Pharm Midterm

Drug

Any chemical that affects the physiological processes of a living organism

Pharmacology

Broadest term for the study or science of drugs

Chemical name

Describes the drug’s chemical composition and molecular structure

Generic name (nonproprietary, official name)

Name given to a drug approved by Health Canada

Trade name (proprietary name)

The drug has a registered trademark; use of the name is restricted by the drug’s patent owner (usually the manufacturer)

Chemical name for Ibuprofen

(+/-)-2-(p-isobutylphenyl) propionic acid

Generic name for (+/-)-2-(p-isobutylphenyl) propionic acid

ibuprofen

Trade name for ibuprofen or (+/-)-2-(p-isobutylphenyl) propionic acid

Advil, Motrin, etc.

Pharmacological Principles

• Pharmaceutics

• Pharmacokinetics

• Pharmacodynamics

• Pharmacogenomics (pharmacogenetics)

• Pharmacotherapeutics

• Pharmacognosy

• Pharmacoeconomics

• Toxicology

Pharmaceutics

• Study of how various drug forms influence the way in which the drug affects the body

• Dissolution

  • Dissolving of solid dosage forms and their absorption

  • SR (slow realse)

  • SA (slow action)

  • CR (controled realse)

  • XL (extened legth)

  • XT (extended time)

  • Thin-film (disvoled in the mouth)

Phases of Drug Activity

Administeration → I Pharmaceutical Phase → Drug available for absorption → II Pharmaceutical Phase → Drug availble for action → III Pharmaceutical Phase → Effect

I Pharmaceutical Phase

Disinegration of dosage from dissoultion of drug

II Pharmaceutical Phase

Absorption, distribution, metabolism, exertion

III Pharmaceutical Phase

Drug-receptor interaction

Pharmacokinetics

• The study of what the body does to the drug

• From the time drug is put into the body until the parent drug and metabolites have left the body

  • Absorption

  • Distribution

  • Metabolism (the liver and kidney’s mainly)

  • Excretion

Bioequivalent

Two pharmaceutical products that contain the same active ingredient, have the same dosage form, and are expected to have similar bioavailability when administered in the same molar dose under similar conditions.

Enteral Route

• The drug is absorbed into the systemic circulation through the mucosa of the stomach, or intestine

  • Oral (Nasogastric, g-tube, j-tube)

  • Sublingual

  • Buccal (between cheek and gum)

  • Rectal (can also be topical)

Parenteral Route

• Intravenous

  • fastest due to direct delivery into the blood circulation

• Intramuscular

• Subcutaneous

• Intradermal

• Intra-arterial

• Intrathecal

• Intra-articular

Intravenous

Administered directly into a vein, allowing for rapid absorption into the bloodstream. Commonly used for delivering medications, fluids, and nutrients.

Intramuscular

A method allowing for faster absorption of medications compared to subcutaneous injections. Common sites include the deltoid, thigh, and gluteal muscles. It’s often used for vaccines, hormones, and certain medications.

Subcutaneous

Located or occurring beneath the skin, this layer is composed of fat and connective tissue. It plays a crucial role in insulation, energy storage, and cushioning of underlying structures. This area is often targeted for injections, as it allows for slower absorption of medications into the bloodstream.

Intradermal

A method of injection where a substance is administered into the dermis, the layer of skin just beneath the epidermis.

Intrathecal

A method of delivering medication directly into the spinal canal or cerebrospinal fluid.

Topical Route (local and systemic effects)

• Skin (including transdermal patches)

• Eyes

• Ears

• Nose

• Lungs (inhalation)

• Rectum (mixed first-pass)

• Vagina

Distribution

• Transport of a drug by the bloodstream to the drug’s site of action

• Drugs distributed first to areas with extensive blood supply

  • Heart, liver, kidneys and brain

Albumin

The most common blood protein and carries most protein-bound drug molecules.

Distribution: Protein Binding

• If a given drug binds to albumin, only a limited amount of the drug is not bound.

• This unbound portion is active and is considered “free” drug.

• Certain conditions lead to low albumin, increasing the chance of toxicity. (burns)

• Drug interactions can happen if drugs fight to bind

Blood-brain barrier

A selective permeability barrier that separates the circulating blood from the brain and extracellular fluid in the central nervous system. It protects the brain from potentially harmful substances while allowing essential nutrients to pass through. This structure is formed by tightly packed endothelial cells and is crucial for maintaining the brain's homeostasis. Disruption can lead to neurological disorders.

Blood-placenta barriers

Serves to prevent the direct mixing of maternal and fetal blood, allowing for nutrient and gas exchange while protecting the fetus from potential toxins and pathogens.

Metabolism

• Also referred to as biotransformation

• Biochemical alteration of a drug into any of the following:

  • an inactive metabolite

  • a more soluble compound

  • a more potent metabolite (as in the conversion of an inactive prodrug to its active form)

  • a less active metabolite

Where are drug mainly metabolized

Kidney and liver

Fastest to Slowest Oral drug absorption

• Liquids

• Suspension solutions

• Powders

• Capsules

• Tablets

• Coated Tablets

• Enteric-coated tablets

Hepatic Metabolism

• Cytochrome P-450 enzymes AKA microsomal enzymes

• Lipophilic (“fat loving”)

• Hydrophilic (“water loving”)

• Substrates

• Enzyme inhibitors (meds delay metabolism)

• Enzyme inducers (speed up metabolism)

Excretion

• Elimination of drugs from the body

  • Primary organ responsible is kidney (GF)

  • Liver and bowel also play a role

  • Renal excretion

  • Biliary excretion

Enzyme inhibitors

Substances that decrease or halt the activity of enzymes by binding to them. These inhibitors play crucial roles in regulating metabolic pathways and are often used in pharmaceuticals to target specific enzymes in disease treatment.

Enzyme inducers

Substances that increase the activity of enzymes responsible for drug metabolism. This often leads to a faster breakdown of medications, potentially reducing their effectiveness.

Pharmacokinetics

• Onset of action: time required till therapeutic response

• Peak level: highest blood level of a drug

• Trough level: lowest blood level of a drug

• Toxicity: occurs if the peak blood level of the drug is too high

• Therapeutic drug monitoring

• The length of time until the onset and peak of action and the duration ofaction play an important part in determining the peak level (highest bloodlevel) and trough level (lowest blood level) of a drug. If the peak blood levelis too high, then drug toxicity may occur

Pharmacodynamics

• The study of what the drugdoes to the body

  • The mechanism of drugactions in cells and tissues

  • Therapeutic effect

    • The goal of drug therapy

  • Mechanism of action {MOA}

  • Receptor interactions

  • Enzyme interactions

  • Nonselective (chemo)

Mechanism of action {MOA}

A term used to describe how a drug or other substance produces an effect in the body

Enzyme interactions

Specific interactions between different enzymes, which can occur when they are present in the same cell compartment. Drugs can inhibit the activity of the enzyme by binding to its active site where substrate molecule bind

Receptor interactions

Involve the binding of the drug to the receptor. Involving all known types of bond: ionic, hydrogen, van der Waals, covalent.

Nonselective (chemo)

Pharmacotherapeutics

• The clinical use of drugs to prevent and treat diseases

• Desired therapeutic outcomes is patient-specific, established in collaboration with the patient

• Outcome goals need to be realistic

• Contraindications

Pharmacotherapeutics (Types of Therapy)

• Acute -(nausa)

• Maintenance -(chronic)

• Supplemental (or replacement) - (defincianty)

• Palliative - (comfort)

• Supportive - (chronic)

• Prophylactic - (prevention)

• Empirical - (what the science say, if it looks like a duck…)

Pharmacotherapeutics (Monitoring)

• Therapeutic action

  • Beneficial effects

• Adverse effects

  • Predictable adverse drug reactions

• Toxic effects

• Therapeutic index (low = small gap between therapeutic and toxic)

• Drug concentration

• Patient condition

Physical dependence

Physiological need for a drug to avoid physical withdrawal symptoms

Psychological dependence (addiction):

Obsessive desire for a drug

Drug interactions - Additive effects (1+1=2)

When two or more substances are combined, their effects on the body enhance each other, leading to a greater overall effect than when each is taken individually. This can result in increased efficacy or heightened side effects, necessitating careful monitoring and dosage adjustments.

Drug interactions - Synergistic effects (1+1=>2)

When two or more substances enhance each other's effects, leading to a greater combined effect than the sum of their individual effects. This can increase therapeutic outcomes but also raises the risk of adverse effects or toxicity.

Drug interactions - Antagonistic effects (1+1=<2)

A situation where two or more drugs work against each other, reducing the effectiveness of one or more of the medications. This can lead to decreased therapeutic effects or increased side effects, complicating treatment plans.

Drug interactions - Incompatibility (1+1=0) *2 parenteral in same IV bag

A situation where two or more drugs react negatively when combined, leading to reduced effectiveness, increased toxicity, or harmful side effects.

Medication error

An event that leads to the inappropriate use of a medication, potentially causing harm to the patient.

Adverse drug withdrawal event

Adverse drug reaction

Carcinogenic

A substance or agent that is capable of causing cancer in living tissue. Exposure can occur through inhalation, ingestion, or skin contact, and it may lead to mutations in DNA, disrupting normal cell function and growth. Common examples include certain chemicals, radiation, and viruses.

Mutagenic

Factor that causes changes or mutations in the DNA of an organism. These changes can lead to alterations in genetic information, potentially resulting in harmful effects, such as cancer or genetic disorders. Can be physical, chemical, or biological.

Teratogenic

Factors that can cause malformation or abnormalities in a developing embryo or fetus. These can include certain drugs, chemicals, infections, and environmental factors that disrupt normal development during pregnancy.

Pharmacotherapeutics (Ten Rights of Medication)

• Right drug

• Right dose

• Right time

• Right route

• Right patient

• Right reason

• Right documentation

• Right evaluation for right assessment

• Right patient education

• Right to refuse

Pharmacognosy

• The process of identifying medicinal plans and their ingredients, pharmacological effects, and therapeutic efficacy

• Four main sources for drugs: plants, animals, minerals, and laboratory synthesis

Pharmacoeconomics

• Study of the economic factors influencing the cost of drug therapy

• Cost–benefit analysis

Toxicology

• Science of poisons and unwanted responses to both drugs and chemicals

• Clinical toxicology deals specifically with the care of poisoned patients

Changes Across the Lifespan

• Age related changes have a dramatic effect on pharmacokinetics

• Increased risk of adverse effects and toxicity at both ends of spectrum of life

Drug Therapy During Pregnancy

• Drugs cross the placenta primarily by diffusion.

• Factors affecting safety:

  • Drug properties

  • Fetal gestational age

  • Maternal factors (liver & kidney function)

• US FDA and Health Canada have pregnancy and lactation safety categories and or warnings

Drug Therapy During Breastfeeding

• Breastfed infants are at risk for exposure to drugs consumed by the mother

• Consider risk–benefit ratio

• Pump and dump sometimes an option

Neonatal and Pediatric Considerations: Absorption

• Gastric pH less acidic until 1 to 2 years of age

• Gastric emptying slowed

• First-pass elimination reduced

• Reduced bile salt formation decreases bioavailability

• Intramuscular absorption faster and irregular

Neonatal and Pediatric Considerations: Distribution

• Total body water differences result in increased distribution and dilution of water-soluble drugs.

• Greater total body water means lower fat content.

• Decreased level of protein binding

• Immature blood–brain barrier means more drugs enter the brain.

Neonatal and Pediatric Considerations: Metabolism

• Liver immature; does not produce enough microsomal enzymes

• Older children may have increased metabolism, requiring higher doses or more frequent administration than infants.

• Other factors: liver enzyme production, genetic differences, and substances to which the mother may have been exposed during pregnancy

Neonatal and Pediatric Considerations: Excretion

• Kidney immaturity affects glomerular filtration rate and tubular secretion.

• Decreased perfusion rate of the kidneys may reduce excretion of drugs.

Factors Affecting Pediatric Drug Dosages

• Skin is thin and permeable.

• Stomach lacks acid to kill bacteria.

• Lungs have weaker mucus barriers.

• Body temperatures are less well regulated, and dehydration occurs easily.

• Liver and kidneys are immature, impairing drug metabolism and excretion

Dosage Calculation for Pediatric Patients

• Body surface area method (chemo, preemies)

  • Uses the West nomogram

• Always use weight in kilograms, not pounds.

• Always use height in centimeters, not inches.

• Body weight dosage calculations

  • Uses mg/kg

Considerations for Older Adult Patients

• Older than age 65 years

• High use of medications

• Polypharmacy (Taking lots of medication, they are fighting each other)

• Nonadherence

• Increased incidence of chronic illnesses

• Sensory and motor deficits

Older Adults: Absorption

• Gastric pH less acidic

• Movement through GI tract slowed because of decreased muscle tone and activity

• Blood flow to GI tract reduced

• Absorptive surface of GI tract reduced

Older Adults: Distribution

• Lower total body water percentages

• ↑ fat content

• ↓ production of proteins by the liver, resulting in ↓ protein binding of drugs (and ↑ circulation of free drugs)

Older adults: Metabolism

• Aging liver produces fewer microsomal enzymes, affecting drug metabolism.

• Blood flow to the liver is reduced.

• Leads to a prolonged half-life of many drugs

  • Potential for accumulation if not monitored

Older adults: Excretion

• ↓ glomerular filtration rate

• ↓ number of intact nephrons

Seizure

Brief episode of abnormal electrical activity

Convulsion

Involuntary spasmodic contractions of any or all voluntary muscles

Epilepsy

Chronic, recurrent pattern of seizures

Primary (idiopathic)

• Seizures with no identifiable cause, often linked to genetic factors.

• Typically, it occurs without any underlying neurological disorder.

• Includes generalized seizures (e.g., absence, tonic-clonic) and focal seizures.

• Diagnosed based on clinical history, EEG findings, and exclusion of secondary causes.

• Antiepileptic medications are commonly prescribed to manage symptoms.

Secondary (symptomatic)

• Seizures that occur as a result of an identifiable underlying condition, such as a brain injury, infection, or metabolic disturbance. Such as:

  • Head trauma

  • Stroke

  • Tumors

  • Infections (e.g., meningitis)

  • Metabolic imbalances (e.g., low blood sugar)

• May vary in type and severity depending on the underlying cause.

• Diagnosis Requires medical evaluation, including imaging and laboratory tests to identify the cause.

Classification of Epilepsy

• Generalized onset seizures

• Partial onset seizures

• Unclassified seizures

Generalized onset seizures

Tonic-clonic seizures and Atonic seizures

Partial onset seizures

• Localized or focal region

• Simple

• Complex

• Secondary generalized tonic-clonic

Status Epilepticus

A single seizure lasting more than 5 minutes, or 2 or more seizures within a 5-minute period without the person returning to normal between them. Can result in hypotension, hypoxia, brain damage, and possibly death

Hypotension

Low blood pressure, is a condition where blood pressure readings are lower than normal, typically below 90/60 mmHg.

Hypoxia

Insufficient oxygen reaches the tissues.

Goals of Antiepileptic Drugs

• To control or prevent seizures while maintaining a reasonable quality of life

• To minimize adverse effects and drug-induced toxicity

Antiepileptic Drugs

• Also known as anticonvulsants

• Antiepileptic drug (AED) therapy is usually lifelong

• A combination of drugs may be used

• Serum drug concentrations must be measured

• Traditionally used to manage seizure disorders:

  • Barbiturates

  • Hydantoins

  • Iminostilbenes plus valproic acid

  • Second- and third-generation antiepileptics

Difference between epilepsy and convulsion

• Epilepsy: A chronic neurological disorder characterized by recurrent, unprovoked seizures due to abnormal electrical activity in the brain. It can have various causes and types.

• Convulsion: A physical manifestation of a seizure, often involving violent muscle contractions. Convulsions can occur in various conditions, not just epilepsy.

In summary, epilepsy is a condition, while convulsions are symptoms of seizures that can occur in epilepsy and other disorders.

Antiepileptic Drugs - Mechanism of Action

• Exact mechanism of action is not known.

• Pharmacological effects

  • Reduce nerve’s ability to be stimulated

  • Suppress transmission of impulses from one nerve to the next

  • Decrease speed of nerve impulse conduction within a neuron

Antiepileptic Drug Effects

• Numerous adverse effects; vary per drug

• Adverse effects often necessitate a change in medication.

• Long-term therapy with phenytoin (Dilantin®) may cause gingival hyperplasia, acne, hirsutism, and Dilantin facies.

Dilantin®

phenytoin - Useful for the prevention of tonic-clonic seizures and focal seizures, but not absence seizures.

Examples of common Antiepileptic Drugs

• phenytoin (Dilantin)

• carbamazepine (Mazepine®)

• ethosuximide (Zarontin®)

• levetiracetam (Keppra®)

• lamotrigine (Lamictal®)

• topiramate (Topamax®)

• valproic acid (Depakene®)

• perampanel (Fycompa®)

• phenobarbita

Barbiturates

• Primidone is metabolized in the liver to phenobarbital

• Most common adverse effect is sedation

• Therapeutic effects: serum drug levels of 15 to 40 mcg/mL

• Contraindications:

  • known drug allergy, porphyria, liver or kidney impairment, respiratory illness

• Adverse effects:

  • cardiovascular, central nervous system (CNS), gastrointestinal (GI), and dermatological reactions

Hydantoins: phenytoin sodium

• Phenytoin (Dilantin®) has been used as a first-line drug formany years and is the prototypical drug.

• Long-term therapy adverse effects:

  • gingival hyperplasia

  • acne

  • hirsutism - the growth of excessive male-pattern hair in women

  • Dilantin facies - Swelling, especially of your face

  • osteoporosis - low bone mass

• Therapeutic drug levels are usually 10 to 20 mcg/mL.

Hydantoins: phenytoin sodium - Intravenous (IV) administration

• Very irritating to veins

• Slow IV directly into a large vein through a large-gauge (20-gauge orlarger) venous catheter

• Diluted in normal saline for IV infusion

• Filter must be used

• Saline flush

Hydantoins: fosphenytoin (Cerebyx®)

• Injectable prodrug of phenytoin

• Water-soluble phenytoin derivative that can be given intramuscularly or intravenously—by IV push or continuous infusion—without causing burning on injection associated with phenytoin

• Adverse effects

  • nystagmus - eyes make rapid, repetitive, uncontrolled movements

  • dizziness

  • pruritus - itchiness

  • somnolence - a strong desire for sleep

  • ataxia - loss of muscle control

Carbamazepine (Tegretol®)

• Second most commonly prescribed antiepileptic drug in Canada after phenytoin

• Autoinduction of hepatic enzymes

• Adverse reactions

  • skin rash

  • dizziness

  • drowsiness,

  • ataxia - loss of muscle control

  • nausea and vomiting

• Drug interactions

  • medicines to help prevent blood clots

  • antibiotics or antifungals

  • medicines used for depression or anxiety

Pregabalin (Lyrica) or Gabapentin (Neurontin)

• Structurally related to GABA

• Indication: focal seizures

• Most common uses:

  • Adjunct therapy for neuropathic pain

  • postherpetic neuralgia

• Contraindication: known drug allergy

• Adverse drug reactions: primarily CNS related

• Oral use only

lamotrigine (Lamictal®)

• Also used for the treatment of bipolar disorder

• Contraindications: drug allergy

• Common adverse effects:

  • Relatively minor CNS and GI symptoms and possible Stevens-Johnson syndrome

• Oral use only