19550_drugs and bugs

8/19/2019 19550_drugs and Bugs

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Phase 2

Sarah Foster


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• Core pharmacology

• Antibiotics

• HIV

• TB

• Hepatitis

• Malaria

•Quiz

Aims


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BP = CO X PVR

CO = HR X SV

Pharmacology - Cardiac


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Hypertension

Angina

MI

Clotting

Hypercholesterolaemia

AF

Pharmacology - Cardiac


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Pharmacology - HTN

ACEi

ARB

Diuretics


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Pharmacology - HTN

ACE inhibitors What? Inhibit ACE in the lungs

Function? Reduces BP, vNa/H2O retention

Example? Ramipril

SE? Cough due to bradykinin -> switch to ARB

ARBs

What: Angiotensin II Receptor BlockersFunction? Reduces BP by inhibiting effects of AT II

Example? Losartan

SE? Dizziness, Headache, Hyperkalaemia


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Pharmacology - HTN

Calcium channel blockersWhat? Block influx of Ca into cells

Function? Reduces BP, Vasodilatation,

- Ionotrope (v contractn) - Dromotrope (v HR)

Example? Verapamil/diltiazem/amlodipine

SE? Ankle swelling

Diuretics PCT CA mannitol -> osmotic diuresis -> v ICP

Loop NKCC2 furosemide, bumetanide

DCT NCC bendroflumethiazide

C.duct ENaC amiloride/spironolactone -> K+ sparing


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Pharmacology - Angina

NitratesWhat? Generates NO

Function? Cause Vasodilatation = v PVR -> vBP

Example? Glyceryl Trinitrate (GTN) spray

SE? Postural Hypotension, Headaches

Myocardial Infarction

MORPHINE Pain relief, some vasodilatation OXYGEN ^O2 to ischaemic tissuesNITRATES Vasodilatation

ASPIRIN COX1 inhibitor, x platelet aggregation


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Pharmacology - MI


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Pharmacology - Clotting

ANTIPLATELETSClopidogrel Platelet aggregation inhibitor (ADP cant bind)

Ticagrelor Platelet aggregation inhibitor (binds P2Y12

receptor -> ADP cant bind)

Aspirin Inhibits thromboxane production, lasts 7 days

ANTICOAGULANTS

Dalteparin Direct thrombin inhibitor, LMWH

Warfarin Vitamin K inhibitor (Clotting factors II, VI, XI,X)

-> monitor INR, interactions

Dabigatran Direct thrombin inhibitor

Rivaroxaban Factor Xa Inhibitor


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Pharmacology - ^Cholesterol

STATINSWhat? HMG CoA Reductase Inhibitor

Function? Reduce cholesterol

Stabilise plaque

Anti-inflammatory properties

Example? Simvastatin

SE? Rhabdomyolysis

->Muscles break down

->Haematuria


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Pharmacology - AF

What: Atrial Tachyarrythmia, commonRapid irregularly irregular pulse

Why: ^ATRIAL PRESSURE e.g. HTN, Hyperthyroid

^ATRIAL MUSCLE MASS e.g CM, HF

ATRIAL INFLAMMATION e.g. Surgery, MI

PC: Asymptomatic, heart palpitations,

chest pain, stroke/TIA, dyspnoea,

fatigue, syncope, lightheadedness


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Pharmacology - AF

Types: PAROXYSMAL

PERSISTENT

PERMANENT

Ix: ECG

Underlying cause e.g. TFTs


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Pharmacology - AF

Tx: Underlying cause e.g. Alcohol, thyroid

Rate control e.g. beta blockers

Rhythm control i.e. Cardioversion

Anticoagulants based on CHA2DS

2-VASc score

e.g. Aspirin, Warfarin


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Pharmacology - AF

CHA2DS2-VASc

SCORE

O = Low risk No treatment

1 = Moderate risk Oral anticoagulants e.g. Aspirin

2+ = High risk Oral anticoagulants e.g. Dabigatran


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Pharmacology - AFBETA BLOCKERS

What? Block beta adrenoreceptors

Function? v HR and force of contraction, v BP

Example? Bisoprolol

SE? Bradycardia -> dizzy

CARDIOVERSION

What? Drugs/Transthoracic electrical shock

Function? Restore sinus rhythmExample? Pharmacological e.g. Amiodarone

Electrical

SE? Failure, VF with ECV, emboli


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Asthma

COPD

Pneumonia

TB

Pharmacology - Respiratory


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What: Reversible bronchoconstriction due toinflammation in hyperactive airways.

Type 1 HS

Tx: SABA (Salbutamol = Ventolin) -> RELIEVE

Beta agonists are sympathomimetics

Cause bronchodilatation

Steroids (Beclemetasone) -> PREVENT

Inhibit Phospholipase A2, v inflammation

Pharmacology – Asthma


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Steroids (Beclemetasone, Budesonide) -> PREVENT


INFLAMMATION

AIRWAY INFLAMMATION


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Tx: Poor control:

LABA (Salmetarol)

Leukotriene Receptor Antagonist (Montelukast)

Oral SteroidsLAMA (Ipratropium Bromide = Atrovent)

Life threatening Asthma attack: O2

IV Salbutamol, Theophyllines (aminophylline),

MgS04

, Hydrocortisone



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What: Progressive airflow limitation, not fullyreversible

Bronchitis/emphysema

Tx: Stop smoking

Inhaled LABA, SABA and LAMA

Mucolytics (Carbocysteine)

O2

Vaccines

Pharmacology – COPD


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Epilepsy

Myasthenia Gravis

Parkinson’s Disease

Huntington’s Disease

Alzheimer’s Disease

Headaches

Pharmacology - Neuro


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What: Spontaneously recurring seizures otherthan febrile convulsions without metabolic

abnormality or acute cerebral insult.

A seizure is a clinical event due to abnormal XS

neuronal DC leading to a sudden disturbance of

neurological function

Types: FOCAL – any age, intracerebral defectGENERALISED –


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FOCAL

1. Simple Partial -> no LOC, Jacksonian march

2. Complex Partial -> usually temporal, smell/taste, visual

hallucinations

3. 2o

generalised -> whole brain affected w/LOCTx: Carbamazepine

IDIOPATHIC 1o GENERALISED

1. Childhood absence -> petit mal

2. 1o generalised tonic-clonic -> grand mal on waking

3. Juvenile myclonic epilepsy -> morning clumsiness

Tx: Sodium Valproate

Pharmacology - Epilepsy


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CarbamazepineFunction: Inhibits sodium channels

SE: Drowsiness, ataxia, dizzy, vNa, Neutropenia

Sodium Valproate

Function: Inhibits Na/Ca channels, ^GABA -> inhibitory

SE: Teratogenic, hepatotoxic

Lamotrigine

Function: Inhibits Na/Ca channels

SE: Steven-Johnson Syndrome

Pharmacology - Epilepsy


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What: Autoimmune disease with AChR antibodies,inhibit action of Ach on postsynaptic membrane

PC: Fatiguable muscle weakness, N reflexes

Ix: Tensilon Test (edrophonium), Antibody screenTx: Acetylcholinesterase Inhibitor – Pyridostigmine

Stops breakdown of ACh so around longer to

stimulate receptor

Remember LEMS in SCLC

->VGCC -> v Reflexes

Pharmacology - MG


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What: Degeneration of dopaminergic neurons in the SNpc

PC: Tremor, Rigidity, Bradykinesia

Ix: Clinical diagnosis

Tx: L-dopa (can cross BBB -> DDC -> Dopamine)

DA agonists e.g. Bromocriptine, Pramipexole

MAO-B Inhibitors e.g. Seligiline, ^ synaptic DA

COMT inhibitors e.g. Entacapone, v L-dopa metabolism

Cholinergic antagonists e.g. Orphenadrine, v SEs

Manage Depression

Respite care

Pharmacology - PD


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What: v GABA synthesis in basal gangliaPC: Chorea, Psychosis, Dementia

Tx: GABA agonist e.g. Baclofen

DA antagonist e.g. Chlorpromazine

What: Loss of cholinergic neurons in nuclei

Neurofibrillary tangles with tau protein

Tx: Cholinesterase Inhibitors to ^ Ach

e.g. Donepezil, Rivastigmine

Pharmacology – Alzheimer’s

Pharmacology - HD


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ClusterTriptans e.g. Sumatriptan (5HT agonists vasoconstrict -> v inflamm)

Ca Channel blockers e.g. Verapamil

Trigeminal Neuralgia

Antiepileptics e.g. Carbamazepine

HeadacheCOX1 Inhibitor e.g. Aspirin

Triptans

Ergotamine (vasoconstriction, inhibit trigeminal NT)

Pharmacology - Headache


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Temporal ArteritisSteroids e.g. Prednisolone ASAP before Bx

Bacterial Meningitis

3rd generation Cephalosporin e.g. Ceftriaxone ASAP

Pharmacology - Headache


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Vomiting

Constipation

Pharmacology - GI


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ANTI-EMETICSH2 Receptor Antagonist e.g. Cyclizine

(v gastric acid)

D2 Receptor Antagonist e.g. Metoclopramide, Domperidone

(CTZ in CNS)

5HT antagonists e.g. Ondansetron( vagus nerve and CTZ)

Pharmacology - Vomiting


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LAXATIVESBulking agents e.g. Methylcellulose, Fybogel

(^ faecal mass = ^ peristalsis)

Stimulants e.g. Docusate, Glycerol suppository

(^motility)

Stool softeners e.g.Arachis Oil enema

Osmotic e.g. Lactulose, Phosphate enema

(retain fluid in bowel)

Pharmacology - Constipation


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RHEUMATOID ARTHRITISWhat: Chronic systemic inflammatory disease

Symmetrical deforming peripheral polyarthritis

Does not affect DIP joints

Ix: RhF 70%, Anti-CCP 98%Anaemia of Chronic Disease, ^Platelets, ^ ESR/CRP

Tx: NSAIDs

Steroids for acute flareDMARDs

e.g. Methotrexate – folic acid antagonist

pancytopenia, teratogenic, pneumonitis, ulcers

Pharmacology - MSK


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TNF alpha INHIBITORSWhy? NICE – failed 2 DMARDs after adequate trial

Examples: Infliximab anti-TNF antibody

Etanercept TNF alpha receptor

Adalimumab Monoclonal TNF IgIssues: Expensive, 35% no response

RITUXIMAB

What? Anti-CD20 monoclonal antibody -> B cell cytopenia

+MTX in severe RA if no response MTX/anti-TNF

Pharmacology - MSK


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Acromegaly

Thyroid

Conn’s Syndrome

Hypokalaemia

Hyperkalaemia

Pharmacology - Endocrine


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What: Excessive growth hormone after fusion of epiphyses(growth plates)

Why: Pituitary adenoma (99%)

PC: Due to XS hormones, local pressure and hypopituitarism,

sweating headache, increase size of hands feet jaw,

oligo/amenorrhoea, infertility

O/E: Coarse facies (prominent supraorbital ridges, prognathism)

increased interdental spacing, macroglossia, doughy spade

like hands, CTS, bitemporal hemianopia

Pharmacology - Acromegaly


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Ix: OGTT and GH, normally ^ gluc would inhibit GH releaseMRI pituitary fossa

Tx: Transphenoidal removal of the tumour

Somatostatin analogues inhibit GH release from a.pituitarye.g.Octreotide

Issues: DM

Vascular (HTN, Cardiomyopathy, HF)OP

OSA

Pharmacology - Acromegaly


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HYPERTHYROIDThyroidectomy

Radioactive Iodine

Carbimazole

->stops coupling and iodination of thyroglobulin by TPO

-> Reduce T3 and T4

HYPOTHYROIDThyroxine

T4, metabolised slowly so OD

Replaces deficiency

Pharmacology - Thyroid


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What: Primary Hyperaldosteronism

Why: Adrenal adenoma 2/3, Adrenal hyperplasia 1/3

PC: Hypertension, Polyuria, Polydipsia, weakness due to vK+,headaches, lethargy

Ix: Bloods - ^Na+, vK+, v Renin

ABG – metabolic alkalosisCT/MRI

Tx: Surgical removal of adenoma

Spironolactone (aldosterone antagonist) ^ K+

Pharmacology – Conn’s


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What:


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Ix: Bloods -> U&Es vK+, vNa+ (diuretics), Mg2+, GlucoseECG

Tx: K+ replacement – Sando K

Pharmacology - HypoK


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What: >5.5mmol/LMEDICAL EMERGENCY

Myocardial excitability -> VF -> Arrest

Why: Oliguric renal failure K + sparingMetabolic acidosis (DKA) Addison’s

Crush # Haemolysis of sample

PC: Asymptomatic, Fast irregular pulse, Chest pain,

Palpitations, Weakness, Lightheadedness

Pharmacology - HyperK


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Ix: Bloods - ^K+ECG

Tx: Stabilise heart, Shift K+ to IC , Promote renal excretion

IV access, Cardiac monitor

10mL Calcium Gluconate 10% IV -> ^ threshold potentialInsulin -> moves K+ into cells, Glucose

?Nebulised Salbutamol -> moves K+ IC

Polystyrene Sulfonate Resin

Dialysis

Pharmacology - HyperK

http://4.bp.blogspot.com/-LE4drC0qT6I/TaXbs79DNZI/AAAAAAAAFi0/ftTks3a4pj0/s1600/hyperkECG.jpg


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BACTERIA

Obligate IC ? Gram Stain?

C.Trachomatis

Yes No M. Tuberculosis

Rods Cocci Clostridium, Listeria Staph, Strep

E.coli, Salmonella, Neisseria

Shigella, Pseudomonas

Helicobacter

Microbiology


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GRAM + COCCI

Chains? Clusters?

Streptococcus Staphylococcus

Blood agar? Coagulase/DNAse?

Alpha haemolysis Beta haemolysis Positive Negative

Optochin? Strep. Pyogenes (GBS) S.Aureus S.epidermidis

Tx: Flucloxacillin/Vancomycin MRSA

+ Strep. Pneumoniae - Strep. Viridans Tx: Amoxicillin

Microbiology


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GRAM – RODSFerment lactose on Maclonkey/CLED?

Yes No

Escherichia Coli Oxidase?

+ -

Pseudomonas Proteus

Microbiology


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INHIBIT CELL WALL SYNTHESIS = Beta lactams

e.g. Penicillins, Cephalosporins, Carbapanems

Antibiotics


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INJURE PLASMA MEMBRANE

e.g. Antifungals - Nystatin

Antibiotics


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INHIBIT NUCLEIC ACID REPLICATION

e.g. DNA Gyrases – Ciproflaxacin (C.diff) Rifampicin

Antibiotics


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INHIBIT PROTEIN SYNTHESIS

e.g. Chloramphenicol , Erythromycin, Doxycycline (teeth)

Antibiotics


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INHIBIT METABOLITE PRODUCTION

e.g. Trimethoprim for UTIs (creatinine)

Antibiotics


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What: Infection with Mycobacterium Tuberculosis/

Mycobacterium Bovis.

Who: 1/3 of the world population affected

How: Airborne droplets.

Risks: Immunodeficiency, overcrowding, poor

ventilation, household contact, extremes age

TUBERCULOSIS (TB)

l


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Bacilli settle

in lung Apex

The Lungs

Macrophages + lymphocytes

seal in and contain and kill

Infecting bacilli

Pulmonary TB

l


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Bacilli settle

in apex andgranuloma

forms

In apex of lung there

Is more air and less

blood supply

The Lungs

Bacilli taken in

lymphatics

to hilar lymph

nodes

Granuloma + Lymphatics + Lymph nodes = Primary Complex

Pulmonary TB

TB d b d h l


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Bacilli settle

in lung Apex

The Lungs

Bacilli taken

to hilar lymph

nodes

TB Meningitis

Miliary TB

Pleural TB

Bone and Joint TB

Genito urinary TB

TB spreads beyond the lungs


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PC: GeneralWeight loss

Night sweats

Lethargy

Pulmonary TB

Haemoptysis

Chest pain

Chronic dry cough

TB Meningitis

MSK TbPott’s Disease

Septic Arthritis

Abdominal TBPeritonitis

Ascites

Genitourinary TB

Dysuria

Sterile Pyuria

TB


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Ix: Sputum culture x 3 Ziehl Neelson/Lowenstein-Jenson stain

CXR

Mantoux test Latent/vaccination

Quantiferon

TB


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Tx: Rifampicin (6/12) – red/orange urine

Isoniazide (6/12) – Hepatitis (severe)

Pyrazinimide (2/12) – Hepatitis (common)Ethambutol (2/12) – Ocular toxicity

12/12 for TB Meningitis

Up to 2 years for MDR-TB

TB


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What: Retrovirus (RNA) affecting CD4 cells (Th)

Who: 33 million people affected worldwide

UK – 77,400 (>80% heterosexual sex)

Sheffield 700 patients

How: Mother to child

Risky sexual behaviour

Blood-blood (transfusions/ IVDU’s)

HIV


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HIV


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PC: Acute sero-conversion illness

2-6 weeks after exposure

Non-specific illness. Fever, myalgia, lethargy.

Late presentation of HIV

Chronic diarrhoea (>3months)

Persistent generalised lymphadenopathy (PGL)Weight loss, infections, night sweats,fever.

Opportunistic infections.

HIV

HIV


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HIV

HIV AIDS


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What: Acquired Immunodeficiency Syndrome

PC: Usually CD4


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Ix: HIV ELISA test (> 3 months after exposure)

RDT

Tx: HAART – usually combination

Contact tracing

Prophylaxis - co-trimoxazole (septrin)

Prevention!

Pregnancy – Csection, Bottle feed, Tx baby

HIV


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What: Blood borne parasitic infection

Vector: Female anopheles mosquito saliva

Types: Plasmodium falciparum

Plasmodium Malariae

Plasmodium Vivax

Plasmodium Ovale

Malaria


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Lifecycle:

Malaria

Hypnozoites

RELAPSE


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Who:Pregnancy, kids, foreign travelers, HIV

PC: Fever in a returning traveller

Myalgia, Malaise, D&V, Headache

OE: Splenomegaly Hypoglycaemia

Jaundice Tachycardia

Anaemia Tachypnoea

Malaria


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Ix: Serial thick and thin blood films

Tx: ABCDE – Supportive

Antimalarials e.g. Quinine, Artesenate

Issues: Cerebral Malaria, Resp. Acidosis, Anaemia

Hypoglycaemia, Co-infection

Malaria


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Prevention:

1. Vector Control

e.g. mosquito nets, residual spraying

2. Appropriate anti-malarial prophylaxis

e.g. Malarone, Doxycycline, Chloroquine

Malaria


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What: Inflammation of the liver

Why: Infection (Hepatitis, Herpes) , Malignancy,

Inflammation (cholecystitis/pancreatitis)

Drugs ( paracetamol, alcohol)

PC: Jaundice, Fever, Abdo Pain, Malaise, N&V

OE: Jaundice, ^Temp, Tender RUQ

Hepatitis


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Types: A/E Faecal Oral Route

B/C Blood products

D IVDU users, need Hep B

Who: 90% babies chronic Hep B

90% adults clear Hep B

Tx: Supportive

Prevent hepatic failure

Hepatitis


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Core Antigen cAg = ACUTE ^^^ Virus replication

Envelope Antigen eAg = Over time

Surface Antigen sAg =

Protection, clearance, vaccination

Hepatitis Serology


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^^^LFTs, AntiHBc IgM = ACUTE

^LFTs, AntiHBc IgG = CARRIER

N LFTs, AntiHBs = VACCINATION

N LFTs, AntiHBs, Anti HBc IgG = RECOVERY

Hepatitis Serology


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Arthur, 60 year old male diabetic has sore, hot red legafter tripping over 3 days ago. No calf tenderness, leg

swelling or chest pain.

What: ?

Bug: ?

Ix: ?

Tx: ?

Quiz


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Arthur, 60 year old male diabetic has sore, hot red legafter tripping over 3 days ago. No calf tenderness, leg

swelling or chest pain.

What: Cellulitis

Bug: Staphylococcus Aureus/Epidermidis

Ix: Blood cultures, wound swab

Tx: Flucloxacillin/Vancomycin

Quiz


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Scarlett, 18 year old female student, 2 day history of fever,vomiting and headache.

What: ?

Bug: ?

Ix: ?

Tx: ?

Quiz


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Scarlett, 18 year old female student, 2 day history of fever,vomiting and headache.

What: Meningitis

Bug: NHS N.MeningitidesH. Influenzae

Strep.Pneumoniae

Ix: LP, Bloods, blood cultures, ABG, ECG

Tx: Benzylpenicillin, CEFTRIAXONE STAT

Quiz


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Betty, an adorable 87 year old lady has had a cough for3/7. She becomes very short of breath, pyrexic and is

coughing up green sputum.

What: ?

Bug: ?

Ix: ?

Tx: ?

Issues: ?

Quiz


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Betty, an adorable 87 year old lady has had a cough for3/7. She becomes very short of breath, pyrexic and is

coughing up green sputum.

What: Community acquired pneumonia

Bug: Strep.Pneumoniae

Ix: CXR, Sputum culture, NPA, FBC

Tx: Amoxicillin, ?O2

Issues: CURB65 score (score 5 = ^^^mortality)

Quiz


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Andy, a 22 year old med student has just got back from hiselective in Namibia. He is feeling very tired and has a

fever.

What: ?

Bug: ?

Ix: ?

Tx: ?

Quiz


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Andy, a 22 year old med student has just got back from hiselective in Namibia. He is feeling very tired and has a

fever.

What: Malaria until proven otherwise!

Bug: Plasmodium

Ix: Serial thick and thin blood films, Bloods

Tx: Antimalarials, Tx Hypoglycaemia, Fluids

Quiz


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Andy’s friend Lee, went to Ibiza for a lads holiday. He hashad R-sided chest pain, SOB and a dry cough for 8/7. He

now has a headache, chills and myalgia.

HR 125, BP 75/50, RR 40, Temp 38.5oC, O2 89%

What: ?

Ix: ?

Bug: ?

Tx: ?

Quiz


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Andy’s friend Lee, went to Ibiza for a lads holiday. He hashad R-sided chest pain, SOB and a dry cough for 8/7. He

now has a headache, chills and myalgia.

HR 125, BP 75/50, RR 40, Temp 38.5oC, O2 89%

What: An atypical pneumonia

Ix: CXR (Right apex), Bloods (vNa), Cultures (Gram -)

Bug: Legionella Pneumophila

Tx: IV Erythromycin

Quiz

h k i ?


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Thank you – questions?

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