spectrum
- IV rather than orally due to inappetence and regurgitation
Minimal improvement; return of BALF culture and sensitivity

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33
Q

What is pharmacovigilance?

A

Activities relating to the detection, assessment, understanding and prevention of adverse reactions or other medicine-related problems

Veterinary pharmacovigilance = any concerns over the safety of veterinary medicines used for treatment, prevention or diagnosis of disease in animals.

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34
Q

What is veterinary medicine directorate (VMD)?

A

RESPONSIBILITIES:
- Monitoring and acting on reports of adverse events from veterinary medicines

  • Testing for residues of veterinary medicines or illegal substances in animals and animal products
  • Assessing applications for and authorising companies to sell Veterinary medicines
  • Controlling how veterinary medicines are made and distributed
  • Advising government ministers on developing Veterinary medicines policy and putting it into action
  • Making, updating and enforcing the veterinary medicines regulation
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35
Q

What is the definition of a drug interaction?

A

A change in the action of one drug resulting from:
- Administration of other drugs
- Concurrent food intake
- Also drug-herb interaction

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36
Q

What may a drug interaction be?

A

Clinically insignificant (most common situation), but can also:

  • Produce a favourable effect
    –> A planned additive or synergistic effect or reduced toxicity
  • Lead to an adverse outcome
    –> I.e. toxicity or therapeutic failure
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37
Q

What is toxicity likelihood?

A

Toxicity is most likely to occur when drugs have a low therapeutic index.

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38
Q

What is therapeutic index?

A

The ratio of the toxic dose (TD50)/therapeutic dose (ED50)

It is used as a measure of the relative safety of the drug

39
Q

How may Drug-Drug interaction alter drug effect?

A

Additive effect: 1 + 1 = 2
Synergistic effect: 1 + 1 > 2
Potentiation effect: 1 + 0 = 2
Antagonism: 1 + 1 = 0

40
Q

What are some general points for drug interactions?

A

Drug interactions may explain poor efficacy or toxic effects

Knowledge of drug Pharmacokinetics and Pharmacodynamics should enable planned, desirable, effects to be achieved with combinations of drugs and unwanted effects to be avoided

Avoid unnecessary use of more than one drug (poly-pharmacy)

Use drugs that have a low therapeutic index with caution

41
Q

What are pharmacodynamic interactions?

A

Drugs that act on a common (or a different) target molecule

Drugs with actions on the same (or different) body system

42
Q

What are examples of enhanced effect of pharmacodynamic interactions between two drugs that work on the same body system?

A

The cardiovascular system:
- Beta blockers and calcium channel blockers
To increase hypotensive effects

The lungs:
- ß2 agonists (salbutamol), and glucocorticoids
A combination of direct and indirect bronchodilation, which is used in the treatment of inflammatory airway disease

43
Q

What are examples of enhanced effect of pharmacodynamic interactions between two drugs that work on different body systems?

A
  • Drugs that act on different target sites to produce the same effect can also be used in combination to reduce toxicity for the patient
    e.g. combinations of anti-cancer drugs
44
Q

What are examples of antagonistic effect of pharmacodynamic interactions?

A

Same target molecule:

E.g. Naloxone, an opioid receptor antagonist, which reverses the sedative effect and respiratory depression of morphine
—> A desirable effect

Administration of a beta blocker to a patient with respiratory disease taking a beta 2 receptor agonist
–> An undesirable effect

45
Q

What are some drug specific toxicity and antidotes?

A

OPIOIDS (morphine):
- Toxicity; Sedation, bradycardia, respiratory depression
- Antidote; Naloxone, diprenorphine

ALPHA-2 AGONISTS (Medetomidine, xylazine):
- Toxicity; Sedation, low heart rate
- Antidote; Atipamezole, Yohimbine

BENZODIAZEPINES (Diazepam):
- Toxicity; Sedation
- Antidote; Flumazenil

46
Q

What are examples of antagonistic effect of pharmacodynamic interactions?

A

Same body system:
- E.g. the kidney and anti-hypertension
- NSAIDs and ACE inhibitors - reduced hypotensive action of ACE inhibitors (opposite effects on renal excretion of sodium)
—> An unwanted effect

Different body system:
- E.g. Drugs acting on the heart and kidney
- Furosemide (a potassium losing diuretic) increases the toxicity of class III anti-dysrhythmics (K+ channel blockers)
—> An unwanted effect

47
Q

What are some interactions with bacteria as the target for drug action?

A

Can lead to enhanced OR decreased effects.

E.g. Combinations of antibacterial drugs used to:
- Increase spectrum of activity

Antimicrobials when used in combination can also be less effective:
- E.g. Combining drugs with bacteriostatic and bactericidal properties (in theory)

Enhanced toxicity can also occur when antimicrobials are used in combination with other drugs:
- E.g. Aminoglycosides (gentmycin) and NSAIDs:
- Increased risk of renal toxicity

48
Q

What are drug interactions prior to drug administration?

A

e.g. when mixed in a syringe

Examples of how you might be be able to recognise an incompatibility:
- Change in colour
- Increase in turbidity
- Formation of precipitates

Sometimes you won’t see it

49
Q

Some drugs may react with the environment (e.g. during storage or on administration) how?

A

Problems during storage:
- Out of date drugs lose potency
–> If stored correctly, 90% of drug activity should remain as active at the end of the shelf life
- Effect of storage temperature
- Some drugs break down to toxic products during storage.

Problems during dosing:
- Drugs given by infusion: Some drugs adhere to plastic and/or glass
–> Benzodiazepines (diazepam) binds to plastic when infused
–> Light sensitive drugs may decompose

50
Q

What are pharmacokinetic interactions?

A

One drug affects the rate or extent of:
- Absorption
- Distribution
- Metabolism
- Elimination
…Of another drug

51
Q

What is an example of how drug absorption can be affected?

A

A reduction in absorption due to altered pH
- E.g. Antacids or H2 blockers will increase gastric pH and reduce the absorption of weakly acidic drugs

Adsorbents (like sucralfate) will decrease drug absorption

52
Q

How can food affect drug absorption?

A

The rate and extent of absorption can be affected

Some drugs better on an empty stomach
- E.g. Ampicillin, tetracyclines, robenacoxib

Some drugs are absorbed better with food
- E.g. griseofulvin (ringworm treatment), metronidazole

53
Q

How can drug distribution be affected?

A

Unlikely to produce a clinically significant effect unless:
- Displaced drug is injected quickly
E.g. Propofol or barbiturates for induction of general anaesthesia (highly protein bound drugs)

A highly plasma protein bound drug with a low therapeutic index is involved

54
Q

What do we know about hepatic metabolism of drugs?

A

The cytochrome P450-dependent microsomal enzymes (phase I reactions: Oxidation, reduction, hydrolysis)
- Have varying specificities
- Metabolise many drugs with different structures

The enzymes can be induced or inhibited by drugs
- E.g. phenobarbitone and phenytoin enhance the microsomal activity (cytochrome induction)
- Cimetidine and chloramphenicol reduce microsomal enzyme activity (cytochrome inhibition)

55
Q

What do we know about renal excretion of drugs?

A

Drugs may compete for active secretory processes e.g. penicillins and probenecid (anti-gout drug): Competition for organic ion transporter (OAT) (Used during WW2)

The pH of tubular fluid, which can be altered by administration of acidifying or alkalinising agents - can affect drug excretion
- Excretion of weak acids is favoured in alkaline urine
- Excretion of weak bases is favoured in acid urine

NB. Urine pH may affect the solubility of drugs causing them to precipitate.

56
Q

What is the definition of drug delivery?

A

The appropriate administration of drugs through various routes in the body for the purpose of improving health

It is highly interdisciplinary

It has recently evolved to take into consideration:
- Drug physics-chemical properties and solubility
- Drug biological interaction with the body
- Desired pharmacological effect (site, duration, intensity)
- Patient comfort and well-being

57
Q

What are the typical drug formulations human vs veterinary medicine?

A

HUMAN:
- Large scale
- Cost effective
- Oral administration
- Nasal or pulmonary

Tech transfers with Small animal/Sport

SMALL ANIMAL/SPORT:
- Similar to humans
- Individual bass
- More expensive and targeted formulations

Animal studies before licensing drugs for humans

FOOD PRODUCING ANIMALS:
- Individual or group treatment
- Cost conscious
- One shot (Convenience/ safety)
- Antibacterial drugs, antiparasitics, vaccines

58
Q

What are the advantages and traditional delivery system/devices of Intravenous (IV) administration?

A

ADVANTAGES:
- Drug 100% bioavailable
- Rapid response
- Predictable control of blood concentration
- Only possible route for some drugs (critical antibiotics, chemotherapy)

TRADITIONAL DELIVERY SYSTEM/DEVICES:
- Injection - bolus
- IV bag - infusion

59
Q

What are the disadvantages of IV administration?

A
  • Invasive: Intravenous catheterisation
  • Difficult to administer:
    –> Hospital setting
    –> Trained personnel
  • Sterility
    –> Formulation
    –> Catheter handing to prevent catheter infection
  • Difficult to keep the IV route patent (Dwell time)
60
Q

What are some devices for prolonged IV access?

A

PICC - Peripherally inserted central catheter - line:
- Inserted aseptically from a peripheral vessel
- Tip of the catheter in vena cava
- Duration up to 3 months

Implantable vascular access port:
- Surgical implantation
- Chamber with silicone membrane
- Longer term access (life)

61
Q

What is Plasma concentration-time profiles after IV administration?

A

Simple IV bolus
Continuous rate infusion (CRI): Steady state after 5 Half lives
Loading dose and CRI (target control infusion)

62
Q

What are the assumptions in a single compartment model?

A

Body: One compartment characterised by a volume of distribution - Vd

Vd = amount of drug in the body (A) / Plasma drug concentration (C)

Drug is confined to the single space and equally distributed through the body

63
Q

What do we know about a One-compartment model with absorption?

A

Absorption occurs from site of administration

Absorption can be fast or slow

Slow absorption may represent drug entry through GI tract or leakage into circulation after subcutaneous injection

Drugs require multiple doses to maintain drug concentration within the therapeutic window

Absorption –> C, Vd –> Elimination clearance

64
Q

What is bioavailability as a measure of absorption?

A

Bioavailability (F) is:

The fraction of the administered dose that reaches the systemic circulation in an active form

Expressed as a percentage of the total administered

Bioavailability = AUC non-vascular / AUC IV x 100%

65
Q

What is Oral administration of drugs?

A

Traditional oral delivery systems

Tablets (compressed powder and coating)
- Immediate release
- Modified release (extended release, gastro-resistant, delayed release)
- Hard capsules (filled with powder)
- Soft gelatine capsules (reduced variability)
- Suspensions

66
Q

What are the advantages of Oral administration?

A

Patient:
- Convenience
- Non-invasive
- Higher compliance

Manufacture:
- Well established process, widely available
- No need for sterility

67
Q

What are the disadvantages of Oral administration?

A
  • Unconscious patients cannot take dose
  • Problem drugs:
    –> Low solubility
    –> Low permeability
  • First pass mechanism
    –> Gut
    –> Liver
  • Irregular absorption, food interactions
68
Q

What do we know about absorption of drugs from the gastro-intestinal tract?

A

Dissolution in lumen

Mainly passive transfer through enterocytes (small intestine), sometimes active transporters

Portal circulation empties into the liver

Entero-hepatic loop

69
Q

What is the first pass effect (oral route)

A

Gut lumen
- Some drugs may go straight to faeces (poor solubility

Gut wall
- Some drugs metabolised in the gut
- Degradation by enzymes or bacterial flora

Liver
- Some may go to hepatic metabolism
- Hepatic metabolism
- Cellular efflux pumps

Some travels to site of measurement

70
Q

What is the biopharmaceutics classification system (BCS class)?

A

Class I;
Well absorbed, absorption rate usually > excretion rate

Class II;
Bioavailability is limited by solvation rate (predicted by in vitro studies)

Class III;
Limited by permeation rate (requires work on formulation)

Class IV;
Usually poor bioavailability and high variability of absorption

From class I –> IV: Chance of non-oral dosage required

71
Q

What drug administrations bypass the first pass effect?

A
  • Intravenous
  • Sublingual route
  • Rectal route
  • Directly to vena cava without transiting the liver
  • Higher bioavailability
72
Q

What are the advantages and traditional delivery system/devices of Buccal/sublingual administration?

A

ADVANTAGES:
- Bypass first pass metabolism
- Rapid absorption
- Low enzymatic activity

TRADITIONAL DELIVERY SYSTEM/DEVICES:
- Tablets
- Chewing gum

73
Q

What are the disadvantages of Buccal/sublingual administration?

A
  • Small doses
  • Probability of swallowing - loss of effect
  • Discomfort during dissolution
74
Q

What is an example of a buccal drug in industry?

A

Oral-lyn
- Liquid formulation of human insulin administered to buccal mucosa by aerosolisation
- Drug carried in lipid micelles

75
Q

What are dosing considerations of long-acting oral formulations?

A

Can you dose a cow?

Panacur bolus TM (MSD animal health), intra-ruminal

Fenbendazone (antiparasitic), up to 140 days coverage

76
Q

What are the advantages and traditional delivery system/devices of Rectal administration?

A

ADVANTAGES:
- Bypass first pass metabolism
- Useful for unconscious patients

TRADITIONAL DELIVERY SYSTEMS/DEVICES:
- Suppository
- Enema

77
Q

What are the disadvantages and an example of rectal administration?

A
  • Degradation by bacterial flora
  • Uncomfortable

Diazepam in seizing dogs (no IV yet)

78
Q

What are the advantages and typical delivery system of Parenteral injection administration (non-enteral)?

A

ADVANTAGES:
- For drugs with poor oral bioavailability
- No first-pass effect
- Catheter not needed

TYPICAL DELIVERY SYSTEM:
- Single vial or
- Multiple use, preservative, airtight vial
- Excipients (for adjusting pH, stability and solubility)

79
Q

What are the disadvantages of parenteral injection administration (non-enteral)?

A

Sterile formulation needed

80
Q

What are the advantages and disadvantages of Subcutaneous and intramuscular injection administration?

A

ADVANTAGES:
- Patient self-administration
- Slow, complete absorption
- No first-pass effect

DISADVANTAGES:
- Invasive
- Irritation, inflammation
- Max volume - 1ml (SC) - 4ml (IM)
- May require some training (IM)

81
Q

What do we know about long-acting injectable formulations?

A

Treatment requires drug exposure for several days (antibiotic for example)

Convenience of long-acting formulations: Single visit to the farm

Injection can last up to 120h (Tulathromycin draxxin)

82
Q

What are the advantages and requirements of Topical/transdermal administration?

A

ADVANTAGES:
- Local effect (topical) or systemic absorption
- Ease of administration (cream, gel, patches)

REQUIREMENTS:
- Low dosage <10mg a day
- MW<500, logP: 1-4
- Suitable formulation

83
Q

What are the disadvantages of topical/transdermal administration?

A
  • Stratum corneum barrier
  • Low absorption for some drugs
  • Slow onset
84
Q

What do we know about Patch and transdermal technology?

A

Sustained release or controlled release technology

Human medicine:
- Nicotine
- Oestrogens
- Scopolamine (nausea)
- Rivastigmine (Alzheimer’s disease)

Zero order delivery is important (nicotine patch, immediate bioavailability would be lethal)

Variability in skin structure between species

85
Q

What are enhancement strategies for transdermal delivery?

A

Penetration enhancers (modify stratum corneum)
- Alcohols, DMSO, terpenes

Energy-driven release methods (electric current or ultrasounds)

Microneedles, different types (bypass stratum corneum)

86
Q

What are the advantages of respiratory administration (inhalers)?

A

ADVANTAGES:
- Drugs for local or systemic effect
- Portability
- Bypass first pass metabolism
- Gases are rapidly absorbed

87
Q

What are the disadvantages of respiratory administration (inhalers)?

A

DISADVANTAGES:
- Propelled liquids or solids (powders) can be absorbed if size is below 0.5 µm
- Patient training and proficiency

88
Q

What do we know about inhalation general anaesthesia?

A

Volatiles anaesthetic agents –> Alveolar uptake

Systemic effects (anaesthesia): immobility, muscle relaxation and unconsciousness

Speed of uptake related to blood-gas solubility

89
Q

What are the advantages of nasal administration?

A

ADVANTAGES:
- Localised or systemic action
- Over the counter medications (decongestants)
- Hormones (insulin) or vaccines

90
Q

What are the disadvantages of nasal administration?

A

DISADVANTAGES:
- Drugs can be degraded locally
- Clearance by cilia (nasopharynx)
- Need improved formulations to increase uptake

91
Q

What do we know about nose to Brain delivery?

A
  • Direct access to brain (bypasses blood brain barrier)
  • New area of CNS research (anti-alzheimer drugs)
  • Anatomical differences between animal species (models)
92
Q

What do we know about nanotechnologies?

A

Structures 1 to 100nm

Includes antibodies, polymer conjugates, nanoparticles and liposomes

Enhanced solubility and dissolution rate (BCS II and IV)

93
Q

What are the factors affecting the selection of the delivery route?

A

Drug physico-chemical properties:
- Drug molecular weight
- Chemical size
- Particle size

Desired pharmacological effect:
- Local vs systemic
- Immediate/delayed response
- Dose size

Solubility:
- Hydrophobicity / hydrophilicity
- pH/temperature
- pKa - ionisation
- Concentration / crystallinity

Drug biological interactions:
- half life
- Sensitive to first pass effect
- Drug interactions

Patient factor:
- Preference - lifestyle
- Dexterity - cooperation
- Conscious or not

Principles of Pharmacology (5 decks)

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