Pharmacology 1

Question 1

What is a medicine or drug?

Answer 1

• A substance when administered to a person (or other living entity) that produces a change in function.
• Often, the term refers to any substance that is used to diagnose, treat or cure an illness.
• A chemical substance with a specific structure
• That specific structure gives the substance certain,
  predictable chemical and biological properties.
• Those properties define the effects produced by the drug.

Question 2

Pharmacuetical interventions

Answer 2

• Particle size
• Enteric coated tablets
• Slow / delayed release preparations
• Osmotic mini pumps

Question 3

Drug effects

Answer 3

• Therapeutic effects
• The intended effects
• Side effects
• Not necessarily harmful but a bit ‘off piste’ from what was intended
• Adverse effects
• Potential harmful, undesired effects
• Toxic Effects
• Poisoning, harmful, may be life threatening

Question 4

Types of transport

Answer 4

• Diffusion- passive transport
• Facillitated diffusion- passive transport
• Active transport

Question 5

Types of transmembrane transport

Answer 5

• Ion channels-
• Uniport
• Symport- co-transport
• antiport- co-transport

Question 5

Drug receptor complex e.g. GPCR

Answer 5

• A signaling molecule binds to the GPCR
• The GPCR changes shape
• The GPCR activates a G protein
• The G protein activates second messengers
• The second messengers trigger a series of events that change cell function

Question 6

Absorption- important factors relating to absorption

Answer 6

*Important factors relating to absorption
 Route of administration
 Blood flow at administration site  Dose
 Solubility of drug
 Soluble in water / body fluids?  Soluble in lipids?

Question 7

Absorption- process

Answer 7

Passive diffusion
 Active transport
 Carrier mediated transport  Facilitated diffusion

Question 8

Absorption-related food/drug interactions

Answer 8

Grapefruit juice increases absorption of antihistamines,
codeine, tranquilizers, cardiovascular & antiretroviral drugs
Vegetables or vitamins with iron can decrease absorption of erythromycin
Dairy foods or other calcium rich items decrease absorption of tetracycline

Question 9

Oral administration

Answer 9

• Major administration route
• Usually most convenient, safest and cheapest route
• Little absorption occurs until drug reaches small intestine
• Usually drugs given orally absorbed in 1-3hrs
• Can be affected by
  – GI motility (can be a large effect, with / not with a meal)
  – Blood flow
  – Particulate size and formulation – Physicochemical factors

Question 10

Rectal adminstration

Answer 10

• Most oral drugs can
  also be administered
  rectally.
  –E.g. NSAIDs in folk with inflammatory bowel disease
  – Diazepam in epileptics when tricky to establish IV access
  – Laxatives

Question 11

Sublingual administration

Answer 11

• Absorption directly from oral cavity
  – Through mucous membrane, gives a rapid response
• Useful when
  – Rapid response required
  – Drug is unstable at gastric pH – Drug metabolised by liver
• E.G. Glyceryl trinitrate – Angina Rx

Question 12

Injection- subcutaneous

Answer 12

• Quicker onset than oral
• Rate of absorption dependent on injection site and various physiological factors.
  –E.g. local blood flow * Insulin

Question 13

Injection- IV

Answer 13

• Quickest and most reliable route
• High, virtually instantaneous plasma drug concentrations
• E.G. Heparin, diazepam
• Drug availability depends on factors such as blood flow, disease state etc.

Question 15

Injection- IM

Answer 15

• Preferable to subcutaneous route when larger volumes of drug needed.
• Usually injected into upper arm, thigh, buttock
• Absorption determined by blood supply
  – E.g. diazepam – Vit B12
  – Steroids
  – Antibiotics
  – Adrenaline

Question 16

Intrathecal injection

Answer 16

Injection into the spinal canal, or into the subarachnoid space so it reaches the cerebrospinal fluid.
Useful in spinal
anaesthesia, chemotherapy,
or pain management applications

Question 17

Transdermal patch

Answer 17

• Drug within a patch stuck to skin
  – Even rate of delivery
• Easy to remove if AEs develop
• Used for lipid soluble drugs
• E.g.
  – Hormone replacement Therapy – Nicotine – smoking cessation

Question 18

Topical

Answer 18

• Drugs applied to skin for local effects
  – E.g.Hydrocortisone cream for eczema
• Most drugs poorly absorbed through skin due to low lipid solubility
• However, in some circumstances significant absorption may occur and lead to adverse systemic effects.

Question 19

Inhalation

Answer 19

• Volatile gases / anaesthesia
  – Lungs used for both administration and excretion
  – Rapid adjustments of plasma concentration possible
• Drugs used for local
  effects on the lung
  – Aerosol or powder
  – High concentration in the lung, minimal elsewhere
  – Poor absorption due to molecule size and lack of lipid solubility

Question 20

Drug distribution

Answer 20

 Happens when the drug reaches the circulation
Once a drug enters into systemic circulation by absorption or direct administration, it must be distributed into interstitial and intracellular fluids.
Each organ or tissue can receive different doses of the drug and the drug can remain in the different organs or tissues for a varying amount of time.

Question 21

Influences on drug absorption

Answer 21

 Blood flow in the area
 Reduced in some patients, e.g.diabetics
 Capillary Structure / Permeability  Lipid solubility of the drug
 Barriers to diffusion
 Tissue binding
 Plasma protein binding
 Chemical nature of the drug  Volume of distribution

Question 22

Distribution

Answer 22

• Drugs are transported in the bloodstream via plasma proteins – mainly albumin  Free (unbound) drug
   Partially reversibly bound
• Only unbound drug or “free” drug may:
   Diffuse through capillary walls  Produce a therapeutic effect
   Be metabolised
   Be excreted
• Concentration of unbound drug determines the drug concentration and therefore efficacy of the drug

Question 23

Blood brain barrier

Answer 23

 Only very lipid-soluble drugs and very small molecules are capable of penetrating the junction of cells which comprise the blood-brain barrier (BBB) and exert a pharmacological effect on the brain.
 The lipid solubilty is used in drug design to alter the drug distribution to the brain
 E.g. Second generation antihistamines (loratadine), achieve far lower brain concentrations compared with some of the first generation antihistamine (diphenhydramine), and thus are classified as non-sedating

Question 24

Methods to cross bbb

Answer 24

1. Paracellular transport (water soluble) 2. Diffusion- lipid soluble agents- nicotine, antidepressants 3. Protein transports- Gabapentin, cyclosporin 4. Receptor-mediated transcytosis- insulin 5. Adsorptive transcytosis- albumin

Question 25

Metabolism of drugs

Answer 25

*  The liver is the main site of drug metabolism.  Enzymes in the liver chemically alter the drug to form metabolites. This can also be called biotransformation. They may be either:  Inactive  Equally or more active than the ‘parent’ drug  This may involve 1 or 2 phases or both  Phase 1: Oxidation or hydrolysis of the drug, usually involves Cytochrome P450 Isoenzymes.  Phase 2: Conjugation of the phase 1 metabolite or drug with something else. E.g. Glutathione to inactivate it or aid in its elimination.

Question 26

Pro-drugs

Answer 26

Some drugs are administered in an inactive form They undergo metabolism (Phase 1, Phase 2 or both) It is the metabolite that is pharmacologically active Drugs which are pharmacology active following metabolism are known as pro-drugs, e.g. enalapril=> enalprilat

Question 27

Factors affecting drug metabolism

Answer 27

* Genetic factors (Pharmacogenetics) * Other drugs - Hepatic enzyme inducers  Increase the rate of another drug’s metabolism - Hepatic enzyme inhibitors  Decrease the rate of another drug’s metabolism * Foods * Grapefruit juice, brassicas * Age - Impaired hepatic enzyme activity * Elderly * Children < 6 months

Question 28

First pass metabolism

Answer 28

The hepatic metabolism of a drug and its movement into the circulation.  If a drug is administered orally much of it will be extensively metabolised in the liver prior to it reaching the systemic circulation (High first pass effect)  If the same drug were to be given IV, this would not go to the liver and thus would prevent ‘first pass’ metabolism from occurring, thus more is available in the circulation to have it’s intended effect.

Question 29

Effects of the GI system

Answer 29

 The stomach is acidic and will destroy some drugs before they can have an effect, e.g. insulin  All blood in the GI tract passes into the hepatic portal vein and then to the liver  Thus, many drugs lose much of their effectiveness or are totally deactivated if given orally.

Question 30

Drug administered orally

Answer 30

Question 31

Bioavailability- what is it and what is it affected by

Answer 31

The amount of active drug that reaches the systemic circulation Affected by: * Dosage form * Dissolution and absorption of drug * Route of administration * Stability of the drug in the GI tract (if oral route) * Extent of drug metabolism before reaching systemic circulation e.g. First Pass metabolism * Presence of food/drugs in GI tract This fraction is the drug's bioavailability.