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Pharmacokinetic principles

In pharmacokinetics, drug routes, absorption, dosage, frequency, distribution, and serum levels are considered.

Factors to understand here include:

  • The doses needed for the recipient and the rate of clearance of the drug they are given
  • The volume of distribution
  • The elimination half-life as well as the context-sensitive half-life
  • Recovery time
  • Effect-site equilibrium
  • Bioavailability of the drugs

Pharmacodynamic principles

Drug administration can have both therapeutic and adverse biological effects over time and that’s what this principle relates to. 

When determining these effects, it’s important to consider drug transport and absorption, the way it’s eliminated, and its half-life.

Feedback from pharmacodynamic principles allows for medication dosage modification (pharmacokinetics).

Drug clearance and first pass metabolism

The ability of a drug to be removed from the body is known as drug clearance and this is dealt with in the body by the liver (through bile) and kidneys (through urination). 

Ingested drugs that enter the hepatic portal system through the gastrointestinal tract are subject to first pass metabolism.

This means that they are dealt with by the liver and this can significantly affect some drugs and their bioavailability. 

Enterohepatic recirculation and renally-excreted drugs

In this process, a drug is removed from circulation and then reabsorbed into the body.

The duration of action of the drugs is increased because of this but the clearance is reduced. 

With drugs that are renally-excreted, the liver will metabolize them so that the kidneys can excrete them. 

For those with renal problems, drugs that rely on clearance from the kidneys should not be administered. 

Routes of administration and absorption

There are different absorption characteristics for drugs dependent on their routes of administration.

  • Oral: Here the small intestine is where most of the absorption will occur and various factors can play a role in the rate thereof. First pass metabolism should be taken into account too if drugs are administered orally
  • Intravenous: This has a 100% absorption rate. Some drugs cannot be given in this manner, however, because of toxicity or vein irritation characteristics
  • Intramuscular: As muscle tissue is highly vascularized, drugs injected into it are absorbed at a relatively rapid pace.
  • Subcutaneous: Because the dermis is not as vascularized as muscle, drugs injected beneath the skin will absorb at a slower rate.

Medication side effects

Side effects must always be taken into account when administering drugs.

These three steps should be followed at all times in this regard:

  • Find out if the patient has any allergies or if they have had reactions to drugs before
  • All side effects that could occur from the drug should be passed on to the patient beforehand
  • Be careful of potential multiple drug combinations, or combinations between drug and food that could be dangerous

Adult medication administration principles

Classification of drugs

Drugs can be classified as:

  • Therapeutic
  • Pharmacological

Drugs also form part of different schedules as per the Controlled Substances Act, which you can read up on in your coursework.

In total, there are five different schedules under which drugs fall. 

Medical administration: The 5 Rights

As a way to prevent medication errors from occurring in medical facilities, the 5 rights of medication administration should be followed. 

These are:

  • The right patient
  • The right drug
  • The right dosage
  • The right route to be administered
  • The right time/frequency

Drug administration routes

Here are the most common routes of drug administration:

  • Enteral which includes by feeding tube, orally or rectally
  • Topical which includes inhaled, vaginal, in the nose, in the eyes, or on the skin 
  • Parenteral which includes a variety of options like IV, subcutaneous, epidural, intracardiac, intradermal, intramuscular, and more

Note that there are a range of variations on these common routes.

The following should be considered when deciding on the best one:

  • The speed at which the patient needs the drug
  • The effectiveness of the given route
  • The chances of toxicity occurring 
  • What discomfort levels the chosen route will cause
  • Will the patient comply with the route chosen
  • A route’s potential to play into a patient’s addiction

Pharmacology: Cardiovascular 

Pharmacology of Cardiovascular 

There’s lots covered in your coursework when it comes to cardiovascular pharmacology and all of it will be critical for the exam, so we won’t try to summarize it here.

Here’s the important parts that you should go through:

  • Medications: Anti-hypertensive including the various types of diuretics 
  • Antidysrhythmic drugs from Class 1 to Class IV as well as those that are unclassified
  • Muscle relaxants
  • Calcium channel blockers
  • Vasodilators
  • Inotropic agents
  • Heart failure medications
  • Glycoprotein IIB/IIIA inhibitors

Pharmacology: Respiratory

Pharmacology of Respiratory problems

Asthma: Pharmacological agents

Here’s a list of the various pharmacological agents used to help control asthma. 

This is both to provide relief for acute episodes as well as long-acting options to prevent asthma attacks.

  • Adrenergic agonists 
  • Anticholinergics
  • Corticosteroids
  • Methylxanthines
  • Magnesium sulfate
  • Heliox
  • Leukotriene inhibitors

Pulmonary pharmacology: Additional agents

In this regard, a variety of agents are used depending on the type and severity of the disease. 

These include:

  • Opioid analgesics
  • Neuromuscular blockers
  • Human B-type natriuretic peptides
  • Surfactants
  • Alkalinizers
  • Pulmonary vasodilator 
  • Methylxanthines
  • Diuretics 
  • Nitrates
  • Antibiotics
  • Antimycobacterials
  • Antivirals

Your coursework will have all the information that you need on these agents.

Pharmacology: Endocrine

Pharmacology of Endocrine

Oral hypoglycemic agents

These are generally used to treat Type II diabetic patients. 

You will find five categories of oral hypoglycemic agents:

  • Sulfonylureas
  • Biguanides
  • Meglitinides
  • Competitive inhibitors of alpha-glucosidases
  • Thiazolidinediones

Recently, two more classes have been introduced in the form of DPP-4 and SGLT2 inhibitors. 

Metformin is often an example of a biguanide oral hypoglycemic agent.

Insulin treatments for glycemic disorders

A range of insulin treatments exist for glycemic disorders.

How they are prescribed often is based on each individual in terms of their level of activity, their intake as well as their metabolism. 

These treatments include:

  • Humalog
  • Regular
  • NPH
  • Insulin glargine
  • Combined NPH/regular

Pharmacology: Immunologic and Oncologic

Pharmacology Immunologic and Oncologic

Immunosuppressant drugs

The following are a list of immunosuppressant drugs that you will need to know in terms of both action and what their side effects are. 

  • Corticosteroids
  • Ciclosporin
  • Intravenous immuno-globulin G (IVIG)

Chemotherapy

Chemotherapy is used to treat cancer patients, particularly to control cancer-related symptoms and prolong their lives. 

Chemotherapeutic agents include the following:

  • Alkylating agents
  • Nitrosoureas
  • Antimetabolites
  • Antitumor antibiotics
  • Plant (vinca) alkaloids
  • Steroid hormones 

When it comes to chemotherapy delivery, there are a few options. 

These include oral, intravenous, and intramuscular delivery. 

In terms of side effects, well these vary greatly from patient to patient although some can be controlled through medication.

These effects include suppression of bone marrow, hair loss, mouth ulcers, sore gums, sore throat, vomiting, nausea, heartburn, weight loss, and more. 

The risks of chemotherapy include infection, anemia, neurological damage, retina damage, kidney damage, and heart damage if not monitored properly. 

Pharmacology: Hematological

Pharmacology of Hematological studies

Anticoagulants 

Here’s a common list of anticoagulants that are used in the hospital environment:

  • Antithrombin activators
  • Direct thrombin inhibitors
  • Direct Xa inhibitors
  • Antithrombin (AT)
  • Warfarin

You can read up on all of these in your coursework.

Thrombolytics

Should a patient need to dissolve clots as a result of a DVT, pulmonary embolism, ischemic stroke, or myocardial infarction, they would take thrombolytic medication. 

At times, and as a way to increase anticoagulation effects, thrombolytics are given together with heparin. 

As for administration, this should occur 90 mins following an event but never more than six hours after as this greatly increases the chance of a hemorrhage occurring. 

Here’s a list of common thrombolytics:

  • Alteplase tissue-type plasminogen activator
  • Anistreplase
  • Reteplase
  • Streptokinase
  • Tenecteplase

Thrombolytic therapy contraindications include:

  • Hemorrhage (both cerebral or subarachnoid) or other forms of the patient bleeding internally
  • Seizures and hypertension that cannot be controlled
  • Intracranial AVM, aneurysm, and neoplasm
  • Low platelet count

Anticonvulsants 

Here’s a list of anticonvulsants that might appear in the exam:

  • Carbamazepine
  • Clonazepam
  • Ethosuximide
  • Felbamate
  • Fosphenytoin
  • Gabapentin
  • Lamotrigine
  • Levetiracetam
  • Oxcarbazepine
  • Phenobarbital
  • Phenytoin
  • Primidone
  • Tiagabine
  • Topiramate
  • Valproate/Valproic acid
  • Zonisamide

Administration of Hypertonic Saline Solution (HSS)

HSS is used to treat patients that have traumatic brain injuries, specifically as a way to lower intracranial pressure through osmosis that removes fluid from the tissue. 

HSS concentrations are between 2% and 23.4%. 

In addition to expanding plasma and increasing CCP as well, HSS counteracts hyponatremia.

Mannitol 

This osmotic diuretic helps to reduce brain mass and intracranial pressure through the excretion of water and sodium.

It can be used to help other medications breach a blood-brain barrier as well. 

Pharmacology: Pharmacology

Woman hands holding bunch of medical pills isolated over white background

Histamine receptor antagonists

When heartburn and GERD caused by excessive stomach acids are affecting a patient, they can be treated through histamine receptor antagonists. 

This form of medication will block specific stomach histamine 2 cell receptors.

Because of this, acid production is significantly reduced. 

While these are not used as much as proton-pump inhibitors nowadays, the most common of these antagonists are:

  • Cimetidine
  • Famotidine
  • Nizatidine 

Antacids

Antacids work in a few ways to relieve indigestion and heartburn. 

First, they reduce the acids in the stomach. 

This is achieved by elevating the pH level. 

Secondly, the acids that are present in the stomach are also neutralized by the antacids. 

Types of antacid medication include:

  • Aluminum hydroxide
  • Magnesium hydroxide
  • Aluminum hydroxide with magnesium hydroxide
  • Calcium carbonate
  • Alka-Seltzer
  • Bismuth subsalicylate

Proton pump inhibitors (PPIs)

These have become far more popular in the medical field when compared to histamine receptor antagonists. 

Stomach acid is reduced as the stomach wall is impacted by the PPI when taken which causes it to produce fewer enzymes that produce acid. 

PPIs can be used in several ways and particularly as a way to treat ulcers, GERD, and more.

They do have some side effects, however, which can result in GI upsets and headaches while occasionally, taking PPIs can lead to intense muscle pain. 

They can also mess with how other drugs are absorbed into the body. 

Pharmacology: Pain management 

Pharmacology for Pain management 

WHO Pain ladder

This is an algorithm that was specifically drawn up as a way to help treat pain for both adult and pediatric patients through medication.

The medication given, however, increases progressively in strength. 

Always start with the medication that’s the least potent and gets stronger (if need be) until the patient experiences pain relief.

There are three steps to the WHO pain ladder:

  • Step 1: This sees non-opioid medication administered to the patient. This can be together with or without additional adjuvant therapies
  • Step 2: If there is no change in the level of pain experienced by the patient, opioids that relieve mild to moderate pain can be introduced. If adjuvants therapies have not been used in step 1, they can be brought in now as well
  • Step 3: If there is no change in the pain experienced by the patient, they can now be treated with moderate to severe pain-relieving opioids while adjuvants are continued as well

Pain medication: Scheduling

Acetaminophen, alternated with ibuprofen or other NSAIDs are given to patients with mild to moderate pain and given when needed or on a regularly scheduled basis.

Opioid pain medications are given for those with severe chronic pain as a way to control and prevent it and include MS Contin, Duragesic, and OxyContin. 

Supplementary medications may also be necessary, specifically once that act in the short term.

The use of opioids must be strictly monitored as they have many side effects and patients can become addicted to them.

These side effects include:

  • Respiratory depression
  • Analgesia
  • Sedation
  • Euphoria
  • Miosis
  • Nausea
  • Suppressing coughs
  • Vomiting
  • Truncal rigidity
  • Constipation
  • Hypotension 
  • And more

There are numerous opioids covered in your coursework that we won’t go through in great detail here, but include:

  • Fentanyl citrate
  • Methadone
  • Oxycodone
  • Hydromorphone
  • Morphine

Ketamine

As a way to complement opioids or even as an alternative to them, Ketamine, a dissociative anesthetic can be given to patients that are experiencing pain. 

An initial bolus of 0.1mg/kg IV is given to the patient and if no relief is forthcoming, a double dose can be given in 5 minutes and repeated as needed.

The treatment of breakthrough pain

Let’s look at ways in which the three types of breakthrough pain can be treated.

  • Incident pain is pain that’s linked to an event or activity, for example, changing the dressing on a wound, or a patient undergoing physical therapy. Before the event, this can be treated with an analgesic that’s short-acting
  • Spontaneous pain is there’s no time or event that this can be pinpointed to and this pain is mostly unpredictable. Adjuvant therapy is one way to combat neuropathic pain that’s spontaneous but an analgesic that’s short-acting and acts rapidly can also be used
  • End-of-dose failure is a pain that occurs as levels of the medication in the blood begin to drop at the end of a routine dosing cycle where analgesics have been administered

Neuropathic pain treatment

The three most successful classes of drugs for treating this kind of pain are anticonvulsants, anesthetics, and antidepressants. 

For the most part, these are given as a constant dose with 24-hour symptom control but can be given instead when needed by patients.

The type of disorder and its overall progression will play a role in which type of medication is chosen.

Bone pain treatment

The causative agent related to the pain plays a role in the selection of the kind of treatment for bone pain in cancer patients.

Treatment options include:

  • Systematic treatment (chemotherapy, radiation)
  • Hormone therapy
  • Bisphosphonates

Surgery might have to be an option too, especially where cancerous growths can be removed safely while opioids and NSAIDs/COX-2 inhibitors can provide pain relief too.

End-of-life patient pain medication concerns 

There are several concerns that need to be taken into account when dealing with medication for end-of-life patients. 

First, adequacy

Many patients raise concerns regarding the medication they will receive and whether it will be adequate enough to deal with the pain they are experiencing.

Second, sedation/addiction.

Patients and family members often raise concerns regarding the pain meds given to patients in terms of how it might affect their overall cognition, or if they will become disorientated, confused, or permanently sedated.

Other questions may arise regarding addiction to pain medication, especially if the patient is in the early part of the end-of-life cycle. 

Third, adverse effects

Patients and their families will also raise questions about the adverse effects that medications could cause, for example, nausea or vomiting, which can be debilitating.

Psychosocial pharmacology

Psychosocial pharmacology

Antipsychotic medications

When we talk about antipsychotic medications, there are two generations to discuss.

First-generation antipsychotic medications are not as prevalent as they once were but are still in use.

They include:

  • Chlorpromazine
  • Thioridazine hydrochloride
  • Haloperidol
  • Pimozide
  • Fluphenazine hydrochloride
  • Molindone Hydrochloride
  • Trifluoperazine hydrochloride

Second-generation antipsychotic medications (SGAs) are often used for people suffering from psychosis, and schizophrenia, as well as those with bipolar disorders. 

These include:

  • Aripiprazole
  • Clozapine
  • Olanzapine
  • Quetiapine
  • Risperidone
  • Ziprasidone

Antidepressants

These are used on patients that suffer from depression mainly, but this can be expanded even more to include people with atypical and severe depression as well as those with anxiety disorders. 

In some cases, they can be used in other ways, for example, treating those with insomnia, attention deficit disorder, chronic pain syndrome, and premenstrual syndrome. 

SSRIs

This class of antidepressants known as selective serotonin reuptake inhibitors, helps to reduce both anxiety and depression.

They do this by stopping the presynaptic member from serotonin reuptake. 

Examples of SSIs include citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline.

Tricyclic antidepressants

These are similar to SSRIs in the fact that they stop serotonin reuptake but they also do more. 

There are three other receptors that they block and these are the muscarinic, cholinergic, and histamine H1 receptors. 

While this has nothing to do with depression, these being blocked is crucial in stopping the patient experiencing some of the side effects that taking tricyclic depressants brings. 

Anti-anxiety medications

Benzodiazepines

For those suffering from anxiety, this is what’s often prescribed for them. 

Common benzodiazepines include:

  • Chlordiazepoxide
  • Diazepam
  • Flurazepam
  • Lorazepam
  • Triazolam

This medication targets the neurotransmitter GABA and enhances it which lowers the neuronal firing rates and helps anxiety symptoms to decrease. 

They can be used in other ways too, for example, for patients with insomnia (because of their sedative effects), as a way to help with seizure control, to help with alcohol withdrawal, and to reduce anxiety.

Geriatric pharmacology

Geriatric pharmacology

As people get older, the chance that they may experience adverse effects from medication grows.

Around 10% of elderly patients affected by adverse drug reactions (ADRs) will require hospitalization. 

Most of these side effects include the likes of vomiting, edema, loose stools, constipation, urinary retention, bewilderment, and others.

It’s important to not misidentify what the problem is, for example, is it simply a result of their aging, or another condition altogether.

Older adult pharmacokinetics 

When it comes to pharmacokinetics there are four steps to consider and all of these are affected by a patient’s age as well as in what condition their organs are involved in these steps. 

  • Absorption: The small intestine deals with this for most drugs and because of decreased blood flow to this area in older patients, this may cause a delay or decrease in absorption
  • Distribution: A change in body composition will alter how the drug is distributed. In the elderly, there is a lower percentage of lean muscle mass as well as decreased total body water. Also, the duration of the action of lipid-soluble drugs can be increased due to higher total body fat
  • Metabolization: It’s in the liver or the kidneys where most drugs will be metabolized. They will be a delay in metabolization when these organs are operating at a decreased function level 
  • Renal function and elimination effectiveness: As a person gets older, this will decline. Because of that, the kidneys become less effective in taking medications and toxins out of the body. This means smaller doses in the elderly because drugs stay in the body for more extended periods of time. 

Beers List

This highlights medication that should not be used for older adults. 

Using the list, one can determine which medications are most beneficial and which pose the greatest risk for patients.

Medication use difficulties elderly patients may encounter

Medication use in elderly patients can lead to these common difficulties

  • Prescription medication overuse
  • Issues regarding medication adherence and compliance
  • Not knowing how to use the medication properly as a result of not hearing correctly or not comprehending what the patient has been told
  • Not remembering how the drugs should be used in terms of the amount that should be taken, how often should be taken, or the reason that it should be taken
  • Cost factors (they cannot afford the prescribed medication)
  • Misreading labels and dosage errors because of vision issues
  • Struggling to open medication packaging, losing pills because they are small and other problems

Prescription medication: Common adverse reactions

These include:

  • Bewilderment
  • Weakness
  • Low energy
  • Constipation
  • Diarrhea 
  • GI Upset
  • Tinnitus
  • Urinary retention
  • Low blood pressure (Orthostatic)
  • Depression
  • Vertigo

Polypharmacy

In this case, multiple medications are used inappropriately at the same time.

It happens when medications are taken that are not prescribed, multiple medications interact adversely with each other, or when contradictory medications are taken by patients.

Obtaining a detailed drug history from the patient at each visit can help stop this. 

Rational drug therapy: MASTER rules

The MASTER rules system can be used to help determine if a drug should be used or not be used by a patient:

  • M: Minimize the number of drugs taken by the patient
  • A: Instead of drugs, look for alternative treatments that can be effective and use that instead, if possible
  • S: Dosages should start as low as possible. They can be increased if need be
  • T: Titration or adapting the drug amounts for individual patients over time
  • E: The patient should be educated regarding the medications they are prescribed
  • R: Drugs prescribed and the dosage thereof should be reviewed regularly

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