Case 8 Alice Benson

Antibiotics with significant drug interactions

- rifampicin - macrolides (clarithromycin) - ciprofloxacin - metronidazole - azole antifungals (itraconazole)

Menopause definition

"The permanent ceasing of menstruation" - the LAST menstrual period No further production of oestrogen and progesterone Iatrogenic Menopause- Surgery, Radiotherapy, Chemotherapy

Ways of preventing infection

(decontamination, personal protective equipment (PPE), management of sharps, waste disposal)

7 Step medication review

- Aims -Need -Efficacy -safety - cost effectiveness - patient centered

Breif mechanism of menopause hormonally

- The number and responsiveness of ovarian follicles will decline after the age of 40 Decrease of estrogen and inhibin B. - As oestrogen and inhibin fall there is a reduction on the negative feedback loop on GNRH and FsH - Response from responsive follicles During the perimenopause estrogen is erratic and the levels will fluctuate between normal, high and low. - Eventually there are no responsive follicles and the negative feedback loop ends. FSH levels remain high LH levels also remain high, which stimulates the stromal cells to make androgen. - Post menopause the estrogen comes from adipose tissue or ovarian stromal cells. - In the adipose tissue Androgens are aromatised to oestrogens > but this particular form of estrogen AESTROME is less effective than normal oestrogen (estrodiral from ovaries)

Wnt family

. Under conditions of mechanical loading, sclerostin production by osteocytes is inhibited, allowing bone formation to proceed, stimulated by members of the Wnt family of signalling proteins. The Wnt molecules stimulate bone formation by activating members of the lipoprotein receptor-related protein (LRP) family, the most important of which are LRP4, LRP5 and LRP6. Sclerostin antagonises the effects of Wnt family members by blocking their interaction with LRP family members

Multi-drug resistance

1 or more drugs in 2 classes

Main mechanisms of antibiotic resistance

1. Chemically modify the antibiotic (penicillinases, betalactamasas,carbapenemases) 2. Render it inactive through physical removal from the cell (efflux pumps) 3. Modify the target site so that it is not recognised by the antibiotic.

Stages of fracture healing

1. Fracture hematoma 2. Granulation tissue 3. Callus formation 4. Ossification 5. Consolidation 6. Remodeling

Functions of the vertebral column

1. Protects the spinal cord 2. Supports the weight of the body above the pelvis 3. Provides an axis for the body and a support for the head 4. Involved in posture and locomotion

extensively drug-resistant

3 or more classes

Statistics antibiotics

7% (35,000) of all deaths in the UK are caused by infectious diseases. • Without antimicrobials, the rate of post-operative infection for clean surgery could be up to 50%. ~30% of those with a serious infection would die. • 66 different antibiotics - top 15 account for 98% in general practice and 88% in hospitals. • 35 million courses of antibiotics are prescribed by GPs in England each year.

Menopause effect on bones

A decline in circulating estrogen is primarily responsible for bone loss following both natural and surgical menopause, which is mediated primarily through upregulation of cytokines (most notably RANKL) and a resultant increase in the number, activity, and depth of osteoclast-mediated bone resorption sites. In addition, OPG production is diminished, further amplifying bone resorption, although estrogen replacement can restore OPG production while reducing RANKL expression and thereby help mitigate bone loss during this period

second stage of menopause related bone loss

After 4-8 years, the second phase exhibits a persistent, slower loss of both trabecular and cortical bone, and is mainly attributed to reduced bone formation.11 This is age related bone loss, which is the only phase that also happens in men.

Bone health diet

Although the majority of body calcium is stored in the skeleton, there is controversy about the role of dietary calcium intake in the aetiology and prevention of osteo-porosis. However, there appears to be a role for dietary calcium intake in the attainment of peak adult bone density. Moreover, a daily dietary calcium intake of around 800 mg/day in premenopausal women and 1200 mg/day in postmenopausal women is generally considered appropriate to avoid negative calcium balance. Sodium intake could also be related. Sodium loading results in increased renal calcium excretion, which has led to the suggestion that lowering dietary sodium intake diminishes age-related bone loss. Excessive protein and caffeine intakes are associated with bone loss.

Medications that increase risks of falls

Antihypertensives Diuretics Sedatives/Hypnotics Opioids Oral Hypoglycaemics Antidepressants Antipsychotics Sedating antihistamines Anticholinergics/antimuscarinics: ACB (anticholinergic burden) risk of falls

effects of ageing on the cardiovascular system

Arteries develop atherosclerotic change - walls thicken and elasticity reduced, reduction in NO production Baroreceptors (regulation cerebral blood flow) - troubles with postural blood flow. More susceptible to fits and fainting. become less sensitive Heart valves thicken Apoptosis atrial pacemaker cells Decreased responsiveness to adrenoceptor stimulation Decrease in maximal achievable heart rate

Steroids are used for

Asthma (inhaled and oral formulations) • Rheumatoid Arthritis • Other autoimmune disease (SLE) • Inflammatory Diseases (Crohn's Disease)

reasons for hysterectomy

Benign- heavy menstrual bleeding, prolapse, endometriosis Cancer- endometrial cancer, ovarian cancer, cervical cancer, breast cancer Salpingoophrectomy- removal of ovaries and fallopian tubes Ovarian conservation

Bone health excercise

Bone is responsive to physical strain. Changes in the forces applied to bone produce effects in bone. For example, weightlessness and immobilization induce marked degrees of bone loss. On the other hand, athletes tend to have greater bone mineral density, although this effect is often site specific. For example, tennis players have increased bone density in their dominant but not non-dominant arm and weight lifters have greater femoral bone density than other athletes. This is consistent with a local effect of exercise on bone.

HRT after cancer

Breast cancer Avoid systemic HRT, can use topical oestrogen, consider clonidine or paroxetine Cervical cancer If young, ovarian conservation recommended. Systemic HRT can be used Endometrial cancer If stage 1- can consider ovarian conservation or HRT. If later stage, HRT usually contraindicated. Ovarian cancer HRT not usually contraindicated, unless tumour has oestrogen receptors

estrogen dependant tissues

Breast, hair, ovary, endometrium, testes, colon, bone, blood vessels, fat

Calcitonin

Calcitonin is a 32-amino acid peptide secreted by the parafollicular cells of the thyroid gland. calcitonin can directly inhibit osteoclastic bone resorption, it appears to play a relatively minor role in calcium homeostasis in normal adults.

Nervous system

Cerebral Blood flow decreases 10% loss in weight of brain More susceptible to damage Some slowing of thought and reflexes from 30

symptoms of infection

Certain symptoms indicate that the body is trying to combat invading microorganisms. Inflammation or fever is usually the first sign that your immune system is at work. Inflammation occurs when the innate immune system is attempting to flush a specific area with phagocytes. A fever occurs when the adaptive immune system is combating invading microorganisms. It is the body's attempt to kill the disease-causing agents by increasing the temperature of their environment above that which is conducive to their existence.

Acute clinical symptoms of menopause

Cessation of Menses Vasomotor Symptoms- Hot Flushes (face and neck 1-5 minutes and sweating . occurs in 70-90% women, happens because of narrowing of the hypothalamus thermal regulatory setpoints, increasing the chances of sensitivity to intense heat in internal and external symptoms), Night Sweats Mood swings, depression, forgetfulness Headaches

Somatic DNA damage theory

DNA mutations accumulate with more division

Hospital Delirium

Delirium is very common among hospitalized seniors, usually affecting about half of the population. And it's linked with both short and long-term negative impacts: Short-term problems include a greater probability of a fall and a longer hospital stay, and long-term consequences include faster cognitive decline—sometimes even progressing to full-scale dementia.

Tetracyclines side effects

Discoloration and inadequate calcification of primary teeth of fetus if taken during pregnancy or early childhood. Phototoxic Reactions (sunburn type of reaction to sun)

Tips for good prescribing practice

Dosing: minimum for desired effect Duration: minimum to limit long term risks Taper dose before stopping For high dose/long-term use consider bone protection gastric protection monitor blood glucose Review regularly

DAME falls

Drugs, Age related changes, Medical problems, Environmental hazards

protein synthesis 50s inhibitors

Erythromycin Chloramphenicol Clindamycin Lincomycin

Fall prevention strategies

Excercise Calcium and Vit D Home modification Medication Review Cataract surgery Anti Slip shoes Cardiac pacemaker for carotid sinus hypersensitivity

How to diagnose premature menopause

FSH test AMH Antral Follicle Count on Ultrasound

Staphylococcus

Facultative anaerobes • Classified according to ability to coagulase serum • Staphylococcus aureus (coagulase positive) is the main pathogen. • Coagulase-negative staphylococci (CNS) are less pathogenic • Sensitivity varies but Staphylococcus aureus normally susceptible to "staphylococcal" penicillins but resistance is common amongst CNS • Form biofilms rapidly and are a common finding in medical device associated infections

Drugs effect on bone health

Glucocorticoids or corticosteroids are commonly used to treat inflammatory diseases, including arthritis and asthma. Corticosteroids affect calcium metabolism deleteriously in a variety of ways. The most important effect is to inhibit osteo-blastic bone formation directly. They also decrease calcium absorption in the intestine, increase urinary calcium excretion and enhance osteoclast activity by inhibiting OPG. These mechanisms cause rapid bone loss when corticosteroids are used in high doses for prolonged periods.

Endocrine system

Growth hormone levels decrease Reduction in insulin sensitivity Reduction in adrenal hormones with stimulation Female menopause - reduction Oestrogen

HRT for osteoporosis

HRT has a very significant benefit in reducing the incidence of osteoporosis and osteoporotic fractures. Administration of oestrogen decreases fracture risk; however, it is not recommended as a first-line treatment, as the long-term risks (particularly stroke) are considered to outweigh the benefits

TREATMENTS for osteoporosis

HRT, biphosphates, SERMs, Calcium and vit d, PTH, Denosumab

treatment of temporal arteritis

High-dose steroids. prednisone or prednisolone. Once symptoms have resolved the dose is then decreased by about 15% per month. Other medications that may be recommended include bisphosphonates to prevent bone loss and a proton-pump inhibitor to prevent stomach problems

What does MRSA cause?

Hospital-acquired MRSA (HA-MRSA) causes invasive disease, especially in immunocompromised individuals, including pneumonia, endocarditis, deep wound infections, and/or osteomyelitis.

Side effects of glucocorticoids

Immunodeficiency (see section below) Hyperglycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance ("steroid diabetes"); caution in those with diabetes mellitus Increased skin fragility, easy bruising Negative calcium balance due to reduced intestinal calcium absorption[42] Steroid-induced osteoporosis: reduced bone density (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair)

Immune system

Immunosenescence Reduction in haematopoietic stem cells Reduction in number and effect of phagocytes Reduction in cell mediated immunity Reduction in humoral immunity

Physical effects of Long term hospital stays - elderly

Inadequate diet, interrupted sleep, and general poor care from often overworked nurses can result in delirium, infection, and pressure ulcers. Aside from these, bed rest can weaken elderly patients enormously, making it difficult for the to return to an autonomous life upon discharge. Cognitive impairment and weakened strength can result in a greater risk of falls,

SUMMARY of hormones at menopause

Increase in FSH and LH. Decrease in Oestrogen, Testosterone, Inhibin B, AMH

function of intervertebral discs

Increase size of intervertebral foramen Act as shock absorbers Permit movement

nucleus polposus

It forms a gelatinous mass that is comprised of water, a few collagen fibres and some cartilage cells.

Vision and hearing

Lens stiffens - difficulty focusing close objects Lens denser - reduced night vision Retina less sensitive to light Pupils react more slowly Presbyacusis - loss high pitched hearing

factors effecting drug distribution

Less body water and less muscle mass. More fat Lipid-soluble drugs greater volume of distribution can accumulate in fat and brain tissue e.g. benzodiazepines Water-soluble drugs smaller volume of distribution can lead to higher serum levels e.g. aminoglycosides, digoxin toxicity if drug has narrow therapeutic index

Lifestyle measures to reduce the effects of menopause

Lifestyle Measures Exercise, Lighter Clothing, Stress Reduction, Trigger Avoidance Non-hormonal therapy Non-pharmacological Vaginal moisturisers Complementary therapies Phytoeostrogens - japanese women have lower levels of Herbal remedies

osteporosis definition

Loss of bone substance, such that fractures of non-traumatic origin are sustained (vertebral "ghosts" on X ray - spinal osteoporosis) BMD that is 2.5 SD's or more below a normal healthy control (T score and z score)

how does DEXA work

Lower spine and hips • X ray sent via 2 energy streams • One absorbed by soft tissue, the other denotes total absorption, subtract soft tissue from total to obtain bone results • Bone mineral density is computed over the area measured

sclerostin

Made by osteocytes and suppresses bone formation

Comprehensive geriatric assessment

Medical problems Mental health Function Social circumstances Environmental assessment

Appropriate polypharmacy

Medicines use optimised Each medicines achieves its intended benefit No ADRs or interactions

ALP (alkaline phosphatase)

Mineralisation of bone is critically dependent on the enzyme alkaline phosphatase (ALP), which is produced by osteoblasts and degrades pyrophosphate, an inhibitor of mineralisation. Bone remodelling is predominantly regulated at a local level but can be influenced by circulating hormones or mechanical loading, which can up-regulate or down-regulate remodelling across the whole skeleton

Problematic polypharmacy

Multiple medicines prescribed inappropriately Intended benefit of each medicine is not achieved ADRs and interactions Adverse drug reactions (ADRs) / side-effects Drug-drug interactions Older patients more susceptible to ADRs and interactions due to: Changes in pharmacokinetics Changes in pharmacodynamics(↑ sensitivity)

Risk factors for falls

Muscle weakness • History of falls • Gait or balance abnormality • Use of a walking aid • Visual impairment • Arthritis • Impaired activities of daily living • Depression • Cognitive impairment • Age over 80 years • Psychotropic medication

transverse process

Name this specific part of the atlas (C1).

pedicle

Name this specific part of the thoracic vertebra.

spinous process

Name this specific part of the thoracic vertebra.

superior articular facet

Name this specific part of the thoracic vertebra.

Renal system

Number of nephrons declines by 30-40% Kidneys shrink Less efficient in clearing waste Men - prostatic hypertrophy v common Women - urinary incontinence common

osteoblast

OSTEOBLASTS are the cells that form new bone. They also come from the bone marrow and are related to structural cells. They have only one nucleus. Osteoblasts work in teams to build bone. They produce new bone called "osteoid" which is made of bone collagen and other protein.

Preparations of HRT

Oestrogen Transdermal- patch or gel - local skin irritation Oral oestrogen - cost effective, acceptable route Vaginal Oestrogen Cream, tablets or vaginal rings Local delivery Urogenital symptoms- dryness, painful intercourse Progesterone Micronised progesterone Oral deriatives Mirena Coil- progesterone released intrauterine coil

Regimens of HRT

Oestrogen only Sequential combined regimens Continuous combined regimens Synthetic steroid alternatives

Howship's lacunae

Once formed, mature osteoclasts attach to the bone surface by a tight sealing zone and secrete hydrochloric acid and proteolytic enzymes, including cathepsin K, into the space underneath, which is known as the Howship's lacuna.

osteoid

Osteoid is an unmineralized organic tissue that eventually undergoes calcification and is deposited as lamellae or layers in the bone matrix.

Long term side effects menopause

Osteoporosis Metabolic Consequences Obesity Type 2 Diabetes and Dyslipidaemia - increased total body fat Cardiovascular Consequences Endothelial Dysfunction Hypertension Atherosclerosis Mood Disorders - starting HRT can reduce dementia aslo. Menopause leads to a decline in synthesis of neurotransmitters ACTH dopamine and serotonin. Also contributes to insomnia. Early menopause is associated with an increased risk of CHD, stroke and death

PTH

Parathyroid hormone is an 84-amino acid peptide secreted by the four parathyroid glands located adjacent to the thyroid gland in the neck. PTH acts on the kidney to increase calcium reabsorption, phosphate excretion and 1,25-dihydroxyvitamin D production.

Bone loss menopause epidemiology

Perhaps most important for women, rates of bone loss increase substantially in the perimenopausal and early postmenopausal years, amounting to losses of 1 to 5% per year. Unfortunately, there are currently no biologic markers that help determine which women a priori are "rapid losers." Bone loss is slower in obese women, likely because of higher estrogen levels afforded by production through aromatization in adipose tissue

Contraindications for HRT

Pregnancy Undiagnosed vaginal bleeding Active/ recent VTE or heart attack Suspected or active breast or endometrial cancer Acute liver disease Porphyria cutanea tarda

How to prevent damaging effects of polypharmacy

Sensible prescribing practice -think twice Is this an iatrogenic illness? (caused by medical treatment) Consider non-pharmacological approaches Use a limited formulary Start low and go slow in older patients Review regularly Explain clearly

Sepsis

Sepsis is a complex clinical syndrome in which a dysregulated host response to infection leads to life-threatening organ dysfunction. The incidence of sepsis and the extent to which it manifests depend on host comorbidities, infectious exposures, and immune system integrity. Patients present with symptoms of specific infection and superimposed signs of systemic illness such as fever or hypothermia, tachycardia, tachypnea, hypotension, and altered mental status without focal deficits

septic shock

Sepsis that leads to persistent hypotension despite fluid resuscitation is termed septic shock, a distinct clinical entity associated with substantially increased mortality.

effects of ageing on the muscoskeletal system

Skeletal Muscles lose cells and weight Loss fast twitch fibres >slow twitch. Problem for falls, no explosive movements. Hormonal loss (GH testosterone) and denervation atrophy Exacerbated by inactivity (illness/ hospitalisation) Decreased bone mineral density Cartilage thins Ligaments less elastic

factors effecting drug absorption in older people

Some slowing of gastric emptying / motility Some reduction in gastric acid secretion Reduced total surface area and reduced secretion of some enzymes Potential decrease in absorption of drugs (small change)

Staphylococcus aureus

Superficial skin lesions (impetigo, styes) and localised abscesses. • Deep-seated infections, such as pneumonia, osteomyelitis and endocarditis and more serious skin infections (often associated with Panton-Valentine Leukocidin (PVL toxin) production). • A major cause of hospital acquired (nosocomial) infections of surgical wounds. • Food poisoning by releasing toxins into food. • Toxic shock syndrome by releasing toxins into the blood stream. Tampons. • S. aureus and S. epidermidis are common causes of infections associated with indwelling devices (joint prostheses, cardiovascular devices and artificial heart valves) • S. saprophyticus causes urinary tract infections, especially in girls.

Methods of treating infections

Symptomatically (viral infections) 2. Topically (superficial infections) 3. By removing the focus of the infection (lines) 4. Surgically (abscesses, biofilms) 5. Immunotherapies (antibodies) 6. By prescribing antimicrobials

Temporal arteritis

Temporal arteritis (giant cell arteritis) is where the arteries, particularly those at the side of the head (the temples), become inflamed. It's serious and needs urgent treatment. a form of vasculitis that can cause headaches, visual impairment, jaw pain, and other symptoms

Protein synthesis inhibitors 30s

Tetracyclines Aminoglycosides (streptomycin, gentamicin), amikacin

secondary curvatures

The cervical and lumbar are convex anteriorly and are therefore secondary.

Sepsis Management

The cornerstones of management are early antimicrobial therapy and expeditious fluid resuscitation (quick IV rehydration)

quiescence phase

The final osteoblasts turn into lining cells which participate in the minute-to-minute release of calcium from the bones. Some of the osteoblasts also turn into osteocytes which remain in the bone, connected by long cell processes which can sense mechanical stresses to the bones

First stage of menopause related bone loss

The first occurs predominantly in trabecular bone and starting at menopause. It results from estrogen deficiency, and leads to a disproportionate increase in bone resorption as compared with formation. This phase could be defined as menopause related bone loss.

intervertebral discs

The intervertebral discs are fibrocartilage pads that are sandwiched between adjacent vertebral bodies. They are responsible for 25% of the length of the vertebral column

Calcium homeostasis is regulated by

The maintenance of normal serum calcium depends on the interplay of intestinal calcium absorption, renal excretion and skeletal mobilization or uptake of calcium

Resorption phase

The mature osteoclasts resorb bone by forming a space on the matrix surface and secreting hydrogen ions and cathepsin into the space. As the BMU wanders, new osteoclasts are continuously activated and then start resorption. At any one spot on the surface the resorption lasts about two weeks. The osteoclasts then undergo programmed cell death or apoptosis, which is delayed by estrogen deficiency.

Formation Phase

The osteoblast precursors differentiate into mature osteoblasts and form new bone during the formation phase. Initially, the matrix is unmineralised (osteoid) but eventually becomes mineralised to form mature bone. Some osteoblasts become trapped in bone matrix and differentiate into osteocytes, which play a key regulatory role in coordinating bone formation and resorption, whereas others differentiate into bone-lining cells.

Reversal Phase

The reversal phase couples bone resorption to bone formation by generating an osteogenic environment at remodeling sites. ... Notably, canopies are brought under the osteogenic influence of capillaries and osteoclasts, whereas bone surface cells become exposed to the eroded matrix and other osteoclast products.

motto of antibiotic stewardship

The right drug at the right time at the right dose via right route for the right duration for the right patient.

Polypharmacy

The use of multiple medications by a patient (usually 5+) Significant in older patients Half of patients over 65 years of age take 5 or more medicines each day

How many of each vertebrae are there?

There are 7 cervical, 12 thoracic, 5 lumbar, 5 sacral (fused) and 4 coccygeal (fused) vertebrae

sacral hiatus of sacrum

Transmits filum terminale, route for injection in caudal epidural anesthesia

antibiotics that target folic acid metabolism

Trimethoprim Sulfonamides

Medium term side effects of menopause

Urogenital Atrophy Vulval, vaginal, urethral and bladder tissues are oestrogen-dependent Epithelium thins, and atrophies Raised vaginal pH- increases bacterial growth and contributes to recurrent urinary infection Urinary incontinence and/or urgency Sexual Problems Vaginal dryness Painful intercourse (dyspareunia) Loss of libido

dowagers hump

Wedge compression fractures of the spine leading to the so-called 'dowager's hump' affect 25% of white women over 60 years of age

sacral promontory

Where the first sacral vertebrae bulges into pelvic cavity

osteocytes

a bone cell, formed when an osteoblast becomes embedded in the material it has secreted. Started as osteoblasts. They transduce mechanical forces to other cells.

lordosis

abnormal anterior curvature of the lumbar spine (sway-back condition)

Scoliosis

abnormal lateral curvature of the spine

osteoprogenitor cells

also known as osteogenic cells, are stem cells located in the bone that play a prodigal role in bone repair and growth. These cells are the precursors to the more specialized bone cells (osteocytes and osteoblasts) and reside in the bone marrow

Pathological fracture

break in a bone weakened by some other disease

vertebral foramen

canal through which spinal cord passes

Regions of the vertebral column

cervical, thoracic, lumbar, sacral, coccygeal

sacral canal

continuation of vertebral canal

Antibiotics that target cell wall synthesis ultimately cause bacterial cell death. eg?

cycloserine, vancomycin

Free Radical Theory

damage cells and organs

osteoprotegerin (OPG)

decoy receptor blocks binding of RANK to RANK-L > reduces osteoclast differentiation increases bone density estrogen decreases OPG > causing osteoporosis

venous thromboembolism

deep vein thrombosis and pulmonary embolism Risk highest in Oral Estrogen - because of the first pass effects on the liver leading to synthetic of increased coagulation factors. No risk with micronized progesterone, non-oral estrogens

cathepsin K

degrades collagen

Aortic dissection

diagnosis in which the arterial wall splits apart

DEXA

dual-energy x-ray absorptiometry

kyphosis

excessive outward curvature of the spine, causing hunching of the back.

Vitamin D

from dietary sources (D 3 ) or synthesized in skin (D 2 ), is converted to 25-hydroxyvitamin D in the liver and then to 1,25-dihydroxyvitamin D in the kidney. D is a potent stimulator of bone resorption and an even more potent stimulator of intestinal calcium (and phosphate) absorption. It is also necessary for bone mineralization. Intestinal calcium absorption is probably the most important calcium homeostatic pathway.

glycolation theory

glycation end products cause cell damage. Krebs cycle causes damage with toxic byproducts.

osteoclast precursors are derived from

haematopoietic stem cells and differentiate into mature osteoclasts in response to M-CSF Macrophage colony-stimulating factor,

Spinal nerves exit the vertebral canal through?

intervertebral foramina

A focal neurologic deficit

is a problem with nerve, spinal cord, or brain function. It affects a specific location, such as the left side of the face, right arm, or even a small area such as the tongue. Speech, vision, and hearing problems are also considered focal neurological deficits

Aminoglycosides & glycopeptides side effects

kidney and ear problems

MRSA

methicillin-resistant staphylococcus aureus is resistant not only to the traditional antistaphylococcal β-lactam antibiotics (methicillin 2 nafcillin, oxacillin, cloxacillin 2 , and dicloxacillin) but also other important β-lactam antibiotics, including the first- to fourth-generation cephalosporins and the carbapenem family, thus eliminating an important class of antibiotics from the clinician's armamentarium. The only β-lactams that have activity against MRSA are the recently approved advanced-generation cephalosporin agents ceftaroline (Teflaro) and ceftobiprole (Zevtera)

Antibiotics that target nucleic acid

metronidazole

Factors that can delay fracture healing

movement • interposed soft tissues • gross misalignment • infection • preexisting bone disease.

Antagonistic pleiotropy

occurs when a mutation with beneficial effects for one trait also causes detrimental effects on other traits

anterior sacral foramina

openings on the anterior side of the sacrum

posterior sacral foramina

openings on the posterior side of the sacrum

anulus fibrosis

outer collar composed of collagen and fibrocartilage

Calcium homeostasis is regulated by three hormones:

parathyroid hormone (PTH), 1,25-dihydroxyvitamin D and calcitonin

lamina

part of the vertebral arch

Corticosteroids function

produces a wide range of effects that influence metabolic pathways, modify response of the immune system and produce anti-inflammatory activity. Useful to treat autoimmune conditions e.g. lupus, or RA when the immune system attacks the body Supress inflammation Reduce redness and swelling Useful in inflammatory conditions e.g.asthma and eczema

Types of HRT drugs

progesterone, estradiol, norethisterone, conjugated equine estrogen. Oestrogen +/- progesterone Progesterone for endometrial protection

The binding of RANKL Receptor activator of nuclear factor kappa-Β ligand to RANK on osetoclast precursors leads to what

promoting osteoclast differentiation and bone resorption.

Stages of bone remodelling

quiescence, resorption, reversal and formation

Antibiotics that target DNYA gyrase

quinolone

FGF23

regulates renal tubular phosphate reabsorption produced by osteocytes for phosphate homeostatis.

Pandrug resistant (PDR)

resistance to all agents in all antimicrobial categories

primary curvature

spine of infants is convex posteriorly. The thoracic and sacral curvatures are primary as they are concave anteriorly.

Gastrointestinal system

taste buds lose sensitivity Gums recede and less saliva produced Food empties from stomach more slowly Gut transit time decreases Liver - loses cells and reduces blood flow. Less effective, more drug toxicity

Oligopharmacy

the deliberate avoidance of polypharmacy

median sacral crest

the fused spinous processes of the sacral vertebrae

Frailty definition

the loss of an individual's ability to withstand minor stresses because the reserves in function of several organ systems are so severely reduced that even a trivial illness or adverse drug reaction may result in organ failure and death

Sarcopaenia

the loss of skeletal muscle mass and strength as a result of ageing

callus bone

the mass of new bone, sometimes with islands of cartilage, is called callus ; that within the medullary cavity is internal callus, while that at the periosteum is external callus.

Vertebral arch

the pedicals and laminae form the arch around each vertebral foramen

perimenopause

the term used to designate the transition phase between regular menstrual periods and no periods at all

Vertebral canal

the tube formed by successive vertebral foramina

disposable soma theory

trade off between maintenance and repair vs reproduction

Empiric therapy

treatment of an infection before specific culture information has been reported or obtained

Where is the spinal cord located?

vertebral canal

Pharmacokinetics

what the body does to the drug

Pharmacodynamics

what the drug does to the body. Think DynamicDRugs D first

When does the cervical curve develop?

when the child begins to hold the head up at about 3 or 4 months & begins to sit alone at about 8 or 9 months

When does the lumbar curve develop?

when the child begins to walk at about 1 to 1.5 yrs of age

prescribing cascade

where a new drug is prescribed to treat an unrecognised ADR or manifestations of a drug-drug interaction between existing medication

ala of sacrum

wings

Action of corticosteroid on bones

• Acts on osteoblasts • Decreases Osteoblast activity (collagen type 1) • Possibly decreases osteoblast number • Complex pathway of osteoblast differentiation from mesenchymal stem cells, in which osteoblasts themselves may have role - some of this is corticosteroid dependent

Markers of Frailty

• Hand grip strength in bottom 20% of healthy elderly distribution * * Varies between populations. Grip cut-off is 30 kg for men and 18 kg for women in US adults; 5 m walk time cut-off is 7 seconds in US adults for both sexes. • Walking speed in bottom 20% of healthy elderly distribution * • Self-reported exhaustion • Physical inactivity • At least 6 kg weight loss within 1 year

Regulation of bone mass in men

• Osteoporosis in male patient with ER mutation (no estrogen response) • Osteoporosis in male patient with Aromatase mutation (no estrogen synthesis) • Falling estrogen levels associated with bone loss in ageing men

targeted therapy

• targeted at microorganisms proven to be causing disease • initiate when culture report is available or change from empiric to targeted